WileyActa Medica Okayama0041-11322026Pediatric autologous peripheral blood stem cell collection without heparin using a highly concentrated sodium citrate anticoagulant: A retrospective comparison with standard ACD-AENKeikoFujiiDepartment of Hematology, Okayama University HospitalWataruKitamuraDepartment of Hematology, Okayama University HospitalKanaWashioDepartment of Pediatrics, Okayama University HospitalKazuhiroIkeuchiDepartment of Hematology, Okayama University HospitalJojiShimonoDepartment of Hematology, Okayama University HospitalHiroyukiMurakamiDepartment of Hematology, Okayama University HospitalFumioOtsukaDivision of Clinical Laboratory, Okayama University HospitalYoshinobuMaedaDepartment of Hematology, Okayama University HospitalNobuharuFujiiDepartment of Hematology, Okayama University HospitalBackground: Heparin combined with sodium citrate has been used in leukocytapheresis for pediatric patients. Since 2022, we have performed leukocytapheresis using a highly concentrated sodium citrate solution (HSC, 5.32%) instead of acid citrate dextrose solution A (ACD-A). We conducted this study to determine whether HSC use reduces run time and the total amount of anticoagulant solution in children.<br>
Study Design and Methods: We retrospectively analyzed data from consecutive autologous peripheral blood stem cell harvests (auto-PBSCHs) between June 2012 and May 2025, including patient characteristics, mobilization methods, protocol used, anticoagulant type, run time, total anticoagulant solution volume, and collection efficiency.<br>
Results: Auto-PBSCH was performed using the mononuclear cell collection (MNC) protocol in 28 procedures and the continuous MNC protocol in 20 procedures. ACD-A was used in 35 procedures and HSC in 13. The run time was significantly shorter (204 [range, 117–302] vs. 157 min [range, 103–227], p = .02) in the HSC group and also confirmed in multivariable regression analysis (coefficient, −55.6; 95% confidence interval, −106.2 to −5.04; p = .03). In a subgroup analysis of cMNC procedures, CD34+ collection efficiency showed a strong negative correlation with the proportion of run time devoted to establishing the initial interface (r = −.73, p = .0003).<br>
Conclusion: Delays in establishing the initial interface can reduce the duration of the effective MNC collection phase and may negatively affect collection efficiency. Careful attention to the initial interface phase is therefore warranted when using HSC.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama2772-5723522026Feasibility and Diagnostic Utility of Mucosal T-Cell Flow Cytometry for Intestinal Graft-Versus-Host Disease100820ENMasayaIwamuroDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTakumiKondoDepartment of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesDaisukeEnnishiDepartment of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesNobuharuFujiiDepartment of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesMaiHiramatsuDivision of Medical Support, Okayama University HospitalArakiHirabataDivision of Medical Support, Okayama University HospitalTakahideTakahashiDivision of Medical Support, Okayama University HospitalTakehiroTanakaDepartment of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYoshinobuMaedaDepartment of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesMotoyukiOtsukaDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesBackground and Aims: Timely diagnosis of intestinal complications after hematopoietic stem cell transplantation (HSCT), including graft-versus-host disease (GVHD), transplant-associated thrombotic microangiopathy, and cytomegalovirus infection, is essential for appropriate management. This study evaluated whether mucosal T-cell profiling from endoscopic biopsies could support the diagnosis of these post-transplant conditions.<br>
Methods: We prospectively analyzed 58 intestinal biopsy specimens from 21 post-HSCT patients. Paired samples were obtained from the stomach and duodenum during upper endoscopy and from the ileum and large intestine during colonoscopy. Lymphocytes were isolated from each specimen and analyzed using flow cytometry. These data were integrated with those of a previously collected cohort (35 patients, 51 samples) for comparative immunophenotypic analysis across histologically defined groups.<br>
Results: Duodenal biopsies yielded more lymphocytes than did gastric biopsies (mean ± standard deviation: 532 ± 823 vs 233 ± 392 cells; P = .070), with comparable yields between the ileum and colon. Among 41 evaluable cases, the CD56+:CD3+ ratio was significantly lower in patients with GVHD (5.5 ± 2.2%) than in those with nonspecific or no inflammation (28.4 ± 16.3%; P = .006). A cutoff value of <11% provided 85.7% sensitivity and 83.3% specificity for diagnosing GVHD (area under the curve = 0.91).<br>
Conclusion: Mucosal T-cell profiling using endoscopic biopsies is feasible and may aid in the diagnosis of GVHD after HSCT. A decreased CD56+:CD3+ ratio is a promising marker for distinguishing GVHD from other post-transplant intestinal conditions.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0925-571012252025Intravenous umbilical cord-derived mesenchymal stromal cell therapy may improve overall survival in Japanese patients with idiopathic pneumonia syndrome after hematopoietic stem cell transplantation: a multicenter, single-arm, phase II trial733743ENNorikoDokiHematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome HospitalNobuharuFujiiDepartment of Hematology and Oncology, Okayama University HospitalShinichiKakoDivision of Hematology, Jichi Medical University Saitama Medical CenterEmikoSakaidaDepartment of Hematology, Chiba University HospitalYoshinobuKandaDivision of Hematology, Department of Medicine, Jichi Medical UniversityIdiopathic pneumonia syndrome (IPS) is a serious complication of allogeneic hematopoietic stem cell transplantation (HSCT) and has a poor prognosis. Although IPS is often treated with steroids, the disease can become resistant to or dependent on steroid treatment, and there is no effective cure for patients with refractory or steroid-dependent IPS. This multicenter, open-label, single-arm, phase II clinical trial investigated the efficacy and safety of HLC-001 (allogeneic umbilical cord-derived mesenchymal stromal cells) in patients with progressive steroid-dependent or refractory IPS after HSCT. Seven male patients (all male; mean age: 43.3 years) received HLC-001 and three completed the trial. The survival rate at day 56 (primary endpoint) was 71.4% (5/7 patients; 95% confidence interval: 29.0%–96.3%) and was sustained at day 100, suggesting that HLC-001 was more effective than previously reported treatment. Three of the five patients with ≥ 100 days of follow-up died. Five patients experienced at least one adverse drug reaction, none of which were serious. These findings indicate that HLC-001 was potentially effective and generally well tolerated in Japanese patients with steroid-dependent or refractory IPS after HSCT. Given there is no effective cure for steroid-dependent or refractory IPS, HLC-001 may be a promising treatment option and further clinical evaluation is warranted.<br>
Trial registration: Japan Registry of Clinical Trials identifier: jRCT2063220014.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama1465-32492782025Clinical outcomes of Japanese patients treated with out-of-specification tisagenlecleucel in a phase 3b trial938943ENKojiKatoDepartment of Hematology, Oncology, and Cardiovascular Medicine, Kyushu University HospitalJunKatoDivision of Hematology, Department of Medicine, Keio University School of MedicineHidekiGotoDivision of Laboratory and Transfusion Medicine, Hokkaido University HospitalTakeshiKobayashiHematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome HospitalYoshiyukiTakahashiDepartment of Pediatrics, Nagoya University Graduate School of MedicineEmikoSakaidaDepartment of Hematology, Chiba University HospitalHidefumiHiramatsuDepartment of Pediatrics, Graduate School of Medicine, Kyoto UniversityMasahideYamamotoDepartment of Hematology, Institute of Science Tokyo HospitalSatoshiYoshiharaDepartment of Hematology, Hyogo Medical University HospitalJunAndoDepartment of Cell Therapy and Transfusion Medicine, Juntendo University Graduate School of MedicineKatsuyoshiKohDepartment of Hematology/Oncology, Saitama Children’s Medical CenterKentaroFukushimaDepartment of Hematology and Oncology, Osaka University Graduate School of MedicineFumikoIwamotoMedical Affairs, Novartis Pharma K.K.RanjanTiwariDevelopment Advance Quantitative Sciences, Novartis Healthcare Private LimitedNobuharuFujiiDepartment of Hematology and Oncology, Okayama University HospitalBackground: The final manufactured tisagenlecleucel product should meet the commercial product release specifications to ensure the quality in terms of safety, purity, identity, and potency. However, it may occasionally fail to meet these specifications due to the nature of patient-derived cells with variable properties as starting material and the complex manufacturing process. The final product that does not meet at least one of the commercial release specifications is referred to as “out-of-specification” (OOS). However, the benefit-risk profile of OOS tisagenlecleucel has not yet been fully elucidated.<br>
Aims: To evaluate the safety and efficacy of OOS tisagenlecleucel in Japanese patients with relapsed or refractory (r/r) diffuse large B-cell lymphoma (DLBCL) and B-cell acute lymphoblastic leukemia (B-ALL).<br>
Methods: This is a single-arm, open-label, multicenter phase 3b study (NCT04094311). Patients consistent with label indication were enrolled and followed-up for 3 months.<br>
Results: Of the 29 patients enrolled between December 2019 and May 2022 across 13 qualified sites in Japan, 28 received tisagenlecleucel, and of these, 23 had r/r DLBCL and 5 had r/r B-ALL. The primary reasons for OOS were low cell viability (15 of 24 batches) and low dose (8 of 23 batches) tisagenlecleucel in the r/r DLBCL group, and high dose (4 of 5 batches) in the r/r B-ALL group. In patients with r/r DLBCL, the grade 3 or 4 cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome occurred in 3 and 1 patients, respectively. Response assessments were performed for 15 of 23 patients with r/r DLBCL: 6 achieved a complete response, and 1 achieved a partial response as the best response within 3 months.<br>
Conclusions: Despite the limited patient sample size, our findings affirm that the infusion of OOS tisagenlecleucel is a viable option, with no observed increase in toxicity and outcomes comparable to those of in-specification products in clinical and real-world studies.No potential conflict of interest relevant to this article was reported.Japanese Society of Internal MedicineActa Medica Okayama0918-291863132024Activated CD4+ T Cell Proportion in the Peripheral Blood Correlates with the Duration of Cytokine Release Syndrome and Predicts Clinical Outcome after Chimeric Antigen Receptor T Cell Therapy18631872ENWataruKitamuraDepartment of Hematology and Oncology, Okayama University HospitalNoboruAsadaDepartment of Hematology and Oncology, Okayama University HospitalShuntaroIkegawaDepartment of Hematology and Oncology, Okayama University Hospital, JapanHideakiFujiwaraDepartment of Hematology and Oncology, Okayama University HospitalChihiroKamoiDepartment of Hematology and Oncology, Okayama University HospitalDaisukeEnnishiCenter for Comprehensive Genomic Medicine, Okayama University HospitalHisakazuNishimoriDepartment of Hematology and Oncology, Okayama University HospitalKeikoFujiiDivision of Clinical Laboratory, Okayama University HospitalNobuharuFujiiDivision of Blood Transfusion, Okayama University HospitalKen-ichiMatsuokaDepartment of Hematology and Oncology, Okayama University HospitalYoshinobuMaedaDepartment of Hematology and Oncology, Okayama University HospitalObjective Chimeric antigen receptor (CAR) T cell therapy is an emerging and effective therapy for relapsed or refractory diffuse large B cell lymphoma (R/R DLBCL). The characteristic toxicities of CAR T cell therapy include cytokine release syndrome (CRS) and prolonged cytopenia. We investigated the factors associated with these complications after CAR T cell therapy by analyzing lymphocyte subsets following CAR T cell infusion.<br>
Methods We retrospectively analyzed peripheral blood samples on days 7, 14, and 28 after tisagenlecleucel (tisa-cel) infusion by flow cytometry at our institution between June 2020 and September 2022.<br>
Patients Thirty-five patients with R/R DLBCL who received tisa-cel therapy were included.<br>
Results A flow cytometry-based analysis of blood samples from these patients revealed that the proportion of CD4+CD25+CD127+ T cells (hereafter referred to as "activated CD4+ T cells" ) among the total CD4+ T cells on day 7 after tisa-cel infusion correlated with the duration of CRS (r=0.79, p<0.01). In addition, a prognostic analysis of the overall survival (OS) using time-dependent receiver operating characteristic curves indicated a significantly more favorable OS and progression-free survival of patients with a proportion of activated CD4+ T cells among the total CD4+ T cells <0.73 (p=0.01, and p<0.01, respectively).<br>
Conclusion These results suggest that the proportion of activated CD4+ T cells on day 7 after tisa-cel infusion correlates with the CRS duration and predicts clinical outcomes after CAR T cell therapy. Further studies with a larger number of patients are required to validate these observations.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7962025Recurrence of FVIII Inhibitor during Surgery in a Patient with Severe Hemophilia A Receiving Emicizumab Prophylaxis451455ENMoeHagiharaDepartment of Hematology and Oncology, Okayama University HospitalKeisukeSeikeDepartment of Hematology and Oncology, Okayama University HospitalKentaHayashinoDepartment of Hematology and Oncology, Okayama University HospitalTakaoYasuharaDepartment of Neurological Surgery, Okayama University HospitalKyoheiKinDepartment of Neurological Surgery, Okayama University HospitalYuichiHirataDepartment of Neurological Surgery, Okayama University HospitalHirokiKobayashiDepartment of Hematology and Oncology, Okayama University HospitalWataruKitamuraDepartment of Hematology and Oncology, Okayama University HospitalHideakiFujiwaraDepartment of Hematology and Oncology, Okayama University HospitalNoboruAsadaDepartment of Hematology and Oncology, Okayama University HospitalNobuharuFujiiDivision of Transfusion and Cell Therapy, Okayama University HospitalYoshinobuMaedaDepartment of Hematology and Oncology, Okayama University HospitalCase Report10.18926/AMO/69848Emicizumab, a bispecific monoclonal antibody, benefits patients with severe hemophilia A. It alters laboratory assessments of coagulation activity, requiring anti-idiotype monoclonal antibodies for accurate monitoring. A 64-year-old man, receiving emicizumab regularly, was admitted for laminoplasty. We planned to use FVIII replacement during the perioperative period after confirming the disappearance of inhibitors, monitoring coagulation activity with anti-idiotype monoclonal antibodies. Activated partial thromboplastin time was prolonged on postoperative day 2, prompting an immediate switch to eptacog alfa. The patient recovered without bleeding. This case underscores the necessity of anti-idiotype monoclonal antibodies for accurate monitoring.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama1473-05026442025Factors affecting the development of hypokalemia during apheresis in healthy donors104195ENWataruKitamuraDepartment of Hematology and Oncology, Okayama University HospitalKeikoFujiiDepartment of Hematology and Oncology, Okayama University HospitalHirokiKobayashiDepartment of Hematology and Oncology, Okayama University HospitalMasayaAbeDepartment of Hematology and Oncology, Okayama University HospitalTakuyaFukumiDepartment of Hematology and Oncology, Okayama University HospitalKazuhiroIkeuchiDepartment of Hematology and Oncology, Okayama University HospitalFumioOtsukaDivision of Clinical Laboratory, Okayama University HospitalYoshinobuMaedaDepartment of Hematology and Oncology, Okayama University HospitalNobuharuFujiiDepartment of Hematology and Oncology, Okayama University HospitalDespite being generally safe, apheresis for peripheral blood stem cell collection potentially disrupts electrolyte balance owing to the use of citric acid as an anticoagulant. As prior research has primarily studied hypocalcemia, information on the kinetics of potassium levels during apheresis in healthy donors is scarce. We investigated the fluctuation in potassium levels during apheresis and the risk factors for hypokalemia. This subanalysis used data from an open-label, randomized controlled trial of “oral calcium supplementation versus placebo in mitigating citrate toxicity” conducted between January 2021 and July 2022, at Okayama University Hospital. Potassium levels were significantly reduced after 5-day granulocyte colony-stimulating factor (G-CSF) administration (p < 0.0001), with seven patients (16.7 %) given oral potassium administration before apheresis because the treating physician deemed potassium levels potentially unsafe and three (7.1 %) presenting with hypokalemia at apheresis. Potassium levels after apheresis were significantly lower than those before apheresis (baseline; p < 0.0001), and 28 of 42 donors (66.7 %) experienced biochemical, clinically unapparent hypokalemia immediately after the completion of apheresis. A > 15 % reduction in potassium levels from baseline was associated with age and the acid citrate dextrose solution A (ACD-A) volume in univariate analysis. In the multivariable analysis, both factors were associated (hazard ratio [HR], 11.60; 95 % confidence interval [CI], 1.60–83.70; p = 0.02 and HR, 17.50; 95 % CI, 1.07–136.00; p = 0.04). In conclusion, G-CSF administration and apheresis ultimately induced hypokalemia in two-thirds of the donors. Older age and higher ACD-A volume may affect potassium levels during apheresis in healthy donors.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama1473-05026462025Novel leukocytapheresis method using highly concentrated sodium citrate solution for the manufacturing of tisagenlecleucel104265ENWataruKitamuraDepartment of Hematology and Oncology, Okayama University HospitalKeikoFujiiDepartment of Hematology and Oncology, Okayama University HospitalMasayaAbeDepartment of Hematology and Oncology, Okayama University HospitalKazuhiroIkeuchiDepartment of Hematology and Oncology, Okayama University HospitalKanaWashioDepartment of Pediatrics, Okayama University HospitalFumioOtsukaDivision of Clinical Laboratory, Okayama University HospitalYoshinobuMaedaDepartment of Hematology and Oncology, Okayama University HospitalNobuharuFujiiDepartment of Hematology and Oncology, Okayama University HospitalFor the manufacturing of tisagenlecleucel (tisa-cel) requires the non-mobilized mononuclear cell collection (MNC). CD3+ cell collection is performed using the same protocol as autologous peripheral blood stem cell harvest (auto-PBSCH), but this procedure necessitates the same target CD3+ cell yields regardless of age or body weight, which may take several days especially in pediatric and small female patients with low white blood cell counts. We previously demonstrated a novel method using highly concentration sodium citrate (HSC), which reduced the need for an anticoagulant (AC) solution and shortened the procedure time in auto-PBSCH. This novel method was expected to offer advantages for smaller patients, prompting us to investigate its application in leukocytapheresis for the manufacturing of tisa-cel. We retrospectively analyzed consecutive leukocytapheresis data obtained using Spectra Optia continuous MNC mode between November 2022 and June 2024 at our institution (n = 9). In six of nine patients, pre-leukocytapheresis CD3+ cell counts were less than 500 /μL, but all could obtain the target CD3+ cell yields in one day upon processing blood volume adjustment. When we compared patients who had received CD3+ cell collection using normal-concentration sodium citrate (NSC) as our previously reported using propensity score-matched pair analysis, the total AC solution volume was significantly lower (1168 vs. 316 mL, p < 0.001) and procedure time was significantly shorter (254 vs. 228 min, p = 0.04) in the HSC group compared to the NSC group. In conclusion, this procedure was also useful for non-mobilized MNC. Our findings warrant validation in a larger patient cohort.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama0041-11326592025Novel method for autologous peripheral blood stem cell harvest using highly concentrated sodium citrate solution replacing acid citrate dextrose solution A16621672ENWataruKitamuraDepartment of Hematology and Oncology, Okayama University HospitalKeikoFujiiDepartment of Hematology and Oncology, Okayama University HospitalMasayaAbeDepartment of Hematology and Oncology, Okayama University HospitalKazuhiroIkeuchiDepartment of Hematology and Oncology, Okayama University HospitalJojiShimonoDepartment of Hematology and Oncology, Okayama University HospitalKanaWashioDepartment of Pediatrics, Okayama University HospitalFumioOtsukaDivision of Clinical Laboratory, Okayama University HospitalYoshinobuMaedaDepartment of Hematology and Oncology, Okayama University HospitalNobuharuFujiiDepartment of Hematology and Oncology, Okayama University HospitalBackground: As the processed blood volume increases, a larger amount of anticoagulant (AC) is required, which leads to a serious issue of fluid dilution in large-volume leukocytapheresis (defined as ≥3-fold total blood volume). We previously reported a novel method for allogeneic peripheral blood stem cell harvest (PBSCH) using highly concentrated sodium citrate (HSC; 5.32%), which shortened the procedure time and reduced the need for an AC solution without heparin. In this study, we extended this novel method to autologous PBSCH (auto-PBSCH) and compared it with patients who received auto-PBSCH using normal concentrated sodium citrate (NSC; 2.2%).<br>
Study Design and Methods: We retrospectively analyzed consecutive auto-PBSCH data obtained using the Spectra Optia continuous mononuclear cell collection mode between May 2017 and May 2025 at our institution.<br>
Results: Leukocytapheresis was performed using NSC in 36 patients and HSC in 22. In the HSC group, patients tended to be younger, had significantly lower body weight, and had significantly fewer hematopoietic tumors as primary diseases compared to the NSC group. After propensity score-matched cohort adjusted for patient background, the total amount of AC solution was significantly lower (694 [range, 77–1648] vs. 298 mL [range, 64–797], p = .02), and procedure time was significantly shorter (224 [range, 117–395] vs. 181 min [range, 103–309], p = .048) in the HSC group. Furthermore, the loss rates of magnesium and potassium were lower in the HSC group.<br>
Conclusion: This novel leukocytapheresis method demonstrated the efficacy and safety in auto-PBSCH, while minimizing the patient burden.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0925-571012252025Cytomegalovirus reactivation in patients with large B-cell lymphoma treated with chimeric antigen receptor T-cell therapy689699ENKentaHayashinoDepartment of Hematology and Oncology, Okayama UniversityKeisukeSeikeDepartment of Hematology and Oncology, Okayama UniversityTaroMasunariDepartment of Hematology, Chugoku Central HospitalRisaHashidaDivision of Hematology, Ehime Prefectural Central HospitalSatoshiOkaDepartment of Hematology and Blood Transfusion, Kochi Health Science CenterYukiFujiwaraDepartment of Hematology and Oncology, Japanese Red Cross Society Himeji HospitalToshikiTeraoDepartment of Hematology and Oncology, Okayama UniversityWataruKitamuraDepartment of Hematology and Oncology, Okayama UniversityHirokiKobayashiDepartment of Hematology and Oncology, Okayama UniversityChihiroKamoiDepartment of Hematology and Oncology, Okayama UniversityTakumiKondoDepartment of Hematology and Oncology, Okayama UniversityHideakiFujiwaraDepartment of Hematology and Oncology, Okayama UniversityNoboruAsadaDepartment of Hematology and Oncology, Okayama UniversityDaisukeEnnishiDepartment of Hematology and Oncology, Okayama UniversityKeikoFujiiDepartment of Hematology and Oncology, Okayama UniversityNobuharuFujiiDepartment of Hematology and Oncology, Okayama UniversityYoshinobuMaedaDepartment of Hematology and Oncology, Okayama UniversityChimeric antigen receptor (CAR) T-cell therapy has improved outcomes of relapsed and/or refractory large B-cell lymphoma (r/r LBCL). However, its off-tumor effects result in severe prolonged humoral immune deficiency. Cytomegalovirus (CMV) is a latent virus that can be life-threatening in immunosuppressed patients. In the setting of CAR T-cell therapy, Asian race is a risk factor for clinically significant CMV infection. However, the effect of CAR T-cell therapy on CMV reactivation in Japanese patients remains unclear. Previous reports used polymerase chain reaction (PCR), but we used the pp65 antigenemia assay to retrospectively investigate long-term effects in patients with r/r LBCL. The study included 46 patients. Nine (19.6%) developed CMV reactivation, with a median onset of 13 days. Six of these patients received preemptive therapy, and none developed CMV end-organ disease. Primary refractory disease, grade 2–4 cytokine release syndrome, and high-dose corticosteroids were risk factors for CMV reactivation. Long-term follow-up showed that CMV reactivation rarely occurred later than 28 days post-infusion. Our study using the pp65 antigenemia assay showed a similar incidence of CMV reactivation, onset, and risk factors to those in the previous reports using PCR.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama2688-6146652025Late‐Onset Invasive Aspergillosis With Pituitary Involvement and Dysfunction Following CD19 Chimeric Antigen Receptor T‐Cell Therapye70138ENDaisukeIkedaDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTomohiroNawadaThe Center for Graduate Medical Education, Okayama University HospitalTakumiKondoDepartment of Hematology and Oncology, Okayama University HospitalTakayukiShinoharaDepartment of Fungal Infection, National Institute of Infectious DiseasesTomohiroNaganoDepartment of Hematology and Oncology, Okayama University HospitalSayaKubotaDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRyuichiroHiyamaDepartment of Hematology and Oncology, Okayama University HospitalMasayaUenoDepartment of Hematology and Oncology, Okayama University HospitalHirokiKobayashiDepartment of Hematology and Oncology, Okayama University HospitalKeisukeSeikeDepartment of Hematology and Oncology, Okayama University HospitalHideakiFujiwaraDepartment of Hematology and Oncology, Okayama University HospitalNoboruAsadaDepartment of Hematology and Oncology, Okayama University HospitalDaisukeEnnishiDepartment of Hematology and Oncology, Okayama University HospitalKeikoFujiiDepartment of Hematology and Oncology, Okayama University HospitalNobuharuFujiiDepartment of Hematology and Oncology, Okayama University HospitalMasanoriMakitaDepartment of Hematology, Chugoku Central HospitalYoshinobuMaedaDepartment of Hematology and Oncology, Okayama University HospitalIntroduction: Invasive fungal infection (IFI) after chimeric antigen receptor (CAR) T-cell therapy is less common than bacterial and viral infections, but can be fatal once it develops. As most cases occur within 30 days after CAR T-cell infusion, late-onset IFI—particularly mould infection—appears to be under-recognised.<br>
Discussion: We report an illustrative case of pituitary aspergillosis developing as late as one year after CD19 CAR T-cell therapy, highlighting a persistent risk in certain patients with delayed immune reconstitution.<br>
Conclusion: This case underscores the need for continued vigilance and individualised antifungal strategies to prevent IFI beyond the early post-infusion period.<br>
Trial Registration: The authors have confirmed clinical trial registration is not needed for this submission.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2168-81841772025Six-Year Remission With No Relapse After Four-Time Weekly Rituximab Only for Bilateral Ocular Adnexal Follicular Lymphomae88945ENToshihikoMatsuoOphthalmology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University, and Okayama University HospitalTakehiroTanakaDepartment of Pathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityNobuharuFujiiDivision of Transfusion and Cell Therapy, Department of Hematology and Oncology, Okayama University HospitalFollicular lymphoma mostly takes an indolent course, and thus, observation with watchful waiting is a main therapeutic strategy. Recent long-term studies suggest earlier treatment with rituximab monotherapy may benefit patients by delaying the need for treatment in the later phase of exacerbation. In this study, we reported a patient with bilateral orbital follicular lymphoma who received four-time weekly rituximab monotherapy as an induction therapy only and maintained the remission for 5 years with no treatment. The patient was a 51-year-old woman who developed a right upper orbital mass and was diagnosed with follicular lymphoma grade 1 by the excisional biopsy. Two years later, at the age of 53 years, she developed a left lacrimal gland mass and underwent excision. The pathological diagnosis was follicular lymphoma grade 1. She did not have any other systemic lesions by fluorodeoxyglucose positron emission tomography. At the age of 54 years, she developed a new mass on the nasal side of the right orbit and underwent weekly rituximab monotherapy (375 mg/m2) four times a month, leading to the reduction of the mass in 3 months. Two high uptake sites on the temporal and nasal side of the right superior orbit by fluorodeoxyglucose positron emission tomography disappeared one year later at the age of 55 years. She was followed with no treatment for 6 years until the age of 60 years at the latest visit. In case of a local orbital relapse, local radiotherapy would be the standard, but rituximab monotherapy as an induction therapy only was chosen in the present patient. Rituximab monotherapy in place of local radiotherapy would be a treatment option for orbital follicular lymphoma.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0925-571012122024Outcomes of allogeneic SCT versus tisagenlecleucel in patients with R/R LBCL and poor prognostic factors232243ENKentaHayashinoDepartment of Hematology and Oncology, Okayama University Hospital, Okayama UniversityToshikiTeraoDepartment of Hematology and Oncology, Okayama University Hospital, Okayama UniversityHisakazuNishimoriDepartment of Hematology and Oncology, Okayama University Hospital, Okayama UniversityWataruKitamuraDepartment of Hematology and Oncology, Okayama University Hospital, Okayama UniversityHirokiKobayashiDepartment of Hematology and Oncology, Okayama University Hospital, Okayama UniversityChihiroKamoiDepartment of Hematology and Oncology, Okayama University Hospital, Okayama UniversityKeisukeSeikeDepartment of Hematology and Oncology, Okayama University Hospital, Okayama UniversityHideakiFujiwaraDepartment of Hematology and Oncology, Okayama University Hospital, Okayama UniversityNoboruAsadaDepartment of Hematology and Oncology, Okayama University Hospital, Okayama UniversityDaisukeEnnishiDepartment of Hematology and Oncology, Okayama University Hospital, Okayama UniversityKeikoFujiiDepartment of Hematology and Oncology, Okayama University Hospital, Okayama UniversityNobuharuFujiiDepartment of Hematology and Oncology, Okayama University Hospital, Okayama UniversityKen-ichiMatsuokaDepartment of Hematology and Oncology, Okayama University Hospital, Okayama UniversityYoshinobuMaedaDepartment of Hematology and Oncology, Okayama University Hospital, Okayama UniversityThis study investigated the efficacy of tisagenlecleucel (tisa-cel) and allogeneic hematopoietic stem cell transplantation (allo-SCT) for patients with relapsed and/or refractory (r/r) large B-cell lymphoma (LBCL) with poor prognostic factors, defined as performance status (PS) ≥ 2, multiple extranodal lesions (EN), chemorefractory disease, or higher lactate dehydrogenase (LDH). Overall, the allo-SCT group demonstrated worse progression-free survival (PFS), higher non-relapse mortality, and a similar relapse/progression rate. Notably, the tisa-cel group showed better PFS than the allo-SCT group among patients with chemorefractory disease (3.2 vs. 2.0 months, p = 0.092) or higher LDH (4.0 vs. 2.0 months, p = 0.018), whereas PFS in the two cellular therapy groups was similar among those with PS ≥ 2 or multiple EN. Survival time after relapse post-cellular therapy in patients with poor prognostic factors was 1.6 with allo-SCT and 4.6 months with tisa-cel. These findings were confirmed in a propensity score matching cohort. In conclusion, tisa-cel resulted in better survival than allo-SCT in patients with poor prognostic factors. However, patients who relapsed post-cellular therapy had dismal outcomes regardless of therapy. Further strategies are warranted to improve outcomes in these patients.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama0041-11322025Novel method of leukocytapheresis using a highly concentrated sodium citrate solution alternative to acid citrate dextrose solution AENMasayaAbeDivision of Transfusion and Cell Therapy, Okayama University HospitalKeikoFujiiDivision of Clinical Laboratory, Okayama University HospitalToshiharuMitsuhashiCenter for Innovative Clinical Medicine, Okayama University HospitalWataruKitamuraDivision of Transfusion and Cell Therapy, Okayama University HospitalKazuhiroIkeuchiDivision of Transfusion and Cell Therapy, Okayama University HospitalTakuyaFukumiDivision of Transfusion and Cell Therapy, Okayama University HospitalKanaWashioDepartment of Pediatric Hematology and Oncology, Okayama University HospitalFumioOtsukaDivision of Clinical Laboratory, Okayama University HospitalYoshinobuMaedaDepartment of Hematology and Oncology, Okayama University HospitalNobuharuFujiiDivision of Transfusion and Cell Therapy, Okayama University HospitalBackground: Large-volume leukocytapheresis is time consuming. The upper limit of the inlet flow rate is determined by the inlet: anticoagulant (AC) ratio and can be changed by combining the AC with heparin. Here, we devised a protocol to increase the AC ratio using a highly concentrated sodium citrate solution without heparin.<br>
Study Design and Methods: We collected data from 40 consecutive apheresis procedures performed using the Spectra Optia system on 40 donors for allogeneic peripheral blood stem cells between June 2022 and June 2023. We used AC containing 2.2% sodium citrate (normal concentrated sodium citrate [NSC]) and 5.32% sodium citrate (highly concentrated sodium citrate [HSC]). The AC ratios were set to 12:1 and 24:1 for the NSC and HSC, respectively.<br>
Results: The processed volume was not different; the maximum inlet flow rate increased, the total processing time was reduced, the AC solution used was reduced, and the product volume was reduced in the HSC group, compared to the NSC group. Although the CD34+ cell CE2 was reduced in the HSC group, no difference was observed in the number of collected CD34+ cells. The incidences of citrate-related reactions were similar.<br>
Discussion: We propose a novel leukocytapheresis method using HSC that shortens the procedure time and reduces the amount of AC solution used compared to the conventional methodNo potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0939-55552025A randomized controlled trial of conventional GVHD prophylaxis with or without teprenone for the prevention of severe acute GVHDENWataruKitamuraDepartment of Hematology and Oncology, Okayama University HospitalKeikoFujiiDepartment of Hematology and Oncology, Okayama University HospitalMitsuruTsugeDepartment of Pediatric Acute Diseases, Okayama University Academic Field of Medicine Dentistry, and Pharmaceutical SciencesToshiharuMitsuhashiCenter for Innovative Clinical Medicine, Okayama University HospitalHirokiKobayashiDepartment of Hematology and Oncology, Okayama University HospitalChihiroKamoiDepartment of Hematology and Oncology, Okayama University HospitalAkiraYamamotoDepartment of Hematology and Oncology, Okayama University HospitalTakumiKondoDepartment of Hematology and Oncology, Okayama University HospitalKeisukeSeikeDepartment of Hematology and Oncology, Okayama University HospitalHideakiFujiwaraDepartment of Hematology and Oncology, Okayama University HospitalNoboruAsadaDepartment of Hematology and Oncology, Okayama University HospitalDaisukeEnnishiDepartment of Hematology and Oncology, Okayama University HospitalKen-ichiMatsuokaDepartment of Hematology and Oncology, Okayama University HospitalNobuharuFujiiDepartment of Hematology and Oncology, Okayama University HospitalYoshinobuMaedaDepartment of Hematology and Oncology, Okayama University HospitalTherapies that effectively suppress graft-versus-host disease (GVHD) without compromising graft-versus-leukemia/lymphoma (GVL) effects is important in allogeneic hematopoietic stem cell transplantation (allo-HSCT) for hematopoietic malignancies. Geranylgeranylacetone (GGA) is a main component of teprenone, a gastric mucosal protectant commonly used in clinical practice. In preclinical models, GGA suppresses proinflammatory cytokines, including interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α), which are associated with GVHD as well as induces thioredoxin-1 (Trx-1), which suppresses GVHD while maintaining GVL effects. Here, we investigated whether the addition of teprenone to standard GVHD prophylaxis could reduce the cumulative incidence of severe acute GVHD (aGVHD) without attenuating GVL effects. This open-label, randomized clinical trial enrolled 40 patients (21 control and 19 teprenone group) who received allo-HSCT between May 2022 and February 2023 in our institution. Patients in the teprenone group received 50 mg of teprenone orally thrice daily for 21 days from the initiation of the conditioning regimen. The cumulative incidence of severe aGVHD by day 100 after allo-HSCT was not significantly different in the two groups (27.9 vs. 16.1%, p = 0.25). The exploratory studies revealed no obvious changes in Trx-1 levels, but the alternations from baseline in IL-1β and TNF-α levels at day 28 after allo-HSCT tended to be lower in the teprenone group. In conclusion, we could not demonstrate that teprenone significantly prevented the development of severe aGVHD. Discrepancy with preclinical model suggests that appropriate dose of teprenone may be necessary to induce the expression of antioxidant enzymes that suppress severe aGVHD. Clinical Trial Registration number:jRCTs 061210072.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0006-497114582025Oral Inflammation and Microbiome Dysbiosis Exacerbate Chronic Graft-versus-host Disease881896ENYuiKambaraDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Medical SchoolHideakiFujiwaraDepartment of Hematology and Oncology, Okayama University HospitalAkiraYamamotoDepartment of Hematology and Oncology, Okayama University HospitalKazuyoshiGotohDepartment of Medical Laboratory Science, Okayama University Graduate School of Health SciencesShumaTsujiDepartment of Microbiology and Genetics, Okayama University Graduate School of Health SciencesMariKunihiroDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTadashiOyamaDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToshikiTeraoDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAyameSatoDivision of Hospital Dentistry, Okayama University HospitalTakehiroTanakaDepartment of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesDanielPeltierDivision of Pediatric Hematology, Oncology, and Stem Cell Transplantation, Department of Pediatrics, Herman B Wells Center for Pediatric Research, Simon Cancer Center, Indiana University School of MedicineKeisukeSeikeDepartment of Hematology and Oncology, Okayama University HospitalHisakazuNishimoriDepartment of Hematology and Oncology, Okayama University HospitalNoboruAsadaDepartment of Hematology and Oncology, Okayama University HospitalDaisukeEnnishiCenter for Comprehensive Genomic Medicine, Okayama University HospitalKeikoFujiiDepartment of Clinical Laboratory, Okayama University HospitalNobuharuFujiiDivision of Blood Transfusion, Okayama University HospitalKen-ichiMatsuokaDepartment of Hematology and Oncology, Okayama University HospitalYoshihikoSogaDivision of Hospital Dentistry, Okayama University HospitalPavanReddyDan L Duncan Comprehensive Cancer Center, Baylor College of MedicineMaedaYoshinobuDepartment of Hematology and Oncology, Okayama University HospitalThe oral microbiota, second in abundance to the gut, is implicated in chronic systemic diseases, but its specific role in graft-versus-host disease (GVHD) pathogenesis has been unclear. Our study finds that mucositis-induced oral dysbiosis in patients after hematopoietic cell transplantation (HCT) associated with increased chronic GVHD (cGVHD), even in patients receiving posttransplant cyclophosphamide. In murine HCT models, oral dysbiosis caused by bilateral molar ligatures exacerbated cGVHD and increased bacterial load in the oral cavity and gut, with Enterococcaceae significantly increasing in both organs. In this model, the migration of Enterococcaceae to cervical lymph nodes both before and after transplantation activated antigen-presenting cells, thereby promoting the expansion of donor-derived inflammatory T cells. Based on these results, we hypothesize that pathogenic bacteria increase in the oral cavity might not only exacerbate local inflammation but also enhance systemic inflammation throughout the HCT course. Additionally, these bacteria translocated to the gut and formed ectopic colonies, further amplifying systemic inflammation. Furthermore, interventions targeting the oral microbiome mitigated murine cGVHD. Collectively, our findings highlight the importance of oral dysbiosis in cGVHD and suggest that modulation of the oral microbiome during transplantation may be an effective approach for preventing or treating cGVHD.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2213-0071512024Protracted coronavirus disease 2019 after chimeric antigen receptor-T cell therapy successfully treated with sequential multidrug therapy102104ENMasahiroYamashitaDepartment of Allergy and Respiratory Medicine, Okayama University HospitalHisaoHigoDepartment of Allergy and Respiratory Medicine, Okayama University HospitalNobuharuFujiiDepartment of Hematology and Oncology, Okayama University HospitalChiakiMatsumotoDepartment of Allergy and Respiratory Medicine, Okayama University HospitalGoMakimotoDepartment of Allergy and Respiratory Medicine, Okayama University HospitalKiichiroNinomiyaCenter for Comprehensive Genomic Medicine, Okayama University HospitalMasanoriFujiiDepartment of Allergy and Respiratory Medicine, Okayama University HospitalKammeiRaiCenter for Innovative Clinical Medicine, Okayama University HospitalEikiIchiharaCenter for Clinical Oncology, Okayama University HospitalKadoakiOhashiDepartment of Allergy and Respiratory Medicine, Okayama University HospitalKatsuyukiHottaCenter for Innovative Clinical Medicine, Okayama University HospitalMasahiroTabataCenter for Clinical Oncology, Okayama University HospitalYoshinobuMaedaDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNobuakiMiyaharaDepartment of Allergy and Respiratory Medicine, Okayama University HospitalA 56-year-old woman who received CD19 chimeric antigen receptor-T cell therapy for refractory diffuse large B-cell lymphoma developed severe coronavirus disease 2019 (COVID-19) and was treated with nirmatrelvir/ritonavir in April 2022. However, she experienced persistent fatigue and cough and fever in June. Computed tomography revealed bilateral ground-glass opacities (GGO), and the patient was treated with corticosteroids for organizing pneumonia after COVID19. Partial improvement was observed, but new GGO appeared despite corticosteroid therapy. Genome analysis of severe acute respiratory syndrome coronavirus 2 detected Omicron variant BA.1.1.2, which was prevalent at the time of initial infection. The patient was diagnosed with protracted COVID-19 and was treated with remdesivir, molnupiravir, nirmatrelvir/ritonavir, and tixagevimab/cilgavimab. These treatments appeared to contribute to the improvement of protracted COVID-19.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama2688-6146542024Combination of reduced post-transplant cyclophosphamide and early tacrolimus initiation increases the incidence of chronic graft-versus-host disease in human leukocyte antigen-haploidentical peripheral blood stem-cell transplantation810814ENToshikiTeraoDepartment of Hematology and Oncology, Okayama University HospitalTakumiKondoDepartment of Hematology and Oncology, Okayama University HospitalMakotoNakamuraDepartment of Hematology and Oncology, Okayama University HospitalHirokiTakasukaDepartment of Hematology and Oncology, Okayama University HospitalHideakiFujiwaraDepartment of Hematology and Oncology, Okayama University HospitalNoboruAsadaDepartment of Hematology and Oncology, Okayama University HospitalDaisukeEnnishiDepartment of Hematology and Oncology, Okayama University HospitalHisakazuNishimoriDepartment of Hematology and Oncology, Okayama University HospitalKeikoFujiiDepartment of Hematology and Oncology, Okayama University HospitalNobuharuFujiiDepartment of Hematology and Oncology, Okayama University HospitalYoshinobuMaedaDepartment of Hematology and Oncology, Okayama University HospitalKen-IchiMatsuokaDepartment of Hematology and Oncology, Okayama University HospitalWe evaluated the clinical impacts of the concurrent modification of post-transplant cyclophosphamide (PTCy) dose and tacrolimus (Tac)-initiation timing in 61 patients with human leukocyte antigen-haploidentical transplantation. Reduced-dose PTCy (80 mg/kg) was associated with a higher incidence of moderate-to-severe chronic graft-versus-host disease (GVHD) than standard-dose PTCy (100 mg/kg) (35.0% vs. 26.6%, p = 0.053). Notably, early-initiation Tac (day -1) increased moderate-to-severe chronic GVHD than standard-initiation Tac (day 5) in the reduced-dose PTCy group (p = 0.032), whereas Tac-initiation timing did not impact chronic GVHD in the standard-dose PTCy group. These data indicate that the combination of reduced-dose PTCy and early-initiation Tac can amplify chronic GVHD.No potential conflict of interest relevant to this article was reported.BMCActa Medica Okayama1471-230X2412024Endoscopic manifestation of intestinal transplant-associated microangiopathy after stem cell transplantation140ENMasayaIwamuroDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesDaisukeEnnishiDepartment of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesNobuharuFujiiDepartment of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKen-IchiMatsuokaDepartment of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTakehiroTanakaDepartment of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesToshihiroInokuchiDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesSakikoHiraokaDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesMotoyukiOtsukaDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesBackground Endoscopic features of intestinal transplant-associated microangiopathy (iTAM) have not been comprehensively investigated. This study aimed to examine the endoscopic characteristics of patients diagnosed with iTAM.<br>
Methods This retrospective analysis included 14 patients pathologically diagnosed with iTAM after stem cell transplantation for hematolymphoid neoplasms (n = 13) or thalassemia (n = 1). The sex, age at diagnosis, endoscopic features, and prognosis of each patient were assessed. Serological markers for diagnosing transplant-associated thrombotic microangiopathy were also evaluated.<br>
Results The mean age at the time of iTAM diagnosis was 40.2 years. Patients diagnosed based on the pathognomonic pathological changes of iTAM presented with diverse symptoms at the times of endoscopic examinations, including diarrhea (n = 10), abdominal pain (n = 5), nausea (n = 4), appetite loss (n = 2), bloody stools (n = 2), abdominal discomfort (n = 1), and vomiting (n = 1). At the final follow-up, six patients survived, while eight patients succumbed, with a median time of 100.5 days (range: 52-247) post-diagnosis. Endoscopic manifestations included erythematous mucosa (n = 14), erosions (n = 13), ulcers (n = 9), mucosal edema (n = 9), granular mucosa (n = 9), and villous atrophy (n = 4). Erosions and/or ulcers were primarily observed in the colon (10/14, 71%), followed by the ileum (9/13, 69%), stomach (4/10, 40%), cecum (5/14, 36%), duodenum (3/10, 30%), rectum (4/14, 29%), and esophagus (1/10, 10%). Cytomegalovirus infection (n = 4) and graft-versus-host disease (n = 2) coexisted within the gastrointestinal tract. Patients had de novo prolonged or progressive thrombocytopenia (6/14, 43%), decreased hemoglobin concentration (4/14, 29%), reduced serum haptoglobin level (3/14, 21%), and a sudden and persistent increase in lactate dehydrogenase level (2/14, 14%). Peripheral blood samples from 12 patients were evaluated for schistocytes, with none exceeding 4%.<br>
Conclusions This study provides a comprehensive exploration of the endoscopic characteristics of iTAM. Notably, all patients exhibited erythematous mucosa throughout the gastrointestinal tract, accompanied by prevalent manifestations, such as erosions (93%), ulcers (64%), mucosal edema (64%), granular mucosa (64%), and villous atrophy (29%). Because of the low positivity for serological markers of transplant-associated thrombotic microangiopathy in patients with iTAM, endoscopic evaluation and biopsy of these lesions are crucial, even in the absence of these serological features.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7822024Sigle Agent of Posttransplant Cyclophosphamide Without Calcineurin Inhibitor Controls Severity of Experimental Chronic GVHD123134ENKyosukeSaekiDepartment of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHideakiFujiwaraDepartment of Hematology and Oncology, Okayama University HospitalKeisukeSeikeDepartment of Hematology and Oncology, Okayama University HospitalTaigaKuroiDepartment of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHisakazuNishimoriDepartment of Hematology and Oncology, Okayama University HospitalTakehiroTanakaDepartment of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKen-ichiMatsuokaDepartment of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNobuharuFujiiDivision of Transfusion, Okayama University HospitalYoshinobuMaedaDepartment of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOriginal Article10.18926/AMO/66915Chronic graft-versus-host disease (GVHD) is a major cause of late death and morbidity following allogeneic hematopoietic cell transplantation (HCT), but its pathogenesis remains unclear. Recently, haplo-identical HCT with post-transplant cyclophosphamide (Haplo-HCT with PTCY) was found to achieve a low incidence rate of acute GVHD and chronic GVHD. However, while the pathogenesis of acute GVHD following Haplo-HCT with PTCY has been well investigated, that of chronic GVHD remains to be elucidated, especially in HLA-matched HCT with PTCY. Based on its safety profile, PTCY is currently applied for the human leucocyte antigen (HLA)-matched HCT setting. Here, we investigated the mechanisms of chronic GVHD following HLA-matched HCT with PTCY using a well-defined mouse chronic GVHD model. PTCY attenuated clinical and pathological chronic GVHD by suppressing effector T-cells and preserving regulatory T-cells compared with a control group. Additionally, we demonstrated that cyclosporine A (CsA) did not show any additional positive effects on attenuation of GVHD in PTCY-treated recipients. These results suggest that monotherapy with PTCY without CsA could be a promising strategy for the prevention of chronic GVHD following HLA-matched HCT.No potential conflict of interest relevant to this article was reported.American Society of HematologyActa Medica Okayama2473-95297242023Distribution and clinical impact of molecular subtypes with dark zone signature of DLBCL in a Japanese real-world study74597470ENTomohiroUrataDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYusukeNaoiDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAixiangJiangBritish Columbia Cancer, Centre for Lymphoid CancerMerrillBoyleBritish Columbia Cancer, Centre for Lymphoid CancerKazutakaSunamiDepartment of Hematology, NHO Okayama Medical CenterToshiImaiDepartment of Hematology and Blood Transfusion, Kochi Health Sciences CenterYuichiroNawaDivision of Hematology, Ehime Prefectural Central HospitalYasushiHiramatsuDepartment of Hematology and Oncology, Japanese Red Cross Society Himeji HospitalKazuhikoYamamotoDepartment of Hematology and Oncology, Okayama City HospitalSoichiroFujiiDepartment of Hematology, Japanese Red Cross Okayama HospitalIsaoYoshidaDepartment of Hematologic Oncology, NHO Shikoku Cancer CenterTomofumiYanoDepartment of Internal Medicine, Okayama Rosai HospitalRyotaChijimatsuCenter for Comprehensive Genomic Medicine, Okayama University HospitalHiroyukiMurakamiDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuhiroIkeuchiDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHirokiKobayashiDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKatsumaTaniDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHidekiUjiieCenter for Comprehensive Genomic Medicine, Okayama University HospitalHirofumiInoueClinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceShutaTomidaCenter for Comprehensive Genomic Medicine, Okayama University HospitalAkiraYamamotoDepartment of Hematology and Oncology, Okayama University HospitalTakumiKondoDepartment of Hematology and Oncology, Okayama University HospitalHideakiFujiwaraDepartment of Hematology and Oncology, Okayama University HospitalNoboruAsadaDepartment of Hematology and Oncology, Okayama University HospitalHisakazuNishimoriDepartment of Hematology and Oncology, Okayama University HospitalKeikoFujiiDepartment of Hematology and Oncology, Okayama University HospitalNobuharuFujiiDepartment of Hematology and Oncology, Okayama University HospitalKen-ichiMatsuokaDepartment of Hematology and Oncology, Okayama University HospitalKeisukeSawadaDepartment of Pathology, Saitama Medical Center, Saitama Medical UniversityShujiMomoseDepartment of Pathology, Saitama Medical Center, Saitama Medical UniversityJun-ichiTamaruDepartment of Pathology, Saitama Medical Center, Saitama Medical UniversityAsamiNishikoriDepartment of Molecular Hematopathology, Okayama University Graduate School of Health SciencesYasuharuSatoDepartment of Molecular Hematopathology, Okayama University Graduate School of Health SciencesTadashiYoshinoDepartment of Pathology, Okayama UniversityYoshinobuMaedaDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesDavid W.ScottBritish Columbia Cancer, Centre for Lymphoid CancerDaisukeEnnishiDepartment of Hematology and Oncology, Okayama University HospitalThe distribution and clinical impact of cell-of-origin (COO) subtypes of diffuse large B-cell lymphoma (DLBCL) outside Western countries remain unknown. Recent literature also suggests that there is an additional COO subtype associated with the germinal center dark zone (DZ) that warrants wider validation to generalize clinical relevance. Here, we assembled a cohort of Japanese patients with untreated DLBCL and determined the refined COO subtypes, which include the DZ signature (DZsig), using the NanoString DLBCL90 assay. To compare the distribution and clinical characteristics of the molecular subtypes, we used a data set from the cohort of British Columbia Cancer (BCC) (n = 804). Through the 1050 patient samples on which DLBCL90 assay was successfully performed in our cohort, 35%, 45%, and 6% of patients were identified to have germinal center B-cell–like (GCB) DLBCL, activated B-cell–like (ABC) DLBCL, and DZsig-positive (DZsigpos) DLBCL, respectively, with the highest prevalence of ABC-DLBCL, differing significantly from the BCC result (P < .001). GCB-DLBCL, ABC-DLBCL, and DZsigpos-DLBCL were associated with 2-year overall survival rates of 88%, 75%, and 66%, respectively (P < .0001), with patients with DZsigpos-DLBCL having the poorest prognosis. In contrast, GCB-DLBCL without DZsig showed excellent outcomes after rituximab-containing immunochemotherapy. DZsigpos-DLBCL was associated with the significant enrichment of tumors with CD10 expression, concurrent MYC/BCL2 expression, and depletion of microenvironmental components (all, P < .05). These results provide evidence of the distinct distribution of clinically relevant molecular subtypes in Japanese DLBCL and that refined COO, as measured by the DLBCL90 assay, is a robust prognostic biomarker that is consistent across geographical areas.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7742023Feasibility of Flow Cytometry Analysis of Gastrointestinal Tract-Residing Lymphocytes in Hematopoietic Stem Cell Transplant Recipients347357ENMasayaIwamuroDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakumiKondoDepartment of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesDaisukeEnnishiDepartment of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNobuharuFujiiDepartment of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKen-ichiMatsuokaDepartment of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakahideTakahashiDivision of Medical Support, Okayama University HospitalArakiHirabataDivision of Medical Support, Okayama University HospitalTakehiroTanakaDepartment of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesFumioOtsukaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoshinobuMaedaDepartment of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroyukiOkadaDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOriginal Article10.18926/AMO/65740The feasibility of lymphocyte isolation and flow cytometry using a single endoscopic biopsy specimen from the gastrointestinal tract of patients who have undergone hematopoietic stem cell transplantation has not been investigated. We acquired 51 endoscopic biopsy specimens from the gastrointestinal tract of 35 patients. We divided the flow cytometry samples into two groups: group A, successful lymphocyte isolation (n=24), and group B, incomplete isolation (n=27). We compared the backgrounds of the samples between the groups to reveal crucial elements in the successful isolation of lymphocytes residing in the gastrointestinal tract. Comparison between the groups revealed lymphocyte isolation success rates differed between biopsy sites. Isolation was most successful in samples from the duodenum (8/9, 88.9%), followed by the ileum (4/8, 50.0%), large intestine (4/11, 36.4%), and stomach (8/23, 34.8%). Tacrolimus was used more frequently in group B (92.6%) than in group A (62.5%) (p=0.015). Logistic regression analysis revealed that isolation from the duodenum or ileum was a significant factor for successful isolation, while tacrolimus use was not statistically significant. In conclusion, the duodenum and ileum are more suitable sites than the stomach and colorectum for acquiring samples for flow cytometry.No potential conflict of interest relevant to this article was reported.SAGE PublicationsActa Medica Okayama2324-7096112023Bilateral Lacrimal Gland Mantle Cell Lymphoma in 11-Year Follow-Up: Case Report and Review of 48 Cases With Ocular Adnexal Presentation in the LiteratureENToshihikoMatsuoOkayama UniversityTakehiroTanakaOkayama UniversityKazuyaOkadaKurashiki Central HospitalKenjiNotoharaKurashiki Central HospitalKeikoFujiiOkayama University HospitalNobuharuFujiiOkayama University HospitalA 63-year-old woman, with 11-year history of breast cancer, showed bilateral lacrimal gland enlargement on magnetic resonance imaging. Gallium-67 scintigraphy, as the standard at that time in 2004, demonstrated abnormally high uptake only in bilateral lacrimal glands. The lacrimal glands were extirpated and the pathological diagnosis was mantle cell lymphoma (MCL). She underwent bilateral orbital radiation, based on no uptake of gallium-67 in other sites of the body. In a month, bone marrow biopsy revealed the infiltration with MCL, positive for cyclin D1. She showed hepatic lymphadenopathy and splenomegaly, and so received 2 cycles of alternating Hyper-CVAD therapy and high-dose methotrexate with cytarabine, combined with rituximab, in 2 months, leading to complete remission. She underwent autologous peripheral blood stem cell transplantation and was well until the age of 68 years when she showed a recurrent intratracheal submucosal lesion of lymphoma and underwent one course of reduced-dose CHOP combined with rituximab. Next year, the left rib resection revealed the metastasis of breast adenocarcinoma, leading to daily oral letrozole. Further 2 years later, computed tomographic scan demonstrated multiple submucosal nodular lesions in the trachea and bronchi, together with cervical and supraclavicular lymphadenopathy, and intratracheal lesion biopsy and bone marrow biopsy proved the involvement with MCL. She underwent 2 courses of bendamustine and rituximab, resulting in complete remission but died of metastatic breast cancer at the age of 74 years. Clinical features in 48 previous cases with ocular adnexal MCL in the literature were summarized in this study.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama0041-11326372023Efficient granulocyte collection method using high concentrations of medium molecular weight hydroxyethyl starch13441353ENTakumiKondoDivision of Transfusion, Okayama University HospitalKeikoFujiiDivision of Clinical Laboratory, Okayama University HospitalNobuharuFujiiDivision of Transfusion, Okayama University HospitalYuichiSumiiDivision of Transfusion, Okayama University HospitalTomohiroUrataDivision of Transfusion, Okayama University HospitalMaikoKimuraDivision of Transfusion, Okayama University HospitalMasayukiMatsudaDivision of Transfusion, Okayama University HospitalShuntaroIkegawaDivision of Transfusion, Okayama University HospitalKanaWashioDepartment of Pediatrics/Pediatric Hematology and Oncology, Okayama University HospitalHideakiFujiwaraDepartment of Hematology and Oncology, Okayama University HospitalNoboruAsadaDepartment of Hematology and Oncology, Okayama University HospitalDaisukeEnnishiDepartment of Hematology and Oncology, Okayama University HospitalHisakazuNishimoriDepartment of Hematology and Oncology, Okayama University HospitalKen‐ichiMatsuokaDepartment of Hematology and Oncology, Okayama University HospitalFumioOtsukaDivision of Clinical Laboratory, Okayama University HospitalYoshinobuMaedaDepartment of Hematology and Oncology, Okayama University HospitalBackground: Granulocyte transfusion therapy is a rational therapeutic option for patients with prolonged, severe neutropenia. Although high molecular weight hydroxyethyl starch (hHES) facilitates the separation of red blood cells during granulocyte collection, renal dysfunction has been noted as a potential side effect. HES130/0.4 (Voluven®) is a medium molecular weight HES (mHES) with superior safety profiles compared to hHES. Although HES130/0.4 is reportedly effective in the collection of granulocytes, we lack studies comparing the efficiency of granulocyte collection using HES130/0.4 and hHES.<br>
Study Design and Methods: We retrospectively collected the data from 60 consecutive apheresis procedures performed on 40 healthy donors at the Okayama University Hospital between July 2013 and December 2021. All procedures were performed using the Spectra Optia system. Based on the HES130/0.4 concentration in the separation chamber, granulocyte collection methods using HES130/0.4 were classified into m0.46, m0.44, m0.37, and m0.8 groups. We used HES130/0.4 and hHES groups to compare the various sample collection methods.<br>
Results: The median granulocyte collection efficiency (CE) was approximately 24.0% and 28.1% in the m0.8 and hHES groups, respectively, which were significantly higher than those in the m0.46, m0.44, and m0.37 groups. One month following granulocyte collection with HES130/0.4, no significant changes were observed in serum creatinine levels compared to those before the donation.<br>
Conclusion: Therefore, we propose a granulocyte collection approach employing HES130/0.4, which is comparable to the use of hHES in terms of the granulocyte CE. A high concentration of HES130/0.4 in the separation chamber was considered crucial for granulocyte collection.No potential conflict of interest relevant to this article was reported.KargerActa Medica Okayama1662-65751532022Sequential Combination of FLAM and Venetoclax plus Azacitidine to Bridge to Cord Blood Transplantation in a Patient with Primary Induction Failure Acute Myeloid Leukemia974979ENHiroyukiMurakamiDepartment of Hematology and Oncology, Okayama University HospitalKen-IchiMatsuokaDepartment of Hematology and Oncology, Okayama University HospitalTakeruAsanoDepartment of Hematology and Oncology, Japanese Red Cross Society Himeji HospitalTakashiMoriyamaDepartment of Hematology and Oncology, Okayama University HospitalAkifumiMatsumuraDepartment of Hematology and Oncology, Okayama University HospitalHideakiFujiwaraDepartment of Hematology and Oncology, Okayama University HospitalNoboruAsadaDepartment of Hematology and Oncology, Okayama University HospitalDaisukeEnnishiDepartment of Hematology and Oncology, Okayama University HospitalHisakazuNishimoriDepartment of Hematology and Oncology, Okayama University HospitalKeikoFujiiDepartment of Hematology and Oncology, Okayama University HospitalNobuharuFujiiDepartment of Hematology and Oncology, Okayama University HospitalTomohiroTojiDepartment of Pathology, Okayama University HospitalTadashiYoshinoDepartment of Pathology, Okayama University HospitalYoshinobuMaedaDepartment of Hematology and Oncology, Okayama University HospitalVenetoclax (VEN) is an oral B-cell lymphoma-2 (BCL-2) inhibitor that has been widely used to treat various hematological disorders. Recent studies have demonstrated that VEN in combination with fludarabine-enhanced high-dose cytarabine (FLA) is effective for treating relapsed or refractory acute myeloid leukemia (AML). In the combination therapy, salvage chemotherapy and VEN are basically concurrently administrated; however, further optimization may enable the treatment to apply to larger numbers of patients with various clinical backgrounds. Here, we describe a case of refractory AML treated with a sequential combination of the intensive chemotherapy (fludarabine, cytarabine, and mitoxantrone; FLAM) and VEN/AZA to bridge to an unrelated cord blood transplantation (uCBT). By continuously adding VEN/AZA after FLAM, the patient achieved morphologic leukemia free state with only minor toxicities. Blood cell counts did not recover until the time of transplantation because of the deep myelosuppression caused by the treatment sequence, but the infection risk was safely managed during this period. After engraftment, maintenance therapy with VEN/AZA was performed, and the patient has survived without disease recurrence for over 9 months after transplantation. Our case suggests that bridging therapy with VEN and AZA from the time of the last chemotherapy to allogeneic transplantation may provide an effective and tolerable treatment strategy for refractory AML. Further studies of larger numbers of cases are needed to validate the effectiveness of this treatment.No potential conflict of interest relevant to this article was reported.Public Library ScienceActa Medica Okayama1932-62031792022Prevention of non-infectious pulmonary complications after intra-bone marrow stem cell transplantation in micee0273749ENYoshikoYamasuji-MaedaDepartment of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHisakazuNishimoriDepartment of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKeisukeSeikeDepartment of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAkiraYamamotoDepartment of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHideakiFujiwaraDepartment of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTaigaKuroiDepartment of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKyosukeSaekiDepartment of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHarukoFujinagaDepartment of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSachiyoOkamotoDepartment of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKen-IchiMatsuokaDepartment of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNobuharuFujiiDepartment of Transfusion Medicine, Okayama University HospitalTakehiroTanakaDepartment of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasahiroFujiiDepartment of Animal Resources, Advanced Science Research Center, Okayama UniversityKatsumiMominokiDepartment of Animal Resources, Advanced Science Research Center, Okayama UniversityTakuroKanekuraDepartment of Dermatology, Kagoshima University Graduate School of Medical and Dental SciencesYoshinobuMaedaDepartment of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNon-infectious pulmonary complications including idiopathic pneumonia syndrome (IPS) and bronchiolitis obliterans syndrome (BOS), which are clinical and diagnostic manifestations of lung chronic graft-versus-host disease (GVHD), cause significant mortality after allogeneic stem cell transplantation (SCT). Increasing evidence suggests that alloantigen reactions in lung tissue play a central role in the pathogenesis of IPS and BOS; however, the mechanism is not fully understood. Several clinical and experimental studies have reported that intrabone marrow (IBM)-SCT provides high rates of engraftment and is associated with a low incidence of acute GVHD. In the present study, allogeneic SCT was conducted in mouse models of IPS and BOS, to compare intravenous (IV)-SCT with IBM-SCT. Allogeneic IBM-SCT improved the clinical and pathological outcomes of pulmonary complications compared to those of IV-SCT. The mechanisms underlying the reductions in pulmonary complications in IBM-SCT mice were explored. The infiltrating lung cells were mainly CD11b+ myeloid and CD3+ T cells, in the same proportions as in transplanted donor cells. In an in vivo bioluminescence imaging, a higher proportion of injected donor cells was detected in the lung during the early phase (1 h after IV-SCT) than after IBM-SCT (16.7 +/- 1.1 vs. 3.1 +/- 0.7 x 10(5) photons/s/animal, IV-SCT vs. IBM-SCT, P = 1.90 x 10(-10)). In the late phase (5 days) after SCT, there were also significantly more donor cells in the lung after IV-SCT than after IBM-SCT or allogeneic-SCT (508.5 +/- 66.1 vs. 160.1 +/- 61.9 x 10(6) photons/s/animal, IV-SCT vs. IBM-SCT, P = 0.001), suggesting that the allogeneic reaction induces sustained donor cell infiltration in the lung during the late phase. These results demonstrated that IBM-SCT is capable of reducing injected donor cells in the lung; IBM-SCT decreases donor cell infiltration. IBM-SCT therefore represents a promising transplantation strategy for reducing pulmonary complications, by suppressing the first step in the pathophysiology of chronic GVHD.No potential conflict of interest relevant to this article was reported.Japanese Society for Lymphoreticular Tissue ResearchActa Medica Okayama1346-42806232022CD19 immunostaining of a stored paraffin-embedded vitrectomy cell block of intraocular lymphoma contributing to chimera antigen receptor T-cell therapy187189ENToshihikoMatsuoRegenerative and Reconstructive Medicine (Ophthalmology), Okayama University Graduate School of Interdisciplinary Science and Engineering in Health SystemsTakehiroTanakaPathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesNobuharuFujiiHematology/Oncology and Division of Blood Transfusion, Okayama University HospitalKentaroFujiiNeurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesEiseiKondoHematology/Oncology, Kawasaki Medical SchoolNo potential conflict of interest relevant to this article was reported.The Japanese Society for Lymphoreticular Tissue ResearchActa Medica Okayama1346-42806212022Transformed diffuse large B-cell lymphoma from marginal zone lymphoma in the anterior mediastinum: A case report and review of the literature3540ENWataruKitamuraDepartment of Hematology and Oncology, Okayama University HospitalNoboruAsadaDepartment of Hematology and Oncology, Okayama University HospitalTetsuyaTabataDepartment of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesReiShibataDepartment of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTatsuyaNishiDepartment of Respiratory and Allergy, Okayama University HospitalYukaKatoCenter for Innovative Clinical Medicine, Okayama University HospitalHirokiTakasukaDepartment of Hematology and Oncology, Okayama University HospitalHideakiFujiwaraDepartment of Hematology and Oncology, Okayama University HospitalDaisukeEnnishiCenter for Comprehensive Genomic Medicine, Okayama University HospitalHisakazuNishimoriDepartment of Hematology and Oncology, Okayama University HospitalNobuharuFujiiDepartment of Transfusion Medicine, Okayama University HospitalKen-IchiMatsuokaDepartment of Hematology and Oncology, Okayama University HospitalKatsuyukiKiuraDepartment of Respiratory and Allergy, Okayama University HospitalTadashiYoshinoDepartment of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYoshinobuMaedaDepartment of Hematology and Oncology, Okayama University HospitalMarginal zone lymphoma (MZL) arising from the anterior mediastinum is rare. In the majority of reported cases, the tumor was incidentally discovered, reflecting its indolent clinical features. We present a 38-year-old woman who had no medical history, and presented with a bulky anterior mediastinal tumor complicated by life-threatening compression of the vasculature and bronchi. Biopsy specimens of the neoplasm suggested transformed diffuse large B-cell lymphoma (DLBCL) from MZL. To our best knowledge, this is the first case report of anterior mediastinum MZL associated with an aggressive clinical course and life-threatening complications likely due to transformation to DLBCL.No potential conflict of interest relevant to this article was reported.The Japanese Society of Internal MedicineActa Medica Okayama0918-291860192021Nodal Peripheral T-cell Lymphoma with T Follicular Helper Phenotype Presenting as Chorea During Treatment: A Case Report and Literature Review31553160ENWataruKitamuraDepartment of Hematology and Oncology, Okayama University HospitalDaisukeEnnishiCenter for Comprehensive Genomic Medicine, Okayama University HospitalRyoyaYukawaDepartment of Hematology and Oncology, Okayama University HospitalRyoSasakiDepartment of Neurology, Okayama University HospitalChikamasaYoshidaDepartment of Hematology, Okayama City HospitalHirokiTakasukaDepartment of Hematology and Oncology, Okayama University HospitalHideakiFujiwaraDepartment of Hematology and Oncology, Okayama University HospitalNoboruAsadaDepartment of Hematology and Oncology, Okayama University HospitalHisakazuNishimoriDepartment of Hematology and Oncology, Okayama University HospitalKeikoFujiiDivision of Clinical Laboratory, Okayama University HospitalNobuharuFujiiDivision of Blood Transfusion, Okayama University HospitalKen-IchiMatsuokaDepartment of Hematology and Oncology, Okayama University HospitalKojiAbeDepartment of Neurology, Okayama University HospitalTadashiYoshinoDepartment of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYoshinobuMaedaDepartment of Hematology and Oncology, Okayama University HospitalA 72-year-old man presented with chorea while undergoing treatment for recurrence of nodal peripheral T-cell lymphoma with T follicular helper (TFH) phenotype. An examination by brain N-isopropyl-p-iodoamphetamine (I-123-IMP)-single photon emission computed tomography (SPECT) revealed no abnormalities other than a decreased cerebral blood flow (CBF) in the left striatum. After four courses of salvage chemotherapy, his clinical symptoms and asymmetric cerebral perfusion improved, suggesting that the decreased CBF had caused chorea. The significance of brain SPECT has not been fully clarified in patients with chorea-associated malignant lymphoma, warranting further investigations. Brain SPECT is an alternative approach to identify abnormalities in such patients.No potential conflict of interest relevant to this article was reported.The Japanese Society of Internal MedicineActa Medica Okayama0918-291860172021Marginal Zone Lymphoma and Lung Adenocarcinoma with an EGFR Exon 19 E746-S752del Mutation in a Patient with IgG4-related Disease28312837ENSachiOkawaDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKammeiRaiDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNobuharuFujiiDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYukaGionDivision of Pathophysiology, Okayama University Graduate School of Health SciencesKiichiroNinomiyaDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYukaKatoDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAkihikoTaniguchiDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToshioKuboDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesEikiIchiharaDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKadoakiOhashiDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNobuakiMiyaharaDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKatsuyukiHottaDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasahiroTabataDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoshinobuMaedaDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKatsuyukiKiuraDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesA 68-year-old man presented with a solid mass at the left renal pelvis and ureter with multiple systemic lymphadenopathies and a mass with a cavity in the right lower lobe of the lung. While a transbronchial lung biopsy revealed no malignancy, a biopsy of the renal pelvis showed marginal zone lymphoma with polyclonal IgG4-positive cells. The serum IgG4 level and presence of a bilateral orbital mass suggested Mikulicz disease. The lesions shrank following the administration of steroids. A rebiopsy confirmed lung adenocarcinoma, and its background showed IgG4-positive cells a year later. IgG4-related diseases require careful follow-up because they can be complicated by malignancy.No potential conflict of interest relevant to this article was reported.The Japanese Society of Internal MedicineActa Medica Okayama0918-291860142021Squamous Metaplasia of the Stomach Associated with Lymphoma Infiltration22292234ENMasayaIwamuroDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesNobuharuFujiiDepartment of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakehiroTanakaDepartment of Pathology, Okayama University HospitalHiromitsuKanzakiDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesSeijiKawanoDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYoshiroKawaharaDepartment of Practical Gastrointestinal Endoscopy, Okayama University HospitalHiroyukiOkadaDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesWe herein report a patient who presented with follicular lymphoma. Although the stomach was initially intact, mucosal redness and multiple erosions appeared in the gastric body owing to infiltration of the follicular lymphoma cells. Subsequently, a slightly depressed, white area lacking gastric mucosal structure was detected in the lesser curvature of the gastric cardia and body, where lymphoma cell infiltration was also pathologically observed beneath the stratified squamous epithelium. This case indicated that, although infrequent, prolonged mucosal injury owing to lymphoma infiltration can cause squamous metaplasia in the stomach.No potential conflict of interest relevant to this article was reported.Japanese Society of Internal MedicineActa Medica Okayama0918-29186072021Acute Kidney Injury Caused by Evans Syndrome with Systemic Lupus Erythematosus and Systemic Sclerosis10551060ENNatsumiMatsuokaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesHarukiWatanabeDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesNaokoKurookaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesSumariKatoDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesChikaHigashiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKatsuyukiTanabeDivision of Hemodialysis and Apheresis, Okayama University HospitalMasaruKinomuraDivision of Hemodialysis and Apheresis, Okayama University HospitalNobuharuFujiiDepartment of Transfusion Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKen-EiSadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesHitoshiSugiyamaDepartment of Human Resource Development of Dialysis Therapy for Kidney Disease, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesA 65-year-old woman with systemic sclerosis and systemic lupus erythematosus developed acute kidney injury (AKI), Coombs-positive autoimmune hemolytic anemia and autoimmune thrombocytopenia; therefore, she was diagnosed with Evans syndrome (ES). Intravascular hemolysis was suggested as the cause of AKI based on the presence of acute tubular injury and trace hemosiderin deposits on the renal biopsy. The renal function, hemolytic anemia and thrombocytopenia were restored by an increased dose of glucocorticoids, hemodialysis, and plasma exchange. Although ES with severe hemolytic anemia is very rare, it is important to detect possible renal dysfunction when encountering patients with severe hemolysis.No potential conflict of interest relevant to this article was reported.The Japanese Society of Internal MedicineActa Medica Okayama1349-723559192020Localized Lymph Node Light Chain Amyloidosis24152418ENAkiraYamamotoDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNobuharuFujiiDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMikakoObikaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTaroYamashitaDepartment of Neurology, Graduate School of Medical Sciences, Kumamoto UniversityFumioOtsukaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesThe prognosis of systemic amyloid light chain (AL) amyloidosis is generally poor, hence requiring chemotherapy or hematopoietic stem cell transplantation, while the prognosis of localized AL amyloidosis without an abnormal monoclonal immunoglobulin light chain is good. Localized AL amyloidosis has been previously reported to be observed in pulmonary, urinary tract, gastrointestinal, oropharyngeal, and laryngeal sites. However, only a few cases of localized lymph node AL amyloidosis have so far been reported. We herein present a case of localized lymph node AL amyloidosis that could possibly be misdiagnosed as systematic AL amyloidosis.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama0918-291859162020Secondary Pulmonary Alveolar Proteinosis Associated with Primary Myelofibrosis and Ruxolitinib Treatment: An Autopsy Case20232028ENHiroyukiSugiuraDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHisakazuNishimoriDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuyaNishiiDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTomohiroTojiDepartment of Pathology, Okayama University HospitalKeikoFujiiDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNobuharuFujiiDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKen-ichiMatsuokaDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKohNakataDepartment of Bioscience Medical Research Center, Niigata University Medical & Dental HospitalKatsuyukiKiuraDepartment of Allergy and Respiratory Medicine, Okayama University HospitalYoshinobuMaedaDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesPulmonary alveolar proteinosis (PAP) is an uncommon lung disorder characterized by the excessive accumulation of surfactant-derived lipoproteins in the pulmonary alveoli and terminal bronchiole. Secondary PAP associated with primary myelofibrosis (PMF) is extremely rare, and to our knowledge, no autopsy case has been reported. We herein report an autopsy case of secondary PAP occurring in a patient with PMF who was treated with the Janus kinase 1/2 inhibitor ruxolitinib. We confirmed a diagnosis of PAP with complications based on the pathological findings at the autopsy. Notably, this case might suggest an association between ruxolitinib treatment and PAP occurrence. No potential conflict of interest relevant to this article was reported.日本内科学会Acta Medica Okayama0918-291859212020Adult T-cell Leukemia-lymphoma with Primary Breast Involvement: A Case Report and Literature Review27572761ENHirokiKobayashiDepartment of Hematology and Oncology, Okayama University HospitalNoboruAsadaDepartment of Hematology and Oncology, Okayama University HospitalTakuroIgawaDepartment of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesMasayaAbeDepartment of Hematology and Oncology, Okayama University HospitalYusukeMeguriDepartment of Hematology and Oncology, Okayama University HospitalDaisukeEnnishiDepartment of Hematology and Oncology, Okayama University HospitalHisakazuNishimoriDepartment of Hematology and Oncology, Okayama University HospitalNobuharuFujiiDepartment of Transfusion Medicine, Okayama University HospitalKen-ichiMatsuokaDepartment of Hematology and Oncology, Okayama University HospitalTadashiYoshinoDepartment of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYoshinobuMaedaDepartment of Hematology and Oncology, Okayama University HospitalBreast involvement of Adult T-cell leukemia-lymphoma (ATLL) is extremely rare, and the data on the characteristics are limited. We herein describe a 49-year-old woman who presented with skin involvement of ATLL. Positron emission tomography/computed tomography showed bilateral breast lesions. Although the patient once achieved a complete metabolic response, a relapse of her ATLL occurred. The patient received subsequent allogeneic hematopoietic stem cell transplantation (HSCT). To our knowledge, only four cases of ATLL with breast involvement have previously been reported, and the prognoses have generally been poor. Breast lesions of ATLL have aggressive features, and intensive systemic chemotherapy and HSCT are required to improve survival. No potential conflict of interest relevant to this article was reported.Nature ResearchActa Medica Okayama2045-232210120205-aminolevulinic acid-mediated photodynamic therapy can target aggressive adult T cell leukemia/lymphoma resistant to conventional chemotherapy17237ENYasuhisaSandoDepartment of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKen-IchiMatsuokaDepartment of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYuichiSumiiDepartment of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakumiKondoDepartment of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShuntaroIkegawaDepartment of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroyukiSugiuraDepartment of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMakotoNakamuraDepartment of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMikiIwamotoDepartment of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYusukeMeguriDepartment of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNoboruAsadaDepartment of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesDaisukeEnnishiDepartment of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHisakazuNishimoriDepartment of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKeikoFujiiDepartment of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNobuharuFujiiDepartment of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAtaeUtsunomiyaDepartment of Hematology, Imamura General HospitalTakashiOkaDepartment of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoshinobuMaedaDepartment of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesPhotodynamic therapy (PDT) is an emerging treatment for various solid cancers. We recently reported that tumor cell lines and patient specimens from adult T cell leukemia/lymphoma (ATL) are susceptible to specific cell death by visible light exposure after a short-term culture with 5-aminolevulinic acid, indicating that extracorporeal photopheresis could eradicate hematological tumor cells circulating in peripheral blood. As a bridge from basic research to clinical trial of PDT for hematological malignancies, we here examined the efficacy of ALA-PDT on various lymphoid malignancies with circulating tumor cells in peripheral blood. We also examined the effects of ALA-PDT on tumor cells before and after conventional chemotherapy. With 16 primary blood samples from 13 patients, we demonstrated that PDT efficiently killed tumor cells without influencing normal lymphocytes in aggressive diseases such as acute ATL. Importantly, PDT could eradicate acute ATL cells remaining after standard chemotherapy or anti-CCR4 antibody, suggesting that PDT could work together with other conventional therapies in a complementary manner. The responses of PDT on indolent tumor cells were various but were clearly depending on accumulation of protoporphyrin IX, which indicates the possibility of biomarker-guided application of PDT. These findings provide important information for developing novel therapeutic strategy for hematological malignancies.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155813212020キメラ抗原受容体導入Ｔ細胞（CAR-T）療法3436ENNobuharuFujiiDivision of Blood Transfusion, Okayama University HospitalNo potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X6952015Primary Duodenal Follicular Lymphoma Treated With Rituximab Monotherapy and Followed-up for 15 Years301306ENAnnaSekiMasayaIwamuroMasaoYoshiokaNobuharuFujiiHiroyukiOkadaSoichiroNoseKatsuyoshiTakataTadashiYoshinoKazuhideYamamotoCase Report10.18926/AMO/53676A 41-year-old woman was diagnosed with duodenal follicular lymphoma. She had no other lesions and was assigned to a "watch and wait" policy. Swelling of the inguinal lymph nodes appeared 45 months later, and rituximab monotherapy resulted in complete remission. However, follicular lymphoma recurred in the stomach, rectum and mesenteric and external iliac lymph nodes 81 months after the therapy. The patient received rituximab monotherapy again and has remained in complete remission in the fifteenth year after the initial diagnosis. This case suggests the usefulness of rituximab monotherapy in the long-term management of intestinal follicular lymphoma.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama0046-81774572014Low-grade B-cell lymphoma presenting primarily in the bone marrow13791387ENKayokoIwataniKatsuyoshiTakataYasuharuSatoTomokoMiyata-TakataNorikoIwakiWeiCuiSeikoSawada-KitamuraHiroshiSonobeMaikoTamuraKatsuhikoSaitoKatsuyaMiyataniRieYamasakiIchiroYamadoriNobuharuFujiiYasushiTerasakiYoshinobuMaedaMitsuneTanimotoNaoyaNakamuraTadashiYoshinoCases of low-grade B-cell lymphoma presenting primarily in the bone marrow are rare, and its clinicopathology remains unclear. We retrospectively examined patients with low-grade B-cell lymphoma presenting primarily in the bone marrow. Fourteen patients met the inclusion criteria, including 5 with lymphoplasmacytic lymphoma (LPL), 3 with chronic lymphocytic leukemia/small lymphocytic lymphoma, 2 with follicular lymphoma (FL), and 4 with low-grade B-cell lymphoma not otherwise specified (LGBCL-NOS). The median age was 69.5 years (range, 42-89 years), and a slight male predominance was noted (9 men and 5 women, 1.8: 1). Immunohistochemically, all cases were positive for CD20. One case was positive for CD138. Both cases of FL were positive for CD10 and B-cell lymphoma 2 (BCL-2), and immunoglobulin heavy locus (IgH)/B-cell lymphoma 2 rearrangement was observed by fluorescence in situ hybridization. The myeloid differentiation primary response gene (88) leucine to proline mutation was observed in 3 of 5 LPL, 1 of 2 FL, and 2 of 4 LGBCL-NOS patients. Paraproteinemia was observed in 10 patients; IgM and IgG paraproteinemia were observed in 6 and 3 patients, respectively. In this patient series, 3 patients had died at a median follow-up of 36.5 months; the cause of death of 1 LPL patient was malignant lymphoma itself. Thus, low-grade B-cell lymphoma presenting primarily in the bone marrow has various subtypes, and approximately one-third of the patients had LGBCL-NOS. The immunophenotypic features and myeloid differentiation primary response gene (88) leucine to proline mutation data of LGBCL-NOS suggested that some cases present with characteristics similar to those of LPL or marginal zone lymphoma.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama1083-87912022014Mammalian Target of Rapamycin Inhibitors Permit Regulatory T Cell Reconstitution and Inhibit Experimental Chronic Graft-versus-Host Disease183191ENHarukoSugiyamaYoshinobuMaedaHisakazuNishimoriYoshikoYamasujiKen-ichiMatsuokaNobuharuFujiiEiseiKondoKatsujiShinagawaTakehiroTanakaKengoTakeuchiTakanoriTeshimaMitsuneTanimotoChronic graft-versus-host disease (GVHD) remains a major late complication of allogeneic bone marrow transplantation (BMT). In a previous study, impaired thymic negative selection of the recipients permitted the emergence of pathogenic T cells that cause chronic GVHD using MHC class II-deficient (H2-Ab1 KO) B6 into OH model and CD4(+) T cells isolated from chronic GVHD mice caused chronic GVHD when administered into the secondary recipients. In this study, we evaluated the kinetics of regulatory T cell (Treg) reconstitution in wild type B6 into C3H model. After myeloablative conditioning, host Tregs disappeared rapidly, followed by expansion of Tregs derived from the donor splenic T cell inoculum. However, the donor splenic T cell derived Treg pool contracted gradually and was almost completely replaced by newly generated donor bone marrow (BM)-derived Tregs in the late post-transplantation period. Next, we compared the effects of cyclosporine (CSA) and mammalian target of rapamycin (mTOR) inhibitors on Treg reconstitution. Administration of CSA significantly impaired Treg reconstitution in the spleen and thymus. In contrast, BM-derived Treg reconstitution was not impaired in mTOR inhibitor-treated mice. Histopathological examination indicated that mice treated with GSA, but not mTOR inhibitors, showed pathogenic features of chronic GVHD on day 120. Mice treated with CSA until day 60, but not mTOR inhibitors, developed severe chronic GVHD followed by adoptive transfer of the pathogenic CD4(+) T cells isolated from H2-Ab1 KO into C3H model. These findings indicated that long-term use of CSA impairs reconstitution of BM-derived Tregs and increases the liability to chronic GVHD. The choice of immunosuppression, such as calcineurin inhibitor-free GVHD prophylaxis with mTOR inhibitor, may have important implications for the control of chronic GVHD after BMT.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama1618-124710022012Histological and immunohistochemical features of gingival enlargement in a patient with AML254257ENNorihiroSonoiYoshihikoSogaHiroshiMaedaKoichiIchimuraTadashiYoshinoKazutoshiAoyamaNobuharuFujiiYoshinobuMaedaMitsuneTanimotoRichardLoganJudithRaber-DurlacherShogoTakashibaHere, we discuss the pathophysiology of leukemia-associated gingival enlargement based on a case of acute myelomonocytic leukemia (AML-M4) with typical gingival enlargement. Uniquely, this patient was well enough to allow full periodontal examination and incisional gingival biopsy to be performed both before and after chemotherapy. The patient was a 39-year-old Japanese woman with AML-M4 showing gingival enlargement. Histological and immunohistochemical features of gingiva and bacterial counts in the periodontal pockets were examined before and after chemotherapy. The results were as follows: (1) infiltration of myelomonocytic blasts in enlarged gingiva; (2) resolution of gingival enlargement with complete remission of AML by anticancer chemotherapy; and (3) the numbers of bacteria in the periodontal pockets were not high and were not altered before or after chemotherapy. In patients with AML-M4, remarkable mucosal enlargement is not generally observed in the body except in the gingiva. We hypothesized that antigens derived from periodontal bacteria, even if they are not present in large numbers, could act as chemoattractants for myelomonocytic leukemic cells.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama0941-43551832010Total bacterial counts on oral mucosa after using a commercial saliva substitute in patients undergoing hematopoietic cell transplantation395398ENYukoSugiuraYoshihikoSogaKokoroYamabeSoichiroTsutaniIchiroTanimotoHiroshiMaedaSusumuKokeguchiNobuharuFujiiFumihikoIshimaruMitsuneTanimotoFusanoriNishimuraShogoTakashibaThe commercial saliva substitute OralbalanceA (R) has been reported to alleviate symptoms of postradiotherapy xerostomia in head and neck cancer patients. OralbalanceA (R) may also be effective for xerostomia in patients undergoing hematopoietic cell transplantation (HCT) with high-dose chemotherapy and total-body irradiation. However, HCT patients are in a severely compromised condition, and saliva substitute must not promote infection. We reported previously that OralbalanceA (R) has antimicrobial effects against microbial species detected during HCT in vitro. This study was performed to determine the in vivo effects of OralbalanceA (R) on oral mucosal total bacterial counts in patients undergoing HCT.
A total of 18 neutropenic patients undergoing HCT were enrolled in this study. Before and after 1 week of OralbalanceA (R) use, bacterial samples were obtained from patients by wiping an area of I center dot 1 cm on the buccal mucosa with sterilized cotton swabs. Total bacterial counts of the obtained samples were examined by quantitative polymerase chain reaction amplification of the bacterial 16S ribosomal RNA gene. As controls, bacterial samples were also obtained from ten healthy subjects, and total bacterial counts were examined.
No significant increase in bacterial count was observed with use of OralbalanceA (R). None of the patients showed bacterial counts above the range found in healthy controls after using OralbalanceA (R).
In neutropenic patients undergoing HCT, OralbalanceA (R) did not increase the total counts of oral mucosal bacteria beyond the range found in healthy controls. Oral care using OralbalanceA (R) may alleviate the symptoms induced by hyposalivation without promoting infection.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama0941-435516102008Evaluation of xerostomia in hematopoietic cell transplantation by a simple capacitance method device11971200ENYukoSugiuraYoshihikoSogaSachikoNishideKotoeKonoKanayoTakahashiNobuharuFujiiFumihikoIshimaruMitsuneTanimotoFusanoriNishimuraShogoTakashibaGoals Hematopoietic cell transplantation (HCT) may lead to the development of xerostomia. However, there have been few reports of xerostomia in HCT patients based on objective data. We investigated moisture in the oral mucosa in patients undergoing HCT by the capacitance method using a convenient device, Moisture Checker for Mucus (R) (MCM; Life Co., Ltd., Saitama, Japan).
Subjects and methods Thirty-six patients undergoing HCT at Okayama University Hospital of Medicine and Dentistry (Male=22, Female=14; age=41.6 +/- 16.2 years old) were enrolled in this study. Moisture in the oral mucosa was measured by MCM in accordance with the manufacturer's instructions. The results were obtained as MCM values (%), which are the weight percentage of water content in the oral mucosal epithelium. As controls, moisture of the oral mucosa was also examined in healthy volunteers (Male=27, Female=35; age=43.0 +/- 14.6 years old).
Main results Throughout the examination period, MCM values were significantly lower in patients who underwent HCT than in controls. The degree of mucosal moisture in HCT patients showed wide interindividual differences.
Conclusion The degree of mucosal moisture in HCT patients was low and showed wide interindividual differences. Evaluation of xerostomia using such a device may contribute to appropriate oral care with saliva substitute.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama0941-43551642008Antimicrobial effects of the saliva substitute, Oralbalance (R), against microorganisms from oral mucosa in the hematopoietic cell transplantation period421424ENYukoSugiuraYoshihikoSogaIchiroTanimotoSusumuKokeguchiSachikoNishideKotoeKonoKanayoTakahashiNobuharuFujiiFumihikoIshimaruMitsuneTanimotoKokoroYamabeSoichiroTsutaniFusanoriNishimuraShogoTakashibaGoals The commercially available saliva substitute Oralbalance (R) has been reported to alleviate symptoms of post-radiotherapy xerostomia in head and neck cancer patients. Oralbalance (R) may also be effective for xerostomia in patients undergoing hematopoietic cell transplantation (HCT) with high-dose chemotherapy and total-body irradiation. However, HCT patients are severely compromised, and saliva substitute must therefore not promote infection. This study was performed to determine the effects of Oralbalance (R) on microbial species identified during HCT.
Patients and methods Microbial identification of oral mucosa was performed in 28 patients undergoing HCT. The antimicrobial effects of Oralbalance (R) against bacteria and fungi detected in the HCT period were examined in vitro. Briefly, bacteria and fungi were spread on agar plates, and 0.1g of Oralbalance (R) gel was applied (about phi 1cm). After incubation at 37 degrees C for 24h, the presence of a transparent zone of inhibition around Oralbalance (R) was observed.
Main results Not only bacterial species constituting normal flora of the oral mucosa but also those not usually constituting normal flora, e.g., coagulase-negative Staphylococcus, were detected. A transparent zone was observed around Oralbalance (R) in all bacterial species examined. No transparent zone was observed for Candida albicans, but growth was inhibited in the area where Oralbalance (R) was applied.
Conclusions Oralbalance (R) does not facilitate increases in microorganisms in the HCT period. Oral care with Oralbalance (R) does not promote infection in patients undergoing HCT.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama2002Expression of minor histocompatibility antigen, HA-1, in solid tumor cellsENNo potential conflict of interest relevant to this article was reported.