Myelodysplastic syndrome (MDS) is a disorder of multipotential hematopoietic stem cells. There is no effective therapy for MDS, especially for MDS associated with an excess of blasts, such as refractory anemia with excess blasts (RAEB) or RAEB in transformation (RAEBt). We previously reported the effect of K-18 (a human IgG-melphalan conjugate) in 15 patients with RAEB or RAEBt. The overall response rate was not high, but no side effects were noted. Although the mode of action of K-18 is not certain, it was suggested that the effect was associated with the activity of melpahlan itself. Therefore, low-dose melphalan therapy was initiated in eldery patients with RAEB or RAEBt. Six patients with RAEB and 12 patients with RAEBt received 2mg oral administration daily. Median age of the patients was 64. Six patients achieved complete remission (CR), one patient showed a partial response and four patients had a minor response. Total dosage of melpahlan for patients who achieved CR was 143±18 mg. Median duration of CR was 14.5 months. Serious toxicity was not encountered in any case and neither marrow suppression nor pancytopenia were observed in cases that achieved CR during the administration of melphalan. Changes in cell surface markers (CD34, CD33, CD13) were examined during the time course of CR in two cases. CD34 + cells decreased rapidly during the first two weeks and CD34-CD33+cells increased after four weeks of melpahlan administration. Studying the clinical course of CR with cell surface marker analysis provided evidence that melphalan therapy induced differentiation of transformed hemopoietic precursors.
We conclude that daily chronic administration of melpahlan is a useful therapy for elderly patients with RAEB or RAEBt.
low dose melpahlan therapy