Allogeneic bone marrow transplantation in patients with myelodysplastic syndromes

Myelodysplastic syndromes (MDS) represent an acquired group of clonal disorders of the pleuripotent stem cells, resulting in progressive life-threatening cytopenias or transformation into acute leukemias. A major issue of using alloBMT in MDS is the criteria used for patient selection. Therapeutic trials of lesser intensity such as differentiating agents, and cytokines could be the preferable choice for patients with good prognostic features. On the other hand, patients with poor prognostic features may urgently need to establish a normal hematopoiesis through allogeneic bone marrow transplantation (alloBMT). Important prognostic indicators in MDS include FAB classification, presence of abnormal localization of immature precursors, degree of cytopenias and cytogenetic abnormalities. We used a novel preparative regimen--"BAC" consisting of the consecutive administration of 1 mg/kg of busulfan every 6 hours for 16 doses followed by 2 g/M2 of cytosine arabinoside (ara-C) given every 12 hours for four doses, and finally 60 mg/kg of cyclophosphamide daily for 2 days. Thirty two patients transplanted had a median age of 33 years. Nine of the patients had either RA or RARS, 21 had RAEB or RAEB-T and 2 were unclassified MDS. Twenty two of our patients had chromosomal abnormalities while 10 had a normal karyotype analysis. Nine of the 32 patients had documented leukemic transformation and received induction therapy prior to BMT. The median time from diagnosis to BMT was 5.6 months, ranging from 1.3 to 30.2 months. Nineteen out of 32 patients are alive without disease, with a median follow up of 24 months. The actuarial event-free survival for the entire group is 52%. Two patients have relapsed with an actuarial relapse rate of 12%. Only significant favorable prognostic indicator for the event-free survival was in the recipient of a genotypically matched graft (76%) compared to recipients of a non-genotypic graft (23%) (p = 0.02). "BAC" is a unique preparative regimen for alloBMT in MDS with excellent results.