Prospective Trial of Pre-Transplant 5-Azacitidine on Hematopoietic Cell Transplantation Outcomes for Myelodysplastic Syndrome and CMML

Abstract 1333

In a prior retrospective analysis, we reported no adverse effects of pre-transplant 5-azacitidine on subsequent allogeneic hematopoietic cell transplantation (HCT) outcomes. We now report the results of a prospective observational clinical trial with the objective of evaluating HCT outcomes following pre-HCT therapy with 5-azacitidine. Twenty-three patients seen in consultation for HCT and medically eligible for a donor search were enrolled and received 5-azacitidine [75mg/m2 for 7 days every 4 weeks] until a suitable donor was identified. Four did not proceed to transplant for the following reasons: failure to obtain insurance approval due to patient age, failure of the pre-HCT organ evaluation although a donor was identified, CNS hemorrhage in setting of chronic anti-coagulation five days prior to HCT admission and one (62 years) declined HCT as only a HLA-A mismatched donor was available. Nineteen patients received a HCT following a myeloablative targeted busulfan fludarabine regimen. Median age at HCT was 57 years (25 – 67), 18 patients were older than 45 years, 7 older than 60 years. Disease at diagnosis was RCMD (3), RAEB2 (11), RAEB1 (3), CMML1 (1) and AMLM6 (1). IPSS at diagnosis was Int-1 (2), Int2 (9) and high (5), CMML1 (1), AMLM6 (1) and not evaluable (NE) (1). Cytogenetic risk was good (7), intermediate (5) and poor (7). Three patients had therapy related MDS. Patients received a median of 4 (1-6) cycles of 5-azacitidine. Median time from diagnosis (or time of progression and start of therapy in 2 patients) to HCT infusion was 195 days (107 – 350). Response to 5-azacitidine prior to HCT by the International Working Group 2006 criteria included partial response (8), stable disease (9) and 2 progressed. Two received leukemic induction chemotherapy prior to HCT. Disease status prior to HCT was RCMD (8), RAEB2 (2), RAEB1 (6), CMML1 (2) and AMLM6 (1). IPSS score prior to HCT was Low (1) Int-1 (6), Int2 (9) and poor (1) and CMML1 (2). Source of donor cells was peripheral blood siblings (7), matched unrelated donors (10) and mismatch unrelated donors (2). Median follow-up from HCT is 440 days (83-696). There are 3 patients who did not achieve remission (1) or relapsed (2) and 1 of the three remains alive with active disease. There are 3 non-relapse deaths, 2 due to infection and 1 due to GVHD. All deaths occurred between days 180 – 262. At one year OS is 69% (SE 0.12) and DFS is 63% (SE 0.12). In conclusion, pre-HCT 5-azacitidine was well tolerated, provided control of disease as a bridge to HCT and did not impose additional toxicity after allogeneic HCT with a promising 1 year progression-free survival. Controlled trials are needed to determine whether post-transplant relapse and survival are improved by pre-transplant 5-azacitidine.