Work

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

Year: 2012

Type: article

Abstract: We report the results of a prospective clinical trial with the objective of evaluating HCT outcomes following pre-HCT therapy with 5-azacitidine. Twenty-five 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 declined HCT as only a HLA-A mismatched donor was available. Twenty-one patients received a HCT following a myeloablative targeted busulfan fludarabine regimen. Median age at HCT was 57 years (25 - 67). IPSS at diagnosis was Int-1 (3), Int2 (10) and high (5), CMML1 (1), AMLM6 (1) and not evaluable (NE) (1). Cytogenetic risk was good (9), intermediate (5) and poor (8). Four 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 in 2 patients) to HCT infusion was 198 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 4 progressed. Three received leukemic induction chemotherapy prior to HCT. IPSS score prior to HCT was Low (1) Int-1 (6), Int2 (10) and high (1), CMML1 (2) and NE (1). Patients received peripheral blood stem cells from siblings (8), matched unrelated donors (11) and mismatch unrelated donors (2). Median follow-up for survivors is 28.3 months (9.6-37.2 months). Five patients did not achieve remission (1) or relapsed (4) and 1 of the five remains alive. There are 6 non-relapse deaths, 4 due to infection and 2 due to GVHD. Two year cumulative incidences of nonrelapse mortality and relapse from time of transplant are 30% (95% confidence interval [CI] 15%-59%) and 24% (95% CI 11%-51%). At two years OS is 50% (95% CI 28%-72%) and DFS is 46% (95% CI 24%-68%). 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 2 year disease free survival. Controlled trials are needed to determine whether post-transplant relapse and survival are improved by pre-transplant 5-azacitidine.

Source: Transplantation and Cellular Therapy

DOI: 10.1016/j.bbmt.2011.12.353