5-Azacitidine for myelodysplasia before allogeneic hematopoietic cell transplantation

Abstract

Relapse remains a leading cause for treatment failure after hematopoietic cell transplantation (HCT) in patients with intermediate-or high-risk myelodysplastic syndrome (MDS). To discern the impact of 5-azacitine treatment pretransplant on the risk for relapse after HCT, we analyzed the post transplant outcomes of all 54 consecutive patients with MDS or chronic myelomonocytic leukemia who received HCT from HLA-compatible donors according to pretransplant 5-azacitidine exposure. Thirty patients received a median of four (1-7) cycles of 5-azacitidine, and 24 patients did not receive 5-azacitidine before HCT. The 1-year estimates of overall survival, relapse-free survival and cumulative incidence of relapse were 47, 41 and 20%, for 5-azacitidine patients and 60, 51 and 32%, respectively, for non-5-azacytidine patients. These observations suggest that outcomes are similar in both groups with a trend toward decreased early relapse in patients receiving 5-azacitidine. 5-Azacitidine may be of value in stabilizing the disease, thereby allowing time for patients to reach transplant and does not appear to affect transplant outcomes.

Feasibility of hypomethylating agents followed by allogeneic hematopoietic cell transplantation in patients with myelodysplastic syndrome

“…HMT can also increase the rates of GVHD and other complications such as infection, contributing to increased treatment-related mortality rate. 21 We observed a treatment-related mortality rate of 11%, similar to previously reported rates, 12 which was even lower than our previously reported one among patients who did not receive HMT before alloHCT. 24 Our findings thus indicate that pre-transplant HMT did not adversely affect post-alloHCT outcomes.…”

“…20 A comparison of patients who did or did not receive AZA before alloHCT showed that the 1-year OS (47 vs 60%) and relapse-free survival (41 vs 51%) rates were similar, with a trend toward decreased early relapse in Table 3 Details on allogeneic hematopoietic cell transplantation and treatment outcomes patients receiving AZA, suggesting that HMA might stabilize the disease and allow time for patients to undergo alloHCT. 21 Another study reported that almost all of the 10 MDS patients who were treated with DEC and underwent subsequent alloHCT after reduced-intensity conditioning, achieved successful engraftment and CR. 22 A recent retrospective analysis showed that pre-alloHCT HMT induced rapid and high level of donor chimerism.…”

Successful treatment of molecular relapse in NPM1-positive AML using 5-azacytidine

“…Whether continuous 5-aza administration beyond 3 cycles also has a curative potential remains to be determined. Similar to recently published results in MDS patients, pretreatment with 5-aza 7 did not result in extraordinary toxicities during conditioning and aplasia. We therefore believe that a prospective trial addressing the role of 5-aza in the treatment of MRD in AML is warranted.…”

The Role of Hypomethylating Agents Prior to Allogeneic Hematopoietic Stem Cells Transplantation in Acute Myeloid Leukemia and Myelodysplastic Syndrome

“…ГМП у пациентов с МДС имеют ряд преимуществ в сравнении с химиотерапией. Они могут рассматриваться как «мостик» к проведению аллоТГСК [6,7] и позволяют подготовить пациентов к трансплантации без накопления дополнительной токсичности при активном контроле опухолевой массы, низком профиле токсичности и существу-ющей возможности амбулаторного лечения [8]. У больных ОМЛ программная химиотерапия является стандартной опцией до проведения аллоТГСК.…”