Comparison of conditioning regimens of various intensities for allogeneic hematopoietic SCT using HLA-identical sibling donors in AML and MDS with <10% BM blasts: a report from EBMT

Abstract

In this multicenter retrospective study, the long-term outcomes of 878 adults with AML and refractory anemia with excess blasts (RAEB) with BM blasts o10% who underwent transplantation with an HLA-identical sibling donor between 1998 and 2004 were analyzed according to four regimens of conditioning intensity: reduced-intensity conditioning (RIC) (either intermediate RIC (IntermRIC) or non-myeloablative (NMA) RIC), and myeloablative conditioning (MC) in 718 patients (either conventional MC or hyperintense MC. In multivariate cox analysis, patients undergoing NMA transplantation had lower non-relapse mortality risk in the first 100 days after transplantation (Po0.01), but a higher risk beyond day þ 100 (P ¼ 0.02), as well as higher relapse incidence in the first 12 months (Po0.01), but the risk was similar in all groups beyond 12 months. The probabilities of PFS and OS up to 7 years were significantly lower only in the NMA subgroup (Pp0.01 for both). The 7-year OS was 53%, 29%, 56% and 51%, respectively. Our data suggest that prospective studies comparing RIC regimens (especially IntermRIC) with MC are appropriate in patients with AML and RAEB who are in a non-advanced disease status.

Reduced-intensity conditioned allogeneic SCT in adults with AML

“…74 Notably, the presentation of GvHD after RIC SCT is often delayed. [75][76][77][78][79][80][81][82] In our experience, more than half of acute GvHD cases present after day 100, a striking difference from myeloablative transplants.…”

“…79 Higher relapse rates were observed after RIC transplants and inferior survival was seen specifically after lower-intensity non-myeloablative conditioning (Flu/TBI2 or Flu/CY), a finding that was supported by a similar EBMT analysis. 82 Specifically, a subset of patients with favorable characteristics in the CIBMTR analysis (age 40-60, good performance status, AML in CR1) had worse DFS with non-myeloablative conditioning (P = 0.006). These results suggest that young and healthy patients with favorable risk AML do not benefit from reduced regimen intensity.…”

Long-term outcomes of allogeneic hematopoietic cell transplantation with intensified myeloablative conditioning for refractory myeloid malignancy

“…7 Although intensified conditioning regimens did not improve short-term OS rates in previous studies because of increased TRM rates despite decreased relapse rates, [8][9][10] long-term follow-up outcomes have not been reported.…”

“…6 Another intensified regimen with BU, CY and TBI provided a 50% DFS rate at 5 years for patients with advanced myeloid malignancies including AML and CML. 7 Although intensified conditioning regimens did not improve short-term OS rates in previous studies because of increased TRM rates despite decreased relapse rates, [8][9][10] long-term follow-up outcomes have not been reported.…”

“…[5][6][7] We previously reported that an intensified conditioning regimen with BU, melphalan (MEL) and TBI provided a 50% DFS rate at 3 years after HCT in patients with high-risk leukemia.6 Another intensified regimen with BU, CY and TBI provided a 50% DFS rate at 5 years for patients with advanced myeloid malignancies including AML and CML.7 Although intensified conditioning regimens did not improve short-term OS rates in previous studies because of increased TRM rates despite decreased relapse rates, [8][9][10] long-term follow-up outcomes have not been reported.We retrospectively evaluated long-term outcomes of 44 consecutive patients who had allogeneic HCT from 1994 to 2003 for chemorefractory AML or CML in blast crisis (CML-BC) with intensified myeloablative conditioning regimens at our institution. Chemorefractory disease was defined as the presence of 45% blasts in bone marrow or the presence of extramedullary disease before starting conditioning regimens.…”