Role of autologous hematopoietic stem cell transplantation according to the NPM1/FLT3‐ITD molecular status for cytogenetically normal AML patients: A GOELAMS study

Abstract

and Patrice Chevallier 18 on behalf of the GOELAMS The choice of postremission therapy for acute myeloid leukemia (AML) patients is now based on the blasts' cytogenetic and molecular profile. However, the potential benefit of autologous hematopoietic stem cell transplantation (auto-HSCT) according to the NPM1/FLT3-ITD status has been poorly studied in AML patients with a normal karyotype (NK). Therefore, we evaluated the NPM1/FLT3-ITD molecular status in 135 NK-AML patients treated by allogeneic HSCT (allo-HSCT), auto-HSCT, or chemotherapy as consolidation therapy within the GOELAMS LAM-2001 trial. In univariate analyzes, 4-year leukemia-free survival (LFS) and overall survival (OS) were significantly higher for NPM11/FLT3-ITD2 patients compared with patients presenting another molecular profile (61 vs. 43% and 72 vs. 48%, P 5 0.02 and P 5 0.01, respectively). In the NPM11/ FLT3-ITD2 subgroup, there was no benefit for allo-HSCT or auto-HSCT vs. chemotherapy (4-year LFS: 71, 56, and 60%; 4-year OS: 73, 71, and 60%, respectively; P 5 NS). For patients with other NPM1/FLT3-ITD molecular profiles, allo-HSCT was found to be the best consolidation therapy, whereas auto-HSCT was associated with a better outcome when compared with chemotherapy (allo-HSCT-, auto-HSCT-, and chemotherapy-related 4-year LFS: 68, 44, and 36%, P 5 0.004; 4-year OS: 68, 52, and 29%, respectively, P 5 0.02). Our study indicates that allo-HSCT and auto-HSCT provide similar outcomes compared with chemotherapy as consolidation for NPM11/FLT3-ITD2 NK-AML patients. For NK-AML patients with an adverse molecular profile, auto-HSCT could represent an alternative therapeutic approach when no human leukocyte antigen-matched allogeneic donor is available. Am. J. Hematol. 87:1052Hematol. 87: -1056Hematol. 87: , 2012

Mutational spectrum and risk stratification of intermediate-risk acute myeloid leukemia patients based on next-generation sequencing

“…For those with intermediate-risk cytogenetics, studies showed that auto-HSCT may represent an alternative therapeutic approach, as some had similar clinical outcomes with allo-HSCT. Still, all of these studies lacked further molecular stratification to the patients [45, 46]. In our study, five patients with intermediate molecular genotypes who received auto-HSCT had similar OS but less transplantation-related morbidity and mortality than those who received allo-HSCT.…”

Hematopoietic stem cell transplantation for adult patients with isolated NPM1 mutated acute myeloid leukemia in first remission

“…Indeed, Ferrara et al showed a significant advantage of high dose chemotherapy and auto‐SCT in 35 AML patients with NPM1 mutations . In another French study of 46 AML patients with i NPM1 m, the authors did not find significant difference in terms of survival between patients who received allo‐SCT or auto‐SCT as consolidation therapy . Considering less toxicity associated with auto‐SCT, auto‐SCT‐based consolidation strategy appears as a good option in this molecular AML subgroup .…”

Should autotransplantation in acute myeloid leukemia in first complete remission be revisited?

“…Nevertheless, even in the favorable AML group there is a benefit for antileukemic effect of alloSCT. On the other hand, the GOELAMS LAM-2001 trial found no benefit of any SCT over chemotherapy in the favorable subgroup [11]. Whether the decision regarding the appropriate postremission therapy in the more favorable group should be tailored individually based on quantitative PCR for the detection of minimal residual disease at CR1 is yet to be determined.…”

“…In the prospective Groupe Ouest-Est d'étude des leucémies et autres maladies du sang (GOELAMS) LAM-2001 study [11], a retrospective subgroup analysis of AML patients in CR1 evaluated the impact of postremission therapy on the outcome in normal karyotype AML according to NPM1 and FLT3-ITD mutational status. Only in the NPM1 negative/FLT3-ITD positive or negative AML there was an advantage of any transplantation over chemotherapy.…”