Transplant Outcomes for Secondary Acute Myeloid Leukemia: Acute Leukemia Working Party of the European Society for Blood and Bone Marrow Transplantation Study

Abstract

Secondary acute myeloid leukemia (sAML) has been associated with inferior outcomes compared with de novo AML. Little is known about patient risk factors and outcomes in sAML after allogeneic hematopoietic stem cell transplantation (HCT); thus, this large systemic analysis of the European Society for Blood and Bone Marrow Transplantation registry was performed. This study included 4997 patients with sAML who received HCT from 2000 to 2016. In univariate analysis the 2-year cumulative incidence of chronic graft-versus-host disease (GVHD), relapse, and nonrelapse mortality (NRM) were 33.5% (95% confidence interval [CI], 32% to 34.9%), 33.7% (95% CI, 32.3% to 35.1%), and 27.5% (95% CI, 26.1% to 28.7%), respectively. Overall survival (OS), leukemia-free survival (LFS), and GVHD-free, relapse-free survival (GRFS) at 2 years were 44.5% (95% CI, 43% to 46%), 38.8% (95% CI, 37.4% to 40.3%), and 27.2% (95% CI, 25.9% to 28.6%), respectively. In multivariate analysis, patients receiving myeloablative regimens had decreased relapse (hazard ratio, .859; 95% CI, .761 to .97; P = .01), higher NRM (hazard ratio, 1.175; 95% CI, 1.03 to 1.341; P = .02), and no differences in OS, LFS, and GRFS compared with patients receiving reduced-intensity conditioning regimens. Active disease, adverse cytogenetics, older age, Karnofsky performance status (≤80%), ex vivo T cell depletion, other malignant hematologic diseases, and patient cytomegalovirus seropositivity were associated with inferior OS and LFS. These variables should be considered in patients with sAML in need of HCT, and further study regarding the impact of conditioning regimens on relapse is needed.

Inferior outcome of allogeneic stem cell transplantation for secondary acute myeloid leukemia in first complete remission as compared to de novo acute myeloid leukemia

“…Although there are no pathognomonic genetic aberrations known for tAML, this subgroup had a worse outcome than MDS-related AML in several studies 2,7,14,24 . In a previous study from our group, slight differences in NRM and survival had been observed between patients with AML evolving from MDS/MPN and other hematologic malignancies, but not solid tumors 8 . In the present analysis, we therefore repeated the Cox model including tAML and AML evolving from another hematologic disease, as covariates.…”

“…Secondary AML was defined as AML with an antecedent MDS, MPN or other malignant hematologic disorder, bone marrow failure syndrome, or solid tumor with prior chemotherapy or radiation 8 . For a subgroup analysis, tAML was defined by previous treatment of solid tumors, Hodgkin or non-Hodgkin Lymphoma (NHL), acute lymphoblastic leukemia (ALL) or chronic lymphocytic leukemia (CLL) using chemotherapy or radiation 14 .…”

“…Allogeneic stem cell transplantation (alloSCT) is regarded as the treatment option for sAML with the best chance of achieving a long-term remission. Considering the transplant setting 8,9 , patients with sAML tend to have less available HLA identical siblings, and the majority receive reduced intensity conditioning (RIC) 10,11 . However, it is not clear whether having sAML per se is a risk factor for outcome after alloSCT, when all wellknown risk factors are controlled for 8 .…”

How to address second and therapy‐related acute myelogenous leukaemia

“…The study reported outcomes for 3,960 patients with sAML who underwent allogeneic HSCT during the years of 2000‒2016 (of whom 41% had active disease not in remission). Two‐year leukaemia‐free survival (see Figure , from Sengsayadeth et al , ), overall survival, and non‐relapse mortality were 39%, 45% and 28%, respectively. In comparison, the subgroup of patients with sAML who had been transplanted and with active disease, had two‐year leukaemia‐free survival, overall survival, and non‐relapse mortality rates of 29%, 35% and 33%, respectively.…”

Cord blood transplantation is associated with good outcomes in secondary Acute Myeloid Leukaemia in first remission

“…This procedure provided a 2-year OS rate of 52.3% (95% CI, 50. 2-54.4) in a recent large retrospective study assessing allo-HSCT from various sources in patients with sAML in CR1 [12]. Further, allo-HSCT has been considered as the only curative treatment for patients with refractory or relapsing sAML, providing 2-year OS rates of 34.5% (95% CI, 32.3-36.7) in the same large retrospective study [12].…”