Abstract
Measurable residual disease (MRD) prior to hematopoietic cell transplant (HCT) for acute myeloid leukemia (AML) in first complete morphological remission (CR1) is an independent predictor of outcome, but few studies address CR2. This analysis by the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation registry assessed HCT outcomes by declared MRD status in a cohort of 1042 adult patients with AML CR2 at HCT. Patients were transplanted 2006–2016 from human leukocyte antigen (HLA) matched siblings (n = 719) or HLA 10/10 matched unrelated donors (n = 293). Conditioning was myeloablative (n = 610) or reduced-intensity (n = 432) and 566 patients (54%) had in-vivo T cell depletion. At HCT, 749 patients (72%) were MRD negative (MRD NEG) and 293 (28%) were MRD positive (MRD POS). Time from diagnosis to HCT was longer in MRD NEG than MRD POS patients (18 vs. 16 months (P < 0.001). Two-year relapse rates were 24% (95% CI, 21–28) and 40% (95% CI, 34–46) in MRD NEG and MRD POS groups (P < 0.001), respectively. Leukemia-free survival (LFS) was 57% (53–61) and 46% (40–52%), respectively (P = 0.001), but there was no difference in terms of overall survival. Prognostic factors for relapse and LFS were MRD NEG status, good risk cytogenetics, and longer time from diagnosis to HCT. In-vivo T cell depletion predicted relapse.
Highlights
Relapse of acute myeloid leukemia (AML) following allogeneic hemopoietic cell transplant (HCT) remains a major cause of treatment failure and indicates the presence of persistent subclinical disease, despite morphological complete remission (CR) at the time of transplant[1,2,3,4]
CMV serological status of patients was similar and more CMV sero-negative donors were selected for measurable residual disease” (MRD) positive than MRD negative patients, this did not reach statistical significance
human leukocyte antigen (HLA)-matched siblings were more likely to be selected as donors for MRD negative than MRD positive patients but this was not statistically significant
Summary
Relapse of acute myeloid leukemia (AML) following allogeneic hemopoietic cell transplant (HCT) remains a major cause of treatment failure and indicates the presence of persistent subclinical disease, despite morphological complete remission (CR) at the time of transplant[1,2,3,4]. MRD status after induction therapy is prognostic of outcome in AML independent of other accepted risk parameters[6,10,12,14,16,17,18,19,20,21,22,23,24,25,26]. Multiple large studies have demonstrated the prognostic importance of MRD pre-HCT in CR1 terms of subsequent relapse incidence (RI), leukemia-free survival (LFS), and overall survival (OS)[6,14,27,28,29,30,31,32,33,34,35]. A previous study undertaken by the European Society for Blood and Marrow Transplantation (EBMT) found that patients with MRD at HCT had inferior survival at 2 years after HCT compared to those with an MRD negative status (56.2% vs. 70% in adults aged less than 50 years and 50.7% vs. 62.1% in patients 50 years and older)[35]
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