Allogeneic hematopoietic cell transplantation for older patients with AML with active disease. A study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation (EBMT)

Enrico Maffini*, Myriam Labopin, Nicolaus Kröger, Jürgen Finke, Matthias Stelljes, Thomas Schroeder, Herman Einsele, Johanna Tischer, Martin Bornhäuser, Wolfgang Bethge, Arne Brecht, Wolf Rösler, Peter Dreger, Kerstin Schäfer-Eckart, Jakob Passweg, Igor Wolfgang Blau, Arnon Nagler, Fabio Ciceri, Mohamad Mohty

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Older adults with acute myeloid leukemia (AML) refractory to initial or reinduction chemotherapy have a dismal prognosis if they do not undergo hematopoietic stem-cell transplantation (HCT). However, data assessing HCT outcomes from different donors are scarce. We evaluated results from a retrospective analysis on patients aged ≥70 years, with AML not in remission who received an allogeneic HCT from HLA-matched sibling donor (MSD), HLA-10/10 matched unrelated donor (MUD), or T-cell replete haploidentical (Haplo) donor, from 2010 to 2021, reported to the ALWP-EBMT database. A total of 360 patients (median age 72 years, range 70–79) were included in the analysis. Median follow-up for the entire population was 35.5 months. Donors were MSD (n = 58), 10/10 HLA-MUD (n = 228), and Haplo (n = 74). A total of 213 (59.2%) patients were primary induction failures, while 147 (40.8%) were in first or subsequent relapse. Graft source was peripheral blood in 92% of the patients. Patients transplanted from Haplo donors more frequently received marrow grafts (p < 0.01) and presented the combination female donor to male recipient (p < 0.01). The overall 2-year rates of overall survival (OS) and leukemia-free survival (LFS) were: 62.4% (95% CI 47.2–74.3) and 47.6% (95% CI 33.1–60.8) for MSD, 43% (95% CI 35.8–49.9), and 37.5% (95% CI 30.7–44.4) for MUD, and 25.9% (95% CI 15.8–37.2), and 26.5% (95% CI 16.3–37.8) for recipients of Haplo transplants. The 2-year cumulative incidence of relapse (RI) was slightly lower for Haplo recipients at 29.6% (95% CI 19–40.9), for MUD it was 30.2% (95% CI 23.9–36.7), and for MSD 34.9% (95% CI 22–48.2); counterbalanced by a higher incidence of non-relapse mortality (NRM) of 43.9% (95% CI 31.6–55.6) for Haplo recipients, 32.2% (95% CI 26–33.1) for MUD and 17.5% (95% CI 8.4–29.3) for MSD. Graft-versus-host disease (GVHD-free, relapse-free survival (GRFS) was 35.3% (95% CI 22.3–48.5) for MSD, 29.6% (95% CI 23.2–36.2) for MUD, and 19.2% (95% CI 10.7–29.6) for Haplo patients. In the multivariate model, compared to the referent group of MSD recipients, the risk of NRM was higher among patients transplanted from Haplo donors ([hazard ratio] HR 5.1, 95% CI 2.23–11.61, p < 0.001) and MUD (HR 3.21, 95% CI 1.48–0.6.94, p = 0.003). Furthermore, both Haplo and MUD were associated with inferior OS, (HR 3.6, 95% CI 1.98–0.6.56, p < 0.001, and HR 2.3, 95% CI 1.37–0.3.88, p = 0.002, respectively), and LFS (HR 2.24, 95% CI 1.31–0.3.84, p = 0.003, and HR 1.64, 95% CI 1.04–0.2.60, p = 0.034, respectively). Patients transplanted from Haplo donors were also associated with worse GFRS (HR 1.72, 95% CI 1.07–2.77, p:0.025) compared with MSD patients. Older adult AML patients with active disease transplanted from MSD experienced prolonged OS and LFS compared to 10/10 MUD and Haplo due to lower NRM. Prospective clinical trials are warranted.

Original languageEnglish
Pages (from-to)983-990
Number of pages8
JournalBone Marrow Transplantation
Volume59
Issue number7
DOIs
StatePublished - Jul 2024

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