Allogeneic hematopoietic cell transplantation in TP53-mutated Acute Myeloid Leukemia patients with active disease: A study from the global committee and the acute leukemia working party of the EBMT

Abstract

Abstract Background Acute myeloid leukemia (AML) harboring TP53 mutations is notoriously challenging to manage, frequently showing resistance to conventional chemotherapy and resulting in poor prognosis. The potential benefits of allogeneic hematopoietic cell transplantation (allo-HCT) for patients with active disease remain poorly defined. Methods Using the EBMT registry, we collected data from 83 centers who participated to the study. The analysis included 183 adult patients with TP53-mutated AML with active disease who underwent their first allo-HCT . Results Among the183 patients, 121 had de novo AML, and 62 had secondary AML. Primary induction failure occurred in 141 cases, while 42 patients experienced relapse or disease progression. The median patient age was 60.3 years (range 52.4–66.2). 64% were male. Donors had a median age of 36 years (range 26.2–47.9), and 71% were male.Transplantation strategies included 41 haploidentical transplants (Haplo), 43 matched sibling donor transplants (MSD), and 99 matched unrelated donor transplants (UD 10/10). Conditioning regimens were reduced-intensity in 92 patients and myeloablative in 87. For graft-versus-host disease (GVHD) prophylaxis, 107 patients received anti-thymocyte globulin (ATG), 37 were given post-transplant cyclophosphamide (PTCy), and 8 received both ATG and PTCy. The HCT-CI scores of 170 patients were distributed as follows: 34 patients (20%) scored 1-2, 114 patients (67%) scored 2.5-3.5, and 22 patients (13%) scored 4-6. Scores were missing in 13 patients. For the 183 TP53-mutated AML patients, with a median follow-up of 3 years (range 2–4.4), the 2-year outcomes post transplant were: Overall survival (OS) 20.5% (14–28%), leukemia-free survival (LFS) 16.7% (10.9–23.5%), and GVHD-free relapse-free survival (GRFS) 9.4% (5.2–15.3%). Disease progression accounted for 48% of deaths, followed by infections, GVHD, and organ toxicity. The 2-year relapse incidence (RI) was 53.2% (44.4–61.3%), and non-relapse mortality (NRM) 30.1% (22.7–37.9%). By donor type: MSD showed OS of 20.2% (8.4–35.7%), LFS of 12.1% (3.8–25.4%), GRFS of 6.2% (1.1–17.8%), RI of 50.3% (32–66.1%), and NRM of 37.6% (21.5–53.7%); Haplo had OS of 19.2% (7.6–34.9%), LFS of 20.6% (8.5–36.3%), GRFS of 14.1% (4.6–29%), RI of 63.4% (43.1–78.2%), and NRM of 16% (5.5–31.3%); UD 10/10 had OS of 21.2% (12.3–31.7%), LFS of 16.8% (9–26.7%), GRFS of 8.8% (3.5–17.2%), RI of 50.2% (37.8–61.3%), and NRM of 33% (22.4–44%). GVHD outcomes showed a 180-day grade II-IV acute GVHD incidence of 31.8% (24–39.9%) and grade III-IV of 11.4% (6.7–17.5%). At 2 years, chronic GVHD occurred in 17% (11.1–24.1%), with 8.6% extensive (4.5–14.3%). By donor type: MSD had a grade II-IV acute GVHD incidence of 29% (14.2–45.6%), grade III-IV of 19.4% (7.7–35%), and extensive chronic GVHD of 9.2% (2.2–22.7%); Haplo had grade II-IV acute GVHD of 25.8% (12–42.1%), grade III-IV of 9.7% (2.4–23.2%), chronic GVHD of 17.9% (5.9–35.2%), and extensive chronic GVHD of 3.2% (0.2–14.4%); UD 10/10 had grade II-IV acute GVHD of 35.7% (24.6–46.9%), grade III-IV of 8.6% (3.5–16.6%), chronic GVHD of 16.2% (8.4–26.3%), and extensive chronic GVHD of 10.6% (4.5–19.7%). ConclusionAllo-HCT appears to confer a modest survival benefit whatever the donor choice for TP53-mutated AML patients with active disease. Nevertheless, the limited efficacy highlights the pressing need for novel treatment strategies to improve outcomes in this high-risk population.