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

doi:10.1038/s41409-024-02275-6

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)

Bone Marrow Transplant. 2024 Mar 30. doi: 10.1038/s41409-024-02275-6. Online ahead of print.

Authors

Enrico Maffini¹, Myriam Labopin², Nicolaus Kröger³, Jürgen Finke⁴, Matthias Stelljes⁵, Thomas Schroeder⁶, Herman Einsele⁷, Johanna Tischer⁸, Martin Bornhäuser⁹, Wolfgang Bethge¹⁰, Arne Brecht¹¹, Wolf Rösler¹², Peter Dreger¹³, Kerstin Schäfer-Eckart¹⁴, Jakob Passweg¹⁵, Igor Wolfgang Blau¹⁶, Arnon Nagler¹⁷, Fabio Ciceri¹⁸, Mohamad Mohty¹⁹

Affiliations

¹ IRCCS Azienda Ospedaliero-Universitaria di Bologna; Istituto "L. e A. Seràgnoli", Bologna, Italy. enrico.maffini@aosp.bo.it.
² EBMT ALWP Statistical Unit, Paris, France.
³ University Medical Center Hamburg, Department for Stem Cell Transplantation, Hamburg, Germany.
⁴ Department of Medicine -Hematology Oncology, University of Freiburg, Freiburg, Germany.
⁵ Department of Medicine A, Hematology, Oncology, and Pneumology, University Hospital Münster, Münster, Germany.
⁶ University Hospital, Department of Bone Marrow Transplantation, Essen, Germany.
⁷ Universitaetsklinikum Wuerzburg, Med. Klinik und Poliklinik II, Wuerzburg, Germany.
⁸ Klinikum Grosshadern, Medizinische Klinik III, Munich, Germany.
⁹ Universitaetsklinikum Dresden, Medizinische Klinik und Poliklinik I, Dresden, Germany.
¹⁰ Universitaet Tuebingen Medizinische Klinik, Tuebingen, Germany.
¹¹ Deutsche Klinik fuer Diagnostik, KMT Zentrum, Wiesbaden, Germany.
¹² University Hospital Erlangen, Department of Internal Medicine 5, Erlangen, Germany.
¹³ University of Heidelberg, Medizinische Klinik u. Poliklinik V, Heidelberg, Germany.
¹⁴ Klinikum Nuernberg, 5. Medizinische Klinik, BMT-Unit, Nuernberg, Germany.
¹⁵ University Hospital, Hematology, Basel, Switzerland.
¹⁶ Medizinische Klinik m. S. Hämatologie, Onkologie und Tumorimmunologie, Charité Universitätsmedizin, Berlin, Germany.
¹⁷ Sheba Medical Center, Tel-Hashomer, Tel-Aviv University, Ramat-Gan, Israel.
¹⁸ Ospedale San Raffaele s.r.l., Haematology and BMT, Milano, Italy.
¹⁹ Sorbonne University, Clinical Hematology and Cellular Therapy Department, Saint Antoine Hospital, INSERM UMRs 938, Paris, France.

PMID: 38555412
DOI: 10.1038/s41409-024-02275-6

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.