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Improved outcomes of acute lymphoblastic leukemia after allogeneic blood or marrow transplantation with high-dose post-transplantation cyclophosphamide in the era of more effective pre-transplant therapy

Division of Hematologic Malignancy, Department of Oncology, Johns Hopkins University, Baltimore, MD
Department of Internal Medicine, Yale University, New Heaven, CT
Division of Biostatistics and Bioinformatics, Department of Oncology, Johns Hopkins University, Baltimore, MD
Division of Hematologic Malignancy, Department of Oncology, Johns Hopkins University, Baltimore, MD
Division of Hematologic Malignancy, Department of Oncology, Johns Hopkins University, Baltimore, MD
Division of Hematologic Malignancy, Department of Oncology, Johns Hopkins University, Baltimore, MD
Division of Hematologic Malignancy, Department of Oncology, Johns Hopkins University, Baltimore, MD
Division of Hematologic Malignancy, Department of Oncology, Johns Hopkins University, Baltimore, MD
Division of Hematologic Malignancy, Department of Oncology, Johns Hopkins University, Baltimore, MD
Division of Hematologic Malignancy, Department of Oncology, Johns Hopkins University, Baltimore, MD
Division of Hematologic Malignancy, Department of Oncology, Johns Hopkins University, Baltimore, MD
Division of Hematologic Malignancy, Department of Oncology, Johns Hopkins University, Baltimore, MD
Division of Hematologic Malignancy, Department of Oncology, Johns Hopkins University, Baltimore, MD
Division of Hematologic Malignancy, Department of Oncology, Johns Hopkins University, Baltimore, MD
Division of Hematologic Malignancy, Department of Oncology, Johns Hopkins University, Baltimore, MD
Division of Hematologic Malignancy, Department of Oncology, Johns Hopkins University, Baltimore, MD
Division of Hematologic Malignancy, Department of Oncology, Johns Hopkins University, Baltimore, MD
Division of Hematologic Malignancy, Department of Oncology, Johns Hopkins University, Baltimore, MD
Division of Hematologic Malignancy, Department of Oncology, Johns Hopkins University, Baltimore, MD
Division of Hematologic Malignancy, Department of Oncology, Johns Hopkins University, Baltimore, MD
Division of Hematologic Malignancy, Department of Oncology, Johns Hopkins University, Baltimore, MD
Division of Hematologic Malignancy, Department of Oncology, Johns Hopkins University, Baltimore, MD
Division of Hematologic Malignancy, Department of Oncology, Johns Hopkins University, Baltimore, MD
Division of Hematologic Malignancy, Department of Oncology, Johns Hopkins University, Baltimore, MD
Division of Hematologic Malignancy, Department of Oncology, Johns Hopkins University, Baltimore, MD, USA; Section of Hematology/Oncology, Department of Medicine, Baylor College of Medicine, Houston, TX
Division of Biostatistics and Bioinformatics, Department of Oncology, Johns Hopkins University, Baltimore, MD
Division of Hematologic Malignancy, Department of Oncology, Johns Hopkins University, Baltimore, MD
Division of Hematologic Malignancy, Department of Oncology, Johns Hopkins University, Baltimore, MD
Haematologica Early view May 8, 2025 https://doi.org/10.3324/haematol.2025.287433

Abstract

The therapeutic landscape in ALL has changed dramatically over the last decade. Allogeneic blood or marrow transplantation (AlloBMT) has also evolved and remains an important option for consolidation. We assessed the interplay between these factors by analyzing the outcomes of 251 adult ALL (214 B and 37 T ALL) patients undergoing alloBMT with post-transplantation cyclophosphamide (PTCy) across two eras: 2008-2014 (ERA1) and 2015-2022 (ERA2). ERA1 patients were younger (median age 45.5 vs. 50, p=0.03), less likely to have an HCT-CI ≥4 (9% vs. 21%, p=0.01), more likely to have MRD by flow cytometry (20% vs. 9%, p=0.01) and receive myeloablative conditioning (56% vs. 3%, p<0.0001). OS (HR 0.54, p=0.005), RFS (HR 0.52, p=0.001), and relapse (HR 0.45, p=0.0005) were improved in ERA2. Non-relapse mortality was similar between eras (HR 0.88, p=0.73). Significant improvements in OS (HR 0.49, p=0.004) and RFS (HR=0.46, p=0.0004) in ERA2 due to fewer relapses (HR 0.38, p=0.0003) were restricted to patients with B ALL. Irrespective of era, B ALL patients transplanted in first remission (CR1) had improved RFS (HR 0.40, p=0.05) if they received pre-transplant blinatumomab. Similarly, Ph+ ALL patients transplanted in CR1 who received 2nd or 3rd generation tyrosine kinase inhibitors at diagnosis had improved RFS (HR 0.29, p=0.0004) and reduced relapse (HR 0.23, p=0.002) compared to those who received imatinib. Improved alloBMT outcomes in ERA2 in spite of older patient age, increased co-morbidities, and less intensive conditioning were due to reductions in relapse likely driven by changes in pretransplant therapy.

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Early view : Articles
 
DOI
https://doi.org/10.3324/haematol.2025.287433
 
Published
2025-05-08
Published By
Ferrata Storti Foundation, Pavia, Italy
Print ISSN
0390-6078
Online ISSN
1592-8721
 
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Copyright (c) 2025 Ferrata Storti Foundation
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

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ISSN 0390-6078 print | ISSN 1592-8721 online