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ACUTE LYMPHOBLASTIC LEUKEMIA

Allogeneic hematopoietic stem cell transplantation for adult patients with t(4;11)(q21;q23) KMT2A/AFF1 B-cell precursor acute lymphoblastic leukemia in first complete remission: impact of pretransplant measurable residual disease (MRD) status. An analysis from the Acute Leukemia Working Party of the EBMT

Leukemia volume 35, pages 2232–2242 (2021)Cite this article

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Abstract

Adult B-cell precursor acute lymphoblastic leukemia (BCP-ALL) with t(4;11)(q21;q23);KMT2A/AFF1 is a poor-prognosis entity. This registry-based study was aimed to analyze outcome of patients with t(4;11) BCP-ALL treated with allogeneic hematopoietic stem cell transplantation (alloHSCT) in first complete remission (CR1) between 2000 and 2017, focusing on the impact of measurable residual disease (MRD) at the time of transplant. Among 151 patients (median age, 38) allotransplanted from either HLA-matched siblings or unrelated donors, leukemia-free survival (LFS) and overall survival (OS) at 2 years were 51% and 60%, whereas relapse incidence (RI) and non-relapse mortality (NRM) were 30% and 20%, respectively. These results were comparable to a cohort of contemporary patients with diploid normal karyotype (NK) BCP-ALL with equivalent inclusion criteria (n = 567). Among patients with evaluable MRD pre-alloHSCT, a negative status was the strongest beneficial factor influencing LFS (hazard ratio [HR] = 0.2, p < 0.001), OS (HR = 0.14, p < 0.001), RI (HR = 0.23, p = 0.001), and NRM (HR = 0.16, p = 0.002), with a similar outcome to MRD-negative NK BCP-ALL patients. In contrast, among patients with detectable pretransplant MRD, outcome in t(4;11) BCP-ALL was inferior to NK BCP-ALL (LFS: 27% vs. 50%, p = 0.02). These results support indication of alloHSCT in CR1 for t(4;11) BCP-ALL patients, provided a negative MRD status is achieved. Conversely, pre-alloHSCT additional therapy is warranted in MRD-positive patients.

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Author notes

  1. These authors contributed equally: Jordi Esteve, Sebastian Giebel

Authors and Affiliations

  1. Hematology Department, Hospital Clínic of Barcelona, IDIBAPS, University of Barcelona, Barcelona, Spain

    Jordi Esteve

  2. Department of Bone Marrow Transplantation and Onco-Hematology, Maria Sklodowska-Curie Institute—Oncology Center, Gliwice Branch, Gliwice, Poland

    Sebastian Giebel & Tomasz Czerw

  3. EBMT Paris Study Office, Department of Hematology and Cell Therapy, Hôpital Saint-Antoine, Paris, France

    Myriam Labopin, Mohamad Mohty & Arnon Nagler

  4. Department of Hematology, The First Hospital Affiliated to Soochow University, Suzhou, China

    Depei Wu

  5. Stem Cell Transplantation Unit, Comprehensive Cancer Center, Helsinki University Hospital, Helsinki, Finland

    Liisa Volin

  6. Division of Hematology, Hospital St Louis and University Paris, Paris, France

    Gerard Socié

  7. Hôpital Claude Huriez, Lille, France

    Ibrahim Yakoub-Agha

  8. University Hospital Gasthuisberg, Leuven, Belgium

    Johan Maertens

  9. Erasmus MC-Daniel den Hoed Cancer Centre, Rotterdam, The Netherlands

    Jan J. Cornelissen

  10. CHU Bordeaux, Hôpital Haut-Lévêque, Pessac, France

    Arnaud Pigneux

  11. Hematology Division, Chaim Sheba Medical Center, Tel-Hashomer, Israel

    Avichai Shimoni & Arnon Nagler

  12. Center for Hematopoietic Cell Transplantation, Deutsche Klinik für Diagnostik Helios Klinik, Wiesbaden, Germany

    Rainer Schwerdtfeger

  13. Hôpital Edouard Herriot, Lyon, France

    Hélène Labussière-Wallet

  14. Nottingham University Hospitals and University of Nottingham, Nottingham, UK

    Nigel Russell

  15. Department of Hematology, Nijmegen Medical Centre, Radboud University, Nijmegen, The Netherlands

    Anton Schattenberg

  16. Department d’Hematologie, CHU Nantes, Nantes, France

    Patrice Chevallier

  17. Charles University Hospital, Pilsen, Czech Republic

    Vladimir Koza

  18. Department of Translational and Precision Medicine, “Sapienza” University, Rome, Italy

    Robin Foà

  19. Department of Hematology and Oncology, Augsburg University Hospital, Augsburg, Germany

    Christoph Schmid

  20. University Hospital Center Zagreb, School of Medicine, University of Zagreb, Zagreb, Croatia

    Zinaida Peric

  21. Department of Hematology, Hospital Saint Antoine, Paris, France

    Mohamad Mohty

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  1. Jordi Esteve
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Esteve, J., Giebel, S., Labopin, M. et al. Allogeneic hematopoietic stem cell transplantation for adult patients with t(4;11)(q21;q23) KMT2A/AFF1 B-cell precursor acute lymphoblastic leukemia in first complete remission: impact of pretransplant measurable residual disease (MRD) status. An analysis from the Acute Leukemia Working Party of the EBMT. Leukemia 35, 2232–2242 (2021). https://doi.org/10.1038/s41375-021-01135-2

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