Journal Article

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

Chevallier, Patrice, Koza, Vladimir, Cornelissen, Jan J., Labopin, Myriam, Wu, Depei, Schattenberg, Anton, Schmid, Christoph, Giebel, Sebastian, Russell, Nigel, Peric, Zinaida, Czerw, Tomasz, Labussière-Wallet, Hélène, Yakoub-Agha, Ibrahim, Foà, Robin, Nagler, Arnon, Maertens, Johan, Shimoni, Avichai, Mohty, Mohamad, Schwerdtfeger, Rainer, Socié, Gerard, Pigneux, Arnaud, Volin, Liisa, Esteve, Jordi

2021

Overview

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.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Springer Nature
• Subject: 692/308 / 692/699/1541/1990/283 / Acute lymphoblastic leukemia / Acute lymphocytic leukemia / Adult / Cancer Research / Care and treatment / Chromosomes, Human, Pair 11 - genetics / Chromosomes, Human, Pair 4 - genetics / Critical Care Medicine / Development and progression / Diploids / DNA-Binding Proteins - genetics / DNA-Binding Proteins - metabolism / Evaluation / Female / Follow-Up Studies / Hematology / Hematopoietic Stem Cell Transplantation - methods / Hematopoietic stem cells / Histocompatibility antigen HLA / Histone-Lysine N-Methyltransferase - genetics / Histone-Lysine N-Methyltransferase - metabolism / Humans / Intensive / Internal Medicine / Karyotypes / Leukemia / Life Sciences / Lymphatic leukemia / Lymphocytes B / Male / Medical prognosis / Medicine / Medicine & Public Health / Myeloid-Lymphoid Leukemia Protein - genetics / Myeloid-Lymphoid Leukemia Protein - metabolism / Neoplasm, Residual - genetics / Neoplasm, Residual - pathology / Neoplasm, Residual - therapy / Oncology / Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - genetics / Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - pathology / Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - therapy / Precursors / Prognosis / Remission / Remission (Medicine) / Remission Induction / Retrospective Studies / Stem cell transplantation / Stem cells / Survival / Survival Rate / Transcriptional Elongation Factors - genetics / Transcriptional Elongation Factors - metabolism / Translocation, Genetic / Transplantation / Transplantation Conditioning / Transplantation, Homologous