Late relapse after hematopoietic stem cell transplantation for acute leukemia: a retrospective study by SFGM-TC
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Elsevier B.V.
Abstract
Late relapse (LR) after allogeneic hematopoietic stem cell transplantation (AHSCT) for acute leukemia is a rare event (nearly 4.5%) and raises the questions of prognosis and outcome after salvage therapy. We performed a retrospective multicentric study between January 1, 2010, and December 31, 2016, using data from the French national retrospective register ProMISe provided by the SFGM-TC (French Society for Bone Marrow Transplantation and Cellular Therapy). We included patients presenting with LR, defined as a relapse occurring at least 2 years after AHSCT. We used the Cox model to identify prognosis factors associated with LR. During the study period, a total of 7582 AHSCTs were performed in 29 centers, and 33.8% of patients relapsed. Among them, 319 (12.4%) were considered to have LR, representing an incidence of 4.2% for the entire cohort. The full dataset was available for 290 patients, including 250 (86.2%) with acute myeloid leukemia and 40 (13.8%) with acute lymphoid leukemia. The median interval from AHSCT to LR was 38.2 months (interquartile range [IQR], 29.2 to 49.7 months), and 27.2% of the patients had extramedullary involvement at LR (17.2% exclusively and 10% associated with medullary involvement). One-third of the patients had persistent full donor chimerism at LR. Median overall survival (OS) after LR was 19.9 months (IQR, 5.6 to 46.4 months). The most common salvage therapy was induction regimen (55.5%), with complete remission (CR) obtained in 50.7% of cases. Ninety-four patients (38.5%) underwent a second AHSCT, with a median OS of 20.4 months (IQR, 7.1 to 49.1 months). Nonrelapse mortality after second AHSCT was 18.2%. The Cox model identified the following factors as associated with delay of LR: disease status not in first CR at first HSCT (odds ratio [OR], 1.31; 95% confidence interval [CI], 1.04 to 1.64; P = .02) and the use of post-transplantation cyclophosphamide (OR, 2.23; 95% CI, 1.21 to 4.14; P = .01). Chronic GVHD appeared to be a protective factor (OR, .64; 95% CI, .42 to .96; P = .04). The prognosis of LR is better than in early relapse, with a median OS after LR of 19.9 months. Salvage therapy associated with a second AHSCT improves outcome and is feasible, without creating excess toxicity. © 2023 The American Society for Transplantation and Cellular Therapy
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Acute leukemia, Hematopoietic stem cell transplantation, Late effects, Relapse, Acute disease, Bone marrow transplantation, Chronic disease, Humans, Leukemia, myeloid, acute, Recurrence, Retrospective studies, Antineoplastic agent, Cyclophosphamide, Cyclosporine, Cytarabine, Hypomethylating agent, Methotrexate, Monoclonal antibody, Mycophenolate mofetil, Nucleophosmin, Protein tyrosine kinase inhibitor, Tacrolimus, Thymocyte antibody, Unclassified drug, Acute graft versus host disease, Acute lymphoblastic leukemia, Acute myeloid leukemia, Adult, Allogeneic hematopoietic stem cell transplantation, Article, Autologous hematopoietic stem cell transplantation, Cancer chemotherapy, Cancer immunotherapy, Cancer mortality, Cancer palliative therapy, Cancer patient, Cancer prognosis, Cancer survival, Cause of death, Chimera, Chronic graft versus host disease, Cohort analysis, Controlled study, De novo acute myeloid leukemia, Female, First-line treatment, Follow up, Gene mutation, Graft versus host reaction, Human, Induction chemotherapy, Intensive care, Leukemia relapse, Low drug dose, Major clinical study, Male, Molecularly targeted therapy, Monoclonal antibody therapy, Monotherapy, Myeloablative conditioning, Overall response rate, Overall survival, Real time polymerase chain reaction, Reduced intensity conditioning, Retrospective study, Salvage therapy, Second-line treatment, Secondary acute myeloid leukemia, Sibling donor, Third-line treatment, Treatment response, Unrelated donor, Virus reactivation, Whole body radiation, Recurrent disease