Acute myeloid leukemia (AML) patients harboring the FLT3-ITD mutation are considered a high risk patient subset preferentially allocated for allogeneic stem cell transplantation in first remission. Whether FLT3-ITD retains a prognostic role in haploidentical stem cell transplantation (haplo-SCT) is unknown. To analyze the prognostic impact of FLT3-ITD in haplo-SCT, we performed a retrospective analysis of the multicenter registry of the acute leukemia working party of the European Society for Blood and Marrow Transplantation. We included all adult AML patients with known FLT3 status who underwent a first T-cell replete related haplo-HCT in first complete remission from 2005 to 2016. We evaluated 293 patients of whom 202 were FLT3 and 91 were FLT3-ITD mutated. FLT3-ITD patients were more likely to be NPM1 mutated as well as be in the intermediate risk cytogenetic risk category. In multivariate analysis, patients with FLT3-ITD had comparable rates of relapse incidence [Hazard ratio (HR) = 1.34, confidence interval (CI) 95%, 0.67-2.7; P = .9] and leukemia-free survival (HR = 0.99, CI 95%, 0.62-1.57; P = .9) to those of FLT3 patients. Overall survival, the incidence of nonrelapse mortality, and graft versus host disease-free/relapse-free survival were not significantly impacted by FLT3-ITD status. Furthermore, relapse and overall survival were comparable between FLT3-ITD patients transplanted from various donor pools, namely matched siblings, unrelated donors, haplo-SCT). Finally, subset analysis of patients with intermediate risk cytogenetics confirmed the absence of a prognostic impact of FLT3-ITD also for this patient segment. In AML patients undergoing T-cell replete haplo-SCT, the FLT3-ITD mutation possibly does not retain its prognostic significance.
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http://dx.doi.org/10.1002/ajh.25082 | DOI Listing |
Front Immunol
January 2025
Cell Therapy and Hematopoietic Stem Cell Transplantation Research Center, Research Institute for Oncology, Hematology and Cell Therapy, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.
Background: With recent advances in clinical practice, including the use of reduced-toxicity conditioning regimens and innovative approaches such as ex vivo TCRαβ/CD19 depletion of haploidentical donor stem cells or post-transplant cyclophosphamide (PTCY), hematopoietic stem cell transplantation (HSCT) has emerged as a curative treatment option for a growing population of patients with inborn errors of immunity (IEI). However, despite these promising developments, graft failure (GF) remains a significant concern associated with HSCT in these patients. Although a second HSCT is the only established salvage therapy for patients who experience GF, there are no uniform, standardized strategies for performing these second transplants.
View Article and Find Full Text PDFFront Immunol
January 2025
Department of Life Sciences, Pohang University of Science and Technology, Pohang, Republic of Korea.
Introduction: T-lymphopenia (TLP) is a frequently observed condition in cancer patients, often exacerbated by conventional chemo/radiotherapy, which impairs the efficacy of subsequent immune checkpoint blockade (ICB) therapy. This study aimed to understand the impact of TLP on ICB responsiveness and explore potential therapeutic strategies to enhance antitumor immunity.
Methods: To investigate ICB responsiveness depending on the severity of TLP, first, we established TLP mouse models that mimic clinically observed mild and severe TLP through thymectomy and anti-Thy1-induced peripheral T cell depletion.
Front Immunol
December 2024
German Cancer Consortium (DKTK), Partner site Frankfurt/Mainz, a partnership between DKFZ and University Medical Center Frankfurt, Frankfurt, Germany.
Introduction: Posttransplant cyclophosphamide (PTCy) has revolutionized the landscape of human leukocyte antigen (HLA)-haploidentical hematopoietic cell transplantation (haplo-HCT), providing a pivotal therapeutic option for patients with hematological malignancies who lack an HLA-matched donor.
Methods: In this retrospective analysis involving 54 adult patients undergoing PTCy-based haplo-HCT, we evaluated the impact of inhibitory killer immunoglobulin-like receptor (KIR)/HLA mismatch, alongside patient, donor, and transplant factors, on clinical outcomes within a homogeneous cohort characterized by a myeloablative conditioning regimen and bone marrow graft.
Results: With a median follow-up of 73.
Int J Hematol
December 2024
Department of Pediatric Oncology, Fukushima Medical University Hospital, 1 Hikariga-oka, Fukushima City, 960-1295, Japan.
T cell-replete haploidentical hematopoietic stem cell transplantation (TCR-haplo-HSCT) is a potentially curative therapy for pediatric intractable hematological malignancies due to its graft-versus-leukemia efficacy. This single-center cohort study examined the effects of graft composition (T cell type and dose) on pediatric TCR-haplo-HSCT outcomes in 32 children with relapsed/intractable hematological malignancies. Graft T cell composition was classified using flow cytometry.
View Article and Find Full Text PDFHaematologica
November 2024
Peking University People's Hospital and Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, 100044; Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing.
Haploidentical-related donor (HID) hematopoietic stem cell transplantation (HSCT) has undergone significant advances in recent decades. Granulocyte colony-stimulating factor- and antithymocyte globulin-based protocols and post-transplantation cyclophosphamide-based regimens represent two of the current T-cell-replete protocols in HID HSCT. Recently, the optimization of several critical transplant techniques has further improved hematopoietic reconstitution, decreased the incidence of relapse and graft-versus-host disease after HID HSCT, and extended the application of HID HSCT to older patients and those with non-malignant hematologic disorders.
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