Delayed T-cell recovery after hematopoietic cell transplantation is associated with decreased overall survival in adults

Allogeneic hematopoietic cell transplantation (allo-HCT) can provide curative treatment for hematologic malignancies but is associated with prolonged lymphopenia that may contribute to an increased risk of infection and relapse, resulting in decreased survival. We hypothesized that patients with rapid and robust CD4 T- and B-cell recovery have improved survival and decreased treatment-related mortality (TRM). A total of 2089 patients were included who underwent first allo-HCT for acute myeloid leukemia/acute lymphoblastic leukemia/myelodysplastic syndrome from 2008 to 2019 reported to the Center for International Blood and Marrow Transplant Research with available CD4 counts at days 100 and 180. Patients (median age, 51 years [range, 2-75]) were categorized into 4 groups based on graft-versus-host disease (GVHD) prophylaxis: ex vivo T-cell depletion (TCD/CD34), posttransplant cyclophosphamide, calcineurin inhibitor alone (CNI), or CNI with antithymocyte globulin. Based upon survival, we could identify optimal cutoff points for CD4+ T cells in pediatric (age of <20 years) patients: 248 × 106/L and 420 × 106/L at days 100 and 180, respectively; and in adult (age of >20 years) patients: 104 × 106/L and 115 × 106/L at days 100 and 180, respectively. In adults, day-100 CD4 count was associated with overall survival (OS), progression-free survival (PFS), and TRM but not relapse, incidence of infections, or chronic GVHD. Similarly, CD4 counts above the cutoff point at day 180 in adults were associated with improved OS, PFS, and TRM but no other outcomes. No clinical associations for CD4 counts were identifiable in pediatric patients. These findings underscore the importance of tailoring transplant strategies for adults to optimize immune recovery and improve patient outcomes.

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Publication Details

Journal
Blood Advances
Published
2025-04-18
DOI
https://doi.org/10.1182/bloodadvances.2024015288
Citations
1
Primary Topic
Hematopoietic Stem Cell Transplantation
Type
article
Field-Weighted Citation Impact
1.77

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article

Delayed T-cell recovery after hematopoietic cell transplantation is associated with decreased overall survival in adults

Michael J. Martens, Laurel A. Thur, Marcie Riches, Paul Szabolcs et al.
1 citations
Blood Advances
Hematopoietic Stem Cell Transplantation
1.77
article

Delayed T-cell recovery after hematopoietic cell transplantation is associated with decreased overall survival in adults

Michael J. Martens, Laurel A. Thur, Marcie Riches, Paul Szabolcs, Gerhard Hildebrandt, Amer Beitinjaneh, Hillard Michael Lazarus, Shahrukh K. Hashmi, Susan E. Prockop, Christopher E. Dandoy, Roy F. Chemaly, Miguel‐Angel Perales, Jeffery J. Auletta, Miguel Ángel Díaz, Naya He
article en
1 citations

Abstract

Allogeneic hematopoietic cell transplantation (allo-HCT) can provide curative treatment for hematologic malignancies but is associated with prolonged lymphopenia that may contribute to an increased risk of infection and relapse, resulting in decreased survival. We hypothesized that patients with rapid and robust CD4 T- and B-cell recovery have improved survival and decreased treatment-related mortality (TRM). A total of 2089 patients were included who underwent first allo-HCT for acute myeloid leukemia/acute lymphoblastic leukemia/myelodysplastic syndrome from 2008 to 2019 reported to the Center for International Blood and Marrow Transplant Research with available CD4 counts at days 100 and 180. Patients (median age, 51 years [range, 2-75]) were categorized into 4 groups based on graft-versus-host disease (GVHD) prophylaxis: ex vivo T-cell depletion (TCD/CD34), posttransplant cyclophosphamide, calcineurin inhibitor alone (CNI), or CNI with antithymocyte globulin. Based upon survival, we could identify optimal cutoff points for CD4+ T cells in pediatric (age of <20 years) patients: 248 × 106/L and 420 × 106/L at days 100 and 180, respectively; and in adult (age of >20 years) patients: 104 × 106/L and 115 × 106/L at days 100 and 180, respectively. In adults, day-100 CD4 count was associated with overall survival (OS), progression-free survival (PFS), and TRM but not relapse, incidence of infections, or chronic GVHD. Similarly, CD4 counts above the cutoff point at day 180 in adults were associated with improved OS, PFS, and TRM but no other outcomes. No clinical associations for CD4 counts were identifiable in pediatric patients. These findings underscore the importance of tailoring transplant strategies for adults to optimize immune recovery and improve patient outcomes.

Blood AdvancesVol. 9(14)
Cincinnati Children's Hospital Medical Center (US), Boston Children's Hospital (US), Nationwide Children's Hospital (US), National Marrow Donor Program (US), Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa (ZA), Mayo Clinic (US), Memorial Sloan Kettering Cancer Center (US), The University of Texas MD Anderson Cancer Center (US), University of Pittsburgh (US), Khalifa University of Science and Technology (AE), University of Washington (US), Medical College of Wisconsin (US), Cornell University (US), University Hospitals of Cleveland (US), WinnMed (US), Fred Hutch Cancer Center (US), Sheikh Shakhbout Medical City (AE), University of Miami Health System (US), Hospital Infantil Universitario Niño Jesús (ES), University of Miami Hospital (US), Cancer Research Center (US), Children's Hospital of Pittsburgh (US), Boston Children's Museum (US), Sylvester Comprehensive Cancer Center (US), Dana-Farber/Boston Children's Cancer and Blood Disorders Center (US), Case Western Reserve University (US), University of Missouri (US)
Gateway for Cancer Research, Amgen, Bristol-Myers Squibb, Pfizer, Astellas Pharma US, AstraZeneca, GlaxoSmithKline, Sanofi, Gilead Sciences, Alexion Pharmaceuticals, HistoGenetics, Novartis Pharmaceuticals Corporation, CSL Behring, Actinium Pharmaceuticals, Vertex Pharmaceuticals, Jazz Pharmaceuticals, Mallinckrodt Pharmaceuticals, Atara Biotherapeutics, CareDx, bluebird bio, Adaptive Biotechnologies, BeiGene, Incyte, Omeros Corporation, Seagen, Kiadis Pharma, Astellas Pharma, Swedish Orphan Biovitrum, MorphoSys, Medac, National Institutes of Health, Health Resources and Services Administration, Takeda Oncology, Pharmacyclics, Legend Biotech, National Heart, Lung, and Blood Institute, Office of Naval Research, National Cancer Institute, National Institute of Allergy and Infectious Diseases
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Openalex Percentile: Top 17%
Hematopoietic Stem Cell Transplantation
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