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. 2025 Jul 22;9(14):3502-3517.
doi: 10.1182/bloodadvances.2024015288.

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

Miguel-Angel Perales  1   2 , Marcie Riches  3 , Naya He  3 , Michael J Martens  3   4 , Roy F Chemaly  5 , Christopher E Dandoy  6 , Joshua A Hill  7   8 , Miguel Angel Diaz  9 , Shahrukh Hashmi  10   11   12 , Susan Prockop  13 , Hillard M Lazarus  14 , Amer M Beitinjaneh  15 , Gerhard C Hildebrandt  16 , Jeffery J Auletta  17   18 , Paul Szabolcs  19   20
Affiliations

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

Miguel-Angel Perales et al. Blood Adv. .

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.

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Conflict of interest statement

Conflict-of-interest disclosure: M.-A.P. reports honoraria from Adicet, Allogene, AlloVir, Caribou Biosciences, Celgene, Bristol Myers Squibb, Equilium, Exevir, ImmPACT Bio, Incyte, Karyopharm, Kite/Gilead, Merck, Miltenyi Biotec, MorphoSys, Nektar Therapeutics, Novartis, Omeros, Orca Bio, Sanofi, Syncopation, VectivBio AG, and Vor Biopharma; serves on data safety monitoring boards for Cidara Therapeutics and SELLAS Life Sciences; serves on the scientific advisory board of NexImmune; has ownership interests in NexImmune, Omeros, and Orca Bio; and has received institutional research support for clinical trials from Allogene, Incyte, Kite/Gilead, Miltenyi Biotec, Nektar Therapeutics, and Novartis. P.S. serves as an ad hoc consultant to Forge Bio. M.R. reports compensation as an employee (executive director, clinical development) of Kura Oncology and reports equity stock options as an employee of Kura Oncology. R.F.C. reports compensation from ADMA Biologics, Janssen, MSD/Merck, Roche, Takeda Pharmaceuticals, Shionogi, Genentech, Astellas Pharma, AiCuris, Adagio Therapeutics, Oxford Immunotec, Karius, Moderna, and Ansun Pharmaceuticals, and significant payments from Merck, Karius, Aicuris, Ansun Pharmaceuticals, Takeda Pharmaceuticals, Genentech, Oxford Immunotec, and Eurofins Viracor. J.A.H. reports compensation for consulting roles from AlloVir, EVERSANA, GeoVax, Grifols, Karius, Modulus, Senti Bio, Takeda Pharmaceuticals, and UpToDate; serves on a data safety monitoring board for Moderna; reports compensation for speaking from Gilead Australia; reports research support from AlloVir, Deverra, GeoVax, Merck, Oxford Immunotec, and Takeda Pharmaceuticals; and received significant payments for participation on advisory board meeting from Takeda Pharmaceuticals. The remaining authors declare no comping financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Recovery of immune subsets at days 100 and 180 in different cohorts based on GVHD prophylaxis (ppx). (A) CD4 T cells; (B) CD8 T cells; (C) natural killer cells; and (D) B cells.
See this image and copyright information in PMC

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