Kinetics of early immune reconstitution and its exploratory association with post-transplant outcomes in patients undergoing haploidentical HCT with post-transplant cyclophosphamide-based GvHD prophylaxis
- 1Department of Hematology, Christian Medical College
- 2Department of Biotechnology-Regional Centre for Biotechnology (RCB)
Abstract
Introduction: Post-transplant cyclophosphamide (PTCy) is widely used for graft-versus-host disease (GvHD) prophylaxis in haploidentical hematopoietic cell transplantation. However, the kinetics of early immune reconstitution in real-world, heterogeneous cohorts, and their relationship with early outcomes, remain incompletely defined.
Methods: In this prospective single-center study, 95 consecutive patients undergoing haploidentical transplantation with PTCy (October 2021 to December 2024) underwent serial multicolor flow cytometry before conditioning, at neutrophil engraftment, and on days +21, +28, +60 and +90. T, B and natural killer (NK) cells were enumerated, along with CD4+ and CD8+ naive, central memory, effector memory and terminal effector subsets. Regulatory T cells were assessed in 50 patients. An exploratory propensity-matched comparison was performed against a contemporaneous HLA-matched donor cohort.
Results: Immune reconstitution followed a sequential pattern: NK cells recovered earliest (from day +21), B-cell recovery was delayed, and T cells expanded gradually, dominated by central and effector memory subsets, while naive and terminal effector subsets remained low through day +90. Grade II to IV acute GvHD occurred in 32.6% of patients, and transplant-related mortality (TRM) was 26.3% by day +100. No lymphocyte subset was significantly associated with acute GvHD, TRM or overall survival, and reconstitution kinetics were similar between myeloablative and reduced-intensity conditioning. In the propensity-matched comparison, day +100 TRM was higher in the haploidentical cohort, whereas acute GvHD and overall survival were comparable.
Discussion: Early immune reconstitution after haploidentical transplantation with PTCy proceeds in a characteristic sequence, but quantitative recovery of circulating lymphocyte subsets alone did not predict acute GvHD or early mortality. Larger studies incorporating functional immune assays and time-to-event modelling are needed to clarify these relationships.
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BibTeX
@article{bijukumar2026kinetics,
title = {{Kinetics of early immune reconstitution and its exploratory association with post-transplant outcomes in patients undergoing haploidentical HCT with post-transplant cyclophosphamide-based GvHD prophylaxis}},
author = {Nayanthara K. Bijukumar and Aswin Anand Pai and Rachel Mariam Renji and Agila Jayaraman and Raveen Stephen Stallon Illangeswaran and Arun Kumar Arunachalam and Phaneendra D. V. and Kavitha M. Lakshmi and Eunice S. Edison and Sushil Selvarajan and Sharon Anbumalar Lionel and Anu Korula and Aby Abraham and Vikram Mathews and Biju George and Sujith Karumathil and Uday Kulkarni and Poonkuzhali Balasubramanian},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1996185},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1996185/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Kinetics of early immune reconstitution and its exploratory association with post-transplant outcomes in patients undergoing haploidentical HCT with post-transplant cyclophosphamide-based GvHD prophylaxis
AU - Nayanthara K. Bijukumar
AU - Aswin Anand Pai
AU - Rachel Mariam Renji
AU - Agila Jayaraman
AU - Raveen Stephen Stallon Illangeswaran
AU - Arun Kumar Arunachalam
AU - Phaneendra D. V.
AU - Kavitha M. Lakshmi
AU - Eunice S. Edison
AU - Sushil Selvarajan
AU - Sharon Anbumalar Lionel
AU - Anu Korula
AU - Aby Abraham
AU - Vikram Mathews
AU - Biju George
AU - Sujith Karumathil
AU - Uday Kulkarni
AU - Poonkuzhali Balasubramanian
PY - 2026
DA - 2026/10/26
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1996185
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1996185/full
AB - Introduction: Post-transplant cyclophosphamide (PTCy) is widely used for graft-versus-host disease (GvHD) prophylaxis in haploidentical hematopoietic cell transplantation. However, the kinetics of early immune reconstitution in real-world, heterogeneous cohorts, and their relationship with early outcomes, remain incompletely defined. Methods: In this prospective single-center study, 95 consecutive patients undergoing haploidentical transplantation with PTCy (October 2021 to December 2024) underwent serial multicolor flow cytometry before conditioning, at neutrophil engraftment, and on days +21, +28, +60 and +90. T, B and natural killer (NK) cells were enumerated, along with CD4+ and CD8+ naive, central memory, effector memory and terminal effector subsets. Regulatory T cells were assessed in 50 patients. An exploratory propensity-matched comparison was performed against a contemporaneous HLA-matched donor cohort. Results: Immune reconstitution followed a sequential pattern: NK cells recovered earliest (from day +21), B-cell recovery was delayed, and T cells expanded gradually, dominated by central and effector memory subsets, while naive and terminal effector subsets remained low through day +90. Grade II to IV acute GvHD occurred in 32.6% of patients, and transplant-related mortality (TRM) was 26.3% by day +100. No lymphocyte subset was significantly associated with acute GvHD, TRM or overall survival, and reconstitution kinetics were similar between myeloablative and reduced-intensity conditioning. In the propensity-matched comparison, day +100 TRM was higher in the haploidentical cohort, whereas acute GvHD and overall survival were comparable. Discussion: Early immune reconstitution after haploidentical transplantation with PTCy proceeds in a characteristic sequence, but quantitative recovery of circulating lymphocyte subsets alone did not predict acute GvHD or early mortality. Larger studies incorporating functional immune assays and time-to-event modelling are needed to clarify these relationships.
SN - 1664-3224
ER -