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Upfront memory T cell add-back with haploidentical TCRαβ-depleted graft in adults with haematological malignancies: a nationwide, multicentre, single-arm, prospective study

Bone Marrow Transplantation (2025)Cite this article

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Abstract

In haploidentical hematopoietic cell transplantation (Haplo-HCT), in vivo or ex vivo T-cell depletion (TCD) can prevent graft-versus-host disease (GVHD) but increase risk of infection and relapse. We hypothesized that TCRαβ-depleted allograft together with upfront infusion with CD45RA-depleted memory T cells (αβTCD + TMDLI) may result in favourable GVHD-free and relapse-free survival (GRFS). Between January 2017 and July 2023, 145 adult patients with various haematological malignancies received αβTCD + TMDLI. All except 2 patients had robust engraftment at a median of 12 days for neutrophil and 11 days for platelet. The cumulative incidence (CI) of CMV, EBV, HHV6 or ADV infection was only 43% (n = 63) at day+120. CI of grade II–IV and III–IV acute GVHD at 180 days was 31% and 8% respectively. Chronic GVHD was seen in only 5 patients with a 2-year CI of 4%. CI of non-relapse mortality and relapse at 2 years were 17% and 22% respectively. At a median follow up of 28 months, 3-year overall (OS), event-free (EFS), and GRFS were 67%, 62%, and 59%, respectively. This was significantly improved over a propensity score-matched contemporary cohort (n = 53) who received PTCy as GVHD prophylaxis. This first multi-center study demonstrated the potential benefits of the αβTCD + TMDLI approach for Haplo-HCT.

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Fig. 1: Cumulative incidence of acute and chronic graft vs host disease (GVHD), viral infection, non-relapse mortality (NRM), and relapse.
Fig. 2
Fig. 3: Comparison of outcomes using αβTCD-TMDLI vs PTCy.

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Acknowledgements

The authors acknowledge the continuous effort of the entire team involved in our transplant program, including junior medical staff, other medical disciplines, transplant coordinators, nurses, laboratory colleagues, pharmacists, and social workers for the excellent support rendered to our patients. Most importantly, we are grateful to all our patients and their families for their courage, trust, and cooperation.

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Authors and Affiliations

  1. Department of Haematology-Oncology, National University Cancer Institute, Singapore, Singapore

    Liang-Piu Koh, Yang Liang Boo, Victor Ling, Michelle Poon, Lip Kun Tan, Jean Rachel M. Catapia, Joanne Lee, Ian Wu, Teck Guan Soh & Yin Jie Koh

  2. Department of Haematology, Singapore General Hospital and National Cancer Center, Singapore, Singapore

    Yeh Ching Linn, Jeffrey Quek, Hein Than, Aloysius Ho, Francesca Lim, William Hwang, Lawrence Ng, Tertius Tansloan Tuy, Gina Gan & Kee Khiang Heng

  3. Center for Clinical Hematology, Mount Elizabeth Novena Medical Center, Singapore, Singapore

    Zi Yi Lim

  4. Parkway Cancer Center, Mount Elizabeth Hospital, Singapore, Singapore

    Colin Phipps Diong

  5. Department of Radiation Oncology, National University Cancer Institute, Singapore, Singapore

    Balamurugan Vellayappan

  6. Department of Haematology, General Medicine, Sengkang General Hospital, Singapore, Singapore

    Ian Wu

  7. Division of Radiation Oncology, National Cancer Center Singapore, Singapore, Singapore

    Kheng Wei Yeoh, Bryan Ho & Wen Shen Looi

  8. Curie Oncology, Mount Elizabeth Hospital, Singapore, Singapore

    Yvonne Loh

  9. Raffles Hospital, Singapore, Singapore

    Yvonne Loh

  10. Department of Paediatric Haematology, KK Women’s and Children’s Hospital, Singapore, Singapore

    Wing Leung

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  1. Liang-Piu Koh
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Contributions

LPK, YCL, and WL conceived and designed the study; LPK, YCL, YBL, VL, ZYL, MP, JQ, HT, CPD, BV, AH, FL, WH, LKT, JRMC, JL, IW, KWY, BH, WSL, LN, TTT, YL, TGS, GG, and KKH provided study material or patients; LPK, YCL, YJK, and WL collected and assembled the data; LPK, YCL, and WL analyzed and interpreted the data; LPK, YCL, and WL wrote the manuscript; and all authors provided final approval of the manuscript.

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Correspondence to Liang-Piu Koh.

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This study was approved by the Institutional Review Board of the National University Hospital (NHG DSRB 2010/00431) and Singapore General Hospital (Singhealth CRIB 2015-2419). All methods were conducted in accordance with the Declaration of Helsinki. Informed consent was obtained from all participants.

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Koh, LP., Linn, Y.C., Boo, Y.L. et al. Upfront memory T cell add-back with haploidentical TCRαβ-depleted graft in adults with haematological malignancies: a nationwide, multicentre, single-arm, prospective study. Bone Marrow Transplant (2025). https://doi.org/10.1038/s41409-025-02728-6

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