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CTLA4Ig-primed donor lymphocyte infusions following haploidentical transplantation improve outcome with a distinct pattern of early immune reconstitution as compared to conventional donor lymphocyte infusions in advanced hematological malignancies

Bone Marrow Transplantation volume 56, pages 185–194 (2021)Cite this article

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Abstract

CTLA4Ig has a unique property to spare or even potentiate natural killer (NK) cell-mediated cytotoxicity, whilst inhibiting T cell activation. We explored the efficacy of prophylactic DLI following CTLA4Ig (CTLA4Ig-DLI group, n = 75), compared to conventional DLI (DLI group, n = 50), in patients with advanced hematological malignancies receiving PTCy-based haploidentical transplantation. Acute and chronic GVHD in the CTLA4Ig-DLI group were 9.6% and 15.3% compared to 18.8% [p = 0.09] and 36.5% [p = 0.01] in the DLI group. Both non-relapse mortality (4% vs 14.4%) and disease progression (DP) (15.7% vs 31.1%) were lower in CTLA4Ig-DLI group (p = 0.04). GVHD and progression-free survival was significantly improved in the CTLA4Ig-DLI group (p = 0.001). The recovery of CD56dimNK cells, NKG2A-KIR + NK subsets and Tregs was significantly better in the CTLA4Ig-DLI group at all time points and memory T cells at day +90. Immune recovery in relation to DP showed distinct patterns, with T cell subsets in the DLI group and NKG2A-KIR+NK cells in CTLA4Ig-DLI group having favorable impact. CTLA4Ig-DLI was thus associated with an improved outcome, possibly on account of the distinct pattern of immune recovery shown with this novel approach.

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Fig. 1: Transplantation protocols.
Fig. 2: Comparison of transplant outcomes.
Fig. 3: GVHD and progression-free survival.
Fig. 4: Comparison of immune reconstitution.

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Acknowledgements

We thank all the patients and family members who participated in this study. We also thank each and every member of our department for their help in patient care and execution of the study.

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Authors and Affiliations

  1. Cellular Therapy and Immunology, Manashi Chakrabarti Foundation, Kolkata, India

    Sarita Rani Jaiswal, Prakash Bhakuni, Rishabh Raj Jaiswal, Aditi Chakrabarti & Suparno Chakrabarti

  2. Department of Blood and Marrow Transplantation, Dharamshila Narayana Superspeciality Hospital and Research Centre, New Delhi, India

    Sarita Rani Jaiswal, Prakash Bhakuni, Mayank Soni & Suparno Chakrabarti

  3. Department of Pathology and Microbiology, Dharamshila Narayana Superspeciality Hospital and Research Centre, New Delhi, India

    Gitali Bhagawati & Hema Malini Aiyer

  4. Department of Radiology, Dharamshila Narayana Superspeciality Hospital and Research Centre, New Delhi, India

    Navneet Sharma

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  1. Sarita Rani Jaiswal
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Contributions

SRJ and SC designed and performed the study. SRJ and PB performed the experiments. HMA, MS, NS and PB collected the data. SRJ, RRJ, GB and SC analyzed the data; SRJ, AC and SC wrote the manuscript. All the co-authors reviewed and approved the manuscript.

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Correspondence to Sarita Rani Jaiswal.

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Jaiswal, S.R., Bhakuni, P., Bhagawati, G. et al. CTLA4Ig-primed donor lymphocyte infusions following haploidentical transplantation improve outcome with a distinct pattern of early immune reconstitution as compared to conventional donor lymphocyte infusions in advanced hematological malignancies. Bone Marrow Transplant 56, 185–194 (2021). https://doi.org/10.1038/s41409-020-01002-1

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