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

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 wit...

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Published in:Bone marrow transplantation (Basingstoke) 2021-01, Vol.56 (1), p.185-194
Main Authors: Jaiswal, Sarita Rani, Bhakuni, Prakash, Bhagawati, Gitali, Aiyer, Hema Malini, Soni, Mayank, Sharma, Navneet, Jaiswal, Rishabh Raj, Chakrabarti, Aditi, Chakrabarti, Suparno
Format: Article
Language:English
Subjects:
Blood diseases
Care and treatment
Cell activation
Comparative analysis
CTLA-4 protein
Cytotoxicity
Development and progression
Graft-versus-host reaction
Health aspects
Hematology
Hematopoietic stem cells
Immune reconstitution
Immunoglobulins
Immunological memory
Immunotherapy
Killer cell immunoglobulin-like receptors
Lymphocytes
Lymphocytes T
Medical protocols
Memory cells
Methods
Natural killer cells
NKG2 antigen
Patient outcomes
Recovery
Stem cell transplantation
Toxicity
Transplantation
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Summary: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 CD56 NK 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.
ISSN:0268-3369
1476-5365
DOI:10.1038/s41409-020-01002-1