High prevalence of CD3, NK, and NKT cells in the graft predicts adverse outcome after matched-related and unrelated transplantations with post transplantation cyclophosphamide

• Published in: Bone marrow transplantation (Basingstoke) Vol. 55; no. 3; pp. 544 - 552
• Main Authors: Moiseev, Ivan S., Babenko, Elena V., Epifanovskaya, Olga S., Sergeev, Vladislav S., Dotcenko, Anna A., Bakin, Evgeny A., Surkova, Elena A., Kuznetsova, Daria A., Lapin, Sergey V., Pirogova, Olga V., Alyanskii, Alexandr L., Golovacheva, Alla A., Darskaya, Elena I., Morozova, Elena V., Markova, Inna V., Bondarenko, Sergey N., Afanasyev, Boris V.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-03-2020; Nature Publishing Group
• Subjects: 13/21; 13/31; 692/308/2171; 692/499; Antilymphocyte serum; Biomarkers; Bone marrow; Bone marrow transplantation; Calcineurin; Calcineurin inhibitors; CD16 antigen; CD3 antigen; CD56 antigen; Cell Biology; Complications and side effects; Composition; Cyclophosphamide; Donors; Enzyme-linked immunosorbent assay; Flow cytometry; Globulins; Graft versus host reaction; Grafting; Hematology; Hematopoietic stem cells; Immunology; Internal Medicine; Leukemia; Lymphocytes; Lymphocytes T; Medicine; Medicine & Public Health; Natural killer cells; Peripheral blood; Prevention; Prophylaxis; Public Health; Risk factors; Stem cell transplantation; Stem Cells; Subpopulations; Tacrolimus; Testing; Thymocytes; Tissue extracts; Transplantation; Russia
• ISSN: 0268-3369; 1476-5365
• DOI: 10.1038/s41409-019-0665-3

The predictive value of graft composition and plasma biomarkers on the outcome of allogeneic HSCT is well known for conventional GVHD prophylaxis based on calcineurin inhibitors with or without antithymocyte globulin. Currently, there is limited data whether these results could be translated to post transplantation cyclophosphamide (PTCy). The prospective extension cohort of NCT02294552 trial enrolled 79 adult patients with acute leukemia in CR. Twenty-six received matched-related bone marrow (BM) grafts with single-agent PTCy and 53 received unrelated peripheral blood stem cell graft (PBSC) with PTCy, tacrolimus, and MMF. The grafts were studied by the flow cytometry, and plasma samples were analyzed by ELISA. In the cluster and major component analysis, we determined that transplantation from donors with high content of CD3, NKT, and CD16-CD56 + subpopulations in the PBSC grafts was associated with poor immunological recovery and compromised event-free survival (50% vs. 80%, HR 2.93,
p
 = 0.015) both due to increased relapse incidence and non-relapse mortality. The significant independent predictor of moderate and severe chronic GVHD was the high prevalence of and iNKT, Vβ11, and double-positive cells in the PBSC grafts from young donors (HR 2.75,
p
 = 0.0483). No patterns could be identified for BM grafts and for plasma biomarkers.