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Effect of Graft-versus-Host Disease Prophylaxis Regimens on T and B Cell Reconstitution after Allogeneic Hematopoietic Stem Cell Transplantation
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2019 (English)In: Biology of blood and marrow transplantation, ISSN 1083-8791, E-ISSN 1523-6536, Vol. 25, no 6, p. 1260-1268Article in journal (Refereed) Published
Abstract [en]

Lymphocyte reconstitution is pivotal for successful long-term outcome after allogeneic hematopoietic stem cell transplantation (HSCT), and conditioning regimen and post-transplantation immunosuppression are risk factors for prolonged immunodeficiency. Nevertheless, the effects of different immunosuppressive protocols on lymphocyte output and replicative capacity have not been investigated. Here we assessed T cell receptor excision circles (TREC), kappa-deleting recombination excision circles (KREC), and T cell telomere length (TL) as proxy markers for immune reconstitution in patients in a prospective randomized trial comparing graft-versus-host disease (GVHD) prophylaxis after transplantation (cyclosporine/methotrexate versus tacrolimus/sirolimus; n = 200). Results showed that medians of TREC, KREC, and TL were not significantly different between the prophylaxis groups at any assessment time point during follow-up (24 months), but the kinetics of TREC, KREC, and TL were significantly influenced by other transplantation-related factors. Older recipient age, the use of antithymocyte globulin before graft infusion, and use of peripheral blood stem cell grafts were associated with lower TREC levels, whereas acute GVHD transiently affected KREC levels. Patients with lymphocyte excision circle levels above the median at ≤6 months post-transplantation had reduced transplantation-related mortality and superior 5-year overall survival (P <.05). We noticed significant T cell telomere shortening in the patient population as a whole during follow-up. Our results suggest that lymphocyte reconstitution after transplantation is not altered by different immunosuppressive protocols. This study has been registered at ClinicalTrials.gov (identifier: NCT00993343). 

Place, publisher, year, edition, pages
Elsevier, 2019. Vol. 25, no 6, p. 1260-1268
Keywords [en]
Allogeneic hematopoietic stem cell transplantation, Clinical trial, GVHD prophylaxis, Immune reconstitution, Lymphocyte excision circles
National Category
Hematology
Identifiers
URN: urn:nbn:se:kth:diva-252244DOI: 10.1016/j.bbmt.2019.01.029ISI: 000472986900027PubMedID: 30710687Scopus ID: 2-s2.0-85062075801OAI: oai:DiVA.org:kth-252244DiVA, id: diva2:1322064
Note

QC 20190610

Available from: 2019-06-10 Created: 2019-06-10 Last updated: 2019-07-31Bibliographically approved

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Uhlin, Michael

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