Influence of Bone Marrow Graft B Lymphocyte Subsets on Outcome after Transplantation from HLA-Identical Siblings.
Authors: Michonneau David , de Latour Regis Peffault , Porcher Raphael , Robin Marie , Benbunan Marc , Rocha Vanderson , Ribaud Patricia , Ferry Christelle , Devergie Agnes , Gluckman Eliane , Marolleau Jean-Pierre , Socie Gerard , Larghero Jerome 
Published: April 2020

Abstract
Background: Bone marrow is a source of hematopoietic stem cells (HSC) in which a high proportion of CD34+ cells co-express the B cell antigen CD19. Although the influence of CD34 cell dose and graft T lymphocyte subsets on the outcome after HSC transplantation have been extensively addressed, the potential role of infused B cell subset have not been yet studied.
Methods: We retrospectively analyzed B lineage-specific Hematopoietic Progenitor Cells (CD34+ CD19+) and B cells (immature and mature B cells, CD34−CD19+) doses on transplant outcome in 85 patients (51 male, 60%) who received a non manipulated marrow graft from an HLA-identical sibling donor from January 1997 and February 2000. Cell doses were categorized according to samples tertiles and their associations with outcomes were tested in a Cox proportional hazards model.
Results: Median age was 35 years (19–42); 73 patients (86%) had hematologic malignancies. All patients received a myeloablative regimen with total body irradiation for 30 patients (35%). Acute graft versus host disease (GVHD) prophylaxis consisted in cyclosporine associated with methotrexate in all patients. Median number of bone marrow nucleated cells and CD34+ cells infused were 2.6 108/Kg and 5 106/Kg, respectively. Median number of CD34+19+ and 34−19+ infused were 0.5 106/Kg and 8.4 106/Kg, respectively. The cumulative incidence (CI) of acute GVHD grade II to IV was 48%. The incidence of acute GVHD was inversely associated to the number of infused CD34+CD19+. Among patients who received less than 0.32 106 CD34+CD19+/Kg (n=28), 19 experienced acute GVHD leading to a CI of 68%. For patients who received more than 0.32 106 but less than 0.91 106 CD34+CD19+/Kg (n=29), 17 presented acute GVHD (CI: 54%) compared to 7 patients (CI: 22%) who received more than 0.91 106 CD34+CD19+/Kg (p=0.004). Of note, a higher but not significant rate of Treatment Related Mortality (TRM) was observed for patients who received less CD34+CD19+/Kg cells. Among patients who received less than 0.32 106 CD34+CD19+/Kg (n=28), the CI of TRM was 50%. For patients who received more than 0.32 106 but less than 0.91 106 CD34+CD19+/Kg (n=29), the CI of TRM was 35% compared to 21% for patients who received more than 0.91 106 CD34+CD19+/Kg (p=0.1). There were no statistically significant associations between B cell subsets and chronic GVHD or survival. Finally, we run a multivariate analysis to ascertain the putative role of the CD34+CD19+ marrow cell subset as risk factor for acute GvHD. After adjustment for recipient age, female to male sex-mismatch, irradiation-based conditioning regimen, this cell subset remained significantly associated with acute GvHD (More than 0.32 106 CD34+CD19+/Kg marrow cells; Relative risk= 0.32, 95%; CI: 0.11–0.92, p=0.035).
Conclusions: A higher graft B lineage-specific Hematopoietic Progenitor Cells (CD34+ CD19+) is associated with a significant decrease incidence of acute GVHD. Further studies on the specific role of those cells are needed.