Influence of bone marrow graft lymphocyte subsets on outcome after HLA-identical sibling transplants

Objective. The aim of this study was to analyze bone marrow lymphocyte subs ets and CD34 cell dose and their influence on the outcomes of bone marrow t ransplantation. Materials and Methods. Forty-eight patients (median age 30 years, range 5-5 4) receiving HLA-identical sibling bone marrow transplantation for hematolo gic malignancies were analyzed. Results. Median number (range) of nucleated cells and CD34(+) cells infused were 2.4 (0.4-6.0) x 10(8)/kg and 3.5 (0.5-13.0) x 10(6)/kg, respectively. Probability of neutrophil recovery was 97%. In a multivariate analysis, ti me to neutrophil recovery was shortened when a higher number of CD3/CD8 cel ls was infused (greater than or equal to1.0 x 10(7)/kg) (hazard ratio [HR] = 2.13, p = 0.018); when the patient was female or had negative cytomegalov irus serology (HR = 2.03, p = 0.03; HR = 0.41, p = 0.009; respectively). Th e incidence of grade II to IV acute graft-vs-host disease (GVHD) was 47%. I nfusion of >1 x 10(7) CD4 infused/kg increased the risk of acute GVHD (HR = 2.86, p = 0.03). Nineteen of 40 patients at risk experienced chronic GVHD, the risk of which was increased by diagnosis of chronic leukemia (p = 0.03 ), <2.0 x 10(8) nucleated cells infused/kg (p = 0.05), and a low number of all lymphocyte subsets, except CD19. Estimated 3-year survival rate was 54% . Risk of death was increased in patients receiving <3.5 x 10(6) CD34 infus ed/kg (HR = 0.37, p = 0.02). Only six patients relapsed. Conclusions. A high cell dose of CD3/CD8 is associated with faster neutroph il recovery, whereas a high cell dose of CD4(+) cells increases the inciden ce of acute GVHD. A high number of nucleated cells and CD34(+)cells infused was associated with decreased risk of chronic GVHD and improved survival, respectively. (C) 2001 International Society for Experimental Hematology. P ublished by Elsevier Science Inc.