Laboratory Correlates of Immune Reconstitution At 1-Year Following Related, Unrelated, and Umbilical Cord Blood Hematopoietic Stem Cell Transplantation: Correlation with Survival

Reconstitution of immune function in recipients of allogeneic hematopoietic cell transplantation is a prolonged process that takes place over several years. Patients who undergo transplantation at our facility are asked to return at the one-year anniversary of their transplant for a comprehensive clinical and laboratory evaluation.  We analyzed the extent to which standard laboratory correlates of hematologic and immune reconstitution at one year posttransplant predict subsequent survival. Of 1273 patients with hematologic malignancies who underwent their first allogeneic transplant between Jan. 1, 2001 and Dec. 31, 2010, and survived at least one year, 875 returned for comprehensive assessment at 12 +/- 2 months posttransplant and were included in this retrospective study. Comparison of the cohort of patients who returned for evaluation and those who did not revealed no significant differences save for a larger proportion of patients (36.3 vs. 45.7%, p = 0.002) with high risk disease in the latter group. Patients were classified by graft sources into 5 groups: matched related, mismatched related, matched unrelated, mismatched unrelated, or unrelated cord blood (UCB). WBC, absolute neutrophil, absolute lymphocyte, and platelet counts determined by automated cell counter were available for all returning patients. Absolute CD4⁺, CD8⁺, CD19⁺, and CD56⁺ cell counts determined by flow cytometry, and serum IgG and IgA levels, were available for 405, 406, 389, 393, 866 and 732 patients, respectively. CD4⁺ lymphocytopenia at one-year posttransplant was extremely common in all groups. Reconstitution of CD19⁺ and CD56⁺ cells in the UCB group was marginally better than in the other groups. However, there were no significant differences in the reconstitution of CD4⁺ and CD8⁺ cells counts and serum IgG and IgA levels according to graft sources. To determine whether any of the common laboratory measures of immune reconstitution observed at one year posttransplant were correlated with subsequent survival, we conducted landmark analyses in which the patients were divided into quartiles according to their hematologic and immunologic indices. WBC and absolute neutrophil counts were not closely correlated with subsequent survival. Patients in the lowest quartile of the absolute lymphocyte and platelet count distributions, however, experienced significantly inferior survival beyond one year (p=0.012 and <0.001, respectively) when compared with patients in the highest quartile (reference group). Patients in the lowest quartiles of the absolute CD4⁺, CD19⁺, CD56⁺, and serum IgG distributions also experienced significantly inferior survival (p=0.019, 0.001, 0.02, and 0.023, respectively). These results demonstrate that poor CD19⁺ B cell recovery at 1 year is associated with inferior survival, and suggest that interventions aimed at enhancing B cell reconstitution may have clinical benefit.