Effect Of Combined Lymphocyte And Monocyte Recovery On Survival Post Myeloablative Allogeneic Hematopoietic Stem Cell Transplant For Acute Leukemia

6561 Background: Many previous studies of immune reconstitution (IR) post-allogeneic hematopoietic stem cell transplantation (HSCT) have focused on lymphocyte recovery. Recognizing that IR involves complex interactions between innate and adaptive immune systems, we hypothesized that monocyte recovery along with lymphocyte recovery could provide additional prognostic information. Methods: To test our hypothesis, we analyzed data from 135 consecutive patients undergoing myeloablative allogeneic HSCT for AML and ALL. The absolute lymphocyte counts and monocyte counts (ALC and AMC, respectively) were determined longitudinally at days +15, +30, +60, +100 and correlated with outcomes. Results: At the day +30 time point, both ALC and AMC > 0.3 x 109 cells/L were strongly associated with improved survival (OS 29.6 months vs. 5.4 months, p=0.006 and 25.3 months vs. 5.1 months, p=0.01 respectively), a pattern that continued through the day +100 evaluation. Multivariate analysis including age at transplant, CD34+ cell dose, related vs. unrelated HSCT, and grade of acute GVHD revealed the following independent prognostic factors: age at transplant (RR 4.31, 95% CI 1.45 – 13.7, p=0.008), day +100 ALC > 0.3 x 109 cells/L (RR 0.34, 95% 0.16 – 0.82, p=0.02) and day +100 AMC > 0.3 x 109 cells/L (RR 0.33, 95% CI 0.18 – 0.67, p=0.002). To further explore whether any patterns in the timing of lymphocyte and monocyte recovery had prognostic value post-HSCT, we performed unsupervised hierarchical clustering on the longitudinal hematopoietic parameters studied in this cohort. Four clusters of patients were identified, clusters A-D. Patient clusters B and D demonstrated improved ALC and AMC recovery at the day +60 and day +100 time points and had significantly improved OS compared with clusters A and C (57.8 months vs. 19.7 and 4.4 months, respectively, p<0.001). Conclusions: IR is paramount to the success of transplant as a therapeutic modality for high-risk hematologic malignancies. Our data suggests that monocyte/macrophage reconstitution may be as important as, and supportive to, lymphocyte recovery post allogeneic HSCT.