The Impact of Leukocyte Dose during Autologous Stem Cell Transplant on Lymphocyte Recovery in Lymphoma Patients

BACKGROUND: CD34+ and CD3 cell-doses given during autologous stem cell transplantation (ASCT) can vary between patients (pts) depending on ability to mobilize and cell collection method. Retrospective studies suggest that immune recovery and absolute lymphocyte count (ALC) may be a predictor of overall survival 
(OS), progression free survival (PFS), and infectious complications in ASCT. However, It is unclear whether there is an optimal CD34+ or CD3 cell-dose that correlates with better outcomes. METHODS: A retrospective analysis of the immune recovery was performed on 24 consecutive lymphoma pts who had undergone ASCT from 1/2012 to 6/2014 at the University of Virginia to determine if a relationship existed between CD34+ or CD3 cell-dose given during ASCT and immune recovery. For each pt, number/type of infections, IgG level, T cells counts (CD4 and CD8), and ALC were collected for the first 100 days post-ASCT. OS and PFS were also assessed for each pt. Cox proportional hazard models were used to estimate the association of cell-dose infused with time to count recovery after ASCT. RESULTS: Median age was 57 years (range from 28-69 years), and 62% were male. Lymphoma subtypes were 62% B cell lymphoma, 21% Hodgkin and 17% systemic T cell. All Pts were with advance stages and heavily pretreated (median 2 lines). Peripheral blood stem cell grafts had a median CD34 of 6.2x10^6, TNC of 10.9 x10^8, and T cells of 154 x10^6. Almost half of the pts (n=11) were mobilized with plerixafor with no chemotherapy. Median follow up was 417 days (102-763). The analysis revealed that a higher CD34+ cell-dose given was significantly (p<0.05) associated with higher IgG at day 30 and earlier platelet recovery (>50,000). Higher T cell dose (>150x10^6) was also associated with higher IgG level at day 30, but unlike CD34 dose, CD3 was associated with higher ALC (>1000 cells/microL) at day 100 (p<0.05). Due to sample size and different disease associated risk factors, effect of cells dose on relapse was not statistically significant. Infection rate (almost half of pts) was similar in high vs. low cells dose. Most of the infections were bacterial and happened early post transplant with the exception of two cases of influenza and CMV. Pts who were mobilized with plerixafor without chemotherapy had a higher dose of CD3 collected compare to pts mobilized with chemotherapy (239 vs. 113. P=0.056). CONCLUSION: These preliminary results suggest that CD3+ cell-dose > 150x10^6
 cells/kg given during ASCT for aggressive lymphoma may be associated with not only better early IgG level and but also with better ALC. However, larger prospective trials are necessary to further define optimal CD3 and CD34+ cell-dose infusion for ASCT in lymphoma pts in order to improve immune recovery and prevent relapse.