Impact of Time to Lymphocyte Recovery on Survival Post Autologous Stem Cell Transplantation.

Several studies have suggested that the peripheral blood absolute lymphocyte count (ALC) at arbitrary time points after ASCT is associated with improved survival and decreased relapse rate. Most reports have focused on one type of hematological malignancy, and different time points (i.e. day 15, day 21) and ALC values (> 0.35×10⁹/L, > 0.5×10⁹/L) have been studied. We hypothesized that the immune recovery post ASCT is an important predictor of long term outcome independent of disease, and that more important than the value of ALC at a specific time point, is the time to lymphocyte recovery post-ASCT.

The medical records of patients that underwent ASCT at our institution from January 2005 until May 2010 were reviewed and information on ALC count at day 15 and time to lymphocyte recovery was retrieved. Lymphocyte recovery was defined as the first of at least two consecutive days with > 0.5×10⁹/L lymphocytes on the peripheral blood. Overall survival was defined as time from ASCT until death from any cause. OS was estimated by Kaplan-Meier and compared by logrank. Cox proportional hazards models was used to determine covariates associated with OS in a multivariate analysis. Variables were entered and selected in a backwards fashion with a p cutoff of 0.05.

Ninety-two patients were analyzed. Diagnosis included: multiple myeloma (N=35), non-Hodgkin's lymphoma (N=33), solid tumors (N=8), Hodgkin's lymphoma (N=8), acute myeloid leukemia (N=4), amyloidosis AL (N=3) and chronic myeloid leukemia (N=1). Median age was 55 years (range 3–74 years). OS at 2 years for the entire cohort was 51% (95% CI 37–66%). There were 47 patients (51%) with an ALC at day 15 (ALC-15) ≥ 0.5×10⁹/L, and these patients had a significantly superior OS compared to patients with an ALC-15 < 0.5×10⁹/L (2-years OS: 68% vs. 35%, p=0.01). Median time to lymphocyte recovery was 15 days (range 8–314 days). Patients with a rapid (≤ 15 days) lymphocyte recovery had superior OS compared to those with a slower (> 15 days) lymphocyte recovery (2-years OS: 66% vs. 31%, p=0.002). Median OS for those with a quick recovery was not reached, while for patients with a slow recovery was 16 months (95% CI 3–29 months). In a Cox proportional hazards analysis, the following variables were added: age, diagnosis of multiple myeloma (yes vs. no), ALC-15 < 0.5×10⁹/L (yes vs. no) and slow lymphocyte recovery (yes vs. no). Only diagnosis of multiple myeloma (hazard ratio [HR] 0.25 [95% CI 0.09–0.67], p=0.006) and slow lymphocyte recovery (HR 3.18, [95% CI 1.44–7.03], p=0.004) were associated with OS, while ALC-15 was not.

Our results suggest that the kinetics of lymphocyte recovery have an important impact on survival post-ASCT. Our findings need to be confirmed in other cohorts. Strategies to modulate immune function post-ASCT should be the subject of future studies.

No relevant conflicts of interest to declare.