Abstract
Background: Day 15 absolute lymphocyte count (ALC-15) ≥500 cells/μl after autologous peripheral blood hematopoietic stem cell transplantation (APHSCT) is a significant predictor for survival. Limitations of previous reports have been their retrospective nature and no ALC-15 lymphocyte subsets analysis. Thus, from 2/2002 until 2/2007, 50 non-Hodgkin lymphoma (NHL) patients were enrolled in a prospective study to address these limitations. Methods: APHSCT eligible NHL patients who signed written consent for additional blood collections participated in the study. The primary end point was to confirm the ALC-15 survival role and to identify the lymphocyte subsets of greatest impact on ALC-15 after APHSCT. Results: The median age of the cohort was 57.7 years (range: 23–73). The groups (ALC-15 ≥500 vs < 500 cells/μl) were balanced to lymphoma type (p = 0.4), gender (p = 0.5), age (p = 0.2), extranodal sites (p = 0.4), lactate dehydrogenase (p = 0.5), performance status (p = 0.5), stage (p = 0.5), international prognostic index (p = 0.9), number of prior chemotherapies (p = 0.1), clinical status at APHSCT (p = 0.2), and infused CD34/kg (p = 0.8). With a median follow-up of 22.2 months (range: 6–63.7 months), patients with an ALC-15 ≥500 cells/μl (n = 35) experienced superior overall survival (OS) and progression-free survival (PFS) compared with those who did not (median OS: not reached vs 19 months, 3 years OS rates of 80% vs 40%, p < 0.0004; median PFS: not reached vs 3.4 months, 3 years PFS rates of 60% vs 14%, p < 0.0001, respectively). By day 15 post-APHSCT 30% of patients achieved a normal CD3, 18% a normal CD4, 38% a normal CD8, 4% a normal CD19, and 76% a normal [CD16+/56+/CD3-] counts. In Univariate analysis CD16+/56+/CD3- natural killer (NK) cells were the only ALC-15 lymphocyte subset that predicted for survival. Patients with a normal absolute NK cell count (≥80 cells/μl, n = 38) experienced superior OS and PFS compared with those who did not (median OS: not reached vs 5 months, 3 years OS rates of 76% vs 36%, p < 0.0001; and median PFS: not reached vs 3 months, 3 years PFS rates of 57% vs 9%, p < 0.0001, respectively). Conclusion: This study confirms the prognostic ALC-15 survival role and identifies NK cells as the key lymphocyte subset affecting clinical outcomes after APHSCT in NHL. This study was supported in part by the Grant CA90628–04A from the National Institute of Health, and the University of Iowa/Mayo Clinic Lymphoma Spore CA97274.
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