A Detailed Flow Cytometry Analysis of the Immune System in Non-Leukemic Cells of Acute Myeloid Leukemia Demonstrates the Prognostic Significance of Lymphocyte Subsets
Robert S Ohgami, Matthew Alcasid, Li Ren, Jason R Gotlib, Daniel A Arber. Stanford, Stanford, CA
Background: While the role of the immune system in modulating the progression of solid tissue tumors has been well studied, its impact on the outcome and progression of hematolymphoid neoplasms is less understood.
Design: Using multiparameter flow cytometry, we report a detailed analysis of 86 patients with acute myeloid leukemia (AML), with immunophenotypic evaluation of lymphocyte subsets including B-cells, T-cells, NK/T-cells and NK cells with long-term clinical follow-up.
Results: Patients with increased populations of CD16+/CD56+ and CD8+ NK cells have improved disease free survival (univariate Hazard ratios of 0.96 and 0.88 respectively; P-values = 0.018 and 0.006 respectively). Furthermore, the prognostic significance of increased CD16+/CD56+ NK-cells was retained in multivariate analysis with a disease free survival Hazard ratio of 0.96 (P-value = 0.015). Interestingly, patients who achieved clinical remission had slightly decreased proportions of T-cells amongst all lymphocytes (70.4% vs 75.5% of lymphocytes; P-value = 0.035) while conversely, increased numbers of mature B-cells were associated with patients who achieved clinical remission (P-value = 0.028) (Table 1). Finally detailed hierarchical clustering analyses also demonstrates that distinct variations in lymphocyte subsets are associated with certain subtypes of AML; AML-M5 shows increased proportions of T-cells with fewer B-cells (Figure 1).
Conclusions: Our findings in total demonstrate that the distribution of immune system lymphocytes is non-random and suggests an important role for distinct lymphocyte subsets in the progression and prognostication of AML.
|Cell Subset||OS (P-value)||DFS (P-value)||CR (P-value)||DFS Hazard Ratio||CR = 0 (Mean % of lymphocytes)||CR = 1 (Mean % of lymphocytes)|