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Lymphocyte Recovery in Advanced Ovarian Cancer Patients after High-Dose Chemotherapy and Peripheral Blood Stem Cell Plus Growth Factor Support

Clinical Implications¹

Departments of Gynecology [G. F., S. M., G. S.] and Hematology [L. P., A. P. S. R., M. L., G. L.], Catholic University of Rome, 00168 Rome, Italy

Purpose: The purpose of this study was to investigate the clinical role of immunological recovery together with selected biological parameters on long-term survival in a series of ovarian cancer administered high-dose chemotherapy with peripheral blood stem cell and growth factor support.

Experimental Design: Thirty-eight patients with stages IIIB–IV epithelial ovarian cancer were studied. Lymphocyte immunophenotyping for the identification of CD3(+), CD4(+), CD8(+), and CD3(-)/CD16(+)CD56(+) natural killer T cells and CD19 B cells was performed.

Results: Twenty-three patients (60%) had a CD3(+) cell count <850 cells/µl. Multivariate logistic regression showed that tumor grading (² = 6.6, P = 0.010) and type of growth factor (² = 4.1, P = 0.042) retained an independent role in predicting T-cell recovery above the value of 850 cells/µl. The 3-year time to progression (TTP) rate was 86% (95% confidence intervals, 70, 102) in cases with high CD3(+) cell count with respect to a 3-year TTP of 23% (95% confidence intervals, 8, 38) in cases with low CD3(+) cell count (P = 0.0026). The absolute number of CD3(+) cells was shown to be inversely associated with risk of progression (² = 4.8; P = 0.028), as assessed by Cox univariate analysis using CD3(+) cell count as continuous covariate. In multivariate analysis only residual tumor and status of CD3(+) cell counts retained an independent association with shorter TTP. Similar results were obtained for overall survival.

Conclusions: Long-term immune reconstitution and particularly the recovery of adequate counts of CD3(+), CD4(+), and CD8(+) T cells are independent markers of longer TTP and overall survival in ovarian cancer patients receiving high-dose chemotherapy with peripheral blood stem cell and growth factor support.

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