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Post-chemotherapy lymphopoiesis in patients with solid tumors is characterized by CD4+ cell proliferation
E Sara1, A Kotsakis, J Souklakos
1Laboratory of Tumor Cell Biology, University of Crete, Heraklion, Greece.
Purpose:
A phenolypic analysis of peripheral blood lymphocytes was carried out in order to investigate the lymphopenia developed in some patients with solid tumors treated with systemic chemotherapy.
Patients And Methods:
Peripheral blood was obtained from 53 cancer patients receiving chemotherapy with more than grade 2 neutropenia, before treatment, during the nadir of neutrophils and after bone marrow recovery. Cell phenotype was performed using monoclonal antibodies while cell proliferation, using 3HTdR uptake, was evaluated after cell stimulation with PHA-P and anti-CD3 moAb.
Results:
Post-chemotherapy myelosuppression and rhG-CSF-induced bone marrow recovery were associated with lymphopenia and lymphocytosis reaching pre-treatment values, respectively; both lymphopenia and lymphocytosis concerned all lymphocyte subpopulations. Lymphocytosis was positively correlated with the absolute number of CD3+, CD4+ and CD20+ cells; in addition, the absolute number of HLA-DR+ and CD25+ cells was also increased. During bone marrow recovery, the absolute number of CD25+ cells was correlated with the increased number of both CD3+/CD25+ and CD4+/CD25+ but not of CD8+/CD25+ or CD20+/CD25+ cells. CD4+ lymphopenia (less than 400 cells/dL) was detected in 58% and 21% of the patients during myelosuppression and bone marrow recovery, respectively. PHA-P and anti-CD3 moAb failed to enhance lymphocyte proliferation in 60% and 44% of the patients during bone marrow recovery, respectively.
Conclusions:
Post-chemotherapy CD4+ cell repopulation is an active phenomenon. However, in several patients CD4 lymphopenia, which could be associated with functional cell abnormalities, may persist during bone marrow recovery leading to impaired cell-mediated immunity.