Basic and clinical research of peripheral blood stem cell transplant (PBSCT) in chemotherapy for lung cancer

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Treatment of inoperable lung cancer consists of radiotherapy and chemotherapy, which have not improved the survival of the patients significantly because of myelosuppression including leukopenia. Peripheral blood stem cell transplant (PBSCT), an alternative of bone marrow transplant, which has recently developed in hematologic malignancy, may improve the survival of the inoperable lung cancer patients in combination with high dose chemotherapy. In this study, we examined the basic and clinical evaluation of PBSCT in patients with lung cancer. Cancer cell contamination was not found in any peripheral blood mononuclear cell sample from 15 patients. Survival rate and cytokine production of mononuclear cells stimulated by IL-12, ratio of CD34+ cell and CD33-/34+ cell, and number of CFU-GM in PBSC samples did not decrease after freezing and thawing. Under written informed consent, we did clinical application of PBSCT for two patients with small cell lung cancer and experienced rapid recovery from chemotherapy-induced myelosuppression. Megakaryocyte proliferation and differentiation induced by SCF closely related to increased expression of cyclin A and phosphorylation of RB tumor suppressor gene product. Natural killer (NK) activity of peripheral blood lymphocyte decreased after initiation of chemotherapy, reached to nadir 2 weeks later, and then recovered to pretreatment level 4-5 weeks later. Suppression of NK activity by high-dose chemotherapy was abrogated by PBSCT.These results suggest that PBSCT may contribute to not only hematopoietic recovery but also antitumor immunological recovery.