RECONSTITUTION OF HEMATOPOIESIS AFTER HIGH-DOSE CHEMOTHERAPY BY AUTOLOGOUS PROGENITOR CELLS GENERATED EX-VIVO

Background. Autologous peripheral-blood progenitor cells can restore h ematopoiesis after high-dose chemotherapy in patients with solid tumor s or hematologic cancers. We investigated the ability of peripheral-bl ood progenitor cells generated ex vivo to restore hematopoiesis in pat ients with cancer who have undergone high-dose chemotherapy. Methods. Ten patients who had received high-dose chemotherapy were given transp lants of autologous progenitor cells that had been generated ex vivo. We used 11 million CD34+ hematopoietic progenitor cells as the startin g population for the cell growth. This number corresponds to less than 10 percent of the usual preparation of peripheral-blood CD34+ mononuc lear cells used in leukapheresis. The CD34+ cells were grown in medium containing autologous plasma, recombinant human stem-cell factor, int erleukin-1 beta, interleukin-3, interleukin-6, and erythropoietin. Res ults. No toxic effects were observed with the infusion of the generate d cells. The cells promoted a rapid and sustained hematopoietic recove ry when transplanted after treatment with high-dose etoposide (1500 mg per square meter of body-surface area), ifosfamide (12 g per square m eter), carboplatin (750 mg per square meter), and epirubicin (150 mg p er square meter), The pattern of hematopoietic reconstitution was iden tical to that in historical controls treated with unseparated mononucl ear cells or positively selected CD34+ cells. Conclusions. A small num ber of peripheral-blood CD34+ cells, when grown ex vivo, can supply a population of hematopoietic precursors that have the ability to restor e blood formation in patients treated with high doses of chemotherapy. This method, which requires only a small volume of the patient's bloo d, may reduce the risk of tumor-cell contamination, circumvent the nee d for leukapheresis, and allow repeated cycles of high-dose chemothera py.