AUTOLOGOUS PERIPHERAL-BLOOD STEM-CELL TRANSPLANTATION AND ADOPTIVE IMMUNOTHERAPY WITH ACTIVATED NATURAL-KILLER-CELLS IN THE IMMEDIATE POSTTRANSPLANT PERIOD

Relapse after high-dose chemotherapy supported by peripheral blood ste m cell transplantation (HDC-PBSCT) is the main cause of therapeutic fa ilure in patients with lymphoma and breast cancer, Adoptive immunother apy with activated natural killer (A-NK) cells and interleukin 2 might eliminate surviving residual tumor without adding to toxicity. Eleven patients with relapsed lymphoma and one with metastatic breast cancer were entered on a pilot clinical trial of HDC-PBSCT followed on day 2 after transplant by infusion of cultured autologous A-NK cells, Simul taneously, recombinant human interleukin 2 (rhIL-2) was initiated as a 4-day continuous i.v. infusion at 2 x 10(6) IU/m(2)/day, referred to as high-dose rhIL-2. Therapy with high-dose rhIL-2 was followed by a 9 0-day continuous i.v. infusion at 3 x 10(5) IU/m(2)/day, referred to a s low-dose rhIL-2, All patients engrafted and nine completed treatment , Posttransplant days to a neutrophil count of 500/mu l and to a plate let count of 50,000/mu l were similar to comparable patients treated w ith HDC-PBSCT alone, Generation of A-NK cells for therapy was feasible in all patients except the three patients with Hodgkin's disease, who se cells did not proliferate in culture, Overall toxicity associated w ith early posttransplant transfer of A-NK cells and interleukin 2 did not differ from that observed with peripheral blood stem cell transpla ntation alone in comparable patients. There was early amplification of natural killer cell activity in the peripheral blood of four patients that appeared to result from the transfused A-NK cells, Adoptive tran sfer of A-NK cells and rhIL-2 during the pancytopenic phase after HDC- PBSCT was feasible and well tolerated, did not adversely affect engraf tment, and resulted in amplified natural killer activity in the periph eral blood during the immediate posttransplantation period.