CONCOMITANT AND SEQUENTIAL ADMINISTRATION OF RECOMBINANT HUMAN GRANULOCYTE-COLONY-STIMULATING FACTOR AND RECOMBINANT HUMAN INTERLEUKIN-3 TOACCELERATE HEMATOPOIETIC RECOVERY AFTER AUTOLOGOUS BONE-MARROW TRANSPLANTATION FOR MALIGNANT-LYMPHOMA

Purpose: To assess the safety, tolerability, and hematopoietic efficac y of sequential and concomitant administration of recombinant human gr anulocyte colony-stimulating factor (rhG-CSF) and recombinant human in terleukin-3 (rhIL-8), to accelerate reconstitution of hematopoiesis fo llowing myeloablative chemotherapy and autologous bone marrow transpla ntation (ABMT) for heavily pretreated lymphoma patients. Patients and Methods: Fifty-four consecutive patients with refractory or relapsed n on-Hodgkin's lymphoma (NHL; n=30) and Hodgkin's disease (HD; n=24) wer e studied. Two different conditioning regimens were used for ABMT: car mustine, cyclophosphamide, etoposide, and cytarabine (BAVC) and carmus tine, melphalan, etoposide, and cytarabine (BEAM) for NHL and HD, resp ectively. Patients were enrolled sequentially onto one of three treatm ent groups: group I,G-CSF (5 mu g/kg/d subcutaneously [SC]) from day 1 after reinfusion of autologous marrow (n=23); group 2, G-CSF from da y +1 combined with IL-3 (10 mu g/kg/d SC) from day +6 (n=22, overlappi ng schedule); and group 3, G-CSF treatment discontinued at day +6 befo re initiation of IL-3 administration (n=9, sequential schedule). In th e three groups, growth factor(s) was administered until the granulocyt e count was greater than 0.5x10(9)/L for 3 consecutive days. Results: The study cytokines were generally well tolerated. No side effects wer e observed when G-CSF was given alone. Four of 31 patients (12.9%) who received SC IL-3 had one severe adverse event defined as World Health Organization (WHO) grade 3 to 4 toxicity (fever, n=2; pulmonary toxic ity, n=2) and were withdrawn from the study. Groups 2 and 3 did not di ffer as for treatment tolerability, whereas we observed a trend toward a faster hematopoietic recovery when IL-3 was administered concomitan t with G-CSF from day 6 (ie, group 2). Pooled together, patients who r eceived IL-3 showed a median time to achieve a granulocyte count great er than 0.1 and greater than 0.5x10(9)/L of 8 and 11 days, respectivel y. The median time to an unsupported platelet count greater than 20 an d 50x10(9)/L was 15 and 20 days, respectively, and only one patient di d not reach a normal platelet count. The median number of days to hosp ital discharge was 16 after ABMT (range, 12 to 29). When the hematolog ic reconstitution of patients in groups 2 and 3 was compared with that of patients in group 1, the addition of IL-3 resulted in a significan t improvement of multilineage hematopoietic recovery, lower transfusio n requirements, a lower number of documented infections, and shorter h ospitalizations. Conclusion: We conclude that the combination of G-CSF and IL-3 is safe and well tolerated in intensively pre-treated lympho ma patients undergoing ABMT and results in rapid hematopoietic recover y following myeloablative chemotherapy. (C) 1996 by American Society o f Clinical Oncology.