Phase I-II study of busulfan and cyclophosphamide conditioning for transplantation in advanced multiple myeloma.
We evaluated a non-radiation containing preparative regimen for persons with myeloma receiving bone marrow (BM) or blood cell transplants. Twenty-three adults with advanced multiple myeloma (15 responsive to chemotherapy, 8 resistant) received cyclophosphamide 120 mg/kg and busulfan 14-16 mg/kg followed by the infusion of BM or blood progenitor cells. Patients were followed for response by monthly skeletal radiographs, urine and serum monoclonal paraprotein measurement, BM evaluation and beta 2-microglobulin. Three of 18 evaluable patients achieved complete response, 13 patients achieved partial response and two a minimal response. Actuarial 1 year survival post-transplant for all patients is 63% (95% confidence interval, 40-86%). Disease stage and response to chemotherapy pre-transplant correlated with survival post-transplant. Actuarial survival for patients with resistant disease was 38% (4-72%); for patients with chemotherapy-responsive disease, it was 78% (48-100%, p = 0.02). Regimen-related toxicity consisted of five early deaths, three from veno-occlusive disease, one from infection and one from multiorgan failure. Fatal and non-fatal hepatic and renal toxicities were related to busulfan dose with most complications occurring at 16 mg/kg. Our studies suggest that busulfan and cyclophosphamide are an effective conditioning regimen in multiple myeloma. Toxicity precludes increasing the total dose of busulfan beyond 14 mg/kg.
Schiller
G
G
Department of Medicine, Jonsson Comprehensive Cancer Center, UCLA School of Medicine.
Nimer
S
S
Vescio
R
R
Lieb
G
G
Lee
M
M
Gajewski
J
J
Territo
M
M
Berenson
J
J
D000328:Adult; D016026:Bone Marrow Transplantation / Q000379:methods* / Q000473:pathology; D002066:Busulfan / Q000008:administration & dosage* / Q000009:adverse effects; D003520:Cyclophosphamide / Q000008:administration & dosage* / Q000009:adverse effects; D004359:Drug Therapy, Combination; D006410:Hematopoiesis; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006801:Humans; D008875:Middle Aged; D009101:Multiple Myeloma / Q000473:pathology / Q000628:therapy*; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous
D003520:Cyclophosphamide; D002066:Busulfan