HIGH-DOSE BUSULFAN AND CYCLOPHOSPHAMIDE ARE AN EFFECTIVE CONDITIONINGREGIMEN FOR ALLOGENEIC BONE-MARROW TRANSPLANTATION IN CHEMOSENSITIVE MULTIPLE-MYELOMA

The present clinical trial was undertaken to investigate the toxicity and antimyeloma activity of busulfan (BU) and cyclophosphamide (CY) at the maximum tolerated doses of, respectively, 16 mg/kg and 200 mg/kg (BU-CY 4) as conditioning therapy for allogeneic bone marrow transplan tation (BMT) in 19 consecutive patients with multiple myeloma (MM). Tw elve (63%) had failed to respond to prior chemotherapy, while the rema ining 37% had chemosensitive disease, No life-threatening or fatal reg imen-related complications were observed. The incidence of veno-occlus ive disease of the liver was zero according to Jones' criteria and 21% according to McDonald's system. Transplant-related mortality was 37%, Using stringent criteria, the frequency of complete remission (CR) wa s 42% among all patients and 53% among those who could be evaluated, W ith a median follow-up of 21 months for all patients and 66 months for survivors, the actuarial probability of survival and event-free survi val at 4 years from BMT was 26% (95% CI: 7-46) and 21% (95% CI: 3-39), respectively. A more favorable outcome of transplantation was observe d in the subgroup of patients with chemosensitive disease who had a tr ansplant-related mortality of 14%, an overall CR rate of 86% (95% CI: 49-97) and a 4-year projected probability of event-free survival of 57 % (95% CI: 20-93), Four of these patients are currently alive in conti nuous CR after 54, 66, 80 and 94 months, respectively. It is concluded that BU-CY 4 as conditioning for allogeneic transplantation for MM is associated with acceptable morbidity and relatively low mortality. Th is regimen exerts substantial antimyeloma activity, resulting in a hig h CR rate and durable responses, especially in patients with chemosens itive disease, Long-lasting remission and probable cure is possible fo llowing allogeneic stem cell transplantation for MM.