Total Marrow Irradiation (TMI), Busulfan, and Cyclophosphamide for Allografting in Multiple Myeloma. A Pilot Study

To reduce the incidence of severe graft versus host disease (GvHD) and lower the treatment related mortality(TRM) in allogeneic stem cell transplantation from HLA-identical siblings patients with multiple myeloma, we incorporated anti-thymocyte globulin (ATG, Fa Fresenius, Bad Homburg, Germany) in the conditioning regimen of 12 patients. The conditioning regimen consisted of modified total body irradiation, busulfan and cyclophoshamide (n=9) or busulfan and cyclophoshamide (n=3). The median age was 44 years (range, 29–53) and the median time from diagnosis to transplant was 12 months (range, 6 to 56). The stem cell source was bone marrow in 10, and peripheral blood stem cells in 2 patients. Grade II-IV acute GvHD occurred in 3 patients (27% percent). Severe grade III and IV GvHD developed in only 1 patient. Major toxicity was mucositis. Grad II according the Bearman score was noted in 10 patients, whereas 2 patients experienced grade III, requiring prophylactic intubation. One patient died of severe GvHD grade IV and one patient developed multi-organ failure on day +13, resulting in a TRM of 17%. A complete response in surviving patients after allogeneic transplantation was seen in 4 (40%), and PR in 6 (60%) patients. Two of the patients with PR received a donor lymphocyte infusion (DLI) for further tumor reduction 8 and 14 months after stem cell transplantation, and converted to CR, which increased the rate of CR up to 60%. After a median follow-up of 25 months (range, 5–62), no patient with CR after allogeneic transplantation relapsed during follow-up, while 3 out of 4 patients with PR. experienced progress within 3 years (p=0.07). The estimated overall survival at three years for all patients is 83 percent (CI 95%: 68%–98%). The estimated progression-free survival at three years is 61 percent (CI 95%: 32%–90%). These results suggest that the incorporation of anti-thymocyte globulin may prevent severe GvHD without obvious increase of relapse. DLI should be administered for patients with incomplete response after transplantation to enhance the rate of complete remission, which results in long term freedom of disease.