Treatment of primary resistant or relapsed multiple myeloma with high-dosechemoradiotherapy, hematopoietic stem cell rescue, and granulocyte-macrophage colony-stimulating factor

In this prospective, multicenter, phase 2 study, multiple myeloma (MM) pati ents with primary resistant disease or recurrent chemosensitive disease, in chemoresistant relapse, or in second or subsequent remission were treated with high-dose chemoradiotherapy followed by autologous peripheral blood st em cell (PBSC) rescue. PBSCs were collected using granulocyte-macrophage co lony-stimulating factor (GM-CSF) 5 mug/kg per day subcutaneously for 3 days . Patients underwent high-dose chemoradiotherapy consisting of melphalan (1 40 mg/m(2) x 1 day), cyclophosphamide (60 mg/kg per day x 2 days), methylpr ednisolone (2 g/d x 7 days), and total body radiation (150 cGy bid x 3 days ) followed by peripheral blood stem cell reinfusion (greater than or equal to1.2 x 10(9) mononucleated cells per kg) and GM-CSF support (5 mug/kg per day) and were evaluated for response, survival, and toxicity. Thirty-six pa tients, median age 53.4 years, completed the study. The mean pretransplanta tion cumulative melphalan dose was 464 +/- 72 mg. Excluding the 3 patients (8.3%) who failed to engraft, the median times to engraftment and platelet recovery were 10 days (range, 8-39 days) and 17 days (range, 7-67 days), re spectively. Four patients (11.1%) died of complications related to the regi men (main causes of death, sepsis and acute respiratory distress syndrome) within the first 100 days. Twenty-two patients (61.1%) achieved complete re sponse (CR), 8 (22.2%) partial response, and 2 (5.5%) no response. Two pati ents developed myelodysplastic syndrome after achieving CR. For all 36 pati ents, the probability of overall survival at 5 years was 27.3%. Median surv ival was 31 months (range, 0.3-81 months) in all patients and 42 months (ra nge, 3.4-81 months) in those with CR. The probabilities of overall and dise ase-free survival at 5 years for the 22 patients who achieved CR were 43.6% and 15.7%, respectively. This high-dose chemotherapy regimen coupled with PBSC rescue is associated with a high CR rate and is capable of inducing lo ng-term survival in a subset of heavily pretreated patients with primary re sistant or recurrent MM.