Single versus double autologous stem-cell transplantation for multiple myeloma. Prospective, randomized study of single compared with double autologous stem-cell transplantation for multiple myeloma: Bologna 96 clinical study.
We conducted a randomized trial of the treatment of multiple myeloma with high-dose chemotherapy followed by either one or two successive autologous stem-cell transplantations.
                At the time of diagnosis, 399 previously untreated patients under the age of 60 years were randomly assigned to receive a single or double transplant.
                A complete or a very good partial response was achieved by 42 percent of patients in the single-transplant group and 50 percent of patients in the double-transplant group (P=0.10). The probability of surviving event-free for seven years after the diagnosis was 10 percent in the single-transplant group and 20 percent in the double-transplant group (P=0.03). The estimated overall seven-year survival rate was 21 percent in the single-transplant group and 42 percent in the double-transplant group (P=0.01). Among patients who did not have a very good partial response within three months after one transplantation, the probability of surviving seven years was 11 percent in the single-transplant group and 43 percent in the double-transplant group (P<0.001). Four factors were significantly related to survival: base-line serum levels of beta2-microglobulin (P<0.01) and lactate dehydrogenase (P<0.01), age (P<0.05), and treatment group (P<0.01).
                As compared with a single autologous stem-cell transplantation after high-dose chemotherapy, double transplantation improves overall survival among patients with myeloma, especially those who do not have a very good partial response after undergoing one transplantation.
                Copyright 2003 Massachusetts Medical Society We performed a prospective, randomized study of single (arm A) versus double (arm B) autologous stem-cell transplantation (ASCT) for younger patients with newly diagnosed multiple myeloma (MM).
                A total of 321 patients were enrolled onto the study and were randomly assigned to receive either a single course of high-dose melphalan at 200 mg/m2 (arm A) or melphalan at 200 mg/m2 followed, after 3 to 6 months, by melphalan at 120 mg/m2 and busulfan at 12 mg/kilogram (arm B).
                As compared with assignment to the single-transplantation group (n = 163 patients), random assignment to receive double ASCT (n = 158 patients) significantly increased the probability to attain at least a near complete response (nCR; 33% v 47%, respectively; P = .008), prolonged relapse-free survival (RFS) duration of 18 months (median, 24 v 42 months, respectively; P < .001), and significantly extended event-free survival (EFS; median, 23 v 35 months, respectively; P = .001). Administration of a second transplantation and of novel agents for treating sequential relapses in up to 50% of patients randomly assigned to receive a single ASCT likely contributed to prolong the survival duration of the whole group, whose 7-year rate (46%) was similar to that of the double-transplantation group (43%; P = .90). Transplantation-related mortality was 3% in arm A and 4% in arm B (P = .70).
                In comparison with a single ASCT as up-front therapy for newly diagnosed MM, double ASCT effected superior CR or nCR rate, RFS, and EFS, but failed to significantly prolong overall survival. Benefits offered by double ASCT were particularly evident among patients who failed at least nCR after one autotransplantation.
We did not consider any study to be sufficiently informative for contemporary treatment decisions concerning the question single versus tandem ASCT in view of inherent biases. In addition, none of the trials integrated the so-called "novel agents" which are now considered standard treatment for MM. To improve the quality of future studies, sample size calculations should consider the potentially steep decrease in compliance with the second ASCT. Reporting of results of treatment- or transplantation-related mortality should clearly specify the type and number of events (the numerator) in a well-defined population (the denominator).