Abstract
In 1992, we published the results of the first multi-institutional study of BuCy2 (busulfan 4mg/kg daily for four days and cyclophosphamide 60mg/kg on each of two days) preparation for allogeneic transplantation using related HLA-identical donors in chronic myeloid leukemia (CML). Median follow-up was 3 years. This report updates outcomes to July 1, 2006 for a total of 294 patients, including the original cohort, who underwent allogeneic transplantation with the BuCy2 regimen at 7 centers between March 1984 and December 1995. The median follow-up of surviving patients is 13 years. Two hundred patients underwent transplantation in chronic phase, 58 in accelerated phase and 36 in blastic phase. One hundred thirty two patients (45%) remain alive. Seventy-nine percent of patients surviving 3 years after transplantation are estimated survivors 13 years after transplantation. The estimated survivals at 3 and 13 years are 69% (95% CI: 57–81%) and 56% (42–70%) for chronic phase patients, 38% (14–62%) and 25% (1–49%) for accelerated phase patients, and 17% (0–41%) and 4% (0–16%) for those in blastic phase. Estimated relapse rates, according to stage of disease, are 6% (0–14%), 21% (1–49%), and 55% (7–100%) respectively at 3 years and 22% (6–38%), 42% (0–84%) and 74% (20–100%) respectively at 13 years. Of 51 patients who developed hematologic or persistent cytogenetic relapse, 28 relapsed within 3 years of transplantation and 23 (45%) relapsed more than 3 years from transplantation (longest: 15 years) Twenty-five of the 28 patients who relapsed within 3 years have died. Of the 23 who relapsed beyond 3 years, 7 have died. Death occurred more frequently (P<0.001) and the interval from relapse to death was shorter (P=0.02) for those who relapsed within 3 years. Of 162 patients who have died, 34 died beyond 3 years, most commonly from chronic GVHD (10), relapse (9), or new malignancies (6). Advanced stage was a risk factor for late failure (death or relapse beyond 3 years, P=0.003), as it was for early failure (P=0.001). Older age (P=0.03) and chronic GVHD (P=0.05) were also risk factors for late failure. For chronic phase patients, risk of late failure was not increased in those who underwent transplantation at longer intervals from diagnosis (P=0.5), in contrast to early failure (P=0.002). In conclusion, approximately four of five patients with CML who underwent allo-transplantation using BuCy2, and were alive 3 years following transplantation, are survivors at 13 years. Late relapse was associated with a significantly better outcome than early relapse. Late deaths occurred most frequently due to chronic GVHD, relapse or new malignancies.
Different immune reconstitution in multiple myeloma, chronic myeloid leukemia and acute myeloid leukemia patients after allogeneic transplantation of peripheral blood stem cells
