Long Term Follow-Up of Patients with Chronic Myeloid Leukemia Receiving BuCy2 as Preparation for Allotransplantation.

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.