Matched Sibling Transplants

Five-year estimates of leukemia-free survival following myeloablative transplantation using sibling donors do not precisely reflect rates of long-term disease-free survival in chronic phase CML. Extended follow-up demonstrates that deaths from chronic GVHD and relapses occur beyond 5 years.2122 However, donor lymphocyte infusion (DLI) results in sustained leukemia-free survival in a substantial proportion of patients who relapse following transplantation, and who would be considered treatment failures by conventional analysis. "Current DFS" 23 more accurately assesses long-term results of allogeneic transplantation by appropriately recognizing patients who achieve sustained remission following DLI. With current approaches, including the use of DLI, approximately two-thirds of patients with chronic phase CML can be cured by myeloablative transplantation. Twenty-five to 30% of patients die from complications of transplantation, and 5% of relapsed disease.

Figure 37.1 Outcomes after transplantation using a targeted BU/CY regimen. Estimates of survival, DFS, and relapse at 3 years after transplantation are 86%, 78%, and 8%, respectively

Along with improvements in supportive care, modifications in preparative regimens may play an important role in improving results. Although busulfan has not been proven statistically superior to total body irradiation (TBI) as preparation for allogeneic transplantation, some studies report lower rates of transplant-related mortality and relapse, and higher rates of leukemia-free survival using busulfan.24-26 Continued refinement of busulfan-based regimens, including the use of intravenous busulfan2728 and/or pharmacological targeting13 of busulfan, appears to improve results. Radich et al. reported that 78% of patients transplanted in Seattle have sustained leukemia-free survival using dose adjustment of busulfan to ensure "targeted" concentrations13 (Figure 37.1).

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