Successful engraftment following reduced-intensity cord blood transplantation with fludarabine and oral busulfan for advanced hematologic diseases

Abstract

7110 Background: Feasibility of reduced-intensity cord blood transplantation (RI-CBT) has been demonstrated in adult patients. Most researchers use preparative regimens containing total body irradiation (TBI) 2–4 Gy, while TBI causes considerable toxicities in elderly patients. We investigated the feasibility of RI-CBT using non-TBI regimen for the treatment of adult hematologic diseases. Methods: Nineteen patients (median age, 61, range, 38–74) with advanced hematological diseases were enrolled in this study. Fifteen patients had chemorefractory diseases at RI-CBT. Preparative regimen comprised fludarabine 180 mg/m2 and oral busulfan 8 mg/kg. Graft-versus-host disease (GVHD) prophylaxis was tacrolimus. Engraftment was defined as an absolute neutrophil count > 0.5 × 10E9/l. Primary graft failure was defined as the complete loss of donor-type hematopoiesis occurring without engraftment. Secondary graft failure was defined as the loss of donor-type hematopoiesis occurring after primary engraftment. Endpoint of this study was engraftment. Median follow-up of surviving patients was 24.7 months (range, 21.6–25.8). Results: All the patients tolerated the preparative regimen. Median dose of infused nuclear cells was 2.7x10E7/kg (range, 1.9–4.6). HLA disparity was found in 2/6 antigens (n=16) and 1/6 antigen (n=3). Eleven patients achieved engraftment at a median of day 18 (range, 9–30). Chimerism analysis was conducted in six of these eleven patients, and complete donor-type chimerism was documented within 30 days of transplant in five patients. Primary graft failure was diagnosed in two patients. The other six patients died without engraftment due to diffuse alveolar hemorrhage(n=1) and disease progression(n=5). No patients developed acute GVHD. Five of the 11 patients who achieved primary engraftment developed secondary graft failure. As of December 2006, four patients survived in complete remission with complete donor-type chimerism. Estimated 1-year overall survival rate was 21.1%. Conclusions: This study demonstrated the feasibility of RI-CBT using non-TBI regimen; however, high incidences of disease progression before engraftment and secondary graft failure were significant problems. No significant financial relationships to disclose.