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

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.

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Successful Engraftment of Cord Blood Transplantation Following Reduced-Intensity Conditioning Regimen Using Fludarabine and Busulfan for Advanced Hematologic Malignancies.

Blood ◽

10.1182/blood.v110.11.5066.5066 ◽

2007 ◽

Vol 110 (11) ◽

pp. 5066-5066

Author(s):

Yuji Satou ◽

Toshiro Nagasawa ◽

Takayuki Azuma ◽

Yuji Miura ◽

Tsunehiko Komatsu

Keyword(s):

Cord Blood ◽

Graft Failure ◽

Cord Blood Transplantation ◽

Conditioning Regimen ◽

Chronic Phase ◽

Hematologic Malignancies ◽

Blood Transplantation ◽

Donor Type ◽

Primary Graft Failure ◽

Reduced Intensity

Abstract Background: The potential role of reduced-intensity cord blood transplantation (RI-CBT) without total body irradiation (TBI) in adults remains unclear. We investigated the feasibility of RI-CBT using non- TBI regimen for the treatment of patients with advanced hematologic malignancies. Methods: Twenty-three patients (median age, 61, range, 38–74) with advanced hematologic malignancies were enrolled in this study (18 patients in refractory or relapsed phase,5 patients in remission or chronic phase). Conditioning regimen comprised of fludarabine 30 mg/m2 on days −8 to −3, busulfan 4 mg/kg p.o. or 3.2 mg/kg i.v. on days −6 to −5. In one cases. we administered busulfan 3.2mg/kg i.v. on days −6 to −3, because of blastic crisis. Graft-versus-host disease (GVHD) prophylaxis was tacrolimus alone. Engraftment was defined as an absolute neutrophil count > 0.5 x 10E9/l. Primary graft failure was defined as the complete loss of donor-type hematopoiesis without engraftment. Secondary graft failure was defined as the loss of donor-type hematopoiesis after primary engraftment. Median follow-up of surviving patients was 1096 days (range, 53–1207). Primary endpoint was engraftment. All patients provided informed consent in accordance with the requirements of Institutional Review Board. Results: All the patients tolerated the conditioning regimen. Median dose of infused nuclear cells was 2.7x10E7 /kg (range, 1.9–4.6). Twelve patients achieved engraftment at a median of day 20.5 (range, 10–36), but two of them developed secondary graft failure. Complete donor-type chimerism was documented within 30 days of transplant in six patients. Primary graft failure was diagnosed in remaining eleven patients. Six of them, underlying disease progressed despite conditioning regimens. As of August 2007, five patients survived (3 patients in complete remission, one patients relapsed after transplantation, the other one not reached remission). Estimated 1-year overall survival rate was 20.7% (95% confidence interval, 3.0–38.4%). Conclusions: Though the pre-transplant condition of patients were not good, engraftment was obtained with approximately the half patients. This study demonstrated the feasibility of RI-CBT using non-TBI regimen for adult patients with advanced hematological diseases; however, high incidences of disease progression before engraftment was significant problem. RI-CBT may become the choice of treatment for patients with advanced hematologic malignancies that are incurable with conventional treatments.

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