A regimen of busulfan and cyclophosphamide (BuCy2) is regarded as the standard myeloablative regimen for SCT. This study evaluated the hypothesis that fludarabine can replace cyclophosphamide for myeloablative allogeneic SCT. Ninety-five patients underwent allogeneic SCT from HLA-identical donors, following BuCy2 (n ¼ 55) or busulfan þ fludarabine (BF, n ¼ 40). The efficacy of fludarabine compared to cyclophosphamide was retrospectively evaluated. The BF group exhibited a shorter duration until engraftment (P ¼ 0.001), lower incidence of acute and chronic GVHD (Po0.001 and P ¼ 0.003, respectively), and non-relapse mortality (NRM) (P ¼ 0.039). Furthermore, the event-free survival and overall survival were significantly higher for the BF group compared to the BuCy2 group (P ¼ 0.004 and 0.002, respectively). After adjusting for age, the risk status of disease, GVHD prophylaxis and donor type, the BF regimen was found to be an independent favorable risk factor for event-free survival (hazard ratio (HR), 0.181; 95% confidence interval, 0.045-0.720; P ¼ 0.016) and overall survival (HR, 0.168;; P ¼ 0.026). The replacement of cyclophosphamide with fludarabine for myeloablative conditioning seems to be more effective in terms of short-term NRM, and GVHD compared to BuCy2 regimen in allogeneic transplantation.
Summary:Few studies have addressed the incidence of graft-versushost disease (GVHD) or survival after ABO-incompatible allogeneic peripheral blood stem cell transplantation (PBSCT). We analyzed the clinical outcome of ABO incompatibility after allogeneic PBSCT. A total of 89 consecutive adult patients with hematological diseases including 49 ABO-identical, 20 major, 15 minor, and five bidirectional ABO-incompatible transplants were enrolled from four medical centers in Korea. No significant difference in engraftment times, graft failure, or transfusion requirements between groups was noted. A clinical diagnosis of severe immune hemolysis or pure red cell aplasia was not made for any patient after transplantation. The incidence of acute or chronic GVHD did not statistically differ between groups. With a median followup duration of 13 months (range, 0.5-61 months), the 3-year overall survival estimates for the ABO-identical, major/bidirectional, and minor group were 44.6.079.0, 43.1711.6, and 43.8713.5%, respectively (P ¼ 0.8652), while the 3-year disease-free survival estimates were 33.877.6, 39.9711.4, and 45.7713.1%, respectively (P ¼ 0.8546). We observed that time to neutrophil, platelet, and red blood cell engraftment, transfusion requirements, incidence of acute or chronic GVHD, relapse, and survival were not influenced by ABO incompatibility after allogeneic PBSCT from HLAmatched sibling donors. Bone Marrow Transplantation (2005) 35, 489-495.
Summary:It is important to optimize methods to mobilize hematopoietic stem cells into peripheral blood (PB) for successful allogeneic peripheral blood stem cell (PBSC) transplantation. Our primary intent was to investigate the role of GM-CSF for mobilization in normal healthy donors and to compare its efficacy in mobilizing stem cells alone, in concurrent combination and in sequential combination with G-CSF in this study. We analyzed the results of the PBSC harvest through large volume leukapheresis from 48 normal healthy donors mobilized by three different regimens including GM-CSF. Donors were assigned sequentially to one of the following regimens for mobilization: GM-CSF 10 g/kg/day alone (group 1, n ؍ 9); concurrent combination (group 2, n ؍ 20) of G-CSF 5 g/kg/day and GM-CSF 5 g/kg/day; sequential combination (group 3, n ؍ 19) of GM-CSF alone 10 g/kg/day for 3 days followed by G-CSF alone 10 g/kg/day for 2-3 days. The harvested CD34 + cell count (P Ͻ 0.05) was statistically higher in group 3 than in group 1 or 2. Pre-collection WBC count in donors (P Ͻ 0.05), harvested MNC (P Ͻ 0.05) and CD3 + cell count (P Ͻ 0.05) of group 2 or 3 were significantly higher than those of group 1. Recipients who received stem cells mobilized with combination regimens showed an earlier recovery of WBC and platelets count than those with GM-CSF alone. The incidence of acute graft-versus-host disease was not statistically different among three recipient groups. GM-CSF-based mobilization was well tolerated in normal healthy donors. The sequential combination regimen appears to be an excellent mobilization strategy and might be preferred as the optimal method in some clinical situations that need a higher number of stem cells.
The current study aimed to evaluate the efficacy and toxicity of a combination of intravenous busulfan, cyclophosphamide and etoposide (i.v. Bu/Cy/E) as a conditioning regimen prior to autologous hematopoietic stem cell transplantation in patients with non-Hodgkin's lymphoma (NHL). Sixty-four patients with relapsed/ refractory (n ¼ 36) or high-risk (n ¼ 28) lymphoma were enrolled. The high-dose chemotherapy consisted of i.v. Bu (0.8 mg kg À1 i.v. q 6 h from day À7 to day À5), Cy (50 mg kg À1 i.v. on day À3 and day À2) and E (400 mg m À2 i.v. on day À5 and day À4). The median age was 43 (range 18-65) years, and 39 patients were male. Diffuse large B-cell lymphoma (40.6%) was the most common histological subtype. All evaluable patients achieved an engraftment of neutrophils (median, day 12) and platelets (median, day 13). Hepatic veno-occlusive disease was observed in four patients (three mild, one moderate grade), and two patients (3.1%) died from treatment-related complications. At a median follow-up of 16.4 months, 15 patients (23.4%) exhibited a relapse or progression, while 13 patients (20.3%) had died of disease. The estimated 3-year overall and progression-free survival for all patients was 72.1 and 70.1%, respectively. In conclusion, the conditioning regimen of i.v. Bu/Cy/E was well tolerated and seemed to be effective in patients with aggressive NHL.
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