Reduced-intensity conditioning by fludarabine/busulfan without additional irradiation or T-cell depletion leads to low non-relapse mortality in unrelated bone marrow transplantation

Abstract

In reduced intensity, allogeneic stem cell transplantation from unrelated donors (u-RIST), graft-versus-host disease (GVHD), graft failure, and non-relapse mortality (NRM) are persistent problems. Although anti-thymocyte globulin, alemtuzumab, and total body irradiation (TBI) have been explored as conditioning modalities for u-RIST, the necessity for T-cell depletion or TBI to prevent GVHD or facilitate engraftment in u-RIST has not been determined. We here report the use of u-RIST with bone marrow grafting, following a simple conditioning regimen of 180 mg/m(2) fludarabine and 8 mg/kg of oral or intravenous busulfan without TBI or T-cell depletion. The study population was exclusively Japanese patients with a history of prior chemotherapy. We retrospectively analyzed 31 consecutive patients (median age 53 years). Twenty-five patients (81%) were transplanted from HLA-A, -B, and -DRB1 allele-matched donors. In all patients, neutrophil engraftment was achieved. The cumulative incidence of grade II-IV acute GVHD was 42%. However, 77% of patients with acute GVHD improved with, and could be managed by, initial, systemic, high-dose steroid treatment alone. Two-year overall and event-free survival was 62 and 53%, respectively. The NRM of 10% at 2 years was relatively low. Our results suggest that u-RIST without TBI or T-cell depletion may improve the prognosis after u-RIST in certain patient populations.

The Incidence and Severity of Oral Mucositis among Allogeneic Hematopoietic Stem Cell Transplantation Patients: A Systematic Review

“…A total of 20 were included based on the strict selection criteria outlined and were categorized according to conditioning regimen or GVHD prophylaxis (Tables 3-7). Seven of these studies included regimens that fit with more than 1 of our predefined categories [22][23][24]26,28,30,32] and 2 of these studies [23,26] included regimens that fell under 3 of our categories. Because of the lack of randomized controlled trials focusing on OM as the primary outcome and heterogeneity of scales used to measure OM, a meta-analysis could not be performed; however, pooled analysis indicated significant differences in incidence of OM with respect to different conditioning regimens.…”

“…We intended to conduct a meta-analysis; however, given the number of studies that focused on OM as a secondary outcome and the variety of scales used to analyze OM incidence, we instead performed a systematic review. None of the studies included information on prior radiation therapy, though some studies included patients who had received previous chemotherapy or transplantation [27,30,32,33].…”

“…Five of the studies were analyzed for incidence per grade with an incidence of 11.0% for grade 1 OM and 65.3% of severe OM, which was defined as grades 3 and 4 OM in 1 study [32]. The percentage of grades 2 to 4 OM, excluding the Nakane et al (2011) study, was 59.7%, which was less than that found for patients given a standard MTX dose (89.5%).…”

Curcumin Enhanced Busulfan-Induced Apoptosis through Downregulating the Expression of Survivin in Leukemia Stem-Like KG1a Cells

“…Combined treatment with CUR may allow a reduction in the clinical dose of BUS for HSCT, with the potential for reducing NRM. Nakane et al showed that reduced-intensity conditioning by BUS was associated with lower NRM in patients undergoing unrelated bone marrow transplantation [ 40 ]. The results of the current study showed a significant reduction in the percentage of cells in G0/G1 phase in the combination group ( Figure 4(d) ), suggesting that cells in G0/G1 phase were more sensitive to this drug combination.…”