Comparison between two fludarabine-based reduced-intensity conditioning regimens before allogeneic hematopoietic stem-cell transplantation: fludarabine/melphalan is associated with higher incidence of acute graft-versus-host disease and non-relapse mortality and lower incidence of relapse than fludarabine/busulfan

Abstract

Comparison between two fludarabine-based reduced-intensity conditioning regimens before allogeneic hematopoietic stem-cell transplantation: fludarabine/melphalan is associated with higher incidence of acute graft-versus-host disease and non-relapse mortality and lower incidence of relapse than fludarabine/busulfan A Shimoni, I Hardan, N Shem-Tov, A Rand, C Herscovici, R Yerushalmi and A NaglerThe Division of Hematology and Bone Marrow Transplantation, Chaim Sheba Medical Center, Tel-Hashomer, IsraelReduced-intensity conditioning (RIC) regimens are increasingly used in allogeneic stem-cell transplantation (SCT). There are no data whether any of these regimens has advantage and in what setting. We retrospectively analyzed SCT outcomes in 151 patients given fludarabine-based RIC for various hematological malignancies; 72 conditioned with fludarabine and intravenousbusulfan (FB) and 79 with fludarabine and melphalan (FM). FM was more myelosuppressive. Grade III-IV organ toxicity occurred in 31 and 53% of FB and FM recipients (P ¼ 0.005) and acute graft-versus-host disease grade II-IV in 33 and 53%, respectively (P ¼ 0.01). Non-relapse mortality rate (NRM) was 16 and 40%, respectively (P ¼ 0.003). Active disease (HR 2.2, P ¼ 0.003) and prior autologous SCT (HR 1.7, P ¼ 0.04) predicted inferior overall survival (OS). Among patients transplanted in remission, OS was 72 and 36% after FB and FM, respectively (P ¼ 0.03) due to increased NRM with FM. Similarly, patients transplanted in active disease experienced higher NRM with FM, however lower relapse rates resulted in equivalent OS. In conclusion, there are marked differences in outcome between RIC regimens that are theoretically dose-equivalent. The FM regimen is more myelosuppressive and toxic but controls disease better. FB was associated with improved survival in patients transplanted in remission. These observations merit further study in prospective studies.

Allo-SCT for AML and MDS with treosulfan compared with BU-based regimens: reduced toxicity vs reduced intensity

“…We have previously shown that acute GVHD rates are lower after BU-based RIC/RTC than MAC, and that severe mucositis, which is rare after FT, is also associated with high rates of acute GVHD. 3,24 Limiting tissue damage may decrease cytokine release and activation of the GVHD cascade. Pre-clinical models have also shown that treosulfan is associated with a favorable pattern of secretion of proinflammatory cytokines, including TNF-a, IFN-g, and in particular IL-2, that is less supportive of acute GVHD.…”

Allogenic hematopoietic stem‐cell transplantation with reduced‐intensity conditioning in patients with refractory and recurrent multiple myeloma

“…Similar effects of dose intensity were seen in acute leukemia and in other hematologic malignancies, especially when the malignancy is not in a good remission. 30,31 However, there is an inherent bias in studies with this methodology related to the difference in patient characteristics between patients allocated to myeloablative conditioning and RIC.…”

“…Chemosensitivity at the time of SCT is one of the most important factors in allogeneic SCT for all hematologic malignancies including myeloma. 30,31 Similarly, the EBMT study demonstrated that patients with progressive disease do not benefit from allogeneic SCT with RIC. 15 The GVM effect may not be potent enough to overcome bulky or highly resistant disease.…”

A novel reduced-intensity umbilical cord blood transplantation using a recombinant G-CSF combined with high-dose Ara-C for active myeloid malignancies

“…HSCT performed with various preconditioning regimens has been attempted to rescue these patients, and some positive effects have been obtained. [4][5][6][7][8][9] HSCT using myeloablative preconditioning regimens resulted in an increased frequency of TRM, [4][5][6] and therefore HSCT with nonmyeloablative preconditioning regimens has also been tried. However, early relapse and remission induction failure were often observed in such patients.…”