Intravenous Busulfan Compared with Treosulfan-Based Conditioning for Allogeneic Stem Cell Transplantation in Acute Myeloid Leukemia: A Study on Behalf of the Acute Leukemia Working Party of European Society for Blood and Marrow Transplantation

Abstract

Dose intensity of the conditioning regimen has significant impact on the outcomes after stem cell transplantation (SCT) for acute myeloid leukemia. Most studies have shown more relapse, less nonrelapse mortality (NRM), and similar overall survival after reduced-intensity and myeloablative conditioning. There are limited data on the dose equivalence and expected outcomes of treosulfan-based compared with busulfan-based conditioning. We compared SCT outcomes after fludarabine with either intravenous busulfan at a myeloablative dose (FB4, 12.8 mg/kg, n = 1265) or a reduced dose (FB2, 6.4 mg/kg, n = 1456) or treosulfan at 42 g/m (FT14, n = 403) or 36 g/m (FT12, n = 168). Median patient age was 48, 60, 57, and 60 years in the FB4, FB2, FT14, and FT12 groups, respectively (P < .0001). Two-year overall survival was 58%, 53%, 53%, and 51%, respectively (P = .25). Multivariate analysis identified advanced age, advanced disease status, and secondary leukemia to be associated with worse survival. Relapse rate was 30%, 35%, 34%, and 40%, respectively. Relapse was more common after FB2, advanced age and disease status, secondary leukemia, and sibling donors. NRM was 17%, 18%, 21%, and 16%, respectively. NRM was least common after FT12 and more common with advanced age and disease status and unrelated donors. Treosulfan-based regimens were associated with lower rates of graft-versus-host disease. There was no difference in any outcome among patients in first complete remission at transplantation. However, there was better survival with treosulfan-based conditioning in advanced leukemia. In conclusion, survival is determined mostly by disease biology and is similar after various regimens. Treosulfan-based conditioning is more similar to myeloablative than to reduced-intensity conditioning but can be administered safely in older patients, with lower rates of graft-versus-host disease and possibly better outcomes in patients with active leukemia.

Risk factors and implications of oral mucositis in recipients of allogeneic hematopoietic stem cell transplantation

“…29 Fludarabine-treosulfan is promising in this regard, as it is considered a high-intensity regimen, but its toxicity is lower than MAC and RIC regimens. [21][22][23] The clinical implications of mucositis in this cohort extend beyond pain and IV morphine requirement. Hospitalization duration was longer by two days in patients who developed mucositis.…”

“…There remains uncertainty regarding the selection of the optimal conditioning regimen to both control disease and limit toxicity . Fludarabine‐treosulfan is promising in this regard, as it is considered a high‐intensity regimen, but its toxicity is lower than MAC and RIC regimens …”

“…total parenteral nutrition requirement, increased analgesic usage, and prolonged hospitalization with an excess cost. 18,19 Given the continuous improvement in supportive care 20 and the growing use of novel high intensity but relatively low-toxicity conditioning regimens (eg, treosulfan-fludarabine [21][22][23] ), we sought to study the burden of OM and identify risk factors in a contemporary cohort of allogeneic-HSCT recipients. We explored the influence of mucositis on hospitalization duration, exposure to intravenous (IV) morphine, infections, GVHD, and survival-related endpoints.…”

Reduced Relapse Incidence with FLAMSA–RIC Compared with Busulfan/Fludarabine for Acute Myelogenous Leukemia Patients in First or Second Complete Remission: A Study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

“…However, in agreement with our study, this did not translate into different LFS or OS. Shimoni et al [28] reported a comparison of 2 BuFlu regimens of different intensity with 2 fludarabine/treosulfan regimens. No differences in RI, NRM, LFS, and OS were seen in patients in CR.…”

Treosulfan–fludarabine–thiotepa-based conditioning treatment before allogeneic hematopoietic stem cell transplantation for pediatric patients with hematological malignancies

“…However, both regimens are associated with a considerable risk of acute and late serious adverse events (AEs) [1][2][3][4][5]. Clinical studies, including prospective phase III trials in adults with AML and MDS, have shown that treosulfan-based conditioning has myeloablative, immunosuppressive, and antineoplastic effects associated with a low non-relapse mortality (NRM) [6][7][8][9][10][11]. Furthermore, several reports have been published that show an indication for treosulfan-based conditioning in children undergoing alloHSCT for nonmalignant and malignant disorders [12][13][14][15][16][17][18][19][20][21].…”