Article,
Low rate of nonrelapse mortality in under 4-year-olds with ALL given chemo-conditioning for HSCT: Phase III FORUM study
Contributors
Bader, Peter
0000-0003-4554-0265
[1]
Moser, Laura M
0000-0002-1241-5137
[4]
Balduzzi, Adriana Cristina
0000-0002-5879-0610
[5]
Ansari, Marc
0000-0002-9649-6498
[6]
Buechner, Jochen
0000-0001-5848-4501
[7]
Güngör, Tayfun
0000-0002-3261-1186
[8]
Ifversen, Marianne R S
0000-0002-2558-1935
[9]
Kriván, Gergely
0000-0003-4853-4354
[10]
Pichler, Herbert
0000-0001-5107-5123
[11]
Sedlacek, Petr
0000-0001-7895-2886
[14]
Truong, Tony H
0000-0002-0991-7961
[16]
Wachowiak, Jacek
0000-0002-4680-603X
[17]
Locatelli, F
0000-0002-7976-3654
[19]
Peters, Christina
0000-0003-0369-8515
[20]
Affiliations
- [1] Goethe University, University Hospital, Department for Children and Adolescents, Division for Stern Cell Transplantation, Immunology and Intensive Care, Frankfurt, Germany, Frankfurt a. Main, Germany [NORA names: Germany; Europe, EU; OECD];
- [2] CCRI, Vienna, Austria [NORA names: Austria; Europe, EU; OECD];
- [3] Hôpital Robert-Debré [NORA names: France; Europe, EU; OECD];
- [4] Goethe University Frankfurt [NORA names: Germany; Europe, EU; OECD];
- [5] University of Milano-Bicocca [NORA names: Italy; Europe, EU; OECD];
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Abstract
ABSTRACT: Allogeneic hematopoietic stem cell transplantation (HSCT) is highly effective for treating pediatric high-risk or relapsed acute lymphoblastic leukemia (ALL). For young children, total body irradiation (TBI) is associated with severe late sequelae. In the FORUM study (NCT01949129), we assessed safety, event-free survival (EFS), and overall survival (OS) of 2 TBI-free conditioning regimens in children aged <4 years with ALL. Patients received fludarabine (Flu), thiotepa (Thio), and either busulfan (Bu) or treosulfan (Treo) before HSCT. From 2013 to 2021, 191 children received transplantation and were observed for ≥6 months (median follow-up: 3 years). The 3-year OS was 0.63 (95% confidence interval [95% CI], 0.52-0.72) and 0.76 (95% CI, 0.64-0.84) for Flu/Thio/Bu and Flu/Thio/Treo (P = .075), respectively. Three-year EFS was 0.52 (95% CI, 0.41-0.61) and 0.51 (95% CI, 0.39-0.62), respectively (P = .794). Cumulative incidence of nonrelapse mortality (NRM) and relapse at 3 years were 0.06 (95% CI, 0.02-0.12) vs 0.03 (95% CI: <0.01-0.09) (P = .406) and 0.42 (95% CI, 0.31-0.52) vs 0.45 (95% CI, 0.34-0.56) (P = .920), respectively. Grade >1 acute graft-versus-host disease (GVHD) occurred in 29% of patients receiving Flu/Thio/Bu and 17% of those receiving Flu/Thio/Treo (P = .049), whereas grade 3/4 occurred in 10% and 9%, respectively (P = .813). The 3-year incidence of chronic GVHD was 0.07 (95% CI, 0.03-0.13) vs 0.05 (95% CI, 0.02-0.11), respectively (P = .518). In conclusion, both chemotherapeutic conditioning regimens were well tolerated and NRM was low. However, relapse was the major cause of treatment failure. This trial was registered at www.clinicaltrials.gov as #NCT01949129.
