Melphalan Dose in Combination With Fludarabine Affects Gastrointestinal Toxicity and Graft-Versus-Host Disease After Allogeneic Transplantation in Acute Myeloid Leukemia and Myelodysplastic Syndromes.

Autor: Albanyan O; Department of Blood and Marrow Transplantation - Cellular Immunotherapy, Moffitt Cancer Center, Tampa, Florida; Department of Hematology and Stem Cell Transplant, King Fahad Specialist Hospital, Dammam, Saudi Arabia., Elmariah H; Department of Blood and Marrow Transplantation - Cellular Immunotherapy, Moffitt Cancer Center, Tampa, Florida., Kalos D; Department of Biostatistics and Bioinformatics, Moffitt Cancer Center, Tampa, Florida., Kim J; Department of Biostatistics and Bioinformatics, Moffitt Cancer Center, Tampa, Florida., Faramand R; Department of Blood and Marrow Transplantation - Cellular Immunotherapy, Moffitt Cancer Center, Tampa, Florida., Sallman D; Department of Hematologic Malignancies, Moffitt Cancer Center, Tampa, Florida., Mishra A; Department of Blood and Marrow Transplantation - Cellular Immunotherapy, Moffitt Cancer Center, Tampa, Florida., Sweet K; Department of Hematologic Malignancies, Moffitt Cancer Center, Tampa, Florida., Perez L; Department of Blood and Marrow Transplantation - Cellular Immunotherapy, Moffitt Cancer Center, Tampa, Florida., Ochoa-Bayona J; Department of Blood and Marrow Transplantation - Cellular Immunotherapy, Moffitt Cancer Center, Tampa, Florida., Nieder M; Department of Blood and Marrow Transplantation - Cellular Immunotherapy, Moffitt Cancer Center, Tampa, Florida., Komrokji R; Department of Hematologic Malignancies, Moffitt Cancer Center, Tampa, Florida., Lancet J; Department of Hematologic Malignancies, Moffitt Cancer Center, Tampa, Florida., Fernandez H; Department of Blood and Marrow Transplantation - Cellular Immunotherapy, Moffitt Cancer Center, Tampa, Florida., Nishihori T; Department of Blood and Marrow Transplantation - Cellular Immunotherapy, Moffitt Cancer Center, Tampa, Florida., Pidala J; Department of Blood and Marrow Transplantation - Cellular Immunotherapy, Moffitt Cancer Center, Tampa, Florida., Anasetti C; Department of Blood and Marrow Transplantation - Cellular Immunotherapy, Moffitt Cancer Center, Tampa, Florida., Bejanyan N; Department of Blood and Marrow Transplantation - Cellular Immunotherapy, Moffitt Cancer Center, Tampa, Florida. Electronic address: nelli.bejanyan@moffitt.org.
Jazyk: angličtina
Zdroj: Transplantation and cellular therapy [Transplant Cell Ther] 2024 Nov; Vol. 30 (11), pp. 1090.e1-1090.e10. Date of Electronic Publication: 2024 Aug 13.
DOI: 10.1016/j.jtct.2024.08.007
Abstrakt: Fludarabine (Flu) and melphalan (Mel) reduced-intensity conditioning is frequently used for allogenic hematopoietic cell transplant (allo-HCT) in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). However, there is limited evidence on the impact of Mel dosing on toxicities and clinical outcomes of allo-HCT. We retrospectively compared 8/8 HLA-matched donor allo-HCT outcomes of 345 patients with AML or MDS receiving total Mel dose of 100 mg/m 2 (Mel-100, n = 62) versus 140 mg/m 2 (Mel-140, n = 283) in combination with Flu. Median age at allo-HCT was 66 years and median follow-up was 36.5 months. For Mel-100 versus Mel-140 groups, any grade gastrointestinal (GI) toxicity rates were 40.3% versus 67.8% (P < .001), day 100 grade II to IV acute graft-versus-host disease (GVHD) rates were 21.0% versus 43.1% (P = .001) and 2-year chronic GVHD rates were 17.4% versus 27.1% (P = .033). In multivariable analysis, Mel-140 resulted in higher risks of GI toxicity (HR = 1.83, P = .013), grade II to IV acute GVHD (HR=2.35, P = .003), and moderate/severe chronic GVHD (HR = 3.13, P = .007). Total Mel dose had no independent impact on oral mucositis, nonrelapse mortality, relapse, relapse-free survival, and overall survival. While independent validation of our observation is warranted, our findings support using Mel-100 in combination with Flu to minimize allo-HCT toxicities and morbidities related to GVHD.
(Copyright © 2024 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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