Reduced intensity conditioning regimen of fludarabine, busulfan, ATG based haploidentical stem cell transplantation for older or unfit patients.

Autor: Pan M; Bone Marrow Transplantation Center of The First Affiliated Hospital & Liangzhu Laboratory, Zhejiang University School of Medicine, 1369 West Wenyi Road, Hangzhou, 311121, China.; Institute of Hematology, Zhejiang University, Hangzhou, China.; Zhejiang Province Engineering Research Center for Stem Cell and Immunity Therapy, Hangzhou, China., Wu Y; Bone Marrow Transplantation Center of The First Affiliated Hospital & Liangzhu Laboratory, Zhejiang University School of Medicine, 1369 West Wenyi Road, Hangzhou, 311121, China.; Institute of Hematology, Zhejiang University, Hangzhou, China.; Zhejiang Province Engineering Research Center for Stem Cell and Immunity Therapy, Hangzhou, China., Yang L; Bone Marrow Transplantation Center of The First Affiliated Hospital & Liangzhu Laboratory, Zhejiang University School of Medicine, 1369 West Wenyi Road, Hangzhou, 311121, China.; Institute of Hematology, Zhejiang University, Hangzhou, China.; Zhejiang Province Engineering Research Center for Stem Cell and Immunity Therapy, Hangzhou, China., Zhu P; Bone Marrow Transplantation Center of The First Affiliated Hospital & Liangzhu Laboratory, Zhejiang University School of Medicine, 1369 West Wenyi Road, Hangzhou, 311121, China.; Institute of Hematology, Zhejiang University, Hangzhou, China.; Zhejiang Province Engineering Research Center for Stem Cell and Immunity Therapy, Hangzhou, China., Shi J; Bone Marrow Transplantation Center of The First Affiliated Hospital & Liangzhu Laboratory, Zhejiang University School of Medicine, 1369 West Wenyi Road, Hangzhou, 311121, China.; Institute of Hematology, Zhejiang University, Hangzhou, China.; Zhejiang Province Engineering Research Center for Stem Cell and Immunity Therapy, Hangzhou, China., Lai X; Bone Marrow Transplantation Center of The First Affiliated Hospital & Liangzhu Laboratory, Zhejiang University School of Medicine, 1369 West Wenyi Road, Hangzhou, 311121, China.; Institute of Hematology, Zhejiang University, Hangzhou, China.; Zhejiang Province Engineering Research Center for Stem Cell and Immunity Therapy, Hangzhou, China., Liu L; Bone Marrow Transplantation Center of The First Affiliated Hospital & Liangzhu Laboratory, Zhejiang University School of Medicine, 1369 West Wenyi Road, Hangzhou, 311121, China.; Institute of Hematology, Zhejiang University, Hangzhou, China.; Zhejiang Province Engineering Research Center for Stem Cell and Immunity Therapy, Hangzhou, China., Zhao Y; Bone Marrow Transplantation Center of The First Affiliated Hospital & Liangzhu Laboratory, Zhejiang University School of Medicine, 1369 West Wenyi Road, Hangzhou, 311121, China.; Institute of Hematology, Zhejiang University, Hangzhou, China.; Zhejiang Province Engineering Research Center for Stem Cell and Immunity Therapy, Hangzhou, China., Yu J; Bone Marrow Transplantation Center of The First Affiliated Hospital & Liangzhu Laboratory, Zhejiang University School of Medicine, 1369 West Wenyi Road, Hangzhou, 311121, China.; Institute of Hematology, Zhejiang University, Hangzhou, China.; Zhejiang Province Engineering Research Center for Stem Cell and Immunity Therapy, Hangzhou, China., Huang H; Bone Marrow Transplantation Center of The First Affiliated Hospital & Liangzhu Laboratory, Zhejiang University School of Medicine, 1369 West Wenyi Road, Hangzhou, 311121, China. huanghe@zju.edu.cn.; Institute of Hematology, Zhejiang University, Hangzhou, China. huanghe@zju.edu.cn.; Zhejiang Province Engineering Research Center for Stem Cell and Immunity Therapy, Hangzhou, China. huanghe@zju.edu.cn., Luo Y; Bone Marrow Transplantation Center of The First Affiliated Hospital & Liangzhu Laboratory, Zhejiang University School of Medicine, 1369 West Wenyi Road, Hangzhou, 311121, China. luoyijr@zju.edu.cn.; Institute of Hematology, Zhejiang University, Hangzhou, China. luoyijr@zju.edu.cn.; Zhejiang Province Engineering Research Center for Stem Cell and Immunity Therapy, Hangzhou, China. luoyijr@zju.edu.cn.
Jazyk: angličtina
Zdroj: Annals of hematology [Ann Hematol] 2024 Aug; Vol. 103 (8), pp. 3105-3119. Date of Electronic Publication: 2024 Jun 03.
DOI: 10.1007/s00277-024-05819-4
Abstrakt: Reduced-intensity conditioning (RIC) regimens allogeneic hematopoietic stem cell transplantation (HSCT) was developed for older patients or those with poor functional status. Haploidentical donor was appropriate alternative donor for patients without matched donors or patients with emergency disease state. However, there was few studies report the outcomes of RIC regimen of anti-thymocyte globulin (ATG) based haploidentical HSCT. The selection of the appropriate RIC regimen based on age and comorbidities in ATG-based haploidentical HSCT remains poorly described. To investigate the safety and efficacy of RIC regimen ATG-based haploidentical HSCT in older or unfit patients. Additionally, to explore the potential factors that impact the prognosis of RIC regimen of ATG-based haploidentical HSCT. We included a retrospective cohort of 63 patients with hematologic malignant diseases who underwent their first RIC haploidentical HSCT from November 2016 to June 2022 at our institutions. The conditioning regimen involved fludarabine (Flu) 30 mg/m²/kg 6 days combined with busulfan 3.2 mg/kg 2 days (Bu2) or 3 days (Bu3). ATG-Fresenius (ATG-F) was administered 10 mg/kg in total, ATG-thymoglobulin (ATG-T) was administered 6 mg/kg in total. The median age of patients in the entire cohort was 60 (32-67) years with a median follow-up of 496 (83-2182) days. There were 29 patients with AML, 20 patients with MDS, and 14 patients with ALL. A total of 32 patients underwent Bu2 RIC haplo-HSCT and 31 patients were treated with Bu3 RIC haplo-HSCT. The 2-year overall survival (OS) and 2-year disease-free survival (DFS) in whole cohort were 67.7% (95% confidence interval [CI], 53.8 - 85.1%) and 61.4% (95% CI, 48.8 - 77.3%) respectively. The cumulative incidence rates of grades II to IV and grades III to IV acute graft-versus-host disease (aGVHD) in whole cohort were 15.8% (95% CI, 4.8 - 19.6%) and 9.7% (95% CI, 0.0 - 11.8%) respectively. The 2-year cumulative incidence of chronic GVHD was 34.0% (95% CI, 18.9 - 46.3%). The 2-year cumulative incidence rates of relapse (IR) and non-relapse mortality (NRM) rates in whole cohort were 27.5% (95% CI, 14.5 - 33.7%) and 11.6% (95% CI, 2.2 - 21.9%) respectively. The probability of 2-year OS were 60.2% (95% CI:42.5-85.3%) in Bu2 and 85.5%(95% CI:73.0-100%) in Bu3 group respectively(P = 0.150). The probability of 2-year DFS were 49.7% (95% CI:33.0-74.8%) in Bu2 and 72.6% (95% CI:55.5-95.5%) in Bu3 group respectively (P = 0.045). The 2-year IR of Bu2 group was significantly higher than Bu3 group (P = 0.045). However, the 2-year NRM were not significantly different between Bu2 and Bu3 group(P > 0.05). In multivariable analysis, RIC regimen of Bu3 had superior OS and DFS than Bu2 group respectively [HR 0.42, 95% CI 0.18-0.98; P = 0.044; HR 0.34, 95% CI 0.14-0.86; P = 0.022]. Besides, RIC regimen of Bu3 had lower IR than Bu2 group [HR 0.34, 95% CI 0.13-0.89; P = 0.029]. The RIC regimen of ATG-based haploidentical HSCT is a safe and effective treatment option for patients who are older or have poor functional status. In particular, a relatively high-intensity pre-treatment regimen consisting of Bu achieves significant improvements in OS and DFS, thus providing more favorable post-transplantation clinical outcomes.
(© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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