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Low-dose post-transplant cyclophosphamide and anti-thymocyte globulin as an effective strategy for GVHD prevention in haploidentical patients

BACKGROUND: Low-dose post-transplant cyclophosphamide (PTCy) in conjunction with anti-thymocyte globulin (ATG) appears as a potentially effective graft-versus-host disease (GVHD) prevention strategy in haploidentical hematopoietic cell transplant (haplo-HCT). Our study aims to assess the efficacy of...

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Autores principales: Wang, Yu, Wu, De-Pei, Liu, Qi-Fa, Xu, Lan-Ping, Liu, Kai-Yan, Zhang, Xiao-Hui, Yu, Wen-Jing, Xu, Yang, Huang, Fen, Huang, Xiao-Jun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6724335/
https://www.ncbi.nlm.nih.gov/pubmed/31481121
http://dx.doi.org/10.1186/s13045-019-0781-y
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author Wang, Yu
Wu, De-Pei
Liu, Qi-Fa
Xu, Lan-Ping
Liu, Kai-Yan
Zhang, Xiao-Hui
Yu, Wen-Jing
Xu, Yang
Huang, Fen
Huang, Xiao-Jun
author_facet Wang, Yu
Wu, De-Pei
Liu, Qi-Fa
Xu, Lan-Ping
Liu, Kai-Yan
Zhang, Xiao-Hui
Yu, Wen-Jing
Xu, Yang
Huang, Fen
Huang, Xiao-Jun
author_sort Wang, Yu
collection PubMed
description BACKGROUND: Low-dose post-transplant cyclophosphamide (PTCy) in conjunction with anti-thymocyte globulin (ATG) appears as a potentially effective graft-versus-host disease (GVHD) prevention strategy in haploidentical hematopoietic cell transplant (haplo-HCT). Our study aims to assess the efficacy of this regimen. METHODS: We extended our prospective study in patients treated with low-dose PTCy (14.5 mg/kg on days 3 and 4) in ATG/granulocyte colony-stimulating factor (G-CSF)-based regimen and compared the results to the contemporary cohort of patients without low-dose PTCy (ATG cohort). Both study cohort and control are transplanted from maternal donor or collateral relatives. RESULTS: We identified 239 consecutive patients (ATG-PTCy cohort = 114; ATG cohort = 125). All patients but one in ATG cohort achieved myeloid engraftment by day 30 post-HCT. We found that both the cumulative incidence of 100-day grade III–IV aGvHD and non-relapse-mortality (NRM) in the ATG-PTCy cohort was significantly reduced than that in the ATG group (5% vs 18%; P = 0.003; and 6% vs 15%; P= 0.045); the 2-year cumulative incidences of relapse and overall survival were comparable between the two cohorts (13% vs 14%; P = 0.62; and 83% vs 77%; P = 0.18, respectively). Furthermore, GVHD-free, relapse-free survival (GRFS) was significantly improved in the ATG-PTCy arm (63% vs 48%; P = 0.039). In multivariate analysis, the joint treatment resulted in lower grade II–IV acute GVHD (HR 0.58; P = 0.036), grade III–IV aGvHD (HR 0.28; P = 0.006), chronic GVHD (HR 0.60; P = 0.047), NRM (HR 0.26; P = 0.014), and higher GRFS (HR 0.59; P = 0.021) but slower myeloid and platelet recovery (HR 0.29 and 0.30; both P < 0.001). CONCLUSIONS: These results suggested that ATG/PTCy (low-dose) can reduce both acute and chronic GVHD as compared with standard ATG-based prophylaxis using maternal donor or collateral relatives at particular high GVHD risk.
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spelling pubmed-67243352019-09-10 Low-dose post-transplant cyclophosphamide and anti-thymocyte globulin as an effective strategy for GVHD prevention in haploidentical patients Wang, Yu Wu, De-Pei Liu, Qi-Fa Xu, Lan-Ping Liu, Kai-Yan Zhang, Xiao-Hui Yu, Wen-Jing Xu, Yang Huang, Fen Huang, Xiao-Jun J Hematol Oncol Research BACKGROUND: Low-dose post-transplant cyclophosphamide (PTCy) in conjunction with anti-thymocyte globulin (ATG) appears as a potentially effective graft-versus-host disease (GVHD) prevention strategy in haploidentical hematopoietic cell transplant (haplo-HCT). Our study aims to assess the efficacy of this regimen. METHODS: We extended our prospective study in patients treated with low-dose PTCy (14.5 mg/kg on days 3 and 4) in ATG/granulocyte colony-stimulating factor (G-CSF)-based regimen and compared the results to the contemporary cohort of patients without low-dose PTCy (ATG cohort). Both study cohort and control are transplanted from maternal donor or collateral relatives. RESULTS: We identified 239 consecutive patients (ATG-PTCy cohort = 114; ATG cohort = 125). All patients but one in ATG cohort achieved myeloid engraftment by day 30 post-HCT. We found that both the cumulative incidence of 100-day grade III–IV aGvHD and non-relapse-mortality (NRM) in the ATG-PTCy cohort was significantly reduced than that in the ATG group (5% vs 18%; P = 0.003; and 6% vs 15%; P= 0.045); the 2-year cumulative incidences of relapse and overall survival were comparable between the two cohorts (13% vs 14%; P = 0.62; and 83% vs 77%; P = 0.18, respectively). Furthermore, GVHD-free, relapse-free survival (GRFS) was significantly improved in the ATG-PTCy arm (63% vs 48%; P = 0.039). In multivariate analysis, the joint treatment resulted in lower grade II–IV acute GVHD (HR 0.58; P = 0.036), grade III–IV aGvHD (HR 0.28; P = 0.006), chronic GVHD (HR 0.60; P = 0.047), NRM (HR 0.26; P = 0.014), and higher GRFS (HR 0.59; P = 0.021) but slower myeloid and platelet recovery (HR 0.29 and 0.30; both P < 0.001). CONCLUSIONS: These results suggested that ATG/PTCy (low-dose) can reduce both acute and chronic GVHD as compared with standard ATG-based prophylaxis using maternal donor or collateral relatives at particular high GVHD risk. BioMed Central 2019-09-03 /pmc/articles/PMC6724335/ /pubmed/31481121 http://dx.doi.org/10.1186/s13045-019-0781-y Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Wang, Yu
Wu, De-Pei
Liu, Qi-Fa
Xu, Lan-Ping
Liu, Kai-Yan
Zhang, Xiao-Hui
Yu, Wen-Jing
Xu, Yang
Huang, Fen
Huang, Xiao-Jun
Low-dose post-transplant cyclophosphamide and anti-thymocyte globulin as an effective strategy for GVHD prevention in haploidentical patients
title Low-dose post-transplant cyclophosphamide and anti-thymocyte globulin as an effective strategy for GVHD prevention in haploidentical patients
title_full Low-dose post-transplant cyclophosphamide and anti-thymocyte globulin as an effective strategy for GVHD prevention in haploidentical patients
title_fullStr Low-dose post-transplant cyclophosphamide and anti-thymocyte globulin as an effective strategy for GVHD prevention in haploidentical patients
title_full_unstemmed Low-dose post-transplant cyclophosphamide and anti-thymocyte globulin as an effective strategy for GVHD prevention in haploidentical patients
title_short Low-dose post-transplant cyclophosphamide and anti-thymocyte globulin as an effective strategy for GVHD prevention in haploidentical patients
title_sort low-dose post-transplant cyclophosphamide and anti-thymocyte globulin as an effective strategy for gvhd prevention in haploidentical patients
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6724335/
https://www.ncbi.nlm.nih.gov/pubmed/31481121
http://dx.doi.org/10.1186/s13045-019-0781-y
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