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HLA-mismatched donor and high ferritin level showed poor clinical outcomes after allogeneic hematopoietic cell transplantation in patients with advanced myelofibrosis

BACKGROUND: Preconditioning intensity, donor choice and graft-versus-host disease (GVHD) prophylaxis of allogeneic hematopoietic cell transplantation (allo-HCT) for advanced myelofibrosis (MF) have not been fully elucidated. METHODS: Thirty-five patients with advanced MF were treated with reduced-in...

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Autores principales: Yoon, Jae-Ho, Min, Gi June, Park, Sung-Soo, Park, Silvia, Lee, Sung-Eun, Cho, Byung-Sik, Kim, Yoo-Jin, Lee, Seok, Kim, Hee-Je, Min, Chang-Ki, Cho, Seok-Goo, Lee, Jong Wook, Eom, Ki-Seong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7502801/
https://www.ncbi.nlm.nih.gov/pubmed/32994911
http://dx.doi.org/10.1177/2040620720936935
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author Yoon, Jae-Ho
Min, Gi June
Park, Sung-Soo
Park, Silvia
Lee, Sung-Eun
Cho, Byung-Sik
Kim, Yoo-Jin
Lee, Seok
Kim, Hee-Je
Min, Chang-Ki
Cho, Seok-Goo
Lee, Jong Wook
Eom, Ki-Seong
author_facet Yoon, Jae-Ho
Min, Gi June
Park, Sung-Soo
Park, Silvia
Lee, Sung-Eun
Cho, Byung-Sik
Kim, Yoo-Jin
Lee, Seok
Kim, Hee-Je
Min, Chang-Ki
Cho, Seok-Goo
Lee, Jong Wook
Eom, Ki-Seong
author_sort Yoon, Jae-Ho
collection PubMed
description BACKGROUND: Preconditioning intensity, donor choice and graft-versus-host disease (GVHD) prophylaxis of allogeneic hematopoietic cell transplantation (allo-HCT) for advanced myelofibrosis (MF) have not been fully elucidated. METHODS: Thirty-five patients with advanced MF were treated with reduced-intensity conditioning (RIC) allo-HCT. We searched for matched sibling donors first, followed by matched or mismatched unrelated donors and familial mismatched donors. Preconditioning regimen consisted of fludarabine (total 150 mg/m(2)) and busulfan (total 6.4 mg/kg) with total body irradiation ⩽400cGy. RESULTS: All showed engraftments, but four showed either leukemic relapse or delayed graft failure. Two-year overall survival (OS) and non-relapse mortality (NRM) was 60.0% and 29.9%, respectively. Acute GVHD was observed in 19 patients, and grade III–IV acute GVHD (eight grade III and four grade IV) was higher in human leukocyte antigen (HLA)-mismatched donor HCT compared with HLA-matched HCT (70% versus 20%). Chronic GVHD was observed in 16 patients, and a cumulative incidence of severe chronic GVHD was 33% in HLA-mismatched donor HCT and 7.7% in HLA-matched HCT. Significant hepatic GVHD was observed in nine patients (five acute, four chronic) and six of them died. Multivariate analysis revealed inferior OS in HLA-mismatched donor HCT (hazard ratio (HR) = 6.40, 95% confidence interval (CI) 1.6–25.7, p = 0.009) and in patients with high ferritin level at the time of pre-conditioning period (HR = 7.22, 95% CI 1.9–27.5, p = 0.004), which were related to higher incidence of hepatic GVHD with high NRM rate. CONCLUSION: RIC allo-HCT can be a valid choice providing graft-versus-fibrosis effect for advanced MF patients. However, HLA-mismatched donor and high pre-HCT ferritin level related to fatal hepatic GVHD should be regarded as poor-risk parameters.
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spelling pubmed-75028012020-09-28 HLA-mismatched donor and high ferritin level showed poor clinical outcomes after allogeneic hematopoietic cell transplantation in patients with advanced myelofibrosis Yoon, Jae-Ho Min, Gi June Park, Sung-Soo Park, Silvia Lee, Sung-Eun Cho, Byung-Sik Kim, Yoo-Jin Lee, Seok Kim, Hee-Je Min, Chang-Ki Cho, Seok-Goo Lee, Jong Wook Eom, Ki-Seong Ther Adv Hematol Original Research BACKGROUND: Preconditioning intensity, donor choice and graft-versus-host disease (GVHD) prophylaxis of allogeneic hematopoietic cell transplantation (allo-HCT) for advanced myelofibrosis (MF) have not been fully elucidated. METHODS: Thirty-five patients with advanced MF were treated with reduced-intensity conditioning (RIC) allo-HCT. We searched for matched sibling donors first, followed by matched or mismatched unrelated donors and familial mismatched donors. Preconditioning regimen consisted of fludarabine (total 150 mg/m(2)) and busulfan (total 6.4 mg/kg) with total body irradiation ⩽400cGy. RESULTS: All showed engraftments, but four showed either leukemic relapse or delayed graft failure. Two-year overall survival (OS) and non-relapse mortality (NRM) was 60.0% and 29.9%, respectively. Acute GVHD was observed in 19 patients, and grade III–IV acute GVHD (eight grade III and four grade IV) was higher in human leukocyte antigen (HLA)-mismatched donor HCT compared with HLA-matched HCT (70% versus 20%). Chronic GVHD was observed in 16 patients, and a cumulative incidence of severe chronic GVHD was 33% in HLA-mismatched donor HCT and 7.7% in HLA-matched HCT. Significant hepatic GVHD was observed in nine patients (five acute, four chronic) and six of them died. Multivariate analysis revealed inferior OS in HLA-mismatched donor HCT (hazard ratio (HR) = 6.40, 95% confidence interval (CI) 1.6–25.7, p = 0.009) and in patients with high ferritin level at the time of pre-conditioning period (HR = 7.22, 95% CI 1.9–27.5, p = 0.004), which were related to higher incidence of hepatic GVHD with high NRM rate. CONCLUSION: RIC allo-HCT can be a valid choice providing graft-versus-fibrosis effect for advanced MF patients. However, HLA-mismatched donor and high pre-HCT ferritin level related to fatal hepatic GVHD should be regarded as poor-risk parameters. SAGE Publications 2020-09-18 /pmc/articles/PMC7502801/ /pubmed/32994911 http://dx.doi.org/10.1177/2040620720936935 Text en © The Author(s), 2020 https://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Original Research
Yoon, Jae-Ho
Min, Gi June
Park, Sung-Soo
Park, Silvia
Lee, Sung-Eun
Cho, Byung-Sik
Kim, Yoo-Jin
Lee, Seok
Kim, Hee-Je
Min, Chang-Ki
Cho, Seok-Goo
Lee, Jong Wook
Eom, Ki-Seong
HLA-mismatched donor and high ferritin level showed poor clinical outcomes after allogeneic hematopoietic cell transplantation in patients with advanced myelofibrosis
title HLA-mismatched donor and high ferritin level showed poor clinical outcomes after allogeneic hematopoietic cell transplantation in patients with advanced myelofibrosis
title_full HLA-mismatched donor and high ferritin level showed poor clinical outcomes after allogeneic hematopoietic cell transplantation in patients with advanced myelofibrosis
title_fullStr HLA-mismatched donor and high ferritin level showed poor clinical outcomes after allogeneic hematopoietic cell transplantation in patients with advanced myelofibrosis
title_full_unstemmed HLA-mismatched donor and high ferritin level showed poor clinical outcomes after allogeneic hematopoietic cell transplantation in patients with advanced myelofibrosis
title_short HLA-mismatched donor and high ferritin level showed poor clinical outcomes after allogeneic hematopoietic cell transplantation in patients with advanced myelofibrosis
title_sort hla-mismatched donor and high ferritin level showed poor clinical outcomes after allogeneic hematopoietic cell transplantation in patients with advanced myelofibrosis
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7502801/
https://www.ncbi.nlm.nih.gov/pubmed/32994911
http://dx.doi.org/10.1177/2040620720936935
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