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No Improvement of Survival for Alveolar Rhabdomyosarcoma Patients After HLA-Matched Versus -Mismatched Allogeneic Hematopoietic Stem Cell Transplantation Compared to Standard-of-Care Therapy

BACKGROUND: Patients with stage IV alveolar rhabdomyosarcoma (RMA) have a 5-year-survival rate not exceeding 30%. Here, we assess the role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for these patients in comparison to standard-of-care regimens. We also compare the use of HLA-m...

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Autores principales: Schober, Sebastian Johannes, Hallmen, Erika, Reßle, Florian, Gassmann, Hendrik, Prexler, Carolin, Wawer, Angela, von Luettichau, Irene, Ladenstein, Ruth, Kazanowska, Bernarda, Ljungman, Gustaf, Niggli, Felix, Lohi, Olli, Hauer, Julia, Gruhn, Bernd, Klingebiel, Thomas, Bader, Peter, Burdach, Stefan, Lang, Peter, Sparber-Sauer, Monika, Koscielniak, Ewa, Thiel, Uwe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9127413/
https://www.ncbi.nlm.nih.gov/pubmed/35619911
http://dx.doi.org/10.3389/fonc.2022.878367
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author Schober, Sebastian Johannes
Hallmen, Erika
Reßle, Florian
Gassmann, Hendrik
Prexler, Carolin
Wawer, Angela
von Luettichau, Irene
Ladenstein, Ruth
Kazanowska, Bernarda
Ljungman, Gustaf
Niggli, Felix
Lohi, Olli
Hauer, Julia
Gruhn, Bernd
Klingebiel, Thomas
Bader, Peter
Burdach, Stefan
Lang, Peter
Sparber-Sauer, Monika
Koscielniak, Ewa
Thiel, Uwe
author_facet Schober, Sebastian Johannes
Hallmen, Erika
Reßle, Florian
Gassmann, Hendrik
Prexler, Carolin
Wawer, Angela
von Luettichau, Irene
Ladenstein, Ruth
Kazanowska, Bernarda
Ljungman, Gustaf
Niggli, Felix
Lohi, Olli
Hauer, Julia
Gruhn, Bernd
Klingebiel, Thomas
Bader, Peter
Burdach, Stefan
Lang, Peter
Sparber-Sauer, Monika
Koscielniak, Ewa
Thiel, Uwe
author_sort Schober, Sebastian Johannes
collection PubMed
description BACKGROUND: Patients with stage IV alveolar rhabdomyosarcoma (RMA) have a 5-year-survival rate not exceeding 30%. Here, we assess the role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for these patients in comparison to standard-of-care regimens. We also compare the use of HLA-mismatched vs. HLA-matched grafts after reduced vs. myeloablative conditioning regimens, respectively. PATIENTS AND METHODS: In this retrospective analysis, we compare event-free survival (EFS), overall survival (OS), and toxicity of HLA-mismatched vs. -matched transplanted patients in uni- and multivariate analyses (total: n = 50, HLA-matched: n = 15, HLA-mismatched: n = 35). Here, the factors age at diagnosis, age at allo-HSCT, sex, Oberlin score, disease status at allo-HSCT, and HLA graft type are assessed. For 29 primarily transplanted patients, three matched non-transplanted patients per one transplanted patient were identified from the CWS registry. Outcomes were respectively compared for OS and EFS. Matching criteria included sex, age at diagnosis, favorable/unfavorable primary tumor site, and metastatic sites. RESULTS: Median EFS and OS did not differ significantly between HLA-mismatched and -matched patients. In the mismatched group, incidence of acute GvHD was 0.87 (grade III–IV: 0.14) vs. 0.80 in HLA-matched patients (grade III–IV: 0.20). Transplant-related mortality (TRM) of all patients was 0.20 and did not differ significantly between HLA-mismatched and -matched groups. A proportion of 0.58 relapsed or progressed and died of disease (HLA-mismatched: 0.66, HLA-matched: 0.53) whereas 0.18 were alive in complete remission (CR) at data collection. Multivariate and competing risk analyses confirmed CR and very good partial response (VGPR) status prior to allo-HSCT as the only decisive predictor for OS (p < 0.001). Matched-pair survival analyses of primarily transplanted patients vs. matched non-transplanted patients also identified disease status prior to allo-HSCT (CR, VGPR) as the only significant predictor for EFS. Here, OS was not affected, however. CONCLUSION: In this retrospective analysis, only a subgroup of patients with good response at allo-HSCT survived. There was no survival benefit of allo-transplanted patients compared to matched controls, suggesting the absence of a clinically relevant graft-versus-RMA effect in the current setting. The results of this analysis do not support further implementation of allo-HSCT in RMA stage IV patients.
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spelling pubmed-91274132022-05-25 No Improvement of Survival for Alveolar Rhabdomyosarcoma Patients After HLA-Matched Versus -Mismatched Allogeneic Hematopoietic Stem Cell Transplantation Compared to Standard-of-Care Therapy Schober, Sebastian Johannes Hallmen, Erika Reßle, Florian Gassmann, Hendrik Prexler, Carolin Wawer, Angela von Luettichau, Irene Ladenstein, Ruth Kazanowska, Bernarda Ljungman, Gustaf Niggli, Felix Lohi, Olli Hauer, Julia Gruhn, Bernd Klingebiel, Thomas Bader, Peter Burdach, Stefan Lang, Peter Sparber-Sauer, Monika Koscielniak, Ewa Thiel, Uwe Front Oncol Oncology BACKGROUND: Patients with stage IV alveolar rhabdomyosarcoma (RMA) have a 5-year-survival rate not exceeding 30%. Here, we assess the role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for these patients in comparison to standard-of-care regimens. We also compare the use of HLA-mismatched vs. HLA-matched grafts after reduced vs. myeloablative conditioning regimens, respectively. PATIENTS AND METHODS: In this retrospective analysis, we compare event-free survival (EFS), overall survival (OS), and toxicity of HLA-mismatched vs. -matched transplanted patients in uni- and multivariate analyses (total: n = 50, HLA-matched: n = 15, HLA-mismatched: n = 35). Here, the factors age at diagnosis, age at allo-HSCT, sex, Oberlin score, disease status at allo-HSCT, and HLA graft type are assessed. For 29 primarily transplanted patients, three matched non-transplanted patients per one transplanted patient were identified from the CWS registry. Outcomes were respectively compared for OS and EFS. Matching criteria included sex, age at diagnosis, favorable/unfavorable primary tumor site, and metastatic sites. RESULTS: Median EFS and OS did not differ significantly between HLA-mismatched and -matched patients. In the mismatched group, incidence of acute GvHD was 0.87 (grade III–IV: 0.14) vs. 0.80 in HLA-matched patients (grade III–IV: 0.20). Transplant-related mortality (TRM) of all patients was 0.20 and did not differ significantly between HLA-mismatched and -matched groups. A proportion of 0.58 relapsed or progressed and died of disease (HLA-mismatched: 0.66, HLA-matched: 0.53) whereas 0.18 were alive in complete remission (CR) at data collection. Multivariate and competing risk analyses confirmed CR and very good partial response (VGPR) status prior to allo-HSCT as the only decisive predictor for OS (p < 0.001). Matched-pair survival analyses of primarily transplanted patients vs. matched non-transplanted patients also identified disease status prior to allo-HSCT (CR, VGPR) as the only significant predictor for EFS. Here, OS was not affected, however. CONCLUSION: In this retrospective analysis, only a subgroup of patients with good response at allo-HSCT survived. There was no survival benefit of allo-transplanted patients compared to matched controls, suggesting the absence of a clinically relevant graft-versus-RMA effect in the current setting. The results of this analysis do not support further implementation of allo-HSCT in RMA stage IV patients. Frontiers Media S.A. 2022-05-10 /pmc/articles/PMC9127413/ /pubmed/35619911 http://dx.doi.org/10.3389/fonc.2022.878367 Text en Copyright © 2022 Schober, Hallmen, Reßle, Gassmann, Prexler, Wawer, von Luettichau, Ladenstein, Kazanowska, Ljungman, Niggli, Lohi, Hauer, Gruhn, Klingebiel, Bader, Burdach, Lang, Sparber-Sauer, Koscielniak and Thiel https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Schober, Sebastian Johannes
Hallmen, Erika
Reßle, Florian
Gassmann, Hendrik
Prexler, Carolin
Wawer, Angela
von Luettichau, Irene
Ladenstein, Ruth
Kazanowska, Bernarda
Ljungman, Gustaf
Niggli, Felix
Lohi, Olli
Hauer, Julia
Gruhn, Bernd
Klingebiel, Thomas
Bader, Peter
Burdach, Stefan
Lang, Peter
Sparber-Sauer, Monika
Koscielniak, Ewa
Thiel, Uwe
No Improvement of Survival for Alveolar Rhabdomyosarcoma Patients After HLA-Matched Versus -Mismatched Allogeneic Hematopoietic Stem Cell Transplantation Compared to Standard-of-Care Therapy
title No Improvement of Survival for Alveolar Rhabdomyosarcoma Patients After HLA-Matched Versus -Mismatched Allogeneic Hematopoietic Stem Cell Transplantation Compared to Standard-of-Care Therapy
title_full No Improvement of Survival for Alveolar Rhabdomyosarcoma Patients After HLA-Matched Versus -Mismatched Allogeneic Hematopoietic Stem Cell Transplantation Compared to Standard-of-Care Therapy
title_fullStr No Improvement of Survival for Alveolar Rhabdomyosarcoma Patients After HLA-Matched Versus -Mismatched Allogeneic Hematopoietic Stem Cell Transplantation Compared to Standard-of-Care Therapy
title_full_unstemmed No Improvement of Survival for Alveolar Rhabdomyosarcoma Patients After HLA-Matched Versus -Mismatched Allogeneic Hematopoietic Stem Cell Transplantation Compared to Standard-of-Care Therapy
title_short No Improvement of Survival for Alveolar Rhabdomyosarcoma Patients After HLA-Matched Versus -Mismatched Allogeneic Hematopoietic Stem Cell Transplantation Compared to Standard-of-Care Therapy
title_sort no improvement of survival for alveolar rhabdomyosarcoma patients after hla-matched versus -mismatched allogeneic hematopoietic stem cell transplantation compared to standard-of-care therapy
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9127413/
https://www.ncbi.nlm.nih.gov/pubmed/35619911
http://dx.doi.org/10.3389/fonc.2022.878367
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