Cargando…
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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1784712348286582784 |
---|---|
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. |
format | Online Article Text |
id | pubmed-9127413 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT schobersebastianjohannes noimprovementofsurvivalforalveolarrhabdomyosarcomapatientsafterhlamatchedversusmismatchedallogeneichematopoieticstemcelltransplantationcomparedtostandardofcaretherapy AT hallmenerika noimprovementofsurvivalforalveolarrhabdomyosarcomapatientsafterhlamatchedversusmismatchedallogeneichematopoieticstemcelltransplantationcomparedtostandardofcaretherapy AT reßleflorian noimprovementofsurvivalforalveolarrhabdomyosarcomapatientsafterhlamatchedversusmismatchedallogeneichematopoieticstemcelltransplantationcomparedtostandardofcaretherapy AT gassmannhendrik noimprovementofsurvivalforalveolarrhabdomyosarcomapatientsafterhlamatchedversusmismatchedallogeneichematopoieticstemcelltransplantationcomparedtostandardofcaretherapy AT prexlercarolin noimprovementofsurvivalforalveolarrhabdomyosarcomapatientsafterhlamatchedversusmismatchedallogeneichematopoieticstemcelltransplantationcomparedtostandardofcaretherapy AT wawerangela noimprovementofsurvivalforalveolarrhabdomyosarcomapatientsafterhlamatchedversusmismatchedallogeneichematopoieticstemcelltransplantationcomparedtostandardofcaretherapy AT vonluettichauirene noimprovementofsurvivalforalveolarrhabdomyosarcomapatientsafterhlamatchedversusmismatchedallogeneichematopoieticstemcelltransplantationcomparedtostandardofcaretherapy AT ladensteinruth noimprovementofsurvivalforalveolarrhabdomyosarcomapatientsafterhlamatchedversusmismatchedallogeneichematopoieticstemcelltransplantationcomparedtostandardofcaretherapy AT kazanowskabernarda noimprovementofsurvivalforalveolarrhabdomyosarcomapatientsafterhlamatchedversusmismatchedallogeneichematopoieticstemcelltransplantationcomparedtostandardofcaretherapy AT ljungmangustaf noimprovementofsurvivalforalveolarrhabdomyosarcomapatientsafterhlamatchedversusmismatchedallogeneichematopoieticstemcelltransplantationcomparedtostandardofcaretherapy AT nigglifelix noimprovementofsurvivalforalveolarrhabdomyosarcomapatientsafterhlamatchedversusmismatchedallogeneichematopoieticstemcelltransplantationcomparedtostandardofcaretherapy AT lohiolli noimprovementofsurvivalforalveolarrhabdomyosarcomapatientsafterhlamatchedversusmismatchedallogeneichematopoieticstemcelltransplantationcomparedtostandardofcaretherapy AT hauerjulia noimprovementofsurvivalforalveolarrhabdomyosarcomapatientsafterhlamatchedversusmismatchedallogeneichematopoieticstemcelltransplantationcomparedtostandardofcaretherapy AT gruhnbernd noimprovementofsurvivalforalveolarrhabdomyosarcomapatientsafterhlamatchedversusmismatchedallogeneichematopoieticstemcelltransplantationcomparedtostandardofcaretherapy AT klingebielthomas noimprovementofsurvivalforalveolarrhabdomyosarcomapatientsafterhlamatchedversusmismatchedallogeneichematopoieticstemcelltransplantationcomparedtostandardofcaretherapy AT baderpeter noimprovementofsurvivalforalveolarrhabdomyosarcomapatientsafterhlamatchedversusmismatchedallogeneichematopoieticstemcelltransplantationcomparedtostandardofcaretherapy AT burdachstefan noimprovementofsurvivalforalveolarrhabdomyosarcomapatientsafterhlamatchedversusmismatchedallogeneichematopoieticstemcelltransplantationcomparedtostandardofcaretherapy AT langpeter noimprovementofsurvivalforalveolarrhabdomyosarcomapatientsafterhlamatchedversusmismatchedallogeneichematopoieticstemcelltransplantationcomparedtostandardofcaretherapy AT sparbersauermonika noimprovementofsurvivalforalveolarrhabdomyosarcomapatientsafterhlamatchedversusmismatchedallogeneichematopoieticstemcelltransplantationcomparedtostandardofcaretherapy AT koscielniakewa noimprovementofsurvivalforalveolarrhabdomyosarcomapatientsafterhlamatchedversusmismatchedallogeneichematopoieticstemcelltransplantationcomparedtostandardofcaretherapy AT thieluwe noimprovementofsurvivalforalveolarrhabdomyosarcomapatientsafterhlamatchedversusmismatchedallogeneichematopoieticstemcelltransplantationcomparedtostandardofcaretherapy |