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A phase 1 trial utilizing TMI with fludarabine-melphalan in patients with hematologic malignancies undergoing second allo-SCT
Relapse after allogeneic stem cell transplantation (allo-SCT) remains the primary cause of treatment failure. A second SCT can result in long-term survival in a subset of patients, but the relapse rate remains high. We conducted a single-center, phase 1, modified 3 + 3 dose-escalation study of the f...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society of Hematology
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9898602/ https://www.ncbi.nlm.nih.gov/pubmed/35851593 http://dx.doi.org/10.1182/bloodadvances.2022007530 |
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author | Tran, Misha C. Hasan, Yasmin Wang, Amy Yenice, Kamil Partouche, Julien Stock, Wendy Larson, Richard A. Kosuri, Satyajit LaBelle, James L. Kline, Justin Riedell, Peter A. Artz, Andrew S. Weichselbaum, Ralph Bishop, Michael R. Aydogan, Bulent Liu, Hongtao |
author_facet | Tran, Misha C. Hasan, Yasmin Wang, Amy Yenice, Kamil Partouche, Julien Stock, Wendy Larson, Richard A. Kosuri, Satyajit LaBelle, James L. Kline, Justin Riedell, Peter A. Artz, Andrew S. Weichselbaum, Ralph Bishop, Michael R. Aydogan, Bulent Liu, Hongtao |
author_sort | Tran, Misha C. |
collection | PubMed |
description | Relapse after allogeneic stem cell transplantation (allo-SCT) remains the primary cause of treatment failure. A second SCT can result in long-term survival in a subset of patients, but the relapse rate remains high. We conducted a single-center, phase 1, modified 3 + 3 dose-escalation study of the feasibility of combining intensity-modulated total marrow irradiation (IM-TMI) with fludarabine and melphalan for conditioning. Between December 2015 and May 2020, 21 patients with relapsed hematologic disease undergoing second or greater allo-SCT were treated with IM-TMI doses of 6 Gy, 9 Gy, or 12 Gy. Dose-limiting toxicity was defined as a grade 3 or higher treatment-related adverse event; mucositis was the primary dose-limiting toxicity. The median times to neutrophil and platelet engraftment were 10 and 18 days, respectively. The 1-year cumulative incidence of graft-versus-host disease was 65% (95% confidence interval CI, 38-83). The nonrelapse mortality at 2 years was 17% (95% CI, 4-39). Cumulative incidence of relapse at 2 years was 35% (95% CI, 13-58). Two-year progression-free survival and overall survival were 48% and 50%. We conclude that combining IM-TMI with fludarabine-melphalan is feasible. We recommend 12 Gy of IM-TMI with fludarabine-melphalan for second SCT, although 9 Gy may be used for older or underweight patients. |
format | Online Article Text |
id | pubmed-9898602 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | The American Society of Hematology |
record_format | MEDLINE/PubMed |
spelling | pubmed-98986022023-02-09 A phase 1 trial utilizing TMI with fludarabine-melphalan in patients with hematologic malignancies undergoing second allo-SCT Tran, Misha C. Hasan, Yasmin Wang, Amy Yenice, Kamil Partouche, Julien Stock, Wendy Larson, Richard A. Kosuri, Satyajit LaBelle, James L. Kline, Justin Riedell, Peter A. Artz, Andrew S. Weichselbaum, Ralph Bishop, Michael R. Aydogan, Bulent Liu, Hongtao Blood Adv Clinical Trials and Observations Relapse after allogeneic stem cell transplantation (allo-SCT) remains the primary cause of treatment failure. A second SCT can result in long-term survival in a subset of patients, but the relapse rate remains high. We conducted a single-center, phase 1, modified 3 + 3 dose-escalation study of the feasibility of combining intensity-modulated total marrow irradiation (IM-TMI) with fludarabine and melphalan for conditioning. Between December 2015 and May 2020, 21 patients with relapsed hematologic disease undergoing second or greater allo-SCT were treated with IM-TMI doses of 6 Gy, 9 Gy, or 12 Gy. Dose-limiting toxicity was defined as a grade 3 or higher treatment-related adverse event; mucositis was the primary dose-limiting toxicity. The median times to neutrophil and platelet engraftment were 10 and 18 days, respectively. The 1-year cumulative incidence of graft-versus-host disease was 65% (95% confidence interval CI, 38-83). The nonrelapse mortality at 2 years was 17% (95% CI, 4-39). Cumulative incidence of relapse at 2 years was 35% (95% CI, 13-58). Two-year progression-free survival and overall survival were 48% and 50%. We conclude that combining IM-TMI with fludarabine-melphalan is feasible. We recommend 12 Gy of IM-TMI with fludarabine-melphalan for second SCT, although 9 Gy may be used for older or underweight patients. The American Society of Hematology 2022-07-20 /pmc/articles/PMC9898602/ /pubmed/35851593 http://dx.doi.org/10.1182/bloodadvances.2022007530 Text en © 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Clinical Trials and Observations Tran, Misha C. Hasan, Yasmin Wang, Amy Yenice, Kamil Partouche, Julien Stock, Wendy Larson, Richard A. Kosuri, Satyajit LaBelle, James L. Kline, Justin Riedell, Peter A. Artz, Andrew S. Weichselbaum, Ralph Bishop, Michael R. Aydogan, Bulent Liu, Hongtao A phase 1 trial utilizing TMI with fludarabine-melphalan in patients with hematologic malignancies undergoing second allo-SCT |
title | A phase 1 trial utilizing TMI with fludarabine-melphalan in patients with hematologic malignancies undergoing second allo-SCT |
title_full | A phase 1 trial utilizing TMI with fludarabine-melphalan in patients with hematologic malignancies undergoing second allo-SCT |
title_fullStr | A phase 1 trial utilizing TMI with fludarabine-melphalan in patients with hematologic malignancies undergoing second allo-SCT |
title_full_unstemmed | A phase 1 trial utilizing TMI with fludarabine-melphalan in patients with hematologic malignancies undergoing second allo-SCT |
title_short | A phase 1 trial utilizing TMI with fludarabine-melphalan in patients with hematologic malignancies undergoing second allo-SCT |
title_sort | phase 1 trial utilizing tmi with fludarabine-melphalan in patients with hematologic malignancies undergoing second allo-sct |
topic | Clinical Trials and Observations |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9898602/ https://www.ncbi.nlm.nih.gov/pubmed/35851593 http://dx.doi.org/10.1182/bloodadvances.2022007530 |
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