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Intensified cytarabine dose during consolidation in adult AML patients under 65 years is not associated with survival benefit: real-world data from the German SAL-AML registry

PURPOSE: Higher doses of cytarabine appear to improve long-term outcome in acute myeloid leukemia (AML), in particular for younger patients. To this end, the optimal dosage of single-agent cytarabine in consolidation therapy remains elusive. Here, we assessed the impact of different dosages of cytar...

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Autores principales: Hanoun, Maher, Ruhnke, Leo, Kramer, Michael, Hanoun, Christine, Schäfer-Eckart, Kerstin, Steffen, Björn, Sauer, Tim, Krause, Stefan W., Schliemann, Christoph, Mikesch, Jan-Henrik, Kaufmann, Martin, Hänel, Mathias, Jost, Edgar, Brümmendorf, Tim H., Fransecky, Lars, Kraus, Sabrina, Einsele, Hermann, Niemann, Dirk, Neubauer, Andreas, Kullmer, Johannes, Seggewiss-Bernhard, Ruth, Görner, Martin, Held, Gerhard, Kaiser, Ulrich, Scholl, Sebastian, Hochhaus, Andreas, Reinhardt, H. Christian, Platzbecker, Uwe, Baldus, Claudia D., Müller-Tidow, Carsten, Bornhäuser, Martin, Serve, Hubert, Röllig, Christoph
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10349710/
https://www.ncbi.nlm.nih.gov/pubmed/36167894
http://dx.doi.org/10.1007/s00432-022-04356-9
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author Hanoun, Maher
Ruhnke, Leo
Kramer, Michael
Hanoun, Christine
Schäfer-Eckart, Kerstin
Steffen, Björn
Sauer, Tim
Krause, Stefan W.
Schliemann, Christoph
Mikesch, Jan-Henrik
Kaufmann, Martin
Hänel, Mathias
Jost, Edgar
Brümmendorf, Tim H.
Fransecky, Lars
Kraus, Sabrina
Einsele, Hermann
Niemann, Dirk
Neubauer, Andreas
Kullmer, Johannes
Seggewiss-Bernhard, Ruth
Görner, Martin
Held, Gerhard
Kaiser, Ulrich
Scholl, Sebastian
Hochhaus, Andreas
Reinhardt, H. Christian
Platzbecker, Uwe
Baldus, Claudia D.
Müller-Tidow, Carsten
Bornhäuser, Martin
Serve, Hubert
Röllig, Christoph
author_facet Hanoun, Maher
Ruhnke, Leo
Kramer, Michael
Hanoun, Christine
Schäfer-Eckart, Kerstin
Steffen, Björn
Sauer, Tim
Krause, Stefan W.
Schliemann, Christoph
Mikesch, Jan-Henrik
Kaufmann, Martin
Hänel, Mathias
Jost, Edgar
Brümmendorf, Tim H.
Fransecky, Lars
Kraus, Sabrina
Einsele, Hermann
Niemann, Dirk
Neubauer, Andreas
Kullmer, Johannes
Seggewiss-Bernhard, Ruth
Görner, Martin
Held, Gerhard
Kaiser, Ulrich
Scholl, Sebastian
Hochhaus, Andreas
Reinhardt, H. Christian
Platzbecker, Uwe
Baldus, Claudia D.
Müller-Tidow, Carsten
Bornhäuser, Martin
Serve, Hubert
Röllig, Christoph
author_sort Hanoun, Maher
collection PubMed
description PURPOSE: Higher doses of cytarabine appear to improve long-term outcome in acute myeloid leukemia (AML), in particular for younger patients. To this end, the optimal dosage of single-agent cytarabine in consolidation therapy remains elusive. Here, we assessed the impact of different dosages of cytarabine consolidation after 7 + 3 induction on outcome in a large real-world data set from the German Study Alliance Leukemia-Acute Myeloid Leukemia (SAL-AML) registry. METHODS: Patients between 18 and 64 years of age, registered between April 2005 and September 2020, who attained complete remission after intensive induction and received at least one consolidation cycle with intermediate (IDAC) or high-dose cytarabine (HiDAC) were selected. To account for differences in patient and disease characteristics between both groups, the average treatment effect was estimated by propensity score weighting. RESULTS: Six-hundred-forty-two patients received HiDAC consolidation with median dosage of 17.6 (IQR (interquartile range), 16.5–18.0) g/m(2) for a median number of 3 cycles (IQR, 2–3), whereas 178 patients received IDAC consolidation with 5.9 (IQR, 5.7–8.6) g/m(2) for a median of 2 cycles (IQR, 1–3). Both groups differed significantly in some important characteristics (age, sex, cytogenetic risk group, ECOG performance status, disease status, HCT-CI, number of induction cycles). After propensity score weighting for differences in patient and disease characteristics, relapse-free survival after 2 years was comparable between HiDAC-treated (55.3%) and IDAC-treated (55.6%) patients (HR = 0.935, p = 0.69). Moreover, no significant differences in overall survival were observed after 2 years (84.7 vs. 80.6%, HR = 1.101, p = 0.65). Notably, more patients treated with IDAC received allogeneic hematopoietic cell transplantation in first remission (37.6 vs. 19.8%, p < 0.001). Censoring for allogeneic hematopoietic cell transplantation in first remission revealed no significant survival difference with regard to cytarabine dosage. Considering only of European LeukemiaNet (ELN) favorable-risk AML patients, there was no significant difference in outcome. Of note, significantly more patients treated with HiDAC suffered from ≥ 3 CTCAE infectious complications (56.7 [95%-CI 52.8–60.6%] vs. 44.1% [95%-CI 36.6–51.7%]; p = 0,004). The rate of other ≥ 3 CTCAE non-hematological toxicities and secondary malignancies was comparable in both treatment groups. CONCLUSIONS: This retrospective analysis suggests no significant benefit of high-dose cytarabine compared to intermediate dosages in consolidation for AML patients under 65 years of age, independent of ELN risk group. TRIAL REGISTRATION: NCT03188874. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00432-022-04356-9.
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spelling pubmed-103497102023-07-17 Intensified cytarabine dose during consolidation in adult AML patients under 65 years is not associated with survival benefit: real-world data from the German SAL-AML registry Hanoun, Maher Ruhnke, Leo Kramer, Michael Hanoun, Christine Schäfer-Eckart, Kerstin Steffen, Björn Sauer, Tim Krause, Stefan W. Schliemann, Christoph Mikesch, Jan-Henrik Kaufmann, Martin Hänel, Mathias Jost, Edgar Brümmendorf, Tim H. Fransecky, Lars Kraus, Sabrina Einsele, Hermann Niemann, Dirk Neubauer, Andreas Kullmer, Johannes Seggewiss-Bernhard, Ruth Görner, Martin Held, Gerhard Kaiser, Ulrich Scholl, Sebastian Hochhaus, Andreas Reinhardt, H. Christian Platzbecker, Uwe Baldus, Claudia D. Müller-Tidow, Carsten Bornhäuser, Martin Serve, Hubert Röllig, Christoph J Cancer Res Clin Oncol Research PURPOSE: Higher doses of cytarabine appear to improve long-term outcome in acute myeloid leukemia (AML), in particular for younger patients. To this end, the optimal dosage of single-agent cytarabine in consolidation therapy remains elusive. Here, we assessed the impact of different dosages of cytarabine consolidation after 7 + 3 induction on outcome in a large real-world data set from the German Study Alliance Leukemia-Acute Myeloid Leukemia (SAL-AML) registry. METHODS: Patients between 18 and 64 years of age, registered between April 2005 and September 2020, who attained complete remission after intensive induction and received at least one consolidation cycle with intermediate (IDAC) or high-dose cytarabine (HiDAC) were selected. To account for differences in patient and disease characteristics between both groups, the average treatment effect was estimated by propensity score weighting. RESULTS: Six-hundred-forty-two patients received HiDAC consolidation with median dosage of 17.6 (IQR (interquartile range), 16.5–18.0) g/m(2) for a median number of 3 cycles (IQR, 2–3), whereas 178 patients received IDAC consolidation with 5.9 (IQR, 5.7–8.6) g/m(2) for a median of 2 cycles (IQR, 1–3). Both groups differed significantly in some important characteristics (age, sex, cytogenetic risk group, ECOG performance status, disease status, HCT-CI, number of induction cycles). After propensity score weighting for differences in patient and disease characteristics, relapse-free survival after 2 years was comparable between HiDAC-treated (55.3%) and IDAC-treated (55.6%) patients (HR = 0.935, p = 0.69). Moreover, no significant differences in overall survival were observed after 2 years (84.7 vs. 80.6%, HR = 1.101, p = 0.65). Notably, more patients treated with IDAC received allogeneic hematopoietic cell transplantation in first remission (37.6 vs. 19.8%, p < 0.001). Censoring for allogeneic hematopoietic cell transplantation in first remission revealed no significant survival difference with regard to cytarabine dosage. Considering only of European LeukemiaNet (ELN) favorable-risk AML patients, there was no significant difference in outcome. Of note, significantly more patients treated with HiDAC suffered from ≥ 3 CTCAE infectious complications (56.7 [95%-CI 52.8–60.6%] vs. 44.1% [95%-CI 36.6–51.7%]; p = 0,004). The rate of other ≥ 3 CTCAE non-hematological toxicities and secondary malignancies was comparable in both treatment groups. CONCLUSIONS: This retrospective analysis suggests no significant benefit of high-dose cytarabine compared to intermediate dosages in consolidation for AML patients under 65 years of age, independent of ELN risk group. TRIAL REGISTRATION: NCT03188874. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00432-022-04356-9. Springer Berlin Heidelberg 2022-09-28 2023 /pmc/articles/PMC10349710/ /pubmed/36167894 http://dx.doi.org/10.1007/s00432-022-04356-9 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research
Hanoun, Maher
Ruhnke, Leo
Kramer, Michael
Hanoun, Christine
Schäfer-Eckart, Kerstin
Steffen, Björn
Sauer, Tim
Krause, Stefan W.
Schliemann, Christoph
Mikesch, Jan-Henrik
Kaufmann, Martin
Hänel, Mathias
Jost, Edgar
Brümmendorf, Tim H.
Fransecky, Lars
Kraus, Sabrina
Einsele, Hermann
Niemann, Dirk
Neubauer, Andreas
Kullmer, Johannes
Seggewiss-Bernhard, Ruth
Görner, Martin
Held, Gerhard
Kaiser, Ulrich
Scholl, Sebastian
Hochhaus, Andreas
Reinhardt, H. Christian
Platzbecker, Uwe
Baldus, Claudia D.
Müller-Tidow, Carsten
Bornhäuser, Martin
Serve, Hubert
Röllig, Christoph
Intensified cytarabine dose during consolidation in adult AML patients under 65 years is not associated with survival benefit: real-world data from the German SAL-AML registry
title Intensified cytarabine dose during consolidation in adult AML patients under 65 years is not associated with survival benefit: real-world data from the German SAL-AML registry
title_full Intensified cytarabine dose during consolidation in adult AML patients under 65 years is not associated with survival benefit: real-world data from the German SAL-AML registry
title_fullStr Intensified cytarabine dose during consolidation in adult AML patients under 65 years is not associated with survival benefit: real-world data from the German SAL-AML registry
title_full_unstemmed Intensified cytarabine dose during consolidation in adult AML patients under 65 years is not associated with survival benefit: real-world data from the German SAL-AML registry
title_short Intensified cytarabine dose during consolidation in adult AML patients under 65 years is not associated with survival benefit: real-world data from the German SAL-AML registry
title_sort intensified cytarabine dose during consolidation in adult aml patients under 65 years is not associated with survival benefit: real-world data from the german sal-aml registry
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10349710/
https://www.ncbi.nlm.nih.gov/pubmed/36167894
http://dx.doi.org/10.1007/s00432-022-04356-9
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