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Donor lymphocyte infusions after first allogeneic hematopoietic stem-cell transplantation in adults with acute myeloid leukemia: a single-center landmark analysis

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is potentially curative for acute myeloid leukemia (AML). The inherent graft-versus-leukemia activity (GvL) may be optimized by donor lymphocyte infusions (DLI). Here we present our single-center experience of DLI use patterns and effect...

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Autores principales: Rettig, Andrés R., Ihorst, Gabriele, Bertz, Hartmut, Lübbert, Michael, Marks, Reinhard, Waterhouse, Miguel, Wäsch, Ralph, Zeiser, Robert, Duyster, Justus, Finke, Jürgen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8357755/
https://www.ncbi.nlm.nih.gov/pubmed/33796897
http://dx.doi.org/10.1007/s00277-021-04494-z
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author Rettig, Andrés R.
Ihorst, Gabriele
Bertz, Hartmut
Lübbert, Michael
Marks, Reinhard
Waterhouse, Miguel
Wäsch, Ralph
Zeiser, Robert
Duyster, Justus
Finke, Jürgen
author_facet Rettig, Andrés R.
Ihorst, Gabriele
Bertz, Hartmut
Lübbert, Michael
Marks, Reinhard
Waterhouse, Miguel
Wäsch, Ralph
Zeiser, Robert
Duyster, Justus
Finke, Jürgen
author_sort Rettig, Andrés R.
collection PubMed
description Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is potentially curative for acute myeloid leukemia (AML). The inherent graft-versus-leukemia activity (GvL) may be optimized by donor lymphocyte infusions (DLI). Here we present our single-center experience of DLI use patterns and effectiveness, based on 342 consecutive adult patients receiving a first allo-HSCT for AML between 2009 and 2017. The median age at transplantation was 57 years (range 19–79), and the pre-transplant status was active disease in 58% and complete remission (CR) in 42% of cases. In a combined landmark analysis, patients in CR on day +30 and alive on day +100 were included. In this cohort (n=292), 93 patients received cryopreserved aliquots of peripheral blood-derived grafts for DLI (32%) and median survival was 55.7 months (2-year/5-year probability: 62%/49%). Median survival for patients receiving a first dose of DLI “preemptively,” in the absence of relapse and guided by risk marker monitoring (preDLI; n=42), or only after hematological relapse (relDLI; n=51) was 40.9 months (2-year/5-year: 64%/43%) vs 10.4 months (2-year/5-year: 26%/10%), respectively. Survival was inferior when preDLI was initiated at a time of genetic risk marker detection vs mixed chimerism or clinical risk only. Time to first-dose preDLI vs time to first-dose relDLI was similar, suggesting that early warning and intrinsically lower dynamics of AML recurrence may contribute to effectiveness of preDLI-modified GvL activity. Future refinements of the preemptive DLI concept will benefit from collaborative efforts to diagnose measurable residual disease more reliably across the heterogeneous genomic spectrum of AML. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00277-021-04494-z.
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spelling pubmed-83577552021-08-30 Donor lymphocyte infusions after first allogeneic hematopoietic stem-cell transplantation in adults with acute myeloid leukemia: a single-center landmark analysis Rettig, Andrés R. Ihorst, Gabriele Bertz, Hartmut Lübbert, Michael Marks, Reinhard Waterhouse, Miguel Wäsch, Ralph Zeiser, Robert Duyster, Justus Finke, Jürgen Ann Hematol Original Article Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is potentially curative for acute myeloid leukemia (AML). The inherent graft-versus-leukemia activity (GvL) may be optimized by donor lymphocyte infusions (DLI). Here we present our single-center experience of DLI use patterns and effectiveness, based on 342 consecutive adult patients receiving a first allo-HSCT for AML between 2009 and 2017. The median age at transplantation was 57 years (range 19–79), and the pre-transplant status was active disease in 58% and complete remission (CR) in 42% of cases. In a combined landmark analysis, patients in CR on day +30 and alive on day +100 were included. In this cohort (n=292), 93 patients received cryopreserved aliquots of peripheral blood-derived grafts for DLI (32%) and median survival was 55.7 months (2-year/5-year probability: 62%/49%). Median survival for patients receiving a first dose of DLI “preemptively,” in the absence of relapse and guided by risk marker monitoring (preDLI; n=42), or only after hematological relapse (relDLI; n=51) was 40.9 months (2-year/5-year: 64%/43%) vs 10.4 months (2-year/5-year: 26%/10%), respectively. Survival was inferior when preDLI was initiated at a time of genetic risk marker detection vs mixed chimerism or clinical risk only. Time to first-dose preDLI vs time to first-dose relDLI was similar, suggesting that early warning and intrinsically lower dynamics of AML recurrence may contribute to effectiveness of preDLI-modified GvL activity. Future refinements of the preemptive DLI concept will benefit from collaborative efforts to diagnose measurable residual disease more reliably across the heterogeneous genomic spectrum of AML. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00277-021-04494-z. Springer Berlin Heidelberg 2021-04-01 2021 /pmc/articles/PMC8357755/ /pubmed/33796897 http://dx.doi.org/10.1007/s00277-021-04494-z Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This 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 Original Article
Rettig, Andrés R.
Ihorst, Gabriele
Bertz, Hartmut
Lübbert, Michael
Marks, Reinhard
Waterhouse, Miguel
Wäsch, Ralph
Zeiser, Robert
Duyster, Justus
Finke, Jürgen
Donor lymphocyte infusions after first allogeneic hematopoietic stem-cell transplantation in adults with acute myeloid leukemia: a single-center landmark analysis
title Donor lymphocyte infusions after first allogeneic hematopoietic stem-cell transplantation in adults with acute myeloid leukemia: a single-center landmark analysis
title_full Donor lymphocyte infusions after first allogeneic hematopoietic stem-cell transplantation in adults with acute myeloid leukemia: a single-center landmark analysis
title_fullStr Donor lymphocyte infusions after first allogeneic hematopoietic stem-cell transplantation in adults with acute myeloid leukemia: a single-center landmark analysis
title_full_unstemmed Donor lymphocyte infusions after first allogeneic hematopoietic stem-cell transplantation in adults with acute myeloid leukemia: a single-center landmark analysis
title_short Donor lymphocyte infusions after first allogeneic hematopoietic stem-cell transplantation in adults with acute myeloid leukemia: a single-center landmark analysis
title_sort donor lymphocyte infusions after first allogeneic hematopoietic stem-cell transplantation in adults with acute myeloid leukemia: a single-center landmark analysis
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8357755/
https://www.ncbi.nlm.nih.gov/pubmed/33796897
http://dx.doi.org/10.1007/s00277-021-04494-z
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