Comparison of Benefits and Risks Associated with Anti-T-Lymphocyte Globulin (ATLG) Serotherapy in Methotrexate (MTX)- versus Mycophenolate Mofetil (MMF)-Based Hematopoietic Stem Cell Transplantation
Background: Serotherapy with anti-T lymphocyte globulin (ATLG, Grafalon, formerly ATG-Fresenius) is established for the prevention of severe graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation (HSCT). The evidence from prospective studies is predominantly derived from a se...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-02-01
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| Series: | Transplantology |
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| Online Access: | https://www.mdpi.com/2673-3943/4/1/5 |
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| author | Alexander Nikoloudis Irene Strassl Michaela Binder Olga Stiefel Dagmar Wipplinger Robert Milanov Christoph Aichinger Emine Kaynak Sigrid Machherndl-Spandl Veronika Buxhofer-Ausch Alexandra Böhm Andreas Petzer Ansgar Weltermann Dominik Wolf David Nachbaur Johannes Clausen |
| author_facet | Alexander Nikoloudis Irene Strassl Michaela Binder Olga Stiefel Dagmar Wipplinger Robert Milanov Christoph Aichinger Emine Kaynak Sigrid Machherndl-Spandl Veronika Buxhofer-Ausch Alexandra Böhm Andreas Petzer Ansgar Weltermann Dominik Wolf David Nachbaur Johannes Clausen |
| author_sort | Alexander Nikoloudis |
| collection | DOAJ |
| description | Background: Serotherapy with anti-T lymphocyte globulin (ATLG, Grafalon, formerly ATG-Fresenius) is established for the prevention of severe graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation (HSCT). The evidence from prospective studies is predominantly derived from a setting where methotrexate (MTX) and a calcineurin inhibitor (CNI) are used as the backbone of GVHD prophylaxis. The efficacy of ATLG in combination with CNI and mycophenolate mofetil (MMF) has not been investigated as much, particularly in terms of a direct comparison with its effects when combined with CNI/MTX. A total of 401 HSCTs from two Austrian transplant centers were retrospectively evaluated. We included peripheral blood transplants from early- or intermediate-stage (excluding advanced/refractory) hematological diseases from matched siblings or 10/10 or 9/10 matched unrelated donors with CNI/MTX or CNI/MMF prophylaxis, either without (n = 219) or with ATLG (n = 182). Overall, ATLG significantly reduced the risk for all-cause mortality by multivariate Cox analysis (HR 0.53; <i>p</i> = 0.002). Stratification by postgrafting prophylaxis type revealed a significant survival advantage for ATLG in the CNI/MMF cohort (HR 0.49; <i>p</i> = 0.001; n = 193), while its effect on survival in the CNI/MTX cohort was not significant (HR 0.87; <i>p</i> = 0.56; n = 208). In unrelated HSCT with CNI/MMF prophylaxis, ATLG exhibited its greatest survival benefit (HR 0.34; <i>p</i> = 0.001; n = 104). In the context of CNI/MMF, ATLG may provide even greater benefits than in the setting of CNI/MTX for post-grafting immunosuppression. Future prospective studies on ATLG should therefore focus on CNI/MMF-based transplants, which are widely performed in elderly or comorbid patients not expected to tolerate a standard course of MTX. |
| first_indexed | 2024-03-11T05:49:22Z |
| format | Article |
| id | doaj.art-821c39888d64463a8b3ef666b5ff18b5 |
| institution | Directory Open Access Journal |
| issn | 2673-3943 |
| language | English |
| last_indexed | 2024-03-11T05:49:22Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Transplantology |
| spelling | doaj.art-821c39888d64463a8b3ef666b5ff18b52023-11-17T14:14:47ZengMDPI AGTransplantology2673-39432023-02-0141223710.3390/transplantology4010005Comparison of Benefits and Risks Associated with Anti-T-Lymphocyte Globulin (ATLG) Serotherapy in Methotrexate (MTX)- versus Mycophenolate Mofetil (MMF)-Based Hematopoietic Stem Cell TransplantationAlexander Nikoloudis0Irene Strassl1Michaela Binder2Olga Stiefel3Dagmar Wipplinger4Robert Milanov5Christoph Aichinger6Emine Kaynak7Sigrid Machherndl-Spandl8Veronika Buxhofer-Ausch9Alexandra Böhm10Andreas Petzer11Ansgar Weltermann12Dominik Wolf13David Nachbaur14Johannes Clausen15Ordensklinikum Linz—Elisabethinen, Department of Internal Medicine I: Hematology with Stem Cell Transplantation, Hemostaseology and Medical Oncology, 4020 Linz, AustriaOrdensklinikum Linz—Elisabethinen, Department of Internal Medicine I: Hematology with Stem Cell Transplantation, Hemostaseology and Medical Oncology, 4020 Linz, AustriaOrdensklinikum Linz—Elisabethinen, Department of Internal Medicine I: Hematology with Stem Cell Transplantation, Hemostaseology and Medical Oncology, 4020 Linz, AustriaOrdensklinikum Linz—Elisabethinen, Department of Internal Medicine I: Hematology with Stem Cell Transplantation, Hemostaseology and Medical Oncology, 4020 Linz, AustriaOrdensklinikum Linz—Elisabethinen, Department of Internal Medicine I: Hematology with Stem Cell Transplantation, Hemostaseology and Medical Oncology, 4020 Linz, AustriaOrdensklinikum Linz—Elisabethinen, Department of Internal Medicine I: Hematology with Stem Cell Transplantation, Hemostaseology and Medical Oncology, 4020 Linz, AustriaOrdensklinikum Linz—Elisabethinen, Department of Internal Medicine I: Hematology with Stem Cell Transplantation, Hemostaseology and Medical Oncology, 4020 Linz, AustriaOrdensklinikum Linz—Elisabethinen, Department of Internal Medicine I: Hematology with Stem Cell Transplantation, Hemostaseology and Medical Oncology, 4020 Linz, AustriaOrdensklinikum Linz—Elisabethinen, Department of Internal Medicine I: Hematology with Stem Cell Transplantation, Hemostaseology and Medical Oncology, 4020 Linz, AustriaOrdensklinikum Linz—Elisabethinen, Department of Internal Medicine I: Hematology with Stem Cell Transplantation, Hemostaseology and Medical Oncology, 4020 Linz, AustriaOrdensklinikum Linz—Elisabethinen, Department of Internal Medicine I: Hematology with Stem Cell Transplantation, Hemostaseology and Medical Oncology, 4020 Linz, AustriaOrdensklinikum Linz—Elisabethinen, Department of Internal Medicine I: Hematology with Stem Cell Transplantation, Hemostaseology and Medical Oncology, 4020 Linz, AustriaOrdensklinikum Linz—Elisabethinen, Department of Internal Medicine I: Hematology with Stem Cell Transplantation, Hemostaseology and Medical Oncology, 4020 Linz, AustriaUniversity Hospital of Internal Medicine V, Hematology & Oncology, Medical University, 6020 Innsbruck, AustriaUniversity Hospital of Internal Medicine V, Hematology & Oncology, Medical University, 6020 Innsbruck, AustriaOrdensklinikum Linz—Elisabethinen, Department of Internal Medicine I: Hematology with Stem Cell Transplantation, Hemostaseology and Medical Oncology, 4020 Linz, AustriaBackground: Serotherapy with anti-T lymphocyte globulin (ATLG, Grafalon, formerly ATG-Fresenius) is established for the prevention of severe graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation (HSCT). The evidence from prospective studies is predominantly derived from a setting where methotrexate (MTX) and a calcineurin inhibitor (CNI) are used as the backbone of GVHD prophylaxis. The efficacy of ATLG in combination with CNI and mycophenolate mofetil (MMF) has not been investigated as much, particularly in terms of a direct comparison with its effects when combined with CNI/MTX. A total of 401 HSCTs from two Austrian transplant centers were retrospectively evaluated. We included peripheral blood transplants from early- or intermediate-stage (excluding advanced/refractory) hematological diseases from matched siblings or 10/10 or 9/10 matched unrelated donors with CNI/MTX or CNI/MMF prophylaxis, either without (n = 219) or with ATLG (n = 182). Overall, ATLG significantly reduced the risk for all-cause mortality by multivariate Cox analysis (HR 0.53; <i>p</i> = 0.002). Stratification by postgrafting prophylaxis type revealed a significant survival advantage for ATLG in the CNI/MMF cohort (HR 0.49; <i>p</i> = 0.001; n = 193), while its effect on survival in the CNI/MTX cohort was not significant (HR 0.87; <i>p</i> = 0.56; n = 208). In unrelated HSCT with CNI/MMF prophylaxis, ATLG exhibited its greatest survival benefit (HR 0.34; <i>p</i> = 0.001; n = 104). In the context of CNI/MMF, ATLG may provide even greater benefits than in the setting of CNI/MTX for post-grafting immunosuppression. Future prospective studies on ATLG should therefore focus on CNI/MMF-based transplants, which are widely performed in elderly or comorbid patients not expected to tolerate a standard course of MTX.https://www.mdpi.com/2673-3943/4/1/5ATLGMTXMMFHSCT |
| spellingShingle | Alexander Nikoloudis Irene Strassl Michaela Binder Olga Stiefel Dagmar Wipplinger Robert Milanov Christoph Aichinger Emine Kaynak Sigrid Machherndl-Spandl Veronika Buxhofer-Ausch Alexandra Böhm Andreas Petzer Ansgar Weltermann Dominik Wolf David Nachbaur Johannes Clausen Comparison of Benefits and Risks Associated with Anti-T-Lymphocyte Globulin (ATLG) Serotherapy in Methotrexate (MTX)- versus Mycophenolate Mofetil (MMF)-Based Hematopoietic Stem Cell Transplantation Transplantology ATLG MTX MMF HSCT |
| title | Comparison of Benefits and Risks Associated with Anti-T-Lymphocyte Globulin (ATLG) Serotherapy in Methotrexate (MTX)- versus Mycophenolate Mofetil (MMF)-Based Hematopoietic Stem Cell Transplantation |
| title_full | Comparison of Benefits and Risks Associated with Anti-T-Lymphocyte Globulin (ATLG) Serotherapy in Methotrexate (MTX)- versus Mycophenolate Mofetil (MMF)-Based Hematopoietic Stem Cell Transplantation |
| title_fullStr | Comparison of Benefits and Risks Associated with Anti-T-Lymphocyte Globulin (ATLG) Serotherapy in Methotrexate (MTX)- versus Mycophenolate Mofetil (MMF)-Based Hematopoietic Stem Cell Transplantation |
| title_full_unstemmed | Comparison of Benefits and Risks Associated with Anti-T-Lymphocyte Globulin (ATLG) Serotherapy in Methotrexate (MTX)- versus Mycophenolate Mofetil (MMF)-Based Hematopoietic Stem Cell Transplantation |
| title_short | Comparison of Benefits and Risks Associated with Anti-T-Lymphocyte Globulin (ATLG) Serotherapy in Methotrexate (MTX)- versus Mycophenolate Mofetil (MMF)-Based Hematopoietic Stem Cell Transplantation |
| title_sort | comparison of benefits and risks associated with anti t lymphocyte globulin atlg serotherapy in methotrexate mtx versus mycophenolate mofetil mmf based hematopoietic stem cell transplantation |
| topic | ATLG MTX MMF HSCT |
| url | https://www.mdpi.com/2673-3943/4/1/5 |
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