Time‐restricted versus standard‐duration immunosuppression after allogeneic hematopoietic stem cell transplantation: Results of the prospective randomized HOVON‐96 trial
Abstract Cyclosporine A combined with mycophenolate mofetil (CsA/MMF) has become an established regimen for the prevention of graft‐versus‐host disease (GVHD) following non‐myeloablative (NMA) allogeneic hematopoietic stem cell transplantation (alloHSCT). However, the optimal duration of immunosuppr...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2024-12-01
|
| Series: | HemaSphere |
| Online Access: | https://doi.org/10.1002/hem3.70040 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841556213323530240 |
|---|---|
| author | Annoek E. C. Broers Ellen Meijer Bronno van der Holt Cornelis N. de Jong Erfan Nur Geerte L. van Sluis Goda Choi Michel van Gelder Johan A. Maertens Jürgen Kuball Dries Deeren Heleen A. Visser‐Wisselaar Lamberdina A. H. M. Meulendijks Jan J. Cornelissen the HOVON Stem Cell Transplantation Working Group |
| author_facet | Annoek E. C. Broers Ellen Meijer Bronno van der Holt Cornelis N. de Jong Erfan Nur Geerte L. van Sluis Goda Choi Michel van Gelder Johan A. Maertens Jürgen Kuball Dries Deeren Heleen A. Visser‐Wisselaar Lamberdina A. H. M. Meulendijks Jan J. Cornelissen the HOVON Stem Cell Transplantation Working Group |
| author_sort | Annoek E. C. Broers |
| collection | DOAJ |
| description | Abstract Cyclosporine A combined with mycophenolate mofetil (CsA/MMF) has become an established regimen for the prevention of graft‐versus‐host disease (GVHD) following non‐myeloablative (NMA) allogeneic hematopoietic stem cell transplantation (alloHSCT). However, the optimal duration of immunosuppression (IS) has not yet been defined and overtreatment is of concern. We hypothesized that time‐restricted IS with CsA/MMF would increase the proportion of patients with non‐severe GVHD compared to standard‐duration IS, thereby resulting in reduction of the relapse rate and improvement of progression‐free survival (PFS) and overall survival (OS). In a prospective randomized, multicenter, phase III trial, patients were allocated (1:1) to standard or time‐restricted IS. A total of 389 patients were randomized, of whom 369 were transplanted (184 vs. 185 patients). The primary endpoint, the proportion of patients with non‐severe GVHD defined as acute GVHD grades I–II without gut involvement or chronic GVHD not requiring systemic treatment within 180 days posttransplant, was 23% after standard‐duration IS versus 24% after time‐restricted IS (odds ratio: 1.02; 95% confidence interval (CI) 0.63–1.66, p = 0.92). The cumulative incidence of grade III–IV acute GVHD at 6 months posttransplant was not significantly different (14% vs. 18%; p = 0.20). The two‐year cumulative incidence of chronic extensive GVHD was 50% versus 46% (p = 0.62). There were no significant differences in the rates of relapse/progression, non‐relapse mortality, PFS, OS, and GVHD‐free, relapse‐free survival. Time‐restricted IS with CsA/MMF did not increase the proportion of patients with non‐severe GVHD, and secondary outcomes were not different compared to standard‐duration IS following NMA‐matched alloHSCT. |
| format | Article |
| id | doaj-art-20a6c3665ee844be8fe5f9b5aab02d5c |
| institution | Kabale University |
| issn | 2572-9241 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | HemaSphere |
| spelling | doaj-art-20a6c3665ee844be8fe5f9b5aab02d5c2025-01-07T12:35:28ZengWileyHemaSphere2572-92412024-12-01812n/an/a10.1002/hem3.70040Time‐restricted versus standard‐duration immunosuppression after allogeneic hematopoietic stem cell transplantation: Results of the prospective randomized HOVON‐96 trialAnnoek E. C. Broers0Ellen Meijer1Bronno van der Holt2Cornelis N. de Jong3Erfan Nur4Geerte L. van Sluis5Goda Choi6Michel van Gelder7Johan A. Maertens8Jürgen Kuball9Dries Deeren10Heleen A. Visser‐Wisselaar11Lamberdina A. H. M. Meulendijks12Jan J. Cornelissen13the HOVON Stem Cell Transplantation Working GroupDepartment of Hematology Erasmus MC Cancer Institute Rotterdam The NetherlandsDepartment of Hematology Amsterdam UMC location VU Amsterdam The NetherlandsDepartment of Hematology Erasmus MC Cancer Institute Rotterdam The NetherlandsDepartment of Internal Medicine Gelderse Vallei Hospital Ede The NetherlandsDepartment of Hematology, Amsterdam UMC University of Amsterdam Amsterdam The NetherlandsDepartment of Hematology Isala Klinieken Zwolle The NetherlandsDepartment of Hematology, UMC Groningen University of Groningen Groningen The NetherlandsDepartment of Hematology Maastricht UMC+ Maastricht The NetherlandsDepartment of Hematology University Hospitals Leuven Leuven BelgiumDepartment of Hematology UMC Utrecht Utrecht The NetherlandsDepartment of Hematology AZ Delta Roeselare BelgiumHOVON Foundation Rotterdam The NetherlandsHOVON Foundation Rotterdam The NetherlandsDepartment of Hematology Erasmus MC Cancer Institute Rotterdam The NetherlandsAbstract Cyclosporine A combined with mycophenolate mofetil (CsA/MMF) has become an established regimen for the prevention of graft‐versus‐host disease (GVHD) following non‐myeloablative (NMA) allogeneic hematopoietic stem cell transplantation (alloHSCT). However, the optimal duration of immunosuppression (IS) has not yet been defined and overtreatment is of concern. We hypothesized that time‐restricted IS with CsA/MMF would increase the proportion of patients with non‐severe GVHD compared to standard‐duration IS, thereby resulting in reduction of the relapse rate and improvement of progression‐free survival (PFS) and overall survival (OS). In a prospective randomized, multicenter, phase III trial, patients were allocated (1:1) to standard or time‐restricted IS. A total of 389 patients were randomized, of whom 369 were transplanted (184 vs. 185 patients). The primary endpoint, the proportion of patients with non‐severe GVHD defined as acute GVHD grades I–II without gut involvement or chronic GVHD not requiring systemic treatment within 180 days posttransplant, was 23% after standard‐duration IS versus 24% after time‐restricted IS (odds ratio: 1.02; 95% confidence interval (CI) 0.63–1.66, p = 0.92). The cumulative incidence of grade III–IV acute GVHD at 6 months posttransplant was not significantly different (14% vs. 18%; p = 0.20). The two‐year cumulative incidence of chronic extensive GVHD was 50% versus 46% (p = 0.62). There were no significant differences in the rates of relapse/progression, non‐relapse mortality, PFS, OS, and GVHD‐free, relapse‐free survival. Time‐restricted IS with CsA/MMF did not increase the proportion of patients with non‐severe GVHD, and secondary outcomes were not different compared to standard‐duration IS following NMA‐matched alloHSCT.https://doi.org/10.1002/hem3.70040 |
| spellingShingle | Annoek E. C. Broers Ellen Meijer Bronno van der Holt Cornelis N. de Jong Erfan Nur Geerte L. van Sluis Goda Choi Michel van Gelder Johan A. Maertens Jürgen Kuball Dries Deeren Heleen A. Visser‐Wisselaar Lamberdina A. H. M. Meulendijks Jan J. Cornelissen the HOVON Stem Cell Transplantation Working Group Time‐restricted versus standard‐duration immunosuppression after allogeneic hematopoietic stem cell transplantation: Results of the prospective randomized HOVON‐96 trial HemaSphere |
| title | Time‐restricted versus standard‐duration immunosuppression after allogeneic hematopoietic stem cell transplantation: Results of the prospective randomized HOVON‐96 trial |
| title_full | Time‐restricted versus standard‐duration immunosuppression after allogeneic hematopoietic stem cell transplantation: Results of the prospective randomized HOVON‐96 trial |
| title_fullStr | Time‐restricted versus standard‐duration immunosuppression after allogeneic hematopoietic stem cell transplantation: Results of the prospective randomized HOVON‐96 trial |
| title_full_unstemmed | Time‐restricted versus standard‐duration immunosuppression after allogeneic hematopoietic stem cell transplantation: Results of the prospective randomized HOVON‐96 trial |
| title_short | Time‐restricted versus standard‐duration immunosuppression after allogeneic hematopoietic stem cell transplantation: Results of the prospective randomized HOVON‐96 trial |
| title_sort | time restricted versus standard duration immunosuppression after allogeneic hematopoietic stem cell transplantation results of the prospective randomized hovon 96 trial |
| url | https://doi.org/10.1002/hem3.70040 |
| work_keys_str_mv | AT annoekecbroers timerestrictedversusstandarddurationimmunosuppressionafterallogeneichematopoieticstemcelltransplantationresultsoftheprospectiverandomizedhovon96trial AT ellenmeijer timerestrictedversusstandarddurationimmunosuppressionafterallogeneichematopoieticstemcelltransplantationresultsoftheprospectiverandomizedhovon96trial AT bronnovanderholt timerestrictedversusstandarddurationimmunosuppressionafterallogeneichematopoieticstemcelltransplantationresultsoftheprospectiverandomizedhovon96trial AT cornelisndejong timerestrictedversusstandarddurationimmunosuppressionafterallogeneichematopoieticstemcelltransplantationresultsoftheprospectiverandomizedhovon96trial AT erfannur timerestrictedversusstandarddurationimmunosuppressionafterallogeneichematopoieticstemcelltransplantationresultsoftheprospectiverandomizedhovon96trial AT geertelvansluis timerestrictedversusstandarddurationimmunosuppressionafterallogeneichematopoieticstemcelltransplantationresultsoftheprospectiverandomizedhovon96trial AT godachoi timerestrictedversusstandarddurationimmunosuppressionafterallogeneichematopoieticstemcelltransplantationresultsoftheprospectiverandomizedhovon96trial AT michelvangelder timerestrictedversusstandarddurationimmunosuppressionafterallogeneichematopoieticstemcelltransplantationresultsoftheprospectiverandomizedhovon96trial AT johanamaertens timerestrictedversusstandarddurationimmunosuppressionafterallogeneichematopoieticstemcelltransplantationresultsoftheprospectiverandomizedhovon96trial AT jurgenkuball timerestrictedversusstandarddurationimmunosuppressionafterallogeneichematopoieticstemcelltransplantationresultsoftheprospectiverandomizedhovon96trial AT driesdeeren timerestrictedversusstandarddurationimmunosuppressionafterallogeneichematopoieticstemcelltransplantationresultsoftheprospectiverandomizedhovon96trial AT heleenavisserwisselaar timerestrictedversusstandarddurationimmunosuppressionafterallogeneichematopoieticstemcelltransplantationresultsoftheprospectiverandomizedhovon96trial AT lamberdinaahmmeulendijks timerestrictedversusstandarddurationimmunosuppressionafterallogeneichematopoieticstemcelltransplantationresultsoftheprospectiverandomizedhovon96trial AT janjcornelissen timerestrictedversusstandarddurationimmunosuppressionafterallogeneichematopoieticstemcelltransplantationresultsoftheprospectiverandomizedhovon96trial AT thehovonstemcelltransplantationworkinggroup timerestrictedversusstandarddurationimmunosuppressionafterallogeneichematopoieticstemcelltransplantationresultsoftheprospectiverandomizedhovon96trial |