Post-transplantation cyclophosphamide reduces the incidence of acute graft-versus-host disease in patients with acute myeloid leukemia/myelodysplastic syndromes who receive immune checkpoint inhibitors after allogeneic hematopoietic stem cell transplantation
Background Immune checkpoint inhibitors (ICIs) are being used after allogeneic hematopoietic stem cell transplantation (alloHCT) to reverse immune dysfunction. However, a major concern for the use of ICIs after alloHCT is the increased risk of graft-versus-host disease (GVHD). We analyzed the associ...
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BMJ Publishing Group
2021-02-01
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| Series: | Journal for ImmunoTherapy of Cancer |
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| author | Maro Ohanian Farhad Ravandi Maria E Suarez-Almazor Adi Diab Noha Abdel-Wahab Houssein Safa Ala Abudayyeh Marina Konopleva Stephen Gruschkus Chantal Saberian May Daher Richard Champlin Kaysia Ludford Gheath Al-Atrash Guillermo Garcia-Manero Naval Daver Hind Rafei Jacinth Joseph Gabriela Rondon Laura Whited Faisal Fa'ak Cristina Knape Mahran Shoukier Megan Marcotulli Alison M Gulbis Betul Oran Uday R Popat Rotesh Mehta Amin M Alousi |
| author_facet | Maro Ohanian Farhad Ravandi Maria E Suarez-Almazor Adi Diab Noha Abdel-Wahab Houssein Safa Ala Abudayyeh Marina Konopleva Stephen Gruschkus Chantal Saberian May Daher Richard Champlin Kaysia Ludford Gheath Al-Atrash Guillermo Garcia-Manero Naval Daver Hind Rafei Jacinth Joseph Gabriela Rondon Laura Whited Faisal Fa'ak Cristina Knape Mahran Shoukier Megan Marcotulli Alison M Gulbis Betul Oran Uday R Popat Rotesh Mehta Amin M Alousi |
| author_sort | Maro Ohanian |
| collection | DOAJ |
| description | Background Immune checkpoint inhibitors (ICIs) are being used after allogeneic hematopoietic stem cell transplantation (alloHCT) to reverse immune dysfunction. However, a major concern for the use of ICIs after alloHCT is the increased risk of graft-versus-host disease (GVHD). We analyzed the association between GVHD prophylaxis and frequency of GVHD in patients who had received ICI therapy after alloHCT.Methods A retrospective study was performed in 21 patients with acute myeloid leukemia (n=16) or myelodysplastic syndromes (n=5) who were treated with antiprogrammed cell death protein 1 (16 patients) or anticytotoxic T lymphocyte-associated antigen 4 (5 patients) therapy for disease relapse after alloHCT. Associations between the type of GVHD prophylaxis and incidence of GVHD were analyzed.Results Four patients (19%) developed acute GVHD. The incidence of acute GVHD was associated only with the type of post-transplantation GVHD prophylaxis; none of the other variables included (stem cell source, donor type, age at alloHCT, conditioning regimen and prior history of GVHD) were associated with the frequency of acute GVHD. Twelve patients received post-transplantation cyclophosphamide (PTCy) for GVHD prophylaxis. Patients who received PTCy had a significantly shorter median time to initiation of ICI therapy after alloHCT compared with patients who did not receive PTCy (median 5.1 months compared with 26.6 months). Despite early ICI therapy initiation, patients who received PTCy had a lower observed cumulative incidence of grades 2–4 acute GVHD compared with patients who did not receive PTCy (16% compared with 22%; p=0.7). After controlling for comorbidities and time from alloHCT to ICI therapy initiation, the analysis showed that PTCy was associated with a 90% reduced risk of acute GVHD (HR 0.1, 95% CI 0.02 to 0.6, p=0.01).Conclusions ICI therapy for relapsed acute myeloid leukemia/myelodysplastic syndromes after alloHCT may be a safe and feasible option. PTCy appears to decrease the incidence of acute GVHD in this cohort of patients. |
| format | Article |
| id | doaj-art-10e93fbbcd6b4e969d6a3f82162fa2d6 |
| institution | Kabale University |
| issn | 2051-1426 |
| language | English |
| publishDate | 2021-02-01 |
| publisher | BMJ Publishing Group |
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| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-10e93fbbcd6b4e969d6a3f82162fa2d62025-08-20T03:53:01ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262021-02-019210.1136/jitc-2020-001818Post-transplantation cyclophosphamide reduces the incidence of acute graft-versus-host disease in patients with acute myeloid leukemia/myelodysplastic syndromes who receive immune checkpoint inhibitors after allogeneic hematopoietic stem cell transplantationMaro Ohanian0Farhad Ravandi1Maria E Suarez-Almazor2Adi Diab3Noha Abdel-Wahab4Houssein Safa5Ala Abudayyeh6Marina Konopleva7Stephen Gruschkus8Chantal Saberian9May Daher10Richard Champlin11Kaysia Ludford12Gheath Al-Atrash13Guillermo Garcia-Manero14Naval Daver15Hind Rafei16Jacinth Joseph17Gabriela Rondon18Laura Whited19Faisal Fa'ak20Cristina Knape21Mahran Shoukier22Megan Marcotulli23Alison M Gulbis24Betul Oran25Uday R Popat26Rotesh Mehta27Amin M Alousi28Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USADepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USASection of Rheumatology and Clinical Immunology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA3The University of Texas MD Anderson Cancer Center, Houston, TX, USASection of Rheumatology and Clinical Immunology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA3University of Texas MD Anderson Cancer Center, Melanoma Medical Oncology, houston, United States of America1 Division of Internal Medicine, Section of Nephrology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA3Albert Einstein College of Medicine, Bronx, NY, USABiostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USAMelanoma Medical Onoclogy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USAThe University of Texas MD Anderson Cancer Center, Houston, TX, USADepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USAUniversity of Texas MD Anderson Cancer Center, Houston, Texas, USAStem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, Texas, USADepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA8The University of Texas MD Anderson Cancer Center, Houston, TX, USAThe University of Texas MD Anderson Cancer Center, Houston, TX, USADepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USADepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USADepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USALaura and Isaac Perlmutter Cancer Center, NYU Langone Health, New York, New York, USADepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USADepartment of General Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USADepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USADepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USADepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USADepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USADepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USADepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USABackground Immune checkpoint inhibitors (ICIs) are being used after allogeneic hematopoietic stem cell transplantation (alloHCT) to reverse immune dysfunction. However, a major concern for the use of ICIs after alloHCT is the increased risk of graft-versus-host disease (GVHD). We analyzed the association between GVHD prophylaxis and frequency of GVHD in patients who had received ICI therapy after alloHCT.Methods A retrospective study was performed in 21 patients with acute myeloid leukemia (n=16) or myelodysplastic syndromes (n=5) who were treated with antiprogrammed cell death protein 1 (16 patients) or anticytotoxic T lymphocyte-associated antigen 4 (5 patients) therapy for disease relapse after alloHCT. Associations between the type of GVHD prophylaxis and incidence of GVHD were analyzed.Results Four patients (19%) developed acute GVHD. The incidence of acute GVHD was associated only with the type of post-transplantation GVHD prophylaxis; none of the other variables included (stem cell source, donor type, age at alloHCT, conditioning regimen and prior history of GVHD) were associated with the frequency of acute GVHD. Twelve patients received post-transplantation cyclophosphamide (PTCy) for GVHD prophylaxis. Patients who received PTCy had a significantly shorter median time to initiation of ICI therapy after alloHCT compared with patients who did not receive PTCy (median 5.1 months compared with 26.6 months). Despite early ICI therapy initiation, patients who received PTCy had a lower observed cumulative incidence of grades 2–4 acute GVHD compared with patients who did not receive PTCy (16% compared with 22%; p=0.7). After controlling for comorbidities and time from alloHCT to ICI therapy initiation, the analysis showed that PTCy was associated with a 90% reduced risk of acute GVHD (HR 0.1, 95% CI 0.02 to 0.6, p=0.01).Conclusions ICI therapy for relapsed acute myeloid leukemia/myelodysplastic syndromes after alloHCT may be a safe and feasible option. PTCy appears to decrease the incidence of acute GVHD in this cohort of patients.https://jitc.bmj.com/content/9/2/e001818.full |
| spellingShingle | Maro Ohanian Farhad Ravandi Maria E Suarez-Almazor Adi Diab Noha Abdel-Wahab Houssein Safa Ala Abudayyeh Marina Konopleva Stephen Gruschkus Chantal Saberian May Daher Richard Champlin Kaysia Ludford Gheath Al-Atrash Guillermo Garcia-Manero Naval Daver Hind Rafei Jacinth Joseph Gabriela Rondon Laura Whited Faisal Fa'ak Cristina Knape Mahran Shoukier Megan Marcotulli Alison M Gulbis Betul Oran Uday R Popat Rotesh Mehta Amin M Alousi Post-transplantation cyclophosphamide reduces the incidence of acute graft-versus-host disease in patients with acute myeloid leukemia/myelodysplastic syndromes who receive immune checkpoint inhibitors after allogeneic hematopoietic stem cell transplantation Journal for ImmunoTherapy of Cancer |
| title | Post-transplantation cyclophosphamide reduces the incidence of acute graft-versus-host disease in patients with acute myeloid leukemia/myelodysplastic syndromes who receive immune checkpoint inhibitors after allogeneic hematopoietic stem cell transplantation |
| title_full | Post-transplantation cyclophosphamide reduces the incidence of acute graft-versus-host disease in patients with acute myeloid leukemia/myelodysplastic syndromes who receive immune checkpoint inhibitors after allogeneic hematopoietic stem cell transplantation |
| title_fullStr | Post-transplantation cyclophosphamide reduces the incidence of acute graft-versus-host disease in patients with acute myeloid leukemia/myelodysplastic syndromes who receive immune checkpoint inhibitors after allogeneic hematopoietic stem cell transplantation |
| title_full_unstemmed | Post-transplantation cyclophosphamide reduces the incidence of acute graft-versus-host disease in patients with acute myeloid leukemia/myelodysplastic syndromes who receive immune checkpoint inhibitors after allogeneic hematopoietic stem cell transplantation |
| title_short | Post-transplantation cyclophosphamide reduces the incidence of acute graft-versus-host disease in patients with acute myeloid leukemia/myelodysplastic syndromes who receive immune checkpoint inhibitors after allogeneic hematopoietic stem cell transplantation |
| title_sort | post transplantation cyclophosphamide reduces the incidence of acute graft versus host disease in patients with acute myeloid leukemia myelodysplastic syndromes who receive immune checkpoint inhibitors after allogeneic hematopoietic stem cell transplantation |
| url | https://jitc.bmj.com/content/9/2/e001818.full |
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