OCTET-CY: a phase II study to investigate the efficacy of post-transplant cyclophosphamide as sole graft-versus-host prophylaxis after allogeneic peripheral blood stem cell transplantation
Corresponding Author
Udo Holtick
Stem Cell Transplantation Program, Department I of Internal Medicine, Center for Integrated Oncology CIO KölnBonn, University Hospital of Cologne, Cologne, Germany
Cologne Interventional Immunology, Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany
Correspondence Udo Holtick, MD, PhD, Cologne Interventional Immunology & Stem Cell Transplantation Program, Department of I of Internal Medicine, University of Cologne, Cologne, Germany. Tel: +49 221 478 4407; Fax: +49 221 478 7170; e-mail: [email protected]Search for more papers by this authorJens-Markus Chemnitz
Stem Cell Transplantation Program, Department I of Internal Medicine, Center for Integrated Oncology CIO KölnBonn, University Hospital of Cologne, Cologne, Germany
Search for more papers by this authorAlexander Shimabukuro-Vornhagen
Stem Cell Transplantation Program, Department I of Internal Medicine, Center for Integrated Oncology CIO KölnBonn, University Hospital of Cologne, Cologne, Germany
Cologne Interventional Immunology, Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany
Search for more papers by this authorSebastian Theurich
Stem Cell Transplantation Program, Department I of Internal Medicine, Center for Integrated Oncology CIO KölnBonn, University Hospital of Cologne, Cologne, Germany
Cologne Interventional Immunology, Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany
Search for more papers by this authorGeothy Chakupurakal
Stem Cell Transplantation Program, Department I of Internal Medicine, Center for Integrated Oncology CIO KölnBonn, University Hospital of Cologne, Cologne, Germany
Cologne Interventional Immunology, Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany
Search for more papers by this authorAnke Krause
Stem Cell Transplantation Program, Department I of Internal Medicine, Center for Integrated Oncology CIO KölnBonn, University Hospital of Cologne, Cologne, Germany
Search for more papers by this authorAnne Fiedler
Cologne Interventional Immunology, Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany
Search for more papers by this authorLeo Luznik
Sidney Kimmel Comprehensive Cancer Center and Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Search for more papers by this authorMartin Hellmich
Institute of Medical Statistics, Informatics and Epidemiology, University of Cologne, Cologne, Germany
Search for more papers by this authorDominik Wolf
Medical Clinic III for Oncology, Haematology and Rheumatology, Center for Integrated Oncology CIO KölnBonn, University Hospital Bonn, Bonn, Germany
Search for more papers by this authorMichael Hallek
Stem Cell Transplantation Program, Department I of Internal Medicine, Center for Integrated Oncology CIO KölnBonn, University Hospital of Cologne, Cologne, Germany
Search for more papers by this authorMichael von Bergwelt-Baildon
Stem Cell Transplantation Program, Department I of Internal Medicine, Center for Integrated Oncology CIO KölnBonn, University Hospital of Cologne, Cologne, Germany
Cologne Interventional Immunology, Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany
Search for more papers by this authorChristof Scheid
Stem Cell Transplantation Program, Department I of Internal Medicine, Center for Integrated Oncology CIO KölnBonn, University Hospital of Cologne, Cologne, Germany
Search for more papers by this authorCorresponding Author
Udo Holtick
Stem Cell Transplantation Program, Department I of Internal Medicine, Center for Integrated Oncology CIO KölnBonn, University Hospital of Cologne, Cologne, Germany
Cologne Interventional Immunology, Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany
Correspondence Udo Holtick, MD, PhD, Cologne Interventional Immunology & Stem Cell Transplantation Program, Department of I of Internal Medicine, University of Cologne, Cologne, Germany. Tel: +49 221 478 4407; Fax: +49 221 478 7170; e-mail: [email protected]Search for more papers by this authorJens-Markus Chemnitz
Stem Cell Transplantation Program, Department I of Internal Medicine, Center for Integrated Oncology CIO KölnBonn, University Hospital of Cologne, Cologne, Germany
Search for more papers by this authorAlexander Shimabukuro-Vornhagen
Stem Cell Transplantation Program, Department I of Internal Medicine, Center for Integrated Oncology CIO KölnBonn, University Hospital of Cologne, Cologne, Germany
Cologne Interventional Immunology, Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany
Search for more papers by this authorSebastian Theurich
Stem Cell Transplantation Program, Department I of Internal Medicine, Center for Integrated Oncology CIO KölnBonn, University Hospital of Cologne, Cologne, Germany
Cologne Interventional Immunology, Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany
Search for more papers by this authorGeothy Chakupurakal
Stem Cell Transplantation Program, Department I of Internal Medicine, Center for Integrated Oncology CIO KölnBonn, University Hospital of Cologne, Cologne, Germany
Cologne Interventional Immunology, Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany
Search for more papers by this authorAnke Krause
Stem Cell Transplantation Program, Department I of Internal Medicine, Center for Integrated Oncology CIO KölnBonn, University Hospital of Cologne, Cologne, Germany
Search for more papers by this authorAnne Fiedler
Cologne Interventional Immunology, Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany
Search for more papers by this authorLeo Luznik
Sidney Kimmel Comprehensive Cancer Center and Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Search for more papers by this authorMartin Hellmich
Institute of Medical Statistics, Informatics and Epidemiology, University of Cologne, Cologne, Germany
Search for more papers by this authorDominik Wolf
Medical Clinic III for Oncology, Haematology and Rheumatology, Center for Integrated Oncology CIO KölnBonn, University Hospital Bonn, Bonn, Germany
Search for more papers by this authorMichael Hallek
Stem Cell Transplantation Program, Department I of Internal Medicine, Center for Integrated Oncology CIO KölnBonn, University Hospital of Cologne, Cologne, Germany
Search for more papers by this authorMichael von Bergwelt-Baildon
Stem Cell Transplantation Program, Department I of Internal Medicine, Center for Integrated Oncology CIO KölnBonn, University Hospital of Cologne, Cologne, Germany
Cologne Interventional Immunology, Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany
Search for more papers by this authorChristof Scheid
Stem Cell Transplantation Program, Department I of Internal Medicine, Center for Integrated Oncology CIO KölnBonn, University Hospital of Cologne, Cologne, Germany
Search for more papers by this authorAbstract
Objective
Post-transplant cyclophosphamide is increasingly used as graft-versus-host disease (GvHD) prophylaxis in the setting of bone marrow transplantation. No data have been published on the use of single-agent GvHD prophylaxis with post-transplant cyclophosphamide in the setting of peripheral blood stem cell transplantation (PBSCT).
Methods
In a phase II trial, 11 patients with myeloma or lymphoma underwent conditioning with fludarabine and busulfan followed by T-replete PBSCT and application of 50 mg/kg/d of cyclophosphamide on day+3 and +4 without other concurrent immunosuppression (IS).
Results
Median time to leukocyte, neutrophil, and platelet engraftment was 18, 21, and 18 d. The incidence of grade II–IV and grade III–IV GvHD was 45% and 27%, with a non-relapse mortality (NRM) of 36% at one and 2 yr. After median follow-up of 927 d, overall and relapse-free survival was 64% and 34%. Three patients did not require any further systemic IS until day+100 and thereafter. Analysis of immune reconstitution demonstrated rapid T- and NK-cell recovery. B- and CD3+/CD161+NK/T-cell recovery was superior in patients not receiving additional IS.
Conclusion
Post-transplant cyclophosphamide as sole IS in PBSCT is feasible and allows rapid immune recovery. Increased rates of severe acute GvHD explain the observed NRM and may advise a temporary combination partner such as mTor-inhibitors in the PBSCT setting.
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