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Bone Marrow Transplant. 2019 Mar 4. doi: 10.1038/s41409-019-0498-0. [Epub ahead of print]

The role of checkpoint blockade after allogeneic stem cell transplantation in diseases other than Hodgkin's Lymphoma.

Author information

1
Department of Hematology, Oncology and Rheumatology, University Hospital Bonn, Bonn, Germany.
2
Department of Medicine III, Hematopoietic Stem Cell Transplantation, University Hospital, LMU Munich, Munich, Germany.
3
Department of Bone Marrow Transplantation, University Hospital of Münster, Münster, Germany.
4
Department of Internal Medicine III, Hematology and Oncology, University Hospital Regensburg, Regensburg, Germany.
5
Department of Stem Cell Transplantation, University Hospital Eppendorf, Hamburg, Germany.
6
Department of Hematology and Oncology, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
7
Department of Hematology and Oncology, Medical Center, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany.
8
Medizinische Fakultät Carl-Gustav-Carus der Technischen Universität, Medizinische Klinik und Poliklinik I, University Hospital Carl-Gustav-Carus, Dresden, Germany.
9
Department of Medicine III, Hematopoietic Stem Cell Transplantation, University Hospital, LMU Munich, Munich, Germany. johanna.tischer@med.uni-muenchen.de.
10
Department of Hematology, Oncology and Rheumatology, University Hospital Bonn, Bonn, Germany. dominik.wolf@i-med.ac.at.
11
UKIM 5, Medical University Innsbruck, Innsbruck, Austria. dominik.wolf@i-med.ac.at.

Abstract

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curative treatment option for many malignant high-risk hematological diseases. The Graft-vs.-Tumor (GvT) effect is the major hallmark of this treatment approach. However, disease relapse remains a major limitation. Boosting the GvT effect by checkpoint inhibitors (CI) is an attractive option in this desperate situation although potentially triggering Graft-vs.-Host Disease (GvHD). Early reports in patients with Hodgkin's lymphoma support the idea that CI therapy after HSCT is feasible and effective. We have retrospectively analyzed CI therapy for treatment of disease recurrence after allo-HSCT other than Hodgkin's lymphoma including 21 patients from eight German transplant centers. The median follow-up was 59 days. The overall response rate (ORR) was 43%. Patients receiving donor lymphocyte infusion (DLI) in combination with CI had superior response (ORR 80%). Severe acute GvHD grade III-IV and moderate to severe chronic GvHD were observed in 29% of all patients. Taken together, CI therapy in relapsed patients after HSCT, especially in combination with DLI, is effective but induces severe GvHD in a considerable proportion of patients. Thus, prospective trials or EBMT registry-based validation of different dosing and application schedules including immunosuppressive regimens in those patients are urgently needed.

PMID:
30833743
DOI:
10.1038/s41409-019-0498-0

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