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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Alloimmunity and Transplantation
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1500177
This article is part of the Research Topic Immunological Advancements in Hematological Therapies: Exploring HSCT and CAR-T Integration View all articles

GVHD after CAR T-cell therapy post allogeneic hematopoietic cell transplantation -successfully treated by extracorporeal photopheresis

Provisionally accepted
Kiavasch M. Farid Kiavasch M. Farid 1Gesine Bug Gesine Bug 2Anita Schmitt Anita Schmitt 1Fabian Lang Fabian Lang 2Maria-Luisa Schubert Maria-Luisa Schubert 1Uwe Haberkorn Uwe Haberkorn 3Carsten Müller-Tidow Carsten Müller-Tidow 1Peter Dreger Peter Dreger 1Michael Schmitt Michael Schmitt 1*
  • 1 Internal Medicine V, Hematology, Oncology and Rheumatology, Heidelberg University Hospital, Heidelberg, Germany
  • 2 Goethe University Frankfurt, University Hospital, Department of Medicine 2, Hematology and Oncology, Frankfurt am Main, Germany
  • 3 Department of Nuclear Medicine, Heidelberg University Hospital, Heidelberg, Baden-Württemberg, Germany

The final, formatted version of the article will be published soon.

    CAR T-cell therapy is highly effective, but also associated with unique toxicities. Due to the origin of T-cells in patients who previously underwent allogeneic hematopoietic cell transplantation (alloHCT), graft-versus-host disease (GVHD) in the post-CAR T-cell setting poses a relevant concern but is only scarcely studied. Potential risk factors and mitigation strategies (from CAR T-cell modifications to clinical management) are yet to be determined. Sharing our own experience and a mini-review of the literature, our aim is to better understand frequency and risk of the potential occurrence of GVHD after CAR T-cells, which are most likely underestimated. Here, we present a cohort of 11 patients with symptoms suggestive of GVHD out of 25 allografted patients treated with CAR T-cells, of whom 3 patients (12%) had GVHD most likely triggered by the preceding CAR T-cell treatment. Severe chronic pulmonary GVHD occurred in a patient after CD19-directed CAR T-cell therapy. Extracorporeal photopheresis (ECP) mediated successful resolution long-term control of GVvHD without causing relapse of the underlying disease. In conclusion, CD19-directed CAR T-cell therapy seems to be feasible in patients after alloHCT but might comprise the potential risk of triggering GVHD, most likely depending on the T-cell source, donor compatibility and the specific CAR construct used.

    Keywords: American Society of Hematology, ATG: anti-thymocyte globulin, BCP: B-cell precursor, BM: Bone Marrow, CAR: chimeric antigen receptor, CR: complete remission, CRS: cytokine release syndrome, DLCO: diffusion capacity of carbon monoxide

    Received: 22 Sep 2024; Accepted: 28 Oct 2024.

    Copyright: © 2024 Farid, Bug, Schmitt, Lang, Schubert, Haberkorn, Müller-Tidow, Dreger and Schmitt. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Michael Schmitt, Internal Medicine V, Hematology, Oncology and Rheumatology, Heidelberg University Hospital, Heidelberg, Germany

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.