Cyclophosphamide for salvage therapy of chronic graft-versus-host disease: a retrospective analysis
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ORIGINAL ARTICLE
Cyclophosphamide for salvage therapy of chronic graft-versus-host disease: a retrospective analysis Matthias A. Fante 1 & Barbara Holler 1 & Daniela Weber 1 & Klemens Angstwurm 2 & Tobias Bergler 3 & Ernst Holler 1 & Matthias Edinger 1 & Wolfgang Herr 1 & Tobias Wertheimer 1 & Daniel Wolff 1 Received: 9 February 2020 / Accepted: 20 July 2020 / Published online: 26 July 2020 # The Author(s) 2020
Abstract We retrospectively analyzed the safety and efficacy of cyclophosphamide (cyclo) for salvage treatment of chronic graft-versushost disease (cGvHD) and cGvHD-associated (glomerulo-)nephritis at our center between 01/2010 and 11/2019. We identified 13 patients (pts) receiving cyclo for treatment of moderate (3/13) and severe (6/13) steroid-refractory cGvHD, cGvHD-associated (glomerulo-)nephritis (3/13), or vasculitis-like CNS manifestation of cGvHD (1/13). Cyclo was started on median day 509 (range 42–8193) after cGvHD onset; the median duration of application was 153 days (range 14–486) with 2/13 currently continuing treatment. The National Institute of Health organ grading and the intensity of immunosuppression (IS) were assessed at cyclo start and repeated after 3, 6, and 12 months. Response assessment was stopped at the start of any additional new IS. The median time of follow up was 407 days (range 86–1534). Best response was 1/13 CR, 6/13 PR, 4/13 SD, 1/13 MR, and 1/13 PD (ORR 54%). Significant and durable response was observed especially in cGvHD-associated (glomerulo-)nephritis (3/3). Infectious complications > CTCAE grade III were observed in 3/12 pts. During cyclo therapy, none of the pts suffered from recurrence of underlying malignancy. Overall, cyclo was relatively well tolerated and showed responses in heavily pretreated patients but requires further evaluation within clinical trials. Keywords Chronic graft versus host disease . Vasculitis-like cGvHD manifestation . Salvage therapy . Cyclophosphamide
Introduction The main benefit of allogeneic stem cell transplantation (alloHSCT) is a sustained graft-versus-malignancy effect, unfortunately often accompanied by graft-versus-host disease (GvHD) significantly contributing to non-relapse mortality and reduced quality of life [1, 2]. Chronic GvHD (cGvHD) is a multistep, host-reactive complication that occurs in up to 70% of patients [3, 4]. The underlying pathophysiology is still Tobias Wertheimer and Daniel Wolff contributed equally to this work. * Matthias A. Fante [email protected] 1
Department of Hematology and Oncology, Internal Medicine III, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg, Germany
2
Department of Neurology, University Hospital Regensburg, Regensburg, Germany
3
Department of Nephrology, University Hospital Regensburg, Regensburg, Germany
not fully understood, but new insights into the complex interplay of damage patterns, alterations in antigen presentation, dysregulation of B- and T-lymphocytes as well as interleukins promoting chronic inflammation, and tissue fibrosis recently ad
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