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Open Access 01-12-2017 | Case report

Compassionate use of ruxolitinib in acute and chronic graft versus host disease refractory both to corticosteroids and extracorporeal photopheresis

Authors: Mauricio Sarmiento Maldonado, Pablo Ramírez Villanueva, Pablo Bertín Cortes-Monroy, Veronica Jara Arias, Katherine Soto Donoso, Pablo Uribe Gonzalez, Mauricio Ocqueteau Tachini, Jose Antonio Perez-Simón

Published in: Experimental Hematology & Oncology | Issue 1/2017

Abstract

Background

Ruxolitinib is a potent inhibitor of JAK1/2 with proven efficacy in myelofibrosis. In recent years, research in graft versus host disease (GVHD) has revealed the role of activation of JAK pathways in alloreactive lymphocytes. Some reports have shown significant responses in refractory GVHD patients.

Cases presentation

In this report we present our experience in 8 patients with acute or chronic GVHD with refractoriness to steroids and extracorporeal photopheresis treated with ruxolitinib. Three patients had acute GVHD (1 pulmonary, 2 cutaneous, 1 multi-systemic) and 5 had chronic GVHD (3 cutaneous); 85% obtained an overall response and 50% a complete response with a tolerable toxicity profile.

Conclusions

In our series, Ruxolitinib was very active as a rescue therapy for patients with acute or chronic GVHD refractory to standard treatment.

Passweg JR, Baldomero H, Bader P, Bonini C, Cesaro S, Dreger P, et al. Hematopoietic stem cell transplantation in Europe 2014: more than 40 000 transplants annually. Bone Marrow Transplant. 2016;51(6):786–92.CrossRefPubMedPubMedCentral

Sureda A, Bader P, Cesaro S, Dreger P, Duarte RF, Dufour C, et al. Indications for allo- and auto-SCT for haematological diseases, solid tumours and immune disorders: current practice in Europe, 2015. Bone Marrow Transplant. 2015;50(8):1037–56.CrossRefPubMed

Presland RB. Biology of chronic graft-vs-host disease: immune mechanisms and progress in biomarker discovery. World J Transplant. 2016;6(4):608–19.CrossRefPubMedPubMedCentral

Levine JE, Logan B, Wu J, Alousi AM, Ho V, Bolanos-Meade J, Weisdorf D. Graft-versus-host disease treatment: predictors of survival. Biol Blood Marrow Transplant. 2010;16(12):1693–9.CrossRefPubMedPubMedCentral

Nassereddine S, Rafei H, Elbahesh E, Tabbara I. Acute graft versus host disease: a comprehensive review. Anticancer Res. 2017;37(4):1547–55.CrossRefPubMed

Abu-Dalle I, Reljic T, Nishihori T, Antar A, Bazarbachi A, Djulbegovic B, et al. Extracorporeal photopheresis in steroid-refractory acute or chronic graft-versus-host disease: results of a systematic review of prospective studies. Biol Blood Marrow Transplant. 2014;20(11):1677–86.CrossRefPubMed

Bittenbring J, Reichrath J. Extracorporeal photopheresis for non-skin GvHD. Anticancer Res. 2016;36(3):1395–6.PubMed

Verstovsek S, Mesa RA, Gotlib J, Gupta V, DiPersio JF, Catalano JV, et al. Long-term treatment with ruxolitinib for patients with myelofibrosis: 5-year update from the randomized, double-blind, placebo-controlled, phase 3 COMFORT-I trial. J Hematol Oncol. 2017;10(1):55.CrossRefPubMedPubMedCentral

Carniti C, Gimondi S, Vendramin A, Recordati C, Confalonieri D, Bermema A, et al. Pharmacologic inhibition of JAK1/JAK2 signaling reduces experimental murine acute GVHD while preserving GVT effects. Clin Cancer Res. 2015;21(16):3740–9.CrossRefPubMed

10.

Shanavas M, Popat U, Michaelis LC, Fauble V, McLornan D, Klisovic R, et al. Outcomes of allogeneic hematopoietic cell transplantation in patients with myelofibrosis with prior exposure to janus kinase 1/2 inhibitors. Biol Blood Marrow Transplant. 2016;22(3):432–40.CrossRefPubMed

11.

Zeiser R, Burchert A, Lengerke C, Verbeek M, Maas-Bauer K, Metzelder SK, et al. Ruxolitinib in corticosteroid-refractory graft-versus-host disease after allogeneic stem cell transplantation: a multicenter survey. Leukemia. 2015;29(10):2062–8.CrossRefPubMedPubMedCentral

12.

Hurabielle C, Sicre de Fontbrune F, Moins-Teisserenc H, Robin M, Jachiet M, Coman T, et al. Efficacy and tolerance of ruxolitinib in refractory sclerodermatous chronic graft-versus-host disease. Br J Dermatol. 2017. https://doi.org/10.1111/bjd.15593 (Epub ahead of print).PubMed

13.

Choi J, Cooper ML, Alahmari B, Ritchey J, Collins L, Holt M, DiPersio JF. Pharmacologic blockade of JAK1/JAK2 reduces GvHD and preserves the graft-versus-leukemia effect. PLoS ONE. 2014;9(10):e109799.CrossRefPubMedPubMedCentral

14.

Khandelwal P, Teusink-Cross A, Davies SM, Nelson AS, Dandoy CE, El-Bietar J, et al. Ruxolitinib as salvage therapy in steroid-refractory acute graft-versus-host disease in pediatric hematopoietic stem cell transplant patients. Biol Blood Marrow Transplant. 2017;23(7):1122–7. https://doi.org/10.1016/j.bbmt.2017.03.029 Epub 2017 Mar 23.CrossRefPubMed

15.

Hart S, Goh KC, Novotny-Diermayr V, Hu CY, Hentze H, Tan YC, et al. SB1518, a novel macrocyclic pyrimidine-based JAK2 inhibitor for the treatment of myeloid and lymphoid malignancies. Leukemia. 2011;25:1751–9.CrossRefPubMed

16.

Okiyama N, Furumoto Y, Villarroel VA, Linton JT, Tsai WL, Gutermuth J, et al. Reversal of CD8 T-cell-mediated mucocutaneous graft-versus-host-like disease by the JAK inhibitor tofacitinib. J Invest Dermatol. 2014;134(4):992–1000.CrossRefPubMed

17.

Kheirkhah A, Di Zazzo A, Satitpitakul V, Fernandez M, Magilavy D, Dana R. A pilot randomized trial on safety and efficacy of a novel topical combined inhibitor of janus kinase 1/3 and spleen tyrosine kinase for GVHD-associated ocular surface disease. Cornea. 2017;36:799–804.CrossRefPubMed

18.

Akpek G, Chinratanalab W, Lee LA, Torbenson M, Hallick JP, et al. Gastrointestinal involvement in chronic graft versus host disease: a clinicopathologic study. Biol Blood Marrow Transplant. 2003;9(1):46–51.CrossRefPubMed

19.

Palmer J, Williams K, Inamoto Y, ChaiX Martin PJ, Tomas LS, et al. Pulmonary symptoms measured by the national institutes of health lung score predict overall survival, non relapse mortality, and patient-reported outcomes in chronic graft-versus host-disease. Biol Blood Marrow Transplant. 2014;20(33):337–44.CrossRefPubMed

Title: Compassionate use of ruxolitinib in acute and chronic graft versus host disease refractory both to corticosteroids and extracorporeal photopheresis
Authors: Mauricio Sarmiento Maldonado
Pablo Ramírez Villanueva
Pablo Bertín Cortes-Monroy
Veronica Jara Arias
Katherine Soto Donoso
Pablo Uribe Gonzalez
Mauricio Ocqueteau Tachini
Jose Antonio Perez-Simón
Publication date: 01-12-2017
Publisher: BioMed Central
Published in: Experimental Hematology & Oncology / Issue 1/2017
Electronic ISSN: 2162-3619
DOI: https://doi.org/10.1186/s40164-017-0092-3

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Abstract

Background

Cases presentation

Conclusions

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