Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Case Reports
. 2016 Aug 8;9(1):67.
doi: 10.1186/s13045-016-0298-6.

Ruxolitinib in steroid refractory graft-vs.-host disease: a case report

Enrico Maffini  1   2 , Luisa Giaccone  3   4 , Moreno Festuccia  3   4 , Lucia Brunello  3   4 , Ilaria Buondonno  5 , Dario Ferrero  3   4 , Mario Boccadoro  4 , Chiara Dellacasa  3 , Alessandro Busca  3 , Domenico Novero  6 , Benedetto Bruno  3   4
Affiliations
Case Reports

Ruxolitinib in steroid refractory graft-vs.-host disease: a case report

Enrico Maffini et al. J Hematol Oncol. .

Abstract

Background: Allogeneic hematopoietic stem cell transplantation (HSCT) is potentially curative in a variety of hematological malignancies. Graft-vs.-host disease (GvHD) remains a life-threatening complication. Standard treatment is high-dose (HD) corticosteroids. Steroid-refractory (SR) GvHD is associated with poor prognosis. At present, second-line treatment is ill-defined and includes a number of agents. Novel insights into the pathophysiology of acute GvHD (aGvHD) highlight the relevant role of the host inflammatory response governed by several kinase families, including Janus kinases (JAK)1/2. Ruxolitinib, a JAK1/2 inhibitor approved for intermediate-2/high-risk myelofibrosis, was recently employed in SR-GvHD with encouraging overall response rates. Clinical experience however remains limited.

Case presentation: A 51-year-old male with refractory anemia with excess blast type-2 underwent a myeloablative allogeneic HSCT from a 9/10 HLA-matched unrelated donor after conditioning with busulfan and cyclophosphamide. GvHD prophylaxis consisted of cyclosporine, methotrexate, and thymoglobulin. CD34(+) cells/kg infused were 8.69 × 10(6) kg. On day 29, the patient developed overall grade IV aGvHD with biopsy proven stage IV gastrointestinal (GI) GvHD refractory to HD corticosteroids. Patient conditions rapidly deteriorated and became critical despite the addition of mycophenolate mofetil and budesonide. On day 33, Ruxolitinib was started, and on day 39 the patient clinical conditions gradually improved. Complete resolution of aGvHD was also confirmed by histology on day 54.

Conclusions: At 5 months from HSCT, the patient is well and in continuous hematological complete remission without flare of GvHD. Ruxolitinib was discontinued on day 156. Ruxolitinib is feasible and effective in SR-aGvHD though large prospective clinical trials are warranted.

Keywords: Allogeneic hematopoietic stem cell transplant (HSCT); Case report; Proinflammatory cytokines; Regulatory T cells (Treg); Ruxolitinib; Steroid-refractory graft-vs.-host disease (SR-GvHD).

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Histology studies (H&E). a–c Gastrointestinal acute grade I GVHD: focal apoptosis of crypt epithelial cells (white arrows) without abscess or crypt destruction. A clear lymphocytic infiltration of the lamina propria is not present. Moderate mucosal atrophy can be observed. d Duodenum at day +54 post-transplant: complete reconstitution of the mucosa with disappearance of apoptotic crypt cells (courtesy of D. Novero, Pathology, University of Turin)
Fig. 2
Fig. 2
Serum levels of TNF-α and IL-6. TNF-α decreased from 10 pg/mL at day 27 (while on high-dose steroids) to 5 pg/mL at day 54, while IL-6 decreased from 2.3 to 1.5 pg/mL (values are expressed as percentage)
See this image and copyright information in PMC

References

    1. Deeg J. How I, treat refractory acute GVHD. Blood. 2007;109(10):4119–4126. doi: 10.1182/blood-2006-12-041889. - DOI - PMC - PubMed
    1. Martin PJ, Rizzo JD, Wingard JR, Ballen K, Curtin PT, Cutler C, Litzow MR, Nieto Y, Savani BN, Schriber JR, Shaughnessy PJ, Wall DA, Carpenter PA. First- and second-line systemic treatment of acute graft-versus-host disease: recommendations of the American Society of Blood and Marrow Transplantation. Biol Blood Marrow Transplant. 2012;18(8):1150–1163. doi: 10.1016/j.bbmt.2012.04.005. - DOI - PMC - PubMed
    1. Xhaard A, Rocha V, Bueno B, et al. Steroid refractory acute GVHD: lack of long-term improved survival using new generation anti cytokine treatment. Biol Blood Marrow Transplant. 2012;18(3):406–413. doi: 10.1016/j.bbmt.2011.06.012. - DOI - PubMed
    1. Robin M, Porcher R, de Castro R, et al. Initial liver involvement in acute GVHD is predictive for non relapse mortality. Transplantation. 2009;88:1131–1136. doi: 10.1097/TP.0b013e3181bc2583. - DOI - PubMed
    1. Inagaki J, Kodama Y, Fukano R, Noguchi M, Okamura J. Mycophenolate mofetil for treatment of steroid-refractory acute graft-versus-host disease after pediatric hematopoietic stem cell transplantation. Pediatr Transplant. 2015;19(6):652–658. doi: 10.1111/petr.12545. - DOI - PubMed

Publication types

MeSH terms