title: Ruxolitinib in steroid refractory graft-vs.-host disease: a case report.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
authors: Department of Oncology, SSCVD Trapianto di Cellule Staminali, A.O.U. Città della Salute e della Scienza di Torino, Torino, Italy. shostakowitsch@libero.it.|Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy. shostakowitsch@libero.it.
authors: Enrico
authors: 0000-0001-7356-2328
authors: E
authors: Maffini
authors: Department of Oncology, SSCVD Trapianto di Cellule Staminali, A.O.U. Città della Salute e della Scienza di Torino, Torino, Italy.|Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy.
authors: Luisa
authors: L
authors: Giaccone
authors: Department of Oncology, SSCVD Trapianto di Cellule Staminali, A.O.U. Città della Salute e della Scienza di Torino, Torino, Italy.|Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy.
authors: Moreno
authors: M
authors: Festuccia
authors: Department of Oncology, SSCVD Trapianto di Cellule Staminali, A.O.U. Città della Salute e della Scienza di Torino, Torino, Italy.|Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy.
authors: Lucia
authors: L
authors: Brunello
authors: Department of Oncology, University of Torino, Torino, Italy.
authors: Ilaria
authors: I
authors: Buondonno
authors: Department of Oncology, SSCVD Trapianto di Cellule Staminali, A.O.U. Città della Salute e della Scienza di Torino, Torino, Italy.|Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy.
authors: Dario
authors: D
authors: Ferrero
authors: Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy.
authors: Mario
authors: M
authors: Boccadoro
authors: Department of Oncology, SSCVD Trapianto di Cellule Staminali, A.O.U. Città della Salute e della Scienza di Torino, Torino, Italy.
authors: Chiara
authors: C
authors: Dellacasa
authors: Department of Oncology, SSCVD Trapianto di Cellule Staminali, A.O.U. Città della Salute e della Scienza di Torino, Torino, Italy.
authors: Alessandro
authors: A
authors: Busca
authors: Department of Pathology, AOU Città della Salute e della Scienza di Torino, University of Torino, Torino, Italy.
authors: Domenico
authors: D
authors: Novero
authors: Department of Oncology, SSCVD Trapianto di Cellule Staminali, A.O.U. Città della Salute e della Scienza di Torino, Torino, Italy.|Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy.
authors: Benedetto
authors: B
authors: Bruno
mesh_terms: D000305:Adrenal Cortex Hormones / Q000494:pharmacology; D000754:Anemia, Refractory, with Excess of Blasts / Q000150:complications / Q000628:therapy; D004351:Drug Resistance; D006086:Graft vs Host Disease / Q000188:drug therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009570:Nitriles; D011720:Pyrazoles / Q000627:therapeutic use*; D011743:Pyrimidines; D012074:Remission Induction; D016879:Salvage Therapy / Q000379:methods*
chemical_list: D000305:Adrenal Cortex Hormones; D009570:Nitriles; D011720:Pyrazoles; D011743:Pyrimidines; C540383:ruxolitinib
keywords: Allogeneic hematopoietic stem cell transplant (HSCT); Case report; Proinflammatory cytokines; Regulatory T cells (Treg); Ruxolitinib; Steroid-refractory graft-vs.-host disease (SR-GvHD)