Ruxolitinib in refractory acute and chronic graft-versus-host disease : a multicenter survey study

Graft-versus-host disease is the main cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation. First-line treatment is based on the use of high doses of corticosteroids. Unfortunately, second-line treatment for both acute and chronic graft-versus-host disease, remains a challenge. Ruxolitinib has been shown as an effective and safe treatment option for these patients. Seventy-nine patients received ruxolitinib and were evaluated in this retrospective and multicenter study. Twenty-three patients received ruxolitinib for refractory acute graft-versus-host disease after a median of 3 (range 1-5) previous lines of therapy. Overall response rate was 69.5% (16/23) which was obtained after a median of 2 weeks of treatment, and 21.7% (5/23) reached complete remission. Fifty-six patients were evaluated for refractory chronic graft-versus-host disease. The median number of previous lines of therapy was 3 (range 1-10). Overall response rate was 57.1% (32/56) with 3.5% (2/56) obtaining complete remission after a median of 4 weeks. Tapering of corticosteroids was possible in both acute (17/23, 73%) and chronic graft-versus-host disease (32/56, 57.1%) groups. Overall survival was 47% (CI: 23-67%) at 6 months for patients with aGVHD (62 vs 28% in responders vs non-responders) and 81% (CI: 63-89%) at 1 year for patients with cGVHD (83 vs 76% in responders vs non-responders). Ruxolitinib in the real life setting is an effective and safe treatment option for GVHD, with an ORR of 69.5% and 57.1% for refractory acute and chronic graft-versus-host disease, respectively, in heavily pretreated patients

Graft versus host disease-related eosinophilic fasciitis: cohort description and literature review

[Background]: Chronic graft versus host disease (cGVHD) simulating eosinophilic fasciitis (EF) is an underdiagnosed and challenging complication due to the lack of knowledge about its pathogenesis, refractoriness to traditional immunosuppressive agents and their negative impact on the physical function and quality of life. The aim of this study is to describe the clinical-biological characteristics and response to treatment of a case series and to provide a comprehensive literature review on cGVHD related EF involvement. [Methods]: Prospective observational study to describe the clinical and diagnostic evaluation characteristics of patients with EF-like follow-up as part of our multidisciplinary cGVHD consultations. In addition, the literature on joint and/or fascial musculoskeletal manifestations due to cGVHD was comprehensively reviewed. [Results]: 118 patients were evaluated in multidisciplinary cGVHD consultations, 39 of whom (33%) developed fasciitis. Notably, 11 patients had isolated joint contractures without sclerotic skin. After a median of three lines of treatment, the vast majority of patients achieved some degree of response. 94 potentially eligible articles were identified by the search strategy, with 17 of them, the majority isolated case reports, making the final selection. The validated staging scales used for the assessment were the Joint and Fascial Score and the Photographic Range of Motion. [Conclusion]: Fascial/articular involvement needs to be recognized and evaluated early. To our knowledge, our cohort is the second largest series to have been reported. Literature addressing fascial/joints complications related to cGVHD is scarce. The search for new biomarkers, the use of advanced imaging techniques and multidisciplinary approach may help improve the prognosis of patients with cGVHD.This work was partially supported by the Education Council and Health Council of the Junta de Castilla y León (GRS 2183/A/20), Spain.Peer reviewe

Efficacy of bortezomib to intensify the conditioning regimen and the graft-versus-host disease prophylaxis for high-risk myeloma patients undergoing transplantation

This multicenter phase I trial was designed to evaluate the safety and efficacy of bortezomib (Bz) as part of both the conditioning regimen and the graft-versus-host disease (GvHD) prophylaxis. Patients received fludarabine, melphalan and Bz (days −9 and −2). GVHD prophylaxis consisted of Bz (days +1, +4, and +7), sirolimus (Siro) from day −5 and tacrolimus (Tk) from −3 (except the first five patients that did not receive Tk). Twenty-five patients with poor prognostic multiple myeloma were included. Eleven out of the 19 patients had high-risk features. Out of the 21 patients evaluable at day +100, 14 were in CR (67%) and 7 (33%) in PR. Cumulative incidence (CI) of nonrelapse mortality at 1 year was 24%. CI of grades 2–4 and 3–4 acute GvHD was 35% and 10%, respectively; CI of chronic GvHD was 35% and 55% at 1 and 2 years, respectively. Overall and event free survival at 2 years were 64% and 31%, respectively. Bz as part of the conditioning regimen and in the combination with Siro/tacrolimus for GvHD prophylaxis is safe and effective allowing an optimal disease control early after transplant and reducing the risk of GvHD.This trial was supported by Janssen and Celgene and the Ministerio de Sanidad y Política Social, convocatoria de concesión de ayudas para el fomento de la investigación clínica independiente 2010 (EC10–289); this study was partially supported by two grants from the Ministry of Health CIBER ONC, code CB16/12/00480. TCV was supported by a grant from Ministerio de Sanidad y Política Social (CM10/00161)