Ruxolitinib for steroid-refractory graft versus host disease in pediatric HSCT: high response rate and manageable toxicity

Mozo, Yasmina; Bueno, David; Sisinni, Luisa; Fernández-Arroyo, Alba; Rosich, Blanca; Pérez‐Martínez, Antonio; Benítez‐Carabante, María Isabel; Alonso, Laura; Uría, María Luz; Heredia, Cristina Díaz de; Mestre-Durán, Carmen; Ferreras, Cristina; Torres, Juan; Losantos, Itsaso; Escudero, Adela; Ruz-Caracuel, Beatriz

doi:10.1080/08880018.2020.1868637

Cited by 22 publications

(29 citation statements)

References 26 publications

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“…A full-text review was sought for assessment if the data were not satisfactorily obtained from the title and abstract. Finally, 19 studies (17 non-RCTs [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] and two RCTs [30,31]) involving a total of 1358 patients met our inclusion criteria were selected. The age of the patients ranged from 0 to 77 years.…”

Section: Resultsmentioning

confidence: 99%

Efficacy and safety of ruxolitinib for steroid-refractory graft-versus-host disease: Systematic review and meta-analysis of randomised and non-randomised studies

et al. 2022

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Background Hematopoietic stem cell transplantation (HSCT) for haematological disorders. Graft-versus-host disease (GVHD), a cause of morbidity and mortality is treated with corticosteroids. However, patients with steroid-refractory GVHD after HSCT have a poor prognosis. Ruxolitinib, a selective Janus kinase inhibitor, is a novel treatment strategy for steroid-refractory GVHD. Objectives To assess the efficacy of ruxolitinib for the treatment of steroid-refractory GVHD and analyse its adverse effects. Study design Meta-analysis. Search methods Randomised controlled trials (RCTs) and non-RCTs of ruxolitinib-based therapy in patients with steroid-refractory GVHD were found in the Cochrane Central Register of Controlled Trials, EMBASE, PubMed, and Web of Science in March 2021. Outcomes included overall response rate, survival, and adverse effects. The Methodological Index for Non-randomised Studies (MINORS) and the Cochrane collaboration risk-of-bias tool were used to assess methodological quality. Funnel plots, Egger’s test, and the trim and fill method were used to assess publication bias. Results In total, 1470 studies were identified; 19 studies (17 non-RCTs, 2 RCTs) involving 1358 patients met our inclusion criteria. Survival rates at the longest follow-up in non-RCTs, were 57.5% (95% CI 46.9–67.4) and 80.3% (95% CI 69.7–87.9) for acute GVHD (aGVHD) and chronic GVHD (cGVHD), respectively. In non-RCTs, the overall response was 74.9% (95% CI 66.6–81.8, I2 = 49%) in aGVHD and 73.1% (95% CI 62.5–81.6, I2 = 49%) in cGVHD. In aGVHD, the response rates were gastrointestinal, 61.4–90.2%; skin, 52.5–80.6%; and liver, 41.8–71.8%. In cGVHD, the response rates were gastrointestinal, 30.1–70.4%; skin, 30.1–84.4%; lung, 27.0–83.0%; and mouth 3.5–98.1%. In addition, a lower aGVHD grade and moderate cGVHD were associated with a better clinical response. Common adverse events were cytopenia and infectious complications. Conclusions Our systematic review and meta-analysis indicated that ruxolitinib therapy could be a potentially effective and safe treatment for patients with steroid-refractory GVHD.

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Section: Resultsmentioning

confidence: 99%

Efficacy and safety of ruxolitinib for steroid-refractory graft-versus-host disease: Systematic review and meta-analysis of randomised and non-randomised studies

et al. 2022

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“…Four patients had treatment failure because of toxicity ( 129 ). In four more-recent studies, better overall response rates of 77–84% and complete response rates of 31–69% were reported ( 130 – 133 ). Adverse events included grade 3 thrombocytopenia and neutropenia, infectious complications, and Epstein-Barr virus post-transplant lymphoproliferative disease ( 130 ).…”

Section: Acute Gvhd Treatmentmentioning

confidence: 98%

Current Prophylaxis and Treatment Approaches for Acute Graft-Versus-Host Disease in Haematopoietic Stem Cell Transplantation for Children With Acute Lymphoblastic Leukaemia

et al. 2022

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Acute graft-versus-host disease (aGvHD) continues to be a leading cause of morbidity and mortality following allogeneic haematopoietic stem cell transplantation (HSCT). However, higher event-free survival (EFS) was observed in patients with acute lymphoblastic leukaemia (ALL) and grade II aGvHD vs. patients with no or grade I GvHD in the randomised, controlled, open-label, international, multicentre Phase III For Omitting Radiation Under Majority age (FORUM) trial. This finding suggests that moderate-severity aGvHD is associated with a graft-versus-leukaemia effect which protects against leukaemia recurrence. In order to optimise the benefits of HSCT for leukaemia patients, reduction of non-relapse mortality—which is predominantly caused by severe GvHD—is of utmost importance. Herein, we review contemporary prophylaxis and treatment options for aGvHD in children with ALL and the key challenges of aGvHD management, focusing on maintaining the graft-versus-leukaemia effect without increasing the severity of GvHD.

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“…Only a few retrospective studies have described the use of ruxolitinib in pediatric chronic GVHD, with small numbers of patients with chronic GVHD of the skin. 4,5 Our patient had complete remission of his severe sclerotic chronic GVHD, although he required a treatment course far longer than the 3 months observed by Mozo et al 5 Ruxolitinib is a promising medication with the potential to effectively treat corticosteroid refractory chronic GVHD of the skin in adolescent patients.…”

Section: Discussionmentioning

confidence: 79%

Ruxolitinib for the treatment of steroid refractory pediatric chronic graft‐versus‐host disease

Belina

Driscoll

Blanchard

et al. 2022

Pediatric Dermatology

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Chronic graft-versus-host disease (cGVHD) of the skin is a serious cause of long-term morbidity and mortality among patients who receive hematopoietic stem cell transplants. Systemic corticosteroids remain first-line treatment for cutaneous cGVHD; however, there is currently no consensus on second-line therapy for steroid-refractory disease. We herein present a case of a pediatric patient with severe cGVHD of the skin, nonresponsive to corticosteroids, who was successfully treated with a prolonged course of ruxolitinib with minimal side effects.

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Ruxolitinib for steroid-refractory graft versus host disease in pediatric HSCT: high response rate and manageable toxicity

Cited by 22 publications

References 26 publications

Efficacy and safety of ruxolitinib for steroid-refractory graft-versus-host disease: Systematic review and meta-analysis of randomised and non-randomised studies

Efficacy and safety of ruxolitinib for steroid-refractory graft-versus-host disease: Systematic review and meta-analysis of randomised and non-randomised studies

Current Prophylaxis and Treatment Approaches for Acute Graft-Versus-Host Disease in Haematopoietic Stem Cell Transplantation for Children With Acute Lymphoblastic Leukaemia

Ruxolitinib for the treatment of steroid refractory pediatric chronic graft‐versus‐host disease

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