Ruxolitinib for the Treatment of Chronic GVHD and Overlap Syndrome in Children and Young Adults

Wang, YunZu Michele; Teusink‐Cross, Ashley; Elborai, Yasser; Krupski, M. Christa; Nelson, Adam; Grimley, Michael; Flannery, Amanda; Mehta, Parinda A.; Bleesing, Jacob; Chandra, Sharat; Kumar, Ashish; Myers, Kasiani C.; Davies, Stella M.; Khandelwal, Pooja

doi:10.1097/tp.0000000000003768

Cited by 12 publications

(17 citation statements)

References 20 publications

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“…There was no significant association between GvHD and severity of GvHD with form of HSCT, matched or mismatched donors ( P = 0.442). Both eltrombopag and ruxolitinib have been applied among post‐HSCT patients with refractory cytopenia or GvHD in our cohort in recent years, which will lead to improved outcomes 35,36 …”

Section: Discussionmentioning

confidence: 99%

Clinical outcome of infantile‐onset inflammatory bowel disease in 102 patients with interleukin‐10 signalling deficiency

Lai

Miao

et al. 2022

Aliment Pharmacol Ther

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Background: Infantile-onset inflammatory bowel disease can be caused by defects in interleukin-10 signalling. The natural history and clinical outcomes of allogeneic haematopoietic stem cell transplantation, medical treatment and surgery have not been thoroughly described.Aims: This study evaluates disease progression and clinical outcome in patients with interleukin-10 signalling deficiency.Methods: One hundred and nine patients with interleukin-10 signalling deficiency were retrospectively reviewed from a single tertiary centre. The Kaplan-Meier method was applied to calculate probabilities of survival and interval between transplant and stoma closure.Results: One hundred and nine patients were reviewed, and 102 patients were included in the survival analysis. One hundred and eight patients were identified with IL10RA mutations, and one patient harboured IL10RB mutation. Seventy-three patients received haematopoietic stem cell transplantation. The overall survival after transplantation was 64.2% (95% confidence interval, 52.8 to 75.6), and without transplantation, it was 47.5% (95% confidence interval, 14.8 to 80.2, P = 0.47). The median timeframe between transplant and stoma closure was 19.6 months. The probability of survival was significantly lower in patients with perforation (P < 0.001), ileus (P = 0.038) and without thalidomide treatment (P < 0.001) among patients who did not receive haematopoietic stem cell transplantation. The survival probability was not associated with timeframe between transplant and onset, graft source and genotypes. Conclusions:The survival probability was not significantly different between patients with transplantation and the non-transplanted patients.

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Section: Discussionmentioning

confidence: 99%

Clinical outcome of infantile‐onset inflammatory bowel disease in 102 patients with interleukin‐10 signalling deficiency

Lai

Miao

et al. 2022

Aliment Pharmacol Ther

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“…Most of them were studied in retrospective analyses or small groups of patients, and there are very few prospective clinical trials regarding paediatric populations with cGvHD. Paediatric data on the use of immunosuppressive and immunomodulating drugs in the treatment of cGvHD are summarised in Table 6 (62,119,120,124,126,130,133,136,.…”

Section: Second-and Late-line Therapy For Cgvhdmentioning

confidence: 99%

Management of Chronic Graft-vs.-Host Disease in Children and Adolescents With ALL: Present Status and Model for a Personalised Management Plan

Sobkowiak-Sobierajska

Lindemans

Sýkora

et al. 2022

Front. Pediatr.

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Herein we review current practice regarding the management of chronic graft-vs.-host disease (cGvHD) in paediatric patients after allogeneic haematopoietic stem cell transplantation (HSCT) for acute lymphoblastic leukaemia (ALL). Topics covered include: (i) the epidemiology of cGvHD; (ii) an overview of advances in our understanding cGvHD pathogenesis; (iii) current knowledge regarding risk factors for cGvHD and prevention strategies complemented by biomarkers; (iii) the paediatric aspects of the 2014 National Institutes for Health-defined diagnosis and grading of cGvHD; and (iv) current options for cGvHD treatment. We cover topical therapy and newly approved tyrosine kinase inhibitors, emphasising the use of immunomodulatory approaches in the context of the delicate counterbalance between immunosuppression and immune reconstitution as well as risks of relapse and infectious complications. We examine real-world approaches of response assessment and tapering schedules of treatment. Furthermore, we report on the optimal timepoints for therapeutic interventions and changes in relation to immune reconstitution and risk of relapse/infection. Additionally, we review the different options for anti-infectious prophylaxis. Finally, we put forth a theory of a holistic view of paediatric cGvHD and its associated manifestations and propose a checklist for individualised risk evaluation with aggregated considerations including site-specific cGvHD evaluation with attention to each individual's GvHD history, previous medical history, comorbidities, and personal tolerance and psychosocial circumstances. To complement this checklist, we present a treatment algorithm using representative patients to inform the personalised management plans for patients with cGvHD after HSCT for ALL who are at high risk of relapse.

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“…Studies have been published reporting 59%-68% overall response rate with a tolerable safety profile (80,82). Most common toxicities included reactivation thrombocytopenia and anemia; some studies have reported increased CMV reactivation, though this is not consistently demonstrated across all studies (80)(81)(82)(83). However, these studies evaluated those 12 years of age or older; studies evaluating effectiveness/dosing in children younger than 12 and dosing are ongoing (81,83).…”

Section: Bronchiolitis Obliteransmentioning

confidence: 99%

“…Most common toxicities included reactivation thrombocytopenia and anemia; some studies have reported increased CMV reactivation, though this is not consistently demonstrated across all studies (80)(81)(82)(83). However, these studies evaluated those 12 years of age or older; studies evaluating effectiveness/dosing in children younger than 12 and dosing are ongoing (81,83). Other agents that are currently under investigation include belumosudil and ibrutinib, though further investigation is needed for use in pediatrics (84,85).…”

Section: Bronchiolitis Obliteransmentioning

confidence: 99%

Pulmonary Complications After Pediatric Stem Cell Transplant

et al. 2021

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The number of disorders that benefit from hematopoietic stem cell transplantation (HSCT) has increased, causing the overall number of HSCT to increase accordingly. Disorders treated by HSCT include malignancy, benign hematologic disorders, bone marrow failure syndromes, and certain genetic diagnoses. Thus, understanding the complications, diagnostic workup of complications, and subsequent treatments has become increasingly important. One such category of complications includes the pulmonary system. While the overall incidence of pulmonary complications has decreased, the morbidity and mortality of these complications remain high. Therefore, having a clear differential diagnosis and diagnostic workup is imperative. Pulmonary complications can be subdivided by time of onset and whether the complication is infectious or non-infectious. While most infectious complications have clear diagnostic criteria and treatment courses, the non-infectious complications are more varied and not always well understood. This review article discusses pulmonary complications of HSCT recipients and outlines current knowledge, gaps in knowledge, and current treatment of each complication. This article includes some adult studies, as there is a significant paucity of pediatric data.

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Ruxolitinib for the Treatment of Chronic GVHD and Overlap Syndrome in Children and Young Adults

Abstract: Supplemental Digital Content is available in the text.

Cited by 12 publications

References 20 publications

Clinical outcome of infantile‐onset inflammatory bowel disease in 102 patients with interleukin‐10 signalling deficiency

Clinical outcome of infantile‐onset inflammatory bowel disease in 102 patients with interleukin‐10 signalling deficiency

Management of Chronic Graft-vs.-Host Disease in Children and Adolescents With ALL: Present Status and Model for a Personalised Management Plan

Pulmonary Complications After Pediatric Stem Cell Transplant

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