Ruxolitinib, a JAK1/JAK2 Selective Inhibitor, Ameliorates Acute and Chronic Steroid-Refractory Gvhd Mouse Models

Huarte, Eduardo; Peel, Michael T.; Juvekar, Ashish; Dubé, Philip E.; Sarah, Sarala; Stephens, Lynn; Stewart, Becky; Long, Brian; Czerniak, Philip M.; Oliver, Jean; Smith, Paul A.

doi:10.2217/imt-2021-0013

Cited by 4 publications

(3 citation statements)

References 38 publications

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“…The JAK1/2 signaling plays an important role in the mechasims of GVHD through mediating the activation and proinflammatoy cytokines release of T cell, neutrophils and dendritic cells (DCs) ( 40 , 41 ). Preclinical studies suggested that ruxolitinib can effectively inhibit JAK1/2 signaling, and ameliorate both acute and chronic GVHD while preserving graft-versus-tumor activity ( 42 , 43 ). For patients with steroid-refractory aGVHD, ruxolitinib orally given at a dose of 5–10 mg achieved a ORR at day 28 of 55–82% with acceptable toxicity ( 24 , 44 , 45 ).…”

Section: Discussionmentioning

confidence: 99%

Second-line therapy for patients with steroid-refractory aGVHD: systematic review and meta-analysis of randomized controlled trials

Luo,

Huang,

Wei

et al. 2023

Front. Immunol.

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ObjectiveSteroids-refractory (SR) acute graft-versus-host disease (aGVHD) is a life-threatening condition in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT), but the optimal second-line therapy still has not been established. We aimed to perform a systematic review and meta-analysis of randomized controlled trials (RCTs) to compare the efficacy and safety of different second-line therapy regimens.MethodsLiterature search in MEDLINE, Embase, Cochrane Library and China Biology Medicine databases were performed to retrieve RCTs comparing the efficacy and safety of different therapy regimens for patients with SR aGVHD. Meta-analysis was conducted with Review Manager version 5.3. The primary outcome is the overall response rate (ORR) at day 28. Pooled relative risk (RR) and 95% confidence interval (CI) were calculated with the Mantel-Haenszel method.ResultsEight eligible RCTs were included, involving 1127 patients with SR aGVHD and a broad range of second-line therapy regimens. Meta-analysis of 3 trials investigating the effects of adding mesenchymal stroma cells (MSCs) to other second-line therapy regimens suggested that the addition of MSCs is associated with significantly improvement in ORR at day 28 (RR = 1.15, 95% CI = 1.01–1.32, P = 0.04), especially in patients with severe (grade III–IV or grade C–D) aGVHD (RR = 1.26, 95% CI = 1.04–1.52, P = 0.02) and patients with multiorgan involved (RR = 1.27, 95% CI = 1.05–1.55, P = 0.01). No significant difference was observed betwwen the MSCs group and control group in consideration of overall survival and serious adverse events. Treatment outcomes of the other trials were comprehensively reviewed, ruxolitinib showed significantly higher ORR and complete response rate at day 28, higher durable overall response at day 56 and longer failure-free survival in comparison with other regimens; inolimomab shows similar 1-year therapy success rate but superior long-term overall survial in comparison with anti-thymocyte globulin, other comparisons did not show significant differences in efficacy.ConclusionsAdding MSCs to other second-line therapy regimens is associated with significantly improved ORR, ruxolitinib showed significantly better efficacy outcomes in comparison with other regimens in patients with SR aGVHD. Further well-designed RCTs and integrated studies are required to determine the optimal treatment.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022342487.

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Section: Discussionmentioning

confidence: 99%

Second-line therapy for patients with steroid-refractory aGVHD: systematic review and meta-analysis of randomized controlled trials

Luo,

Huang,

Wei

et al. 2023

Front. Immunol.

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“…There are limited studies on ruxolitinib among those with SCD. Studies are showing promising results for ruxolitinib among those undergoing HSCT that encounter steroid refractory graft-versus host disease [34]. Still, these findings are limited among those with SCD and often include younger populations.…”

Section: Scdmentioning

confidence: 99%

A Rare Blood Malignancy in a Genetic Hematological Disorder: Polycythemia Vera (PV) in Sickle Cell Disease (SCD)

Edwards,

Scott,

Boggan

et al. 2023

J Clin Haematol

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Objective: To delineate the etiology, symptomatology, and treatment of Polycythemia Vera in adults with Sickle Cell Disease. The current review contains a review of the 4 case reports that we found on the topic. To our knowledge, no other case reports exist. Methods: We reviewed the scientific literature to discover case reports that included the topic of PV. We noted consistencies in presentation, evaluation, treatment, and clinical outcomes. Results: We reviewed 4 case reports and a limited number of clinical papers on PV in SCD. We found and reported on consistencies in clinical presentation and the diversity of treatments. We reported hematological, bone marrow, and radiographic findings. Conclusions: There is great variability in the evaluation and treatment of cases of PV in SCD. We advocate for more research and deconstructing the complicated relationship between these two comorbid disorders.

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“…Ab, antibody; BTK, Bruton’s Tyrosine Kinase; CAR Treg, chimeric antigen receptor T regulatory cell; ECP, extracorporeal photopheresis; FoxP3, forkhead box P3; H-Y Ab, antibodies specific for male (Y) antigens; MCP-1, monocyte chemoattractant protein-1; iNKT, invariant NK T cells; ROCK2, Rho associated coiled-coil containing protein kinase 2; sBAFF, soluble B-cell activating factor; SYK, spleen sssociated tyrosine kinase; TNF-α, tumor necrosis factor alpha. Reference citations used: 5 , 7 , 20 , 21 , 22 , 25 , 27 , 33 , 39 , 43 , 45 , 48 , 53 , 55 , 57 , 58 , 63 , 64 , 72 , 74 , 75 , 96 , 99 , 182 , 183 , 184 , 185 , 186 , 187 , 188 , 189 , 190 , 191 , 192 , 193 , 194 , 195 , 196 , 197 , 198 , 199 , 200 , 201 , 202 , 203 , 204 , 205 , 206 , 207 , 208 , 209 , 210 , 211 , …”

Section: Introductionmentioning

confidence: 99%

Chronic GvHD NIH Consensus Project Biology Task Force: evolving path to personalized treatment of chronic GvHD

et al. 2023

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Chronic GvHD (cGvHD) remains a prominent barrier to allogeneic hematopoietic stem cell transplantion as the leading cause of non-relapse mortality and significant morbidity. Tremendous progress has been achieved in both understanding of pathophysiology and the development of new therapies for cGvHD. While our field has historically approached treatment from an empiric position, research performed at the bedside and bench has elucidated some of the complex pathophysiology of cGvHD. From the clinical perspective, there is significant variability of disease manifestations between individual patients, pointing to diverse biological underpinnings. Capitalizing on progress made to date, the field is now focused on establishing personalized treatment approaches. The manuscript's intent is to concisely review recent knowledge gained and formulate a path towards patient-specific cGvHD therapy.

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Ruxolitinib, a JAK1/JAK2 Selective Inhibitor, Ameliorates Acute and Chronic Steroid-Refractory Gvhd Mouse Models

Cited by 4 publications

References 38 publications

Second-line therapy for patients with steroid-refractory aGVHD: systematic review and meta-analysis of randomized controlled trials

Second-line therapy for patients with steroid-refractory aGVHD: systematic review and meta-analysis of randomized controlled trials

A Rare Blood Malignancy in a Genetic Hematological Disorder: Polycythemia Vera (PV) in Sickle Cell Disease (SCD)

Chronic GvHD NIH Consensus Project Biology Task Force: evolving path to personalized treatment of chronic GvHD

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