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The New England Journal of Medicine Jul 2021Chronic graft-versus-host disease (GVHD), a major complication of allogeneic stem-cell transplantation, becomes glucocorticoid-refractory or glucocorticoid-dependent in... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Chronic graft-versus-host disease (GVHD), a major complication of allogeneic stem-cell transplantation, becomes glucocorticoid-refractory or glucocorticoid-dependent in approximately 50% of patients. Robust data from phase 3 randomized studies evaluating second-line therapy for chronic GVHD are lacking. In retrospective surveys, ruxolitinib, a Janus kinase (JAK1-JAK2) inhibitor, showed potential efficacy in patients with glucocorticoid-refractory or -dependent chronic GVHD.
METHODS
This phase 3 open-label, randomized trial evaluated the efficacy and safety of ruxolitinib at a dose of 10 mg twice daily, as compared with the investigator's choice of therapy from a list of 10 commonly used options considered best available care (control), in patients 12 years of age or older with moderate or severe glucocorticoid-refractory or -dependent chronic GVHD. The primary end point was overall response (complete or partial response) at week 24; key secondary end points were failure-free survival and improved score on the modified Lee Symptom Scale at week 24.
RESULTS
A total of 329 patients underwent randomization; 165 patients were assigned to receive ruxolitinib and 164 patients to receive control therapy. Overall response at week 24 was greater in the ruxolitinib group than in the control group (49.7% vs. 25.6%; odds ratio, 2.99; P<0.001). Ruxolitinib led to longer median failure-free survival than control (>18.6 months vs. 5.7 months; hazard ratio, 0.37; P<0.001) and higher symptom response (24.2% vs. 11.0%; odds ratio, 2.62; P = 0.001). The most common (occurring in ≥10% patients) adverse events of grade 3 or higher up to week 24 were thrombocytopenia (15.2% in the ruxolitinib group and 10.1% in the control group) and anemia (12.7% and 7.6%, respectively). The incidence of cytomegalovirus infections and reactivations was similar in the two groups.
CONCLUSIONS
Among patients with glucocorticoid-refractory or -dependent chronic GVHD, ruxolitinib led to significantly greater overall response, failure-free survival, and symptom response. The incidence of thrombocytopenia and anemia was greater with ruxolitinib. (Funded by Novartis and Incyte; REACH3 ClinicalTrials.gov number, NCT03112603.).
Topics: Adolescent; Adult; Aged; Child; Cytomegalovirus Infections; Female; Glucocorticoids; Graft vs Host Disease; Humans; Immunologic Factors; Janus Kinases; Male; Middle Aged; Nitriles; Photopheresis; Pyrazoles; Pyrimidines; Survival Analysis; Thrombocytopenia; Treatment Failure; Young Adult
PubMed: 34260836
DOI: 10.1056/NEJMoa2033122 -
Leukemia Nov 2022Patients with steroid-refractory graft-versus-host disease (GvHD) are known to have a poor prognosis and for decades no approved drug has been available to treat this... (Review)
Review
Patients with steroid-refractory graft-versus-host disease (GvHD) are known to have a poor prognosis and for decades no approved drug has been available to treat this serious condition. Although ruxolitinib, a selective Janus kinase (JAK)1/2 inhibitor demonstrated significantly higher response rates in randomized trials compared to the best available therapy, and thus, is of benefit in both acute as well as chronic GvHD, there is an urgent medical need to improve results, such as durability of responses, response in eye, liver and lung manifestations and reduction of infectious complications. In this "Review" article we would like to offer strategies for improving treatment results in patients with steroid-refractory GvHD by combining ruxolitinib with extracorporeal photopheresis (ECP), a leukapheresis-based immunomodulatory treatment frequently applied in T-cell mediated immune disease including GvHD. Our article explores key published evidence supporting the clinical efficacy of both ruxolitinib and ECP in the treatment of GvHD and highlights their potentially complementary mechanisms of action.
Topics: Humans; Photopheresis; Graft vs Host Disease; Chronic Disease; Steroids; Acute Disease
PubMed: 36153436
DOI: 10.1038/s41375-022-01701-2 -
Transfusion and Apheresis Science :... Jun 2018
Topics: Adolescent; Adult; Artificial Intelligence; Child; Child, Preschool; Erythrocyte Transfusion; Female; Graft vs Host Disease; Hematopoietic Stem Cells; Humans; Hyperbilirubinemia; Infant; Male; Photopheresis; Transfusion Reaction; Young Adult
PubMed: 29793819
DOI: 10.1016/j.transci.2018.05.003 -
Transfusion Medicine and Hemotherapy :... Jun 2020Extracorporeal photopheresis (ECP) is a leukapheresis-based procedure used in the therapy of acute and chronic graft-versus-host disease (aGvHD, cGvHD) and other... (Review)
Review
BACKGROUND AND SUMMARY
Extracorporeal photopheresis (ECP) is a leukapheresis-based procedure used in the therapy of acute and chronic graft-versus-host disease (aGvHD, cGvHD) and other diseases. Based on the substantial efficacy and the excellent safety profile in the absence of immunosuppression ECP has established itself as a major treatment form for steroid-refractory GvHD. Here we review the current literature on ECP as a treatment option for patients with aGvHD as well as cGvHD.
KEY MESSAGES
ECP is a well-established second-line therapy for cGvHD. Its role in the treatment of aGvHD is less clear but also points towards an effective second-line therapy option. In the future ECP could play a role in the prevention of GvHD. More experimental and randomized controlled trials are needed to define the best patient selection criteria, settings, and therapy regimens for GvHD.
PubMed: 32595426
DOI: 10.1159/000508169 -
Transplantation and Cellular Therapy Sep 2023Graft-versus-host disease (GVHD) is a major cause of mortality and morbidity following allogeneic hematopoietic stem cell transplantation. Extracorporeal photopheresis... (Review)
Review
Graft-versus-host disease (GVHD) is a major cause of mortality and morbidity following allogeneic hematopoietic stem cell transplantation. Extracorporeal photopheresis (ECP), which exposes mononuclear cells to ultraviolet A irradiation in the presence of a photosensitizing agent, has shown efficacy in the treatment of GVHD. Recent observations in molecular and cell biology have revealed the mechanisms by which ECP can reverse GVHD, including lymphocyte apoptosis, differentiation of dendritic cells from circulating monocytes, and modification of the cytokine profile and T cell subpopulations. Technical innovations have made ECP accessible to a broader range of patients; however, logistical constraints may limit its use. In this review, we scrutinize the development of ECP from its origins to recent insights into the biology underlying ECP efficacy. We also review practical aspects that may complicate successful ECP treatment. Finally, we analyze how these theoretical concepts translate into clinical practice, summarizing the published experiences of leading research groups worldwide.
Topics: Humans; Photopheresis; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Monocytes; Transplantation, Homologous
PubMed: 37419324
DOI: 10.1016/j.jtct.2023.07.001 -
Revue Medicale Suisse Mar 2018During the treatment of extracorporeal photopheresis (ECP), white blood cells are collected by apheresis and exposed to ultraviolet A after incubation with...
During the treatment of extracorporeal photopheresis (ECP), white blood cells are collected by apheresis and exposed to ultraviolet A after incubation with 8-methoxypsoralen. Although ECP was first developed for cutaneous T cell lymphoma, it has shown promising efficacy in a number of other serious conditions, like acute and chronic graft-versus-host disease, lung and cardiac transplant rejection and other autoimmune diseases. The ECP has been used for thirty years in some specialized centers but remains unknown to most of the physicians. The aim of this article is to review the practical aspects, the mode of action and the current indications of ECP.
Topics: Autoimmune Diseases; Graft vs Host Disease; Humans; Lymphoma, T-Cell, Cutaneous; Photopheresis
PubMed: 29589657
DOI: No ID Found -
Der Hautarzt; Zeitschrift Fur... Feb 2018Graft-versus-host disease (GvHD) is a complex multiorgan disease, which can occur as a complication following allogeneic stem cell transplantation. Involvement of the... (Review)
Review
BACKGROUND
Graft-versus-host disease (GvHD) is a complex multiorgan disease, which can occur as a complication following allogeneic stem cell transplantation. Involvement of the skin represents the most common appearance of GvHD. The role of the dermatologist is critical for diagnosis and initiation of treatment.
OBJECTIVES
The aim of this article is to provide a comprehensive review of the cutaneous types of GvHD and to present the most recent data on diverse therapy options for its acute and chronic form allowing the clinician to establish a definite diagnosis and to initiate proper therapy.
MATERIALS AND METHODS
Possible clinical appearances and recommended criteria to assist in making the right diagnosis are presented by means of expert recommendations.
RESULTS AND CONCLUSION
GvHD is still a complex entity whose diagnosis is often associated with challenges due to its variable presentation. Proper diagnosis and subsequent therapy is paramount for the optimal clinical outcome.
Topics: Allografts; Diagnosis, Differential; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Interdisciplinary Communication; Intersectoral Collaboration; Photopheresis; Skin Diseases
PubMed: 29344728
DOI: 10.1007/s00105-017-4112-3 -
Clinical Case Reports Jul 2017Nephrogenic systemic fibrosis (NSF) is a fibrosing disorder seen in patients with renal dysfunction, commonly precipitated by administration of gadolinium contrast....
Nephrogenic systemic fibrosis (NSF) is a fibrosing disorder seen in patients with renal dysfunction, commonly precipitated by administration of gadolinium contrast. There is no consistently successful treatment, but oral steroids, topical dovonex, extracorporeal photopheresis, and plasmapheresis have been tried [http://www.icnfdr.org/ Last accessed: 1/6/2017]. Avoidance of gadolinium in such patients is the key to prevention.
PubMed: 28680623
DOI: 10.1002/ccr3.993