Extracorporeal Photopheresis for Steroid Resistant Graft Versus Host Disease in Pediatric Patients

Berger, Massimo; Pessolano, Rosanna; Albiani, Roberto; Sebastian, Asaftei Dorin; Barat, Veronica; Carraro, Francesca; Biasin, Eleonora; Madon, E; Fagioli, Franca

doi:10.1097/mph.0b013e31814d66f5

Cited by 50 publications

(14 citation statements)

References 24 publications

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“…A phase II study of steroidrefractory GVHD showed complete response rates of 60% with overall survival of 59% at 4 years [125]. These data are similar to other studies which have demonstrated complete response rates between 52% and 83% [126–128]. …”

Section: Acute Gvhdsupporting

confidence: 79%

Pathogenesis and Management of Graft-versus-Host Disease

Choi

Levine

Ferrara

2010

Immunology and Allergy Clinics of North America

166

138

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Synopsis Allogeneic hematopoietic cell transplantation (HCT) is an important therapeutic option for a variety of malignant and nonmalignant conditions. As the number of allogeneic HCT continues to increase, greater attention to improvements in supportive care, infectious prophylaxis, immunosuppressive medications and DNA-based tissue typing are continuously being made. However, graft versus host disease (GVHD) remains the most frequent and serious complication following allogeneic HCT and limits the broader application of this important therapy. Recent advances in the understanding of the pathogenesis of GVHD have led to new approaches to its management, including utilizing its role in preserving the graft versus leukemia effect following allogeneic transplant. Here we review the important elements in the complex immunological interactions involving cytokine networks, chemokine gradients and the direct mediators of cellular cytotoxicity that cause clinical GVHD, and discuss the risk factors and strategies for management of GVHD.

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Section: Acute Gvhdsupporting

confidence: 79%

Pathogenesis and Management of Graft-versus-Host Disease

Choi

Levine

Ferrara

2010

Immunology and Allergy Clinics of North America

166

138

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“…Perrotti et al [23] reported that 6 of 8 patients with GI cGVHD responded to ECP, in contrast to Berger et al's report where all 3 patients showed a response [7]. Our meta-analysis indicates a modest response with a half of GI SR-cGVHD patients responding to ECP.…”

Section: Discussioncontrasting

confidence: 48%

“…Kharfan-Dabaja et al [5] conducted a systematic review to evaluate the efficacy of rituximab in SR-cGVHD and reported a pooled proportion overall response rate (ORR) of 0.66 (95% confidence interval [CI], 0.57-0.74). Among the non-pharmacologic modalities, extracorporeal photopheresis (ECP) has acceptable response rates (RR) in both cutaneous and systematic manifestations of cGVHD [6, 7, 8, 9, 10, 11, 12]. In 2010, the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) launched the largest intervention study (BMT CTN #0801) in cGVHD; a phase II/III trial to compare various treatments including ECP.…”

Section: Introductionmentioning

confidence: 99%

Extracorporeal photopheresis for chronic graft-versus-host disease: a systematic review and meta-analysis

et al. 2014

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BackgroundThe safety of extracorporeal photopheresis (ECP) in steroid-refractory chronic graft-versus-host disease (SR-cGVHD) has been explored in multiple studies but reported response rates (RR) vary significantly across studies.MethodsWe conducted a meta-analysis to assess the efficacy of ECP for SR-cGVHD. A search of electronic databases for studies published between 1984 and 2012 was conducted. End points included RR: complete response (CR), overall response rates (ORR), and organ-specific RR. The initial search generated 312 studies, of which 18 met the selection criteria (N=595). A random effects model was used for pooled rates.ResultsPooled CR rates and ORR were 29% (confidence interval [CI], 19-42%) and 64% (CI, 65-82%), respectively. One-year overall survival was available for 4 studies only and was 49% (CI, 29-70%). The pooled RR for skin, liver, ocular, oral, lung, gastrointestinal and musculoskeletal SR-cGVHD was 74%, 68%, 60%, 72%, 48%, 53%, and 64%, respectively. There was a significant heterogeneity among studies due to differences in ECP schedules and duration. No significant differences in responses to ECP for pediatric and adult populations were found. Sensitivity analysis could not be undertaken due to a limited number of prospective studies.ConclusionECP is an effective therapy for oral, skin, and liver SR-cGVHD, with modest activity in lung and gastrointestinal SR-cGVHD.

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“…The clinical efficacy, safety, and tolerability of ECP in the treatment of aGvHD in patients have been demonstrated in several studies, which also show the steroid-sparing effect (82–85). A systematic analysis of prospective studies examining ECP treatment outcomes in corticosteroids refractory/dependent/intolerant aGvHD in adults and children found an overall response rate of almost 70% in all organs, an encouraging result compared to other second-line treatments used (86).…”

Section: Extracorporeal Photopheresis (Ecp)mentioning

confidence: 95%

Treatment of Pediatric Acute Graft-versus-Host Disease—Lessons from Primary Immunodeficiency?

Flinn

Gennery

2017

Front. Immunol.

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Allogeneic hematopoietic stem cell transplant (HSCT) is used to treat increasing numbers of malignant and non-malignant disorders. Despite significant advances in improved human leukocyte antigens-typing techniques, less toxic conditioning regimens and better supportive care, resulting in improved clinical outcomes, acute graft-versus-host disease (aGvHD) continues to be a major obstacle and, although it principally involves the skin, gastrointestinal tract, and liver, the thymus is also a primary target. An important aim following HSCT is to achieve complete and durable immunoreconstitution with a diverse T-cell receptor (TCR) repertoire to recognize a broad range of pathogens providing adequate long-term adaptive T-lymphocyte immunity, essential to reduce the risk of infection, disease relapse, and secondary malignancies. Reconstitution of adaptive T-lymphocyte immunity is a lengthy and complex process which requires a functioning and structurally intact thymus responsible for the production of new naïve T-lymphocytes with a broad TCR repertoire. Damage to the thymic microenvironment, secondary to aGvHD and the effect of corticosteroid treatment, disturbs normal signaling required for thymocyte development, resulting in impaired T-lymphopoiesis and reduced thymic export. Primary immunodeficiencies, in which failure of central or peripheral tolerance is a major feature, because of intrinsic defects in hematopoietic stem cells leading to abnormal T-lymphocyte development, or defects in thymic stroma, can give insights into critical processes important for recovery from aGvHD. Extracorporeal photopheresis is a potential alternative therapy for aGvHD, which acts in an immunomodulatory fashion, through the generation of regulatory T-lymphocytes (Tregs), alteration of cytokine patterns and modulation of dendritic cells. Promoting normal central and peripheral immune tolerance, with selective downregulation of immune stimulation, could reduce aGvHD, and enable a reduction in other immunosuppression, facilitating thymic recovery, restoration of normal T-lymphocyte ontogeny, and complete immunoreconstitution with improved clinical outcome as the ability to fight infections improves and risk of secondary malignancy or relapse diminishes.

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Extracorporeal Photopheresis for Steroid Resistant Graft Versus Host Disease in Pediatric Patients

Cited by 50 publications

References 24 publications

Pathogenesis and Management of Graft-versus-Host Disease

Pathogenesis and Management of Graft-versus-Host Disease

Extracorporeal photopheresis for chronic graft-versus-host disease: a systematic review and meta-analysis

Treatment of Pediatric Acute Graft-versus-Host Disease—Lessons from Primary Immunodeficiency?

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