Infliximab for GVHD therapy in children

Sleight, B.; Chan, Kin‐Sang; Braun, Thomas; Serrano, Amy; Gilman, Andrew L.

doi:10.1038/sj.bmt.1705761

Cited by 49 publications

(53 citation statements)

References 32 publications

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“…In a study of 13 patients with acute GVHD, etanercept was shown to induce responses in 6 patients with maximal benefit seen in patients with GVHD of the gastrointestinal tract [99]. Other small studies have also shown benefit of TNFα inhibitors in treatment of aGVHD [100][101][102]. Combination therapy has shown to be effective as well.…”

Section: Anti-tnfα Agentsmentioning

confidence: 99%

State-of-the-art acute and chronic GVHD treatment

Jamil

Mineishi

2015

Int J Hematol

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owing to the advancement in reduced intensity conditioning (RIC) and in patients without HLA-matched donors due to the use of cord blood and haploidentical HSCT [4][5][6]. Although marked improvement has been made in supportive care, immunosuppressive therapy and DNA-based Human Leukocyte Antigen (HLA) typing, graft vs host disease (GVHD) remains a major cause of morbidity and non-relapse mortality among allogeneic HSCT recipients. It was first described by Billingham in 1966 as a syndrome where immunocompetent T cells from the donor recognize and damage the host tissue in an immunocompromised recipient. It presents with heterogeneous symptoms involving multiple organ systems including gastrointestinal tract, skin, mucosa, liver and lungs [7]. In the past clinical features occurring within 100 days after HSCT was called acute GVHD (aGVHD) and those happening after 100 days were labeled chronic GVHD (cGVHD) [8,9]. This definition was rather unsatisfactory thus National Institute of Health (NIH) consensus criteria were developed and have been revised. The criteria have added new categories such as late-onset aGVHD (acute GVHD occurring after 100 days) and overlap syndrome which includes features of both acute and chronic GVHD to the classification, and also have introduced new definitions for organ system involvement [10][11][12]. The categorization of acute vs chronic GVHD is based on the combination of clinical symptoms rather than the time of onset. Depending upon a number of variables associated with patients, donors, and types of transplant, the incidence of aGVHD varies with incidence of grade II-IV GVHD at 40 % in matched related donor (MRD) transplant to 50 % in MUD transplant. The main risk factors for aGVHD include degree of HLA mismatch, age of the patient, previous all immunization of the donor and the kind of GVHD prophylaxis used. About 30-70 % of allogeneic HSCT recipients alive after 100 days will Abstract Graft-versus-host disease (GVHD) remains as the major obstacle for successful hematopoietic stem cell transplant (HSCT). Roughly half of the patients undergoing HSCT develop GVHD which requires treatment, and above 10 % of the patient may die because of it. However, GVHD presents with anti-tumor activity, called graft-versus-tumor (GVT) effect, and it carries significant anti-tumor activity, thus suppressing GVHD completely may increase the relapse of original disease. Thus, it is important to control GVHD to the appropriate level.

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Section: Anti-tnfα Agentsmentioning

confidence: 99%

State-of-the-art acute and chronic GVHD treatment

Jamil

Mineishi

2015

Int J Hematol

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“…Recurrences were typical after steroid taper and/or infliximab discontinuation, as only two patients were able to maintain long-term responses. 29 As with other agents, infection remained to be a significant cause of mortality. Although retrospective, these data suggest that infliximab may have a role in controlling GVHD, but the high rate of GVHD relapse suggests that this type of therapy may not be sufficiently targeting the cause of GVHD, rather simply one of its mediators.…”

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confidence: 99%

Acute graft-versus-host disease in children

Jacobsohn

2007

Bone Marrow Transplant

118

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Acute graft-versus-host disease (GVHD) is one of the major complications of hematopoietic stem cell transplantation. Many variables including stem cell source, age of donor and recipient, preparative regimen and prophylaxis can impact the likelihood and severity of GVHD. The major portion of this review concentrates on risk factors, treatment and outcome, since here we may see differences between children and adults. Pathophysiology and manifestations/grading of acute GVHD are also briefly presented. An effort has been made to concentrate either on pediatric trials or look specifically at the pediatric subset of larger studies.

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“…The role of pro-inflammatory cytokines e.g. TNF-α in immunological post-transplant complication is well documented and anti-TNF therapy is one of the possibilities of second-line GvHD therapy [18]. In a clinical study, anti-inflammatory cytokine IL-10 spontaneous production in unrelated bone marrow transplant recipients was reported to be associated with fever, transplant-related complications and early deaths [19].…”

Section: Discussionmentioning

confidence: 99%

Immunomodulatory effect of mesenchymal stem cells may depend on secretion of IL-2 and IL-10 and inhibition of TNF-α in pediatric hematopoietic stem cell donors and recipients

Drabko¹,

Winnicka²,

Bojarska‐Junak³

et al. 2013

cejoi

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In the study we aimed to estimate the number of functional MSCs by performing colony-forming unit-fibroblast (CFU-F) cultures from pediatric hematopoietic stem cell transplantation recipients and their healthy donors. Secondly we compared the concentration of cytokines interleukin 2 (IL-2), IL-4, IL-10 and tumor necrosis factor α (TNF-α) in stem cell serum and in supernatant of mesenchymal stem cell cultures. We included into the study 19 consecutive pairs of donors and recipients of allogeneic stem cell transplantation from one pediatric bone marrow transplantation center. Cultures of mesenchymal stem cells were performed according to the research protocol for enumeration of human mesenchymal progenitor cells using the CFU-F assay and the expansion of human mesenchymal cells in vitro (StemCell Technologies, USA). Interleukin 10 and TNF-α concentration were measured by high sensitivity (Quanikine HS) human immunoassay (R&D and Bender, USA). Interleukin 2 and IL-4 concentration were assessed by human IL-2 ELISA Version 2 assay (Bender MedSystems, Austria). The number of CFU-F colonies in cultures increased

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Infliximab for GVHD therapy in children

Cited by 49 publications

References 32 publications

State-of-the-art acute and chronic GVHD treatment

State-of-the-art acute and chronic GVHD treatment

Acute graft-versus-host disease in children

Immunomodulatory effect of mesenchymal stem cells may depend on secretion of IL-2 and IL-10 and inhibition of TNF-α in pediatric hematopoietic stem cell donors and recipients

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