Etanercept plus methylprednisolone as initial therapy for acute graft-versus-host disease

Levine, John E.; Paczesny, Sophie; Mineishi, Shin; Braun, Thomas; Choi, Sung W.; Hutchinson, Raymond J.; Jones, David B.; Khaled, Yasser; Kitko, Carrie L.; Bickley, Daniel; Krijanovski, Oleg I.; Reddy, Pavan; Yanik, Gregory A.; Ferrara, James L.M.

doi:10.1182/blood-2007-09-112987

Cited by 175 publications

(124 citation statements)

References 27 publications

(26 reference statements)

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“…Dac was chosen because at the time of the study there were no other Table 2 Clinical response according to the grade of aGVHD in each organ at day +30 from treatment Grade I 1 1 0 0 1 1 0 0 3 1 2 0 Grade II 1 1 0 0 1 1 0 0 2 0 1 1 Grade III 6 6 0 0 2 2 0 0 3 0 2 1 Grade IV 4 4 0 0 6 1 3 2 1 0 0 1 Total 12 MoAbs with the same characteristics of manageability and safety. 18 As was observed in earlier reported series of patients undergoing second-line treatment for aGVHD, most of our patients also developed opportunistic infections after therapy with Dac, although no major life-threatening infectious episodes occurred. The heterogeneity of earlier administered immunosuppressive treatments and the limited number of patients make it difficult to define the role of Dac in the development of viral infections.…”

Section: Discussionsupporting

confidence: 85%

Daclizumab as useful treatment in refractory acute GVHD: a paediatric experience

Miano

Cuzzubbo

Terranova

et al. 2008

Bone Marrow Transplant

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GVHD remains a serious complication after allogeneic SCT. We describe 13 paediatric patients treated with daclizumab for refractory acute GVHD (aGVHD). After 30 days of daclizumab administration, all patients with cutaneous aGVHD reached complete response. Among patients with gastrointestinal disease, 50 and 30% had complete and partial response, respectively, whereas 11 and 55% of patients with hepatic aGVHD achieved CR and PR, respectively. Overall, complete (46%) and partial (46%) responses were demonstrated in 92% of our patients, whereas the remaining patients (8%) were nonresponders. No life-threatening infectious episodes were recorded within 100 days from transplant in this selected group of paediatric patients. Overall 46% of patients were alive at a median of 461 days from SCT, but 50% of them developed chronic GVHD. In our experience, daclizumab proved to be a useful and safe treatment for refractory and steroid-resistant/dependent aGVHD, in particular for cutaneous and low-moderate intestinal involvement.

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Section: Discussionsupporting

confidence: 85%

Daclizumab as useful treatment in refractory acute GVHD: a paediatric experience

Miano

Cuzzubbo

Terranova

et al. 2008

Bone Marrow Transplant

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“…In a retrospective study, infliximab has been shown to be associated with significant response although the proportion of patients with grade III-IV aGVHD was low and treatment was complicated by infections particularly aspergillus which could be explained by elimination of monocytes-macrophages by infliximab [97,98]. Etanercept also increased infections in clinical trials but not as much as infliximab [81,86]. In a phase III randomized trial of high-dose corticosteroids with or without infliximab including 63 newly diagnosed GVHD patients, no statistically significant difference was found in GVHD-related mortality, non-relapse mortality or overall survival [87].…”

Section: Anti-tnfα Agentsmentioning

confidence: 99%

“…Based on these encouraging results, a randomized phase III trial of steroid and CI with MMF vs steroid and CI has started (BMT CTN Study 0802), but the study was terminated as preliminary results did not show any difference with addition of MMF [82]. Other agents such as basiliximab, daclizumab, antithymocyte globulin (ATG), etanercept and infliximab have also been tested without convincing results [83][84][85][86][87]. Based on these findings, the addition of agents to high-dose steroids in first-line treatment is only recommended in the setting of clinical trials.…”

Section: First-line Treatment Of Acute Gvhdmentioning

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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“…[6][7][8] Such recognition proceeds through a complex cross-talk between host and donor cells, resulting in Graft-versus-host disease S Mastaglio et al the release of soluble effector molecules and activation of cellular players ultimately leading to tissue damage. [9][10][11] Traditionally, the distinction between acute and chronic GvHD was based on the time of onset after transplantation (acute GvHD within 100 days, chronic GvHD 100 days after transplant). More recently, insights into the mechanisms underlying GvHD led to an updated classification based on the specificity of signs and symptoms.…”

Section: Prospectsmentioning

confidence: 99%

“…In the HLA-identical setting, a recent phase II clinical study showed that the combination of etanercept (an antitumor necrosis factor-a,) and systemic corticosteroids is more effective than standard treatment in controlling GvHD (complete response rates: 69 versus 33%; Po0.001), despite similar rates of infectious complications and long-term outcome. 9 In the context of haplo-HSCT, several approaches based on graft manipulation and cell and gene therapy have been developed.…”

Section: Prospectsmentioning

confidence: 99%