Anti-tumor necrosis factor-a for the treatment of steroid-refractory acute graft-versus-host disease

Nogueira, M.C.; Azevedo, Alexandre; Pereira, Simone C. M.; Ferreira, Joana Lima; Lerner, Decio; Lobo, A.M.G.; Tavares, Roberto; Tabak, Daniel; Lorenzi, N.; Renault, Ilana Zalcberg; Bouzas, Luis Fernando

doi:10.1590/s0100-879x2006005000145

Cited by 20 publications

(14 citation statements)

References 25 publications

(22 reference statements)

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“…This finding is similar to that observed in inflammatory bowel diseases12, 13 and raises the hypothesis of a specific role of TNF‐α in cibling bowel damage 23. In the context of HSCT, another interesting finding is that the best responses to infliximab were achieved in patients whose GVHD did not involve the liver 3, 16–19. This suggests that infliximab could be particularly interesting for GVHD following liver transplantation.…”

Section: Discussionsupporting

confidence: 80%

“…In 1992, our center reported for the first time the successful use of home‐made monoclonal anti‐TNF antibodies in refractory GVHD following hematopoietic stem cell transplantation (HSCT) in a pilot study that included 19 patients 15. Since then, various retrospective case series have found encouraging results with infliximab for the treatment of steroid‐refractory acute GVHD following HSCT 3, 16–19. During acute GVHD, TNF‐α is secreted by monocytes and macrophages, leading to donor T cell activation and inducing a cascade of inflammatory cytokine and cell activation and tissue damage 20.…”

Section: Discussionmentioning

confidence: 99%

“…In the present case, a rapid and complete remission of acute GVHD was observed with the administration of 3 perfusions of 10 mg/kg infliximab within 1 week. This regimen used the same cumulative dose but a shorter duration than previously described: in the majority of case series reporting the use of infliximab for acute GVHD following HSCT, a 10 mg/kg/week infliximab regimen was administered for a median duration of 3 weeks 3, 16–19. Because the patient had a life‐threatening relapse after 2 perfusions of anti‐thymocyte globulin and an increase in steroids, and in order to limit the total dose of anti‐thymocyte globulin to 7.5 mg/kg in a patient with a history of cancer, we decided to use a reinforced regimen of infliximab therapy.…”

Section: Discussionmentioning

confidence: 99%

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Infliximab treatment for steroid-refractory acute graft-versus-host disease after orthotopic liver transplantation: A case report

Piton¹,

Larosa²,

Minello³

et al. 2009

Liver Transpl

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Acute graft-versus-host disease (GVHD) following orthotopic liver transplantation is a rare but severe disease with a 75% death rate in adults. Various therapeutic strategies have been proposed for steroid-refractory GVHD, but there is still no consensus. Tumor necrosis factor-alpha is a key inflammatory cytokine involved in acute GVHD physiopathology, and infliximab has shown encouraging results for the treatment of acute GVHD following hematopoietic stem cell transplantation. We report the first case of acute GVHD following liver transplantation that was refractory to steroids and anti-lymphocyte globulin but was successfully treated with infliximab. Liver Transpl 15:682-685, 2009.

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Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Infliximab treatment for steroid-refractory acute graft-versus-host disease after orthotopic liver transplantation: A case report

Piton¹,

Larosa²,

Minello³

et al. 2009

Liver Transpl

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“…recorded in 24% of patients. Other studies in patients with SR aGVHD have reported variable rates of infections, including 83% to 100% (34% to 40% fatal) in patients receiving infliximab [15,36,37], 78% to 100% (8% to 50% fatal) in patients receiving alemtuzumab [14,[38][39][40][41][42], and 67% (12% fatal) in patients receiving etanercept [43]. However, many of those series did not categorize infections by severity.…”

Section: Discussionmentioning

confidence: 99%

Safety and Effectiveness of Vedolizumab in Patients with Steroid-Refractory Gastrointestinal Acute Graft-versus-Host Disease: A Retrospective Record Review

Fløisand

Lazarevic

Maertens

et al. 2019

Biology of Blood and Marrow Transplantation

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A B S T R A C T Allogeneic hematopoietic cell transplantation (allo-HCT) can be curative in patients with hematologic malignancies but carries a significant risk of graft-versus-host disease (GVHD). There are no standard treatments for steroid-refractory (SR) gastrointestinal (GI) acute GVHD (aGVHD). This multicenter, international, retrospective medical record review aimed to evaluate the off-label use of vedolizumab, a gut-selective immunomodulator, for treating SR GI aGVHD. Data were collected from patients' medical records; criteria for extraction included no more than 1 allo-HCT and at least 1 dose of vedolizumab as treatment for SR GI aGVHD (ie, stage 1 to 4 GI aGVHD following 1 previous treatment regimen(s) containing 1 mg/kg methylprednisolone or equivalent). Descriptive analyses of response rate, overall survival (OS), and serious adverse effects (SAEs) were performed. Twenty-nine patients were identified from 7 sites who had received 1 to 10 doses of vedolizumab 300 mg i.v. (median 3 doses) as treatment for SR GI aGVHD. The overall response rate at 6 to 10 weeks after vedolizumab initiation was 64%, and OS at 6 months was 54%. There were 29 SAEs, including 12 infections; 3 SAEs were considered possibly related to vedolizumab, 2 of which were infections. Thirteen SAEs were fatal, 1 of which was possibly vedolizumabrelated. There were 8 nonserious infections and 1 serious infection with confirmed GI origin in 8 patients; there was no apparent pattern in the timing of these infections relative to the initiation of vedolizumab treatment. Further data on the efficacy and safety of vedolizumab in this setting from prospective trials are needed.

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“…In a pilot study assessing the efficacy of infliximab in patients with SR-aGVHD, Couriel et al investigated a cohort of 21 patients and reported an overall response rate (ORR) of 67% [15]. This finding was supported by additional small retrospective studies [16][17][18][19][20][21][22]. A more recent study assessing infliximab salvage therapy in 52 patients reported a complete response (CR) of 15% [23], while a randomized, upfront, phase 3 study comparing infliximab with corticosteroids to corticosteroids alone in aGVHD did not show any benefit [24].…”

Section: Introductionmentioning

confidence: 99%

Safety and Efficacy of Infliximab Therapy in the Setting of Steroid-Refractory Acute Graft-versus-Host Disease

Yalniz

Hefazi

McCullough

et al. 2017

Biology of Blood and Marrow Transplantation

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Acute graft-versus-host disease (aGVHD) is the leading cause of morbidity and mortality after allogenic hematopoietic cell transplantation (HCT). Corticosteroids are the first-line treatment; however, less than one-half of patients achieve durable remission. Studies suggest that TNF-α, a cytokine released from the bone marrow during conditioning, is involved in the pathogenesis of aGVHD. We retrospectively evaluated the outcome of anti-TNF-α therapy with infliximab in 35 patients with steroid refractory (SR) aGVHD. Infliximab was administered intravenously at 10 mg/kg for a median of 4 doses (range, 1 to 6) on a weekly basis. The overall response rates were 40% (17% complete response [CR], 23% partial response [PR]) at 4 weeks, 23% (9% CR, 14% PR) at 8 weeks, and 17% (all CR) at 12 weeks. Twenty-nine (83%) patients had infectious complications within 12 weeks of initiation of infliximab. These infections included 40 bacterial infections, 6 invasive fungal infections, and 5 viral reactivations. Twelve patients (34%) died secondary to infections. Overall survival at 12 weeks and 6 months from the start of infliximab therapy was 37% (13 of 35) and 17% (6 of 35), respectively; with most deaths secondary to complications from GVHD and infections. In conclusion; the use of infliximab therapy in patients with SR-aGVHD is associated with a modest poorly sustained response along with a heightened risk of severe infections. Future studies with more effective and less toxic therapies are needed for these patients.

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Anti-tumor necrosis factor-a for the treatment of steroid-refractory acute graft-versus-host disease

Abstract: Allogeneic stem cell transplantation has been increasingly performed for a variety of hematologic diseases. Clinically significant acute graft-versus-host disease (GVHD) occurs in 9 to 50% of patients who receive allogeneic grafts, resulting in high morbidity and mortality.

Cited by 20 publications

References 25 publications

Infliximab treatment for steroid-refractory acute graft-versus-host disease after orthotopic liver transplantation: A case report

Infliximab treatment for steroid-refractory acute graft-versus-host disease after orthotopic liver transplantation: A case report

Safety and Effectiveness of Vedolizumab in Patients with Steroid-Refractory Gastrointestinal Acute Graft-versus-Host Disease: A Retrospective Record Review

Safety and Efficacy of Infliximab Therapy in the Setting of Steroid-Refractory Acute Graft-versus-Host Disease

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