Dismal response to high-dose methylprednisolone after failure to respond to standard dose in patients with acute GVHD

Schechter, Tal; Macartney, Christine; Finkelstein, Yaron; Gassas, Adam; Husain, Mazhar; Doyle, John; Dupuis, L. Lee

doi:10.1038/bmt.2010.47

Cited by 2 publications

(2 citation statements)

References 22 publications

(21 reference statements)

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“…There is no consensus on the optimal strategy for managing SR patients and it remains an area of unmet medical need. Second-line therapies, such as antithymocyte globulin (ATG) and monoclonal antibodies, have been studied in this setting, but outcomes, especially for advanced aGVHD, remain dismal [6][7][8][9].…”

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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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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“…In the past our center used high-dose methylprednisolone, 1000 mg for 3 days, for refractory aGVHD with poor results, especially in those with severe aGVHD due to GI involvement [6]. Therefore, we adopted a new protocol that incorporated a prospective study of the combination of inolimomab and etanercept.…”

Section: Introductionmentioning

confidence: 99%

Combination Therapy with Inolimomab and Etanercept for Severe Steroid-Refractory Acute Graft-versus-Host Disease

Groningen¹,

Liefferink

Haan

et al. 2016

Biology of Blood and Marrow Transplantation

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Steroid-refractory acute graft-versus-host disease (aGVHD) remains an important cause of morbidity and mortality after allogeneic stem cell transplantation (SCT). A protocol on the management of aGVHD was introduced in our center that incorporated a prospective study on combination therapy with inolimomab (anti-IL-2Rα) and etanercept (anti-tumor necrosis factor-α) for steroid-refractory aGVHD. We evaluated the efficacy and safety in 21 consecutively treated patients. The patients had developed refractory aGVHD after SCT (n = 16) or donor lymphocyte infusion (n = 5), and aGVHD was classified as severe in all patients, mostly due to gastrointestinal involvement stages 2 to 4. No drug-related side effects were observed apart from the infections expected to occur in these severely immunocompromised patients. Overall response at day 28 of second-line therapy was 48% (10/21), with 6 and 4 patients achieving a complete and partial response, respectively. Eventually, 19 patients died (90%), with early mortality (<6 months) predominantly resulting from refractory aGVHD and secondary infections and late mortality resulting from relapse of the underlying disease. With a median follow-up of 55 days, the estimated rates of 6-month and 2-year overall survival were dismal, 29% and 10%, respectively. In conclusion, the combination of inolimomab and etanercept for steroid-refractory aGVHD failed to improve the dismal prognosis of severe steroid-refractory aGVHD.

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Dismal response to high-dose methylprednisolone after failure to respond to standard dose in patients with acute GVHD

Cited by 2 publications

References 22 publications

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

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

Combination Therapy with Inolimomab and Etanercept for Severe Steroid-Refractory Acute Graft-versus-Host Disease

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