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

Fevzi F. Yalniz, Mehrdad Hefazi, Kristen McCullough, Mark R. Litzow, William J. Hogan, Robert Wolf, Hassan Alkhateeb, Ankit Kansagra, Moussab Damlaj, Mrinal M. Patnaik

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)1478-1484
Number of pages7
JournalBiology of Blood and Marrow Transplantation
Volume23
Issue number9
DOIs
StatePublished - Sep 1 2017

Fingerprint

Graft vs Host Disease
Steroids
Safety
Therapeutics
Infection
Poisons
Cell Transplantation
Coinfection
Bacterial Infections
Infliximab
Adrenal Cortex Hormones
Bone Marrow
Cytokines
Morbidity
Survival
Mortality

Keywords

  • Acute graft-versus-host disease
  • Allogeneic hematopoietic cell transplantation
  • Tumor necrosis factor alpha blockade

ASJC Scopus subject areas

  • Hematology
  • Transplantation

Cite this

Yalniz, F. F., Hefazi, M., McCullough, K., Litzow, M. R., Hogan, W. J., Wolf, R., ... Patnaik, M. M. (2017). Safety and Efficacy of Infliximab Therapy in the Setting of Steroid-Refractory Acute Graft-versus-Host Disease. Biology of Blood and Marrow Transplantation, 23(9), 1478-1484. https://doi.org/10.1016/j.bbmt.2017.05.001

Safety and Efficacy of Infliximab Therapy in the Setting of Steroid-Refractory Acute Graft-versus-Host Disease. / Yalniz, Fevzi F.; Hefazi, Mehrdad; McCullough, Kristen; Litzow, Mark R.; Hogan, William J.; Wolf, Robert; Alkhateeb, Hassan; Kansagra, Ankit; Damlaj, Moussab; Patnaik, Mrinal M.

In: Biology of Blood and Marrow Transplantation, Vol. 23, No. 9, 01.09.2017, p. 1478-1484.

Research output: Contribution to journalArticle

Yalniz, FF, Hefazi, M, McCullough, K, Litzow, MR, Hogan, WJ, Wolf, R, Alkhateeb, H, Kansagra, A, Damlaj, M & Patnaik, MM 2017, 'Safety and Efficacy of Infliximab Therapy in the Setting of Steroid-Refractory Acute Graft-versus-Host Disease', Biology of Blood and Marrow Transplantation, vol. 23, no. 9, pp. 1478-1484. https://doi.org/10.1016/j.bbmt.2017.05.001
Yalniz, Fevzi F. ; Hefazi, Mehrdad ; McCullough, Kristen ; Litzow, Mark R. ; Hogan, William J. ; Wolf, Robert ; Alkhateeb, Hassan ; Kansagra, Ankit ; Damlaj, Moussab ; Patnaik, Mrinal M. / Safety and Efficacy of Infliximab Therapy in the Setting of Steroid-Refractory Acute Graft-versus-Host Disease. In: Biology of Blood and Marrow Transplantation. 2017 ; Vol. 23, No. 9. pp. 1478-1484.
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abstract = "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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