Azithromycin for Prevention of Graft-Versus-Host Disease: A Randomized Placebo-Controlled Trial

  • Maryam Barkhordar Hematology-Oncology and Stem Cell Research Center, Tehran University of Medical Sciences, Tehran, Iran
  • Mehdi Mohammadi Department of Clinical Pharmacy, Faculty of Pharmacy, Alborz University of Medical Sciences, Karaj, Iran
  • Ahmad Reza Shamshiri Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
  • Molouk Hadjibabaie Mail Research Center for Rational Use of Drugs, Tehran University of Medical Sciences, Tehran, Iran Department of Clinical Pharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  • Ardeshir Ghavamzadeh Hematology-Oncology and Stem Cell Research Center, Tehran University of Medical Sciences, Tehran, Iran
Keywords:
Azithromycin, Graft-versus-host disease, Mucositis

Abstract

Background: Allogeneic hematopoietic stem cell transplantation has been used widely to treat various types of malignant and non-malignant disorders. Graft-versus-host disease is one of the main complications of this procedure which is associated with considerable mortality and affects quality of life. Despite careful selection of HLA-matched donors and implementing immunosuppressive therapy, the incidence rate of graft-versus-host disease remains high. Macrolide antibiotics are well-known immunomodulatory agents and have been effective as prophylaxis for graft-versus-host disease in preclinical studies.

Materials and Methods: Ninety-six adult patients with acute leukemia were recruited into a double-blind, randomized, placebo-controlled trial. All patients were first-time transplant candidates for a full-matched related or unrelated donor. Patients were allocated to receive azithromycin 500 mg daily (n=48) or placebo (n=48) from day -6 to +12. All patients received high-dose chemotherapy, standard immunosuppressive regimen and supportive care according to institutional protocols.

Results: The incidence of acute graft-versus-host disease grade III-IV and chronic graft-versus-host disease garde I-III was not significantly different between the two study arms. Oral mucositis grade 1-3 occurred in significantly lower number of patients in the azithromycin group compared with placebo.

Conclusion: Based on the results of this study, protective effect of azithromycin on graft-versus-host disease could not be demonstrated.

 

 

References

Marks DI, Alonso L, Radia R. Allogeneic hematopoietic cell transplantation in adult patients with acute lymphoblastic leukemia. Hematol Oncol Clin North Am. 2014; 28(6):995-1009.

Hsieh MM, Kang EM, Fitzhugh CD, et al. Allogeneic Hematopoietic Stem-Cell Transplantation for Sickle Cell Disease. N Engl J Med. 2009;361(24):2309-17.

Sengsayadeth S, Savani BN, Blaise D, et al. Reduced intensity conditioning allogeneic hematopoietic cell transplantation for adult acute myeloid leukemia in complete remission - a review from the Acute Leukemia Working Party of the EBMT. Haematologica. 2015;100(7):859-69.

Cooke KR, Olkiewicz K, Erickson N, et al. The role of endotoxin and the innate immune response in the pathophysiology of acute graft versus host disease. J Endotoxin Res. 2002;8(6):441-8.

Ball LM, Egeler RM, et a.l Acute GvHD: pathogenesis and classification. Bone Marrow Transplant. 2008;41 Suppl 2:S58-64.

Armand P, Kim HT, Sainvil MM, et al. The addition of sirolimus to the graft-versus-host disease prophylaxis regimen in reduced intensity allogeneic stem cell transplantation for lymphoma: a multicentre randomized trial. Br J Haematol. 2016;173(1):96-104.

Windreich RM, Goyal RK, Joshi R, et al. A Pilot Study of Continuous Infusion of Mycophenolate Mofetil for Prophylaxis of Graft-versus-Host-Disease in Pediatric Patients. Biol Blood Marrow Transplant. 2016;22(4):682-689.

Kanoh S, Rubin BK. Mechanisms of Action and Clinical Application of Macrolides as Immunomodulatory Medications. Clin Microbiol Rev. 2010 Jul;23(3):590-615.

Murphy DM, Forrest IA, Corris PA, et al. Azithromycin attenuates effects of lipopolysaccharide on lung allograft bronchial epithelial cells. J Heart Lung Transplant. 2008;27(11):1210-6.

Iwamoto S, Azuma E, Kumamoto T, et al. Efficacy of azithromycin in preventing lethal graft-versus-host disease. Clin Exp Immunol. 2013;171(3):338-45.

Filipovich AH, Weisdorf D, Pavletic S, et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant. 2005;11(12):945-56.

WHO handbook for reporting results of cancer treatment - See more at: http://apps.who.int/iris/handle/10665/37200#sthash.kZJyux8Z.dpuf : Geneva : World Health Organization; 1979. Available from: http://www.who.int/iris/handle/10665/37200.

Carnevale-Schianca F, Leisenring W, Martin PJ, et al. Longitudinal assessment of morbidity and acute graft-versus-host disease after allogeneic hematopoietic cell transplantation: retrospective analysis of a multicenter phase III study. Biol Blood Marrow Transplant. 2009;15(6):749-56.

Socié G, Schmoor C, Bethge WA, et al. Chronic graft-versus-host disease: long-term results from a randomized trial on graft-versus-host disease prophylaxis with or without anti-T-cell globulin ATG-Fresenius. Blood. 2011;117(23):6375-82.

Sonis ST, Elting LS, Keefe D, et al. Perspectives on cancer therapy-induced mucosal injury: pathogenesis, measurement, epidemiology, and consequences for patients. Cancer. 2004;100(9 Suppl):1995-2025.

Aghai ZH, Kode A, Saslow JG, et al. Azithromycin suppresses activation of nuclear factor-kappa B and synthesis of pro-inflammatory cytokines in tracheal aspirate cells from premature infants. Pediatr Res. 2007;62(4):483-8.

Cheung PS, Si EC, Hosseini K. Anti-inflammatory activity of azithromycin as measured by its NF-kappaB, inhibitory activity. Ocul Immunol Inflamm. 2010;18(1):32-7.

Blandizzi C, Malizia T, Lupetti A, et al. Periodontal tissue disposition of azithromycin in patients affected by chronic inflammatory periodontal diseases. J Periodontol. 1999;70(9):960-6.

Published
2018-04-05
How to Cite
1.
Barkhordar M, Mohammadi M, Shamshiri AR, Hadjibabaie M, Ghavamzadeh A. Azithromycin for Prevention of Graft-Versus-Host Disease: A Randomized Placebo-Controlled Trial. Int J Hematol Oncol Stem Cell Res. 12(2):77-83.
Section
Original Article(s)