Tolerability and outcome of once weekly liposomal amphotericin B for the prevention of invasive fungal infections in hematopoietic stem cell transplant patients with graft-versus-host disease

Abstract

Background

Invasive fungal infections remain problematic in immunosuppressed allogeneic stem cell transplant recipients and the use of corticosteroids for the treatment of graft-versus-host-disease can increase the risk threefold. Although antifungal prophylaxis has been shown to decrease the incidence of infection, the optimal antifungal prophylactic regimen in this patient population has yet to be identified.

Since early diagnosis of fungal infections might not be possible and the treatment of established fungal infections might be difficult and associated with high infection-related mortality, prevention has become an important strategy in reducing overall morbidity and mortality. While triazoles are the preferred agents, some patients are unable to tolerate them and an alternative drug is warranted.

Objectives

To assess the tolerability of once weekly liposomal amphotericin B as a prophylactic strategy in patients undergoing stem cell transplantation by evaluating any adverse events leading to its discontinuation. In terms of efficacy, to also compare the outcome and incidence of invasive fungal infections in patients who received amphotericin B, triazoles, and echinocandins.

Results

A total of 101 allogeneic transplant recipients receiving corticosteroids for the treatment of graft-versus-host-disease and antifungal prophylaxis were evaluated from August 2009 to September 2012. Liposomal amphotericin B 3 mg/kg intravenous once weekly was found to be well tolerated. The incidence of invasive fungal infections was 19%, 17%, and 7% in the liposomal amphotericin B, echinocandin, and triazole groups, respectively. Two deaths occurred in the liposomal amphotericin B group and one death occurred in the echinocandin group. None of the deaths were fungal infection related.

Conclusion

Antifungal prophylaxis with liposomal amphotericin B was well tolerated, but the incidence of invasive fungal infections in patients receiving liposomal amphotericin B was higher than other antifungal agents in this study. The optimal dose and schedule of liposomal amphotericin B for antifungal prophylaxis in this patient population are still not known and considering its broad spectrum activity, prospective trials in comparison to triazoles are warranted.

Keywords

Liposomal amphotericin B graft-versus-host-disease invasive fungal infections hematopoietic stem cell transplant corticosteroids prophylaxis

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References

Bow

. Invasive fungal infection in haematopoietic stem cell transplant recipients: epidemiology from the transplant physician’s viewpoint. Mycopathologia 2009; 168: 283–297.

Groll

Silling

Young

. Randomized comparison of safety and pharmacokinetics of caspofungin, liposomal amphotericin B, and the combination of both in allogeneic hematopoietic stem cell recipients. Antimicrob Agents Chemother 2010; 54: 4143–4149.

Wingard

. Fungal infections after bone marrow transplant. Biol Blood Marrow Transp 1999; 5: 55–68.

Bow

. Long-term antifungal prophylaxis in high-risk hematopoietic stem cell transplant recipients. Med Mycol 2005; 43: S277–S287.

Moen

Lyseng-Williamson

Scott

. Liposomal amphotericin B: a review of its use as empirical therapy in febrile neutropenia and in the treatment of invasive fungal infections. Drugs 2009; 69: 361–392.

Tomblyn

Chiller

Einsele

. Guidelines for preventing infectious complications among hematopoietic cell transplant recipients: a global perspective. Bone Marrow Transp 2009; 44: 453–455.

Vehreschild

Sieniawski

Reuter

. Efficacy of caspofungin and itraconazole as secondary antifungal prophylaxis: analysis of data from a multinational case registry. Int J Antimicrob Agents 2009; 34: 446–450.

Amphotericin B (Conventional). Lexi-Drugs Online. Hudson, OH: Lexi-Comp, Inc. http://online.lexi.com (accessed 19 August 2012).

Walsh

Yeldandi

McEvoy

. Safety, tolerance, and pharmacokinetics of a small unilamellar liposomal formulation of amphotericin B (AmBisome) in neutropenic patients. Antimicrob Agents Chemother 1998; 42: 2391–2398.

10.

Mattiuzzi

Estey

Raad

. Liposomal amphotericin B versus the combination of fluconazole and itraconazole as prophylaxis for invasive fungal infections during induction chemotherapy for patients with acute myelogenous leukemia and myelodysplastic syndrome. Cancer 2003; 97: 450–456.

11.

Kelsey

Goldman

McCann

. Liposomal amphotericin (AmBisome) in the prophylaxis of fungal infections in neutropenic patients: a randomised, double-blind, placebo-controlled study. Bone Marrow Transpl 1999; 23: 163–168.

12.

Penack

Schwartz

Martus

. Low-dose liposomal amphotericin B in the prevention of invasive fungal infections in patients with prolonged neutropenia: results from a randomized, single-center trial. Ann Oncol 2006; 17: 1306–1312.

13.

Cordonnier

Mohty

Faucher

. Safety of a weekly high dose of liposomal amphotericin B for prophylaxis of invasive fungal infection in immunocompromised patients: PROPHYSOME study. Int J Antimicrob Agents 2008; 31: 135–141.

14.

Cahuayme-Zuniga

Lewis

Mulanovich

. Weekly liposomal amphotericin B as secondary prophylaxis for invasive fungal infections in patients with hematological malignancies. Med Mycol 2012; 50: 543–548.

15.

Chaftari

Hachem

Ramos

. Comparison of posaconazole versus weekly amphotericin B lipid complex for the prevention of invasive fungal infections in hematopoietic stem-cell transplantation. Transplantation 2012; 94: 302–308.

16.

Cheikh

Castagna

Wang

. Once-weekly liposomal amphotericin B for prophylaxis of invasive fungal infection after graft-versus-host disease in allogeneic hematopoietic stem cell transplantation: a comparative retrospective single-center study. Hematol Oncol Stem Cell Ther 2010; 3: 167–173.

17.

De Pauw

Walsh

Donnelly

. Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin Infect Dis 2008; 46: 1813–1821.

18.

Marr

Crippa

Leisenring

. Itraconazole versus fluconazole for prevention of fungal infections in patients receiving allogeneic stem cell transplants. Blood 2004; 103: 1527–1533.

19.

Winston

Maziarz

Chandrasekar

. Intravenous and oral itraconazole versus intravenous and oral fluconazole for long-term antifungal prophylaxis in allogeneic hematopoietic stem-cell transplant recipients. A multicenter, randomized trial. Ann Intern Med 2003; 138: 705–713.

20.

Ullmann

Lipton

Vesole

. Posaconazole or fluconazole for prophylaxis in severe graft-versus-host disease. N Engl J Med 2007; 356: 335–347.

21.

Cornely

Maertens

Winston

. Posaconazole vs. fluconazole or itraconazole prophylaxis in patients with neutropenia. N Engl J Med 2007; 356: 348–359.

22.

Dusetzina SB, Winn AN, Abel GA, et al. Cost sharing and adherence to tyrosine kinase inhibitors for patients with chronic myeloid leukemia. J Clin Oncol 2013; 32: 306–311.