Top

Journal of Hematology & Oncology

Published in:

Open Access 01-12-2016 | Research

Antifungal prophylaxis of patients undergoing allogenetic hematopoietic stem cell transplantation in China: a multicenter prospective observational study

Authors: Lei Gao, Yuqian Sun, Fanyi Meng, Mingzhe Han, He Huang, Depei Wu, Li Yu, Hanyun Ren, Xiaojun Huang, Xi Zhang

Published in: Journal of Hematology & Oncology | Issue 1/2016

Abstract

Background

Antifungal prophylaxis is currently regarded as the gold standard in situations with allo-genetic hematopoietic stem cell transplantation (allo-HSCT). However, the epidemiological information regarding prophylaxis of invasive fungal diseases (IFDs) is not clear in China.

Methods

We report the first large-scale (1053 patients) observational study of the prophylaxis and management of IFDs among patients with allo-HSCT in China.

Results

The incidence rates of IFD after primary antifungal prophylaxis (PAP), secondary antifungal prophylaxis (SAP), and non-prophylaxis were 22.7 vs. 38.6 vs. 68.6 %, respectively (P = 0.0000). The median time from transplantation to IFD was 45 days in PAP patients, 18 days in SAP patients, and 12 days in non-prophylaxis patients. Aspergillus spp. represents the most common type of fungal infection. Independent risk factors for IFD in allo-HSCT patients with PAP were age, having human leukocyte antigen (HLA)-haploidentical or matched unrelated donor, decreased albumin levels, and the use of itraconazole as the prophylactic antifungal agent. Among SAP transplant recipients, there was no significant risk factor for IFDs. The incidence rates of overall survival (OS) in the PAP, SAP, and no prophylaxis groups were 85.07, 78.80, and 74.82, respectively (P = 0.01).

Conclusions

This observational study indicates that prophylaxis of IFD is helpful to reduce the incidence of IFDs and improve the OS of patients after allo-HSCT.

Girmenia C, Raiola AM, Piciocchi A, Algarotti A, Stanzani M, Cudillo L, et al. Incidence and outcome of invasive fungal diseases after allogeneic stem cell transplantation: a prospective study of the Gruppo Italiano Trapianto Midollo Osseo (GITMO). Biol Blood Marrow Transplant. 2014;20:872–80.CrossRefPubMed

Lv M, Huang XJ. Allogeneic hematopoietic stem cell transplantation in China: where we are and where to go. J Hematol Oncol. 2012;5:10.CrossRefPubMedPubMedCentral

Lin R, Liu Q. Diagnosis and treatment of viral diseases in recipients of allogeneic hematopoietic stem cell transplantation. J Hematol Oncol. 2013;6:94.CrossRefPubMedPubMedCentral

Kontoyiannis DP, Marr KA, Park BJ, Alexander BD, Anaissie EJ, Walsh TJ, et al. Prospective surveillance for invasive fungal infections in hematopoietic stem cell transplant recipients, 2001–2006: overview of the Transplant-Associated Infection Surveillance Network (TRANSNET) Database. Clin Infect Dis. 2010;50:1091–100.CrossRefPubMed

Neofytos D, Horn D, Anaissie E, Steinbach W, Olyaei A, Fishman J, et al. Epidemiology and outcome of invasive fungal infection in adult hematopoietic stem cell transplant recipients: analysis of Multicenter Prospective Antifungal Therapy (PATH) Alliance registry. Clin Infect Dis. 2009;48:265–73.CrossRefPubMed

Pagano L, Caira M, Nosari A, Van Lint MT, Candoni A, Offidani M, et al. Fungal infections in recipients of hematopoietic stem cell transplants: results of the SEIFEM B-2004 studyeSorveglianza Epidemiologica Infezioni Fungine Nelle Emopatie Maligne. Clin Infect Dis. 2007;45:1161–70.CrossRefPubMed

Sun Y, Meng F, Han M, Zhang X, Yu L, Huang H, et al. Epidemiology, management, and outcome of invasive fungal disease in patients undergoing hematopoietic stem cell transplantation in China: a multicenter prospective observational study. Biol Blood Marrow Transplant. 2015;21:1117–26.CrossRefPubMed

Lai Y, Chen Y, Hu D, Jiang M, Liu Q, Liu L, et al. Multicenter phase ii study of a combination of cyclosporine a, methotrexate and mycophenolate mofetil for GVHD prophylaxis: results of the Chinese Bone Marrow Transplant Cooperative Group (CBMTCG). J Hematol Oncol. 2014;7:59.CrossRefPubMedPubMedCentral

Chang Y, Zhao X, Xu L, Zhang X, Wang Y, Han W, et al. Donor-specific anti-human leukocyte antigen antibodies were associated with primary graft failure after unmanipulated haploidentical blood and marrow transplantation: a prospective study with randomly assigned training and validation sets. J Hematol Oncol. 2015;8:84.CrossRefPubMedPubMedCentral

10.

Arendrup MC, Dzajic E, Jensen RH, Johansen HK, Kjaeldgaard P, Knudsen JD, et al. Epidemiological changes with potential implication for antifungal prescription recommendations for fungaemia: data from a nationwide fungaemia surveillance programme. Clin Microbiol Infect. 2013;19:E343–53.CrossRefPubMed

11.

Mousset S, Buchheidt D, Heinz W, Ruhnke M, Cornely OA, Egerer G, et al. Treatment of invasive fungal infections in cancer patients-updated recommendations of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO). Ann Hematol. 2014;93:13–32.CrossRefPubMed

12.

Alothman AF, Al-Musawi T, Al-Abdely HM, Salman JA, Almaslamani M, Yared N, et al. Clinical practice guidelines for the management of invasive Candida infections in adults in the Middle East region: expert panel recommendations. J Infect Public Health. 2014;7:6–19.CrossRefPubMed

13.

Pappas PG, Kauffman CA, Andes D, Benjamin Jr DJ, Calandra TF, Edwards Jr JE, et al. Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis. 2009;48:503–35.CrossRefPubMed

14.

Cornely OA, Böhme A, Buchheidt D, Einsele H, Heinz WJ, Karthaus M, et al. Primary prophylaxis of invasive fungal infections in patients with hematologic malignancies. Recommendations of the Infectious Diseases Working Party of the German Society for Haematology and Oncology. Haematologica. 2009;94:113–22.CrossRefPubMed

15.

Marr KA, Bow E, Chiller T, Maschmeyer G, Ribaud P, Segal B, et al. Fungal infection prevention after hematopoietic cell transplantation. Bone Marrow Transplant. 2009;44:483–7.CrossRefPubMed

16.

Maertens J, Marchetti O, Herbrecht R, Cornely OA, Flückiger U, Frêre P, et al. European guidelines for antifungal management in leucemia and hematopoietic stem cell transplant recipients: summary of the ECIL 3-2009 update. Bone Marrow Transplant. 2011;46:709–18.CrossRefPubMed

17.

Baden LR, Bensinger W, Angarone M, Casper C, Dubberke ER, Freifeld AG, et al. Prevention and treatment of cancer-related infections. J Natl Compr Canc Netw. 2012;10:1412–45.PubMed

18.

Sun Y, Huang H, Chen J, Li J, Ma J, Li J, et al. Invasive fungal infection in patients receiving chemotherapy for hematological malignancy: a multicenter, prospective, observational study in China. Tumor Biol. 2015;36:757–67.CrossRef

19.

De Pauw B, Walsh TJ, Donnelly JP, Stevens DA, Edwards JE, Calandra T, et al. 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;46:1813–21.CrossRefPubMedPubMedCentral

20.

The Chinese Invasive Fungal Infection Committee. The diagnostic criteria and treatment guideline of invasive fungal infection in patients with Hematological disease/malignances (3rd version). Zhonghua Nei Ke Za Zhi [Chinese Journal of Internal Medicine]. 2010;49:451–4 [Article in Chinese].

21.

Girmenia C, Barosi G, Piciocchi A, Arcese W, Aversa F, Bacigalupo A, et al. Primary prophylaxis of invasive fungal diseases in allogeneic stem cell transplantation: revised recommendations from a consensus process by Gruppo Italiano Trapianto Midollo Osseo (GITMO). Biol Blood Marrow Transplant. 2014;20:1080–8.CrossRefPubMed

22.

Allinson K, Kolve H, Gumbinger HG, Vormoor HJ, Ehlert K, Groll AH. Secondary antifungal prophylaxis in paediatric allogeneic haematopoietic stem cell recipients. J Antimicrob Chemother. 2008;61:734–42.CrossRefPubMed

23.

Huang XJ. Current status of haploidentical stem cell transplantation for leukemia. J Hematol Oncol. 2008;1:27.CrossRefPubMedPubMedCentral

24.

Wan L, Zhang Y, Lai Y, Jiang M, Song Y, Zhou J, et al. Effect of granulocyte-macrophage colony-stimulating factor on prevention and treatment of invasive fungal disease in recipients of allogeneic stem-cell transplantation: a prospective multicenter randomized phase IV trial. J Clin Oncol. 2015. [Epub ahead of print].

25.

Montesinos P, Rodríguez-Veiga R, Boluda B, Martínez-Cuadrón D, Cano I, Lancharro A, et al. Incidence and risk factors of post-engraftment invasive fungal disease in adult allogeneic hematopoietic stem cell transplant recipients receiving oral azoles prophylaxis. Bone Marrow Transplant. 2015;50:1465–72.CrossRefPubMed

26.

Wang CH, Kan LP, Lin HA, Chang FY, Wang NC, Lin TY, et al. Clinical efficacy and safety of primary antifungal prophylaxis with posaconazole versus fluconazole in allogeneic blood hematopoietic stem cell transplantation recipients—a retrospective analysis of a single medical center in Taiwan. Microbiol Immunol Infect. 2014. doi:10.1016/j.jmii.2014.07.009 [Epub ahead of print].

27.

Girmenia C, Ferretti A, Barberi W. Epidemiology and risk factors for invasive fungal diseases in hematopoietic stem cell transplantation. Curr Opin Hematol. 2014;21:459–65.CrossRefPubMed

28.

Gao L, Zhang C, Gao L, Liu Y, Su Y, Wang S, et al. Favorable outcome of haploidentical hematopoietic stem cell transplantation in Philadelphia chromosome-positive acute lymphoblastic leukemia: a multicenter study in Southwest China. J Hematol Oncol. 2015;8:90.CrossRefPubMedPubMedCentral

29.

Aguado JM, Vázquez L, Fernández-Ruiz M, Villaescusa T, Ruiz-Camps I, Barba P, et al. Serum galactomannan versus a combination of galactomannan and polymerase chain reaction-based Aspergillus DNA detection for early therapy of invasive aspergillosis in high-risk hematological patients: a randomized controlled trial. Clin Infect Dis. 2015;60:405–14.CrossRefPubMed

30.

White PL, Parr C, Thornton C, Barnes RA. Evaluation of real-time PCR, galactomannan enzyme-linked immunosorbent assay (ELISA), and a novel lateral-flow device for diagnosis of invasive aspergillosis. J Clin Microbiol. 2013;51:1510–6.CrossRefPubMedPubMedCentral

31.

Petrik M, Franssen GM, Haas H, Laverman P, Hörtnagl C, Schrettl M, et al. Preclinical evaluation of two 68Ga-siderophores as potential radiopharmaceuticals for Aspergillus fumigatus infection imaging. Eur J Nucl Med Mol Imaging. 2012;39:1175–83.CrossRefPubMedPubMedCentral

32.

Johnson G, Nolan T, Bustin SA. Real-time quantitative PCR, pathogen detection and MIQE. Methods Mol Biol. 2013;943:1–16.CrossRefPubMed

33.

Marinach-Patrice C, Fekkar A, Atanasova R, Gomes J, Djamdjian L, Brossas JY, et al. Rapid species diagnosis for invasive candidiasis using mass spectrometry. PLoS ONE. 2010;5:e8862.CrossRefPubMedPubMedCentral

34.

Johnson G, Ferrini A, Dolan SK, Nolan T, Agrawal S, Doyle S, et al. Biomarkers for invasive aspergillosis: the challenges continue. Biomark Med. 2014;8:429–51.CrossRefPubMed

35.

Döring M, Eikemeier M, Cabanillas Stanchi KM, Hartmann U, Ebinger M, Schwarze CP, et al. Antifungal prophylaxis with posaconazole vs. fluconazole or itraconazole in pediatric patients with neutropenia. Eur J Clin Microbiol Infect Dis. 2015;34:1189–200.CrossRefPubMedPubMedCentral

36.

Fleming S, Yannakou CK, Haeusler GM, Clark J, Grigg A, Heath CH, et al. Consensus guidelines for antifungal prophylaxis in haematological malignancy and haemopoietic stem cell transplantation, 2014. Intern Med J. 2014;44:1283–97.CrossRefPubMed

37.

Vehreschild MJ, von Bergwelt-Baildon M, Tran L, Shimabukuro-Vornhagen A, Wisplinghoff H, Bangard C, et al. Feasibility and effectiveness of posaconazole prophylaxis in combination with micafungin bridging for patients undergoing allogeneic stem cell transplantation: a 6-yr analysis from the cologne cohort for neutropenic patients. Eur J Haematol. 2014;93:400–6.CrossRefPubMed

38.

Tragiannidis A, Dokos C, Lehrnbecher T, Groll AH, Groll AH. Antifungal chemoprophylaxis in children and adolescents with haematological malignancies and following allogeneic haematopoietic stem cell transplantation. Drugs. 2012;72:685–704.CrossRefPubMed

39.

Wang JF, Xue Y, Zhu XB, Fan H. Efficacy and safety of echinocandins versus triazoles for the prophylaxis and treatment of fungal infections: a meta-analysis of RCTs. Eur J Clin Microbiol Infect Dis. 2015;34:651–9.CrossRefPubMed

40.

Takagi S, Araoka H, Uchida N, Uchida Y, Kaji D, Ota H, et al. A prospective feasibility study of primary prophylaxis against invasive fungal disease with voriconazole following umbilical cord blood transplantation with fludarabine-based conditioning. Int J Hematol. 2014;99:652–8.CrossRefPubMed

41.

Liu Q, Lin R, Sun J, Xiao Y, Nie D, Zhang Y, et al. Antifungal agents for secondary prophylaxis based on response to initial antifungal therapy in allogeneic hematopoietic stem cell transplant recipients with prior pulmonary aspergillosis. Biol Blood Marrow Transplant. 2014;20:1198–203.CrossRefPubMed

42.

Vehreschilda JJ, Sieniawski M, Reuterb S, Arenza D, Reichertd D, Maertense J, et al. Efficacy of caspofungin and itraconazole as secondary antifungal prophylaxis: analysis of data from a multinational case registry. Int J Antimicrobl Agents. 2009;34:446–50.CrossRef

43.

Bow EJ, Vanness DJ, Slavin M, Cordonnier C, Cornely OA, Marks DI, et al. Systematic review and mixed treatment comparison meta-analysis of randomized clinical trials of primary oral antifungal prophylaxis in allogeneic hematopoietic cell transplant recipients. BMC Infect Dis. 2015;15:128.CrossRefPubMedPubMedCentral

44.

Sung AH, Marcella SW, Xie Y. An update to the cost-effectiveness of posaconazole vs fluconazole or itraconazole in the prevention of IFD among neutropenic patients in the United States. J Med Econ. 2015;18:341–8.CrossRefPubMed

45.

Groll AH, Castagnola E, Cesaro S, Dalle JH, Engelhard D, Hope W, et al. Fourth European Conference on Infections in Leukaemia (ECIL-4): guidelines for diagnosis, prevention, and treatment of invasive fungal diseases in paediatric patients with cancer or allogeneic haemopoietic stem-cell transplantation. Lancet Oncol. 2014;15:e327–40.CrossRefPubMed

46.

van Hal SJ, Gilroy NM, Morrissey CO, Worth LJ, Szer J, Tam CS, et al. Survey of antifungal prophylaxis and fungal diagnostic tests employed in malignant haematology and haemopoietic stem cell transplantation (HSCT) in Australia and New Zealand. Intern Med J. 2014;44:1277–82.CrossRefPubMed

47.

Held J, Schmidt T, Thornton CR, Kotter E, Bertz H. Comparison of a novel Aspergillus lateral-flow device and the Platelia® galactomannan assay for the diagnosis of invasive aspergillosis following haematopoietic stem cell transplantation. Infection. 2013;41:1163–9.CrossRefPubMed

48.

Ji Y, Xu LP, Liu DH, Chen YH, Han W, Zhang XH, et al. Positive results of serum galactomannan assays and pulmonary computed tomography predict the higher response rate of empirical antifungal therapy in patients undergoing allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2011;17:759–64.CrossRefPubMed

49.

Omer AK, Ziakas PD, Anagnostou T, Coughlin E, Kourkoumpetis T, McAfee SL, et al. Risk factors for invasive fungal disease after allogeneic hematopoietic stem cell transplantation: a single center experience. Biol Blood Marrow Transplant. 2013;19:190–6.CrossRef

Title: Antifungal prophylaxis of patients undergoing allogenetic hematopoietic stem cell transplantation in China: a multicenter prospective observational study
Authors: Lei Gao
Yuqian Sun
Fanyi Meng
Mingzhe Han
He Huang
Depei Wu
Li Yu
Hanyun Ren
Xiaojun Huang
Xi Zhang
Publication date: 01-12-2016
Publisher: BioMed Central
Published in: Journal of Hematology & Oncology / Issue 1/2016
Electronic ISSN: 1756-8722
DOI: https://doi.org/10.1186/s13045-016-0305-y

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

ACC 2024 Congress

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2016

PEG-aspargase and DEP regimen combination therapy for refractory Epstein–Barr virus-associated hemophagocytic lymphohistiocytosis

H2S protects against fatal myelosuppression by promoting the generation of megakaryocytes/platelets

Phase 1/2 study of pacritinib, a next generation JAK2/FLT3 inhibitor, in myelofibrosis or other myeloid malignancies

Elotuzumab for the treatment of multiple myeloma

Effective adoptive immunotherapy of triple-negative breast cancer by folate receptor-alpha redirected CAR T cells is influenced by surface antigen expression level

Romidepsin for the treatment of relapsed/refractory peripheral T cell lymphoma: prolonged stable disease provides clinical benefits for patients in the pivotal trial

Keynote webinar | Spotlight on antibody–drug conjugates in cancer