Risks and outcomes of invasive fungal infections in the first six months after allogeneic hematopoietic stem cell transplantation in pediatric patients: a Multicenter Cohort Study by the Turkish Pediatric Bone Marrow Transplantation Study Group (TPBMT-SG)

Volkan Hazar* 1, Gulsun Karasu2, Vedat Uygun3, Gulyuz Ozturk4, Suar Caki Kilic2, Alphan Kupesiz5, Hayriye Daloglu3, Serap Aksoylar6, Didem Atay4, Musa Karakukcu7, Namik Ozbek8, Nursah Eker5, Savas Kansoy6, Emel Ozyurek9, Arzu Akcay4, Elif Unal10, Ulker Kocak11, Ekrem Unal7, Orhan Gursel12, Bahattin Tunc8, Funda Tayfun5, Aydan Ikinciogullari13, Salih Gozmen6, Tunc Fiskin9, Fatih Erbey4, Mehmet Ertem10, Gulay Sezgin14, Sebnem Yilmaz15, Zuhre Kaya11, Emin Kurekci12, Figen Dogu13, Vural Kesik16, Atila Tanyeli17, Hale Oren15, Erman Ataş16, Emel Unal18, Nurdan Tacyildiz18, Akif Yesilipek2

Author address: 

1Pediatric Hematology/Oncology and BMT Unit, Medipol University Faculty of Medicine, 2Pediatric BMT Unit, Bahcesehir University Faculty of Medicine Medical Park Goztepe Hospital, Istanbul , 3Pediatric BMT Unit, Bahcesehir University Faculty of Medicine Medical Park Antalya Hospital, Antalya, 4Pediatric BMT Unit, Medical Park Bahcelievler Hospital, Istanbul , 5Pediatric Hematology/Oncology and BMT Unit, Akdeniz University Faculty of Medicine, Antalya, 6Pediatric Oncology and BMT Unit, Ege University Faculty of Medicine, İzmir, 7Pediatric Hematology/Oncology and BMT Unit, Erciyes University Faculty of Medicine, Kayseri, 8Pediatric Hematology/Oncology and BMT Unit, Ankara Child Health and Diseases Hematology and Oncology Training and Research Hospital, Ankara, 9Pediatric BMT Unit, Medical Park Samsun Hospital, Samsun, 10Pediatric Hematology and BMT Unit, Ankara University Faculty of Medicine, 11Pediatric Hematology and BMT Unit, Gazi University Faculty of Medicine, 12Pediatric Hematology and BMT Unit, Gulhane Military Medical Academy, 13Pediatric Immunology and BMT Unit, Ankara University Faculty of Medicine, Ankara, 14Pediatric Hematology and BMT Unit, Cukurova University Faculty of Medicine, Adana, 15Pediatric Hematology and BMT Unit, Dokuz Eylul University Faculty of Medicine, İzmir, 16Pediatric Oncology and BMT Unit, Gulhane Military Medical Academy, Ankara, 17Pediatric Oncology and BMT Unit, Cukurova University Faculty of Medicine, Adana, 18Pediatric Oncology and BMT Unit, Ankara University Faculty of Medicine, Ankara, Turkey

Abstract: 

Introduction: Invasive fungal infections (IFIs) are a major cause of infectious morbidity and mortality after hematopoietic stem cell transplantation (HSCT). Because of limited data, the extend of this problem in children is not clear.
Materials (or patients) and methods: We retrospectively analyzed the incidence, outcome and risk factors of IFI in the first six months after 419 allogeneic HSCT in 412 pediatric patients treated at 16 different centers in Turkey from 1st of January 2013 to 31st of December 2013.
Results: The incidence of IFI in the first six months after allogeneic HSCT in pediatric patients was 10%, consisting of possible, probable and proven IFI at rates of 4%, 2% and 4%, respectively. IFI developed in 41 patients, 33 of which within 100 days, 19 of which occurred in the first month after transplantation. Among all 419 patients, 81 (19%) died after a median 60 days following transplantation (range, 8-180 days). Among 81 patients who died, 8 died due to or associated with IFI. Overall mortality rate attributable to IFI was 2% (8/419) and IFI was responsible or co-responsible for 10% (8/81) of deaths. Although invasive mold infections (n=6 proven mold infection) appear to be more difficult to resolve (33%, 2/6) than invasive yeast infections (n=10 proven yeast infection) (80%, 8/10), the power is lacking for statistical significance. Non-relapse mortality was not significantly different for patients with IFI and those without IFI. Univariate analysis showed that second transplantation (p=0.023), unrelated donor (p=0.042), late or none lymphocyte engraftment (p=0.003), grade II-IV acute graft versus host disease (aGVHD) (p=0.002), corticosteroid dose>2 mg/kg/day for at least 10 days (p=0.021), CMV reactivation (p=0.001), ATG (p=0.001) and Fludarabine (p=0.028) were possible risk factors for IFI. Of these factors, grade II-IV aGVHD [relative risk (RR) of IFI=2.801, p=0.008], ATG (RR of IFI=3.077, p=0.009),       late or none lymphocyte engraftment (RR of IFI=2.451, p=0.013), second transplantation (RR of IFI=5.555, p=0.037) and CMV reactivation (RR of IFI=2.110, p=0.046) were the factors associated with IFI in multivariate analysis.
Conclusion: The incidence and treatment success of IFI in this cohort are comparable to the rate reported in adult and other pediatric patients. Our results suggest that IFI after allogeneic HSCT in children is associated with grade II-IV aGVHD, second transplantation, CMV reactivation and late or none lymphocyte engraftment. Effective anti-fungal prophylaxis for these patients should be considered.

2015

abstract No: 

P593

Full conference title: 

Annual Meeting of European Society for Blood and Marrow Transplantation
    • EBMT 41st (2015)