Main Article Content

Sutatta Supatharawanich
Nattee Narkbunnam
Nassawee Vathana
Chayamon Takpradit
Kamon Phuakpet
Bunchoo Pongtanakul
Sasima Tongsai
Phakatip Sinlapamongkolkul
Popchai Ngamskulrungroj
Wanatpreeya Phongsamart
Kleebsabai Sanpakit
Jassada Buaboonnam


leukemia, aplastic anemia, fungal infection, candida


Although the outcome of childhood leukemia and severe aplastic anemia (SAA) has improved, infectious complications are still the major concern, particularly invasive fungal infection (IFI), which is one of the most common causes of infectious related death in such patients with prolonged neutropenia.  A retrospective study of IFI in pediatric patients with newly diagnosed and relapsed acute leukemia and SAA in Siriraj Hospital, Mahidol University, Thailand, was conducted.   There were 241 patients (150 patients with ALL, 35 patients with AML, 31 patients with relapsed leukemia and 25 patients with SAA) with the median age of 5.4 years (rage, 0.3-16.0 years). The overall prevalence of IFI was 23.2%, and the breakdown prevalence in ALL, AML, relapsed leukemia and SAA were 12.7%, 37.1%, 45.2% and 40.0% respectively. Candida tropicalis was the most common identifiable organism. Pulmonary IFI caused by invasive aspergillosis was the most common site of infection. The overall case-fatality rate was 50.0% with the highest rate in relapsed leukemia of 92.9%. In multivariable analysis, the age > 4 years, AML, relapsed leukemia and SAA were found to be independent risk factors of IFI with adjusted odds ratio of 2.3, 4.1, 5.1 and 3.7 respectively. In SAA group, only very severe aplastic anemia (ANC < 200 mm3) was found to be associated with development of IFI with odds ratio of 32.7. IFI in Thai children with hematologic diseases appeared to be prevalent with high fatality. Anti-fungal prophylaxis should be considered in patients with SAA to prevent IFI.


Download data is not yet available.
Abstract 230 | PDF Downloads 55 HTML Downloads 5


??1? Takahashi H, Kajiwara R, Kato M, et al. Treatment outcome of children with acute lymphoblastic leukemia: the Tokyo Children’s Cancer Study Group (TCCSG) Study L04-16. International Journal of Hematology. 2018;108:98-108.
?2? Larsen EC, Devidas M, Chen S, et al. Dexamethasone and High-Dose Methotrexate Improve Outcome for Children and Young Adults With High-Risk B-Acute Lymphoblastic Leukemia: A Report From Children's Oncology Group Study AALL0232. J Clin Oncol. 2016;34:2380-8.
?3? Tsukimoto I, Tawa A, Horibe K, et al. Risk-stratified therapy and the intensive use of cytarabine improves the outcome in childhood acute myeloid leukemia: the AML99 trial from the Japanese Childhood AML Cooperative Study Group. J Clin Oncol. 2009;27:4007-13.
?4? Reedijk AMJ, Klein K, Coebergh JWW, et al. Improved survival for children and young adolescents with acute myeloid leukemia: a Dutch study on incidence, survival and mortality. Leukemia. 2019;33:1349-59.
?5? Lehrnbecher T, Schöning S, Poyer F, et al. Incidence and Outcome of Invasive Fungal Diseases in Children With Hematological Malignancies and/or Allogeneic Hematopoietic Stem Cell Transplantation: Results of a Prospective Multicenter Study. Frontiers in Microbiology. 2019;10.
?6? Wang SS, Kotecha RS, Bernard A, et al. Invasive fungal infections in children with acute lymphoblastic leukaemia: Results from four Australian centres, 2003-2013. Pediatric Blood & Cancer. 2019;66:e27915.
?7? Castagnola E, Rossi MR, Cesaro S, et al. Incidence of bacteremias and invasive mycoses in children with acute non-lymphoblastic leukemia: results from a multi-center Italian study. Pediatr Blood Cancer. 2010;55:1103-7.
?8? Mor M, Gilad G, Kornreich L, Fisher S, Yaniv I, Levy I. Invasive fungal infections in pediatric oncology. Pediatric Blood & Cancer. 2011;56:1092-7.
?9? Kaya Z, Gursel T, Kocak U, Aral YZ, Kalkanci A, Albayrak M. Invasive fungal infections in pediatric leukemia patients receiving fluconazole prophylaxis. Pediatr Blood Cancer. 2009;52:470-5.
?10? Valdez JM, Scheinberg P, Nunez O, Wu CO, Young NS, Walsh TJ. Decreased infection-related mortality and improved survival in severe aplastic anemia in the past two decades. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2011;52:726-35.
?11? Lertpongpiroon R, Rattarittamrong E, Rattanathammethee T, et al. Infections in patients with aplastic Anemia in Chiang Mai University. BMC Hematology. 2018;18:35.
?12? Bajpai VK, Khan I, Shukla S, et al. Invasive Fungal Infections and Their Epidemiology: Measures in the Clinical Scenario. Biotechnology and Bioprocess Engineering. 2019;24:436-44.
?13? Guinan EC. CLINICAL ASPECTS OF APLASTIC ANEMIA. Hematology/Oncology Clinics of North America. 1997;11:1025-44.
?14? Group TTPO. National protocol for the treatment of childhood cancers 2014. Bangkok: The Thai Society of Hematology; 2014.
?15? Group TTPO. National protocol for the treatment of childhood cancers 2016. Bangkok: The Thai Society of Hematology; 2016.
?16? De Pauw B, Walsh TJ, Donnelly JP, 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.
?17? Rosen GP, Nielsen K, Glenn S, Abelson J, Deville J, Moore TB. Invasive Fungal Infections in Pediatric Oncology Patients: 11-Year Experience at a Single Institution. Journal of Pediatric Hematology/Oncology. 2005;27.
?18? Tang J-L, Kung H-C, Lei W-C, et al. High Incidences of Invasive Fungal Infections in Acute Myeloid Leukemia Patients Receiving Induction Chemotherapy without Systemic Antifungal Prophylaxis: A Prospective Observational Study in Taiwan. PloS one. 2015;10:e0128410-e.
?19? Romani L. Cell mediated immunity to fungi: a reassessment. Medical Mycology. 2008;46:515-29.
?20? van Tilburg CM, van Gent R, Bierings MB, et al. Immune reconstitution in children following chemotherapy for haematological malignancies: a long-term follow-up. Br J Haematol. 2011;152:201-10.
?21? Samanta A, Chandra J, Kaur R, Anand R, Shukla S, Mandal P. Clinical Profile and Microbiologic Spectrum of Febrile Neutropenic Episodes in Children With Severe Aplastic Anemia. J Pediatr Hematol Oncol. 2020;42:193-7.
?22? Quarello P, Saracco P, Giacchino M, et al. Epidemiology of infections in children with acquired aplastic anaemia: a retrospective multicenter study in Italy. Eur J Haematol. 2012;88:526-34.
?23? Valdez JM, Scheinberg P, Nunez O, Wu CO, Young NS, Walsh TJ. Decreased Infection-Related Mortality and Improved Survival in Severe Aplastic Anemia in the Past Two Decades. Clinical Infectious Diseases. 2011;52:726-35.
?24? Pana ZD, Roilides E, Warris A, Groll AH, Zaoutis T. Epidemiology of Invasive Fungal Disease in Children. J Pediatric Infect Dis Soc. 2017;6:S3-s11.
?25? Cleveland AA, Farley MM, Harrison LH, et al. Changes in incidence and antifungal drug resistance in candidemia: results from population-based laboratory surveillance in Atlanta and Baltimore, 2008-2011. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2012;55:1352-61.
?26? Santolaya ME, Alvarado T, Queiroz-Telles F, et al. Active surveillance of candidemia in children from Latin America: a key requirement for improving disease outcome. Pediatr Infect Dis J. 2014;33:e40-4.
?27? Tan BH, Chakrabarti A, Li RY, et al. Incidence and species distribution of candidaemia in Asia: a laboratory-based surveillance study. Clinical Microbiology and Infection. 2015;21:946-53.
?28? Arastehfar A, Daneshnia F, Hafez A, et al. Antifungal susceptibility, genotyping, resistance mechanism, and clinical profile of Candida tropicalis blood isolates. Medical Mycology. 2019;58:766-73.
?29? Pham LTT, Pharkjaksu S, Chongtrakool P, Suwannakarn K, Ngamskulrungroj P. A Predominance of Clade 17 Candida albicans Isolated From Hemocultures in a Tertiary Care Hospital in Thailand. Frontiers in Microbiology. 2019;10.
?30? Tulyaprawat O, Pharkjaksu S, Chongtrakool P, Ngamskulrungroj P. An Association of an eBURST Group With Triazole Resistance of Candida tropicalis Blood Isolates. Frontiers in Microbiology. 2020;11.
?31? Apsemidou A, Petridis N, Vyzantiadis T-A, Tragiannidis A. Invasive Aspergillosis in Children: Update on Current Guidelines. Mediterranean journal of hematology and infectious diseases. 2018;10:e2018048-e.
?32? Lehrnbecher T, Fisher BT, Phillips B, et al. Clinical Practice Guideline for Systemic Antifungal Prophylaxis in Pediatric Patients With Cancer and Hematopoietic Stem-Cell Transplantation Recipients. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2020;38:3205-16.
?33? Kobayashi R, Kaneda M, Sato T, Ichikawa M, Suzuki D, Ariga T. The clinical feature of invasive fungal infection in pediatric patients with hematologic and malignant diseases: a 10-year analysis at a single institution at Japan. J Pediatr Hematol Oncol. 2008;30:886-90.
?34? Pana ZD, Seidel D, Skiada A, et al. Invasive mucormycosis in children: an epidemiologic study in European and non-European countries based on two registries. BMC infectious diseases. 2016;16:667-.
?35? Nucci M, Anaissie E. How we treat invasive fungal diseases in patients with acute leukemia: the importance of an individualized approach. Blood. 2014;124:3858-69.
?36? Gamaletsou MN, Walsh TJ, Zaoutis T, et al. A prospective, cohort, multicentre study of candidaemia in hospitalized adult patients with haematological malignancies. Clin Microbiol Infect. 2014;20:O50-7.
?37? van de Peppel RJ, Dekkers OM, von dem Borne PA, de Boer MG. Relapsed and secondary disease drive the risk profile for invasive aspergillosis prior to stem cell transplantation in patients with acute myeloid leukemia or myelodysplastic syndrome. Med Mycol. 2014;52:699-705.
?38? Qian J, Jiang C, Wenji Q, et al. Inherited NUDT15 Variants Substantially Increased Infection and Related Medical Cost in Children with Acute Lymphoblastic Leukemia. Blood. 2018;132:320-.