Invasive fungal diseases in children with hematologic disorders

GÜNAY, Ünsal; BAYTAN, Birol; Celebi, Solmaz; GÜNEŞ, Adalet Meral

Invasive fungal diseases in children with hematologic disorders

Birol BAYTAN, (Uludağ Üniversitesi, Tıp Fakültesi, Pediatrik Hematoloji Anabilim Dalı, Bursa, Türkiye)

Adalet Meral GÜNEŞ, (Uludağ Üniversitesi, Tıp Fakültesi, Pediatrik Hematoloji Anabilim Dalı, Bursa, Türkiye)

Solmaz ÇELEBİ, (Uludağ Üniversitesi, Tıp Fakültesi, Enfeksiyon Hastalıkları Anabilim Dalı, Bursa, Türkiye)

Ünsal GÜNAY (Uludağ Üniversitesi, Tıp Fakültesi, Pediatrik Hematoloji Anabilim Dalı, Bursa, Türkiye)

Turkish Journal of Hematology

1 0

Yıl: 2009 Cilt: 26 Sayı: 4 Sayfa Aralığı: 190 - 196 Metin Dili: Türkçe İndeks Tarihi: 29-07-2022

Invasive fungal diseases in children with hematologic disorders

Öz:

Amaç: Fungal infeksiyonlar lösemili hastalarda infeksiyonlardan ölümlerde önemli bir sorundur. Bu sorun gelişmekte olanülkelerde iyi dökümente edilmemiştir. Bu çalışmanın amacı, geriye dönük olarak çocuk hastalarda görülen hematolojikhastalıklardaki invazif fungal hastalık (İFH) insidansını, predispozan faktörleri, tanı metodları, tedavi etkiliği ve sonuçlarınıincelemektir.Yöntem ve Gereçler: Merkezimizde Ocak 2003 ve Aralık 2008 tarihleri arasında tedavi edilen 160 lösemili (22 AML, 129ALL) ve 9 aplastik anemili olgu çalışmaya alındı. EORTC-MSG 2008 kriterlerine göre olgulara olası veya kesin İFH tanısıkondu. Antibiyotik tedavisine rağmen 5 günden uzun süren ateş yüksekliği saptanan olgulara ampirik antifungal tedaviolarak L-AmB başlandı. İnvasive aspergillozis (IA) saptanan olgularda tedavi voriconazole (VCZ) değiştirildi. Kurtarma teda- visinde VCZ ve kaspofungin kombinasyonu kullanıldı.Bulgular: Çalışmamızda İFH %14,3 (n: 23) bulundu. 19 lösemili(14 ALL, 5 AML) ve 4 aplastik anemili olguda IFH tanısıkondu. IA en sık rastlanan enfeksiyon oldu (n: 17), diğer 6 olguda kandidiazis saptandı. On olguya kesin ve 13 olguya kuv- vetli olası enfeksiyon tanısı kondu. En sık tutulan enfeksiyon bölgesi akciğerdi. Çalışmamızda, en sık kullanılan tanı yöntem- leri; klinik bulgular (%100) ve radyolojik metodlar (%84) olarak saptandı. Tedavide başarı oranları kandidiasis ve IA’da %60ve %71 bulundu. İFH ile ilişkili ölüm oranı %30 saptandı. Sonuç: Sonuç olarak, İFH hala hematolojik hastalıklı olgularda ciddi mortalite morbitide sebebidir. Ancak yeni antifungalilaçlar ve tanı yöntemleri ile yaşam oranları artmaktadır. (Turk J Hematol 2009; 26: 190-6)

Anahtar Kelime: Tanı Anemi, aplastik Kandidiyaz, invaziv Sebep sonuç ilişkisi Çocuk Görülme sıklığı Lösemi Mikozlar Geriyedönük çalışma

Konular: Hematoloji

Hematolojik hastalıklı çocuklarda invazif fungal infeksiyonu

Öz:

Objective: Fungal infection is a significant problem, causing of infective deaths of leukemic patients. The situation in developing countries is not well documented. The purpose of this study was characterizing IFD by analyzing data retro- spectively to determine the incidence, predisposing factors, diagnostic methods, efficacy of treatment, and the outcome in pediatric patients with hematological disorders.Materials and Methods: There were 160 children with leukemia (22 AML, 129 ALL) and 9 with aplastic anemia (AA). The diagnostic criteria for IFD were defined according to the EORTC/MSG, 2008. IFD was classified as proven or probable. Empiric antifungal treatment with L-AmB was commenced by day 5-7 of persistent fever. Patients with invasive aspergil- losis (IA) who were refractory to primary treatment were commenced on voriconazole (VCZ). Salvage therapy as combina- tion of VCZ and caspofungin was given to those with progressive infection.Results: The incidence of IFD was found 23 (14.3%). 19 with leukemia (14 ALL, 5 AML) and 4 with aplastic anemia were diagnosed as IFD. IA was the dominant cause of infection (n=17) and the rest (n: 6) had candidiasis. Ten children had “proven” infection and 13 children were defined as “probable”. The most frequent site of infection was lungs. In our series, the most frequently used diagnostic methods were clinical findings (100%) and radiologic methods (84%). The success rate of treatment for candidiasis and IA were found 60%, 71% respectively. IFD related death rate was found 30%. Conclusion: IFD is still a major morbidity and mortality reason in children with hematologic disorders. However, the avail- ability of new antifungal treatments and diagnostic tests will improve the survival rates in these children.

Anahtar Kelime: Causality Child Incidence Leukemia Mycoses Retrospective Studies Diagnosis Anemia, Aplastic Candidiasis, Invasive

Konular: Hematoloji

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık

1. Yeh TC, Liu HC, Wang LY, Chen SH, Liang DC. Invasive fungal infection in children undergoing chemotherapy for cancer. Ann Trop Paediatr 2007;27:141-7.
2. Zaoutis TE, Heydon K, Chu JH, Walsh TJ, Steinbach WJ. Epidemiology, outcomes, and costs of invasive aspergillosis in immunocompromised children in the United States, 2000. Pediatrics 2006;117:711-6.
3. El-Mahallawy HA, Attia I, Ali-el-Din NH, Salem AE, Abo-el-Naga S.A prospective study on fungal infection in children with cancer. J Med Microbiol 2002;51:601-5.
4. Hovi L, Saxen H, Saarinen-Pihkala UM, Vettenranta K, Meri T, Richardson M. Prevention and monitoring of invasive fungal infec tions in pediatric patients with cancer and hematologic disorders. Pediatr Blood Cancer. 2007;48:28-34.
5. Freifeld AG, Walsh TJ, Pizzo PA. Infectious complications in the pediatric cancer patient. In: Pizzo PA, Poplack DG (eds) Principles and practice of pediatric oncology, 3rd ed. Philadelphia, Lippincott-Raven. 1997: 1069-114.
6. Denning DW, Marinus A, Cohen J, Spence D, Herbrecht R, Pagano L, Kibbler C, Kcrmery V, Offner F, Cordonnier C, Jehn U, Ellis M, Collette L, Sylvester R. An EORTC multicentre prospective survey of invasive aspergillosis in haematological patients: diag nosis and therapeutic outcome. EORTC Invasive Fungal Infections Cooperative Group. J Infect 1998;37:173-80.
7. Athanassiadou F, Tragiannidis A, Kourti M, Papageorgiou T, Velegraki A, Drevelengas A. Invasive fungal infections in children with hematological malignancies: a 5-year study. Pediatr Hematol Oncol 2006;23:163-6.
8. Schrappe M, Camitta B, Pui CH, Eden T, Gaynon P, Gustafsson G, Janka-Schaub GE, Kamps W, Masera G, Sallan S, Tsuchida M, Vilmer E.Long-term results of large prospective trials in child hood acute lymphoblastic leukemia. Leukemia 2000;14: 2193-4.
9. Webb DK, Harrison G, Stevens RF, Gibson BG, Hann IM, Wheatley K. MRC Childhood Leukemia Working Party. Relationships between age at diagnosis, clinical features, and outcome of therapy in children treated in the Medical Research Council AML 10 and 12 trials for acute myeloid leukemia. Blood 2001;98:1714-20.
10. Hope WW, Walsh TJ, Denning DW. Laboratory diagnosis of inva sive aspergillosis. Lancet Infect Dis 2005;5:609-22.
11. De Pauw B, Walsh TJ, Donnelly JP, Stevens DA, Edwards JE, Calandra T, Pappas PG, Maertens J, Lortholary O, Kauffman CA, Denning DW, Patterson TF, Maschmeyer G, Bille J, Dismukes WE, Herbrecht R, Hope WW, Kibbler CC, Kullberg BJ, Marr KA, Muñoz P, Odds FC, Perfect JR, Restrepo A, Ruhnke M, Segal BH, Sobel JD, Sorrell TC, Viscoli C, Wingard JR, Zaoutis T, Bennett JE. 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.
12. Segal BH, Herbrecht R, Stevens DA, Ostrosky-Zeichner L, Sobel J, Viscoli C, Walsh TJ, Maertens J, Patterson TF, Perfect JR, Dupont B, Wingard JR, Calandra T, Kauffman CA, Graybill JR, Baden LR, Pappas PG, Bennett JE, Kontoyiannis DP, Cordonnier C, Viviani MA, Bille J, Almyroudis NG, Wheat LJ, Graninger W, Bow EJ, Holland SM, Kullberg BJ, Dismukes WE, De Pauw BE. Defining responses to therapy and study outcomes in clinical trials of invasive fungal diseases: Mycoses Study Group and European Organization for Research and Treatment of Cancer consensus criteria. Clin Infect Dis. 2008;47:674-83.
13. 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. J Pediatr Hematol Oncol 2005;27:135-40.
14. 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.
15. Gözdaşoğlu S, Ertem M, Büyükkeçeci Z, Yavuzdemir S, Bengisun S, Ozenci H, Taçyildiz N, Unal E, Yavuz G, Deda G, Aysev D. Fungal colonization and infection in children with acute leukemia and lymphoma during induction therapy. Med Pediatr Oncol. 1999;32:344-8.
16. Torres HA, Bodey GP, Rolston KV, Kantarjian HM, Raad II, Kontoyiannis DP. Infections in patients with aplastic anemia: experience at a tertiary care cancer center. Cancer. 2003;98:86-3.
17. Valdez JM, Scheinberg P, Young NS, Walsh TJ.Infections in patients with aplastic anemia. Semin Hematol. 2009;46:269-76.
18. Pagano L, Caira M, Picardi M, Candoni A, Melillo L, Fianchi L, Offidani M, Nosari A. Invasive Aspergillosis in patients with acute leukemia: update on morbidity and mortality SEIFEM-C Report. Clin Infect Dis 2007;44:1524-5.
19. Bhatti Z, Shaukat A, Almyroudis NG, Segal BH. Review of epidemiology, diagnosis, and treatment of invasive mould infections in allogeneic hematopoietic stem cell transplant recipients. Mycopathologia 2006;162:1-15.
20. Castagnola E, Caviglia I, Pistorio A, Fioredda F, Micalizzi C, Viscoli C, Haupt R. Bloodstream infections and invasive mycoses in children undergoing acute leukaemia treatment: a 13-year experience at a single Italian institution. Eur J Cancer 2005;41:1439-45.
21. Marr KA, Patterson T, Denning D. Aspergillosis. Pathogenesis, clinical manifestations, and therapy. Infect Dis Clin North Am 2002;16:875-94.
22. Groll AH, Kurz M, Schneider W, Witt V, Schmidt H, Schneider M, Schwabe D. Five-year-survey of invasive aspergillosis in a paediatric cancer centre. Epidemiology, management and long-term survival. Mycoses 1999;42:431-42.
23. Nosari A, Oreste P, Cairoli R, Montillo M, Carrafiello G, Astolfi A, Muti G, Marbello L, Tedeschi A, Magliano E, Morra E. Invasive aspergillosis in haematological malignancies: clinical findings and management for intensive chemotherapy completion. Am J Hematol 2001;68:231-6.
24. Tempkin AD, Sobonya RE, Seeger JF, Oh ES. Cerebral aspergillosis: radiologic and pathologic findings. Radiographics 2006;26:1239-42.
25. Kleinschmidt-DeMasters BK. Central nervous system aspergillosis: a 20 year retrospective series. Hum Pathol 2002;33:116-24.
26. Ascioglu S, de Pauw BE, Donnelly JP, Collette L. Reliability of clinical research on invasive fungal infections: a systematic review of the literature. Med Mycol 2001;39:35-40.
27. Althoff Souza C, Müller NL, Marchiori E, Escuissato DL, Franquet T. Pulmonary invasive aspergillosis and candidiasis in immuno compromised patients: a comparative study of the high-resolution CT findings. J Thorac Imaging 2006;21:184-9.
28. Thomas KE, Owens CM, Veys PA, Novelli V, Costoli V. The radiological spectrum of invasive aspergillosis in children: a 10-year review. Pediatr Radiol 2003;33:453-60.
29. Bochennek K, Abolmaali N, Wittekindt B, Schwabe D, Klingebiel T, Lehrnbecher T. Diagnostic approaches for immunocompromised paediatric patients with pulmonary infiltrates. Clin Microbiol Infect 2006;12:199-201.
30. Lass-Flörl C, Resch G, Nachbaur D, Mayr A, Gastl G, Auberger J, Bialek R, Freund MC. The value of computed tomography-guided percutaneous lung biopsy for diagnosis of invasive fungal infection in immunocompromised patients. Clin Infect Dis. 2007;45:101-4.
31. Maertens J, Theunissen K, Verhoef G, et al. Galactomannan and computed tomography-based preemptive antifungal therapy in neutropenic patients at high risk for invasive fungal infection: a prospective feasibility study. Clin Infect Dis 2005;41:1242-50.
32. Rex JH. Galactomannan and the diagnosis of invasive aspergillosis. Clin Infect Dis 2006;42:1428-30.
33. Lim ZY, Ho AY, Devereux S, Mufti GJ, et al. False positive results of galactomannan ELISA assay in haemato-oncology patients: a single centre experience. J Infect 2007;55:201-2.
34. Merlin E, Galambrun C, Ribaud P, Blanc T, Michel G, Auvrignon A, Stéphan JL. Efficacy and safety of caspofungin therapy in children with invasive fungal infections. Pediatr Infect Dis J 2006;25:1186-8.
35. Baker C. Serial Aspergillus antigen monitoring in pediatric bone marrow transplant patients. J Pediatr Oncol Nurs 2006;23:300-4.
36. Racil Z, Kocmanova I, Lengerova M, et al. Intravenous PLASMALYTE as a major cause of false-positive results of platelia Aspergillus test for galactomannan detection in serum.J Clin Microbiol 2007;45:3141-2.
37. Maertens J, Raad I, Petrikkos G, Boogaerts M, Selleslag D, Petersen FB, Sable CA, Kartsonis NA, Ngai A, Taylor A, Patterson TF, Denning DW, Walsh TJ. Caspofungin Salvage Aspergillosis Study Group Efficacy and safety of caspofungin for treatment of invasive aspergillosis in patients refractory to or intolerant of con ventional antifungal therapy. Clin Infect Dis 2004;39:1563-71.
38. Cesaro S, Giacchino M, Locatelli F, Spiller M, Buldini B, Castellini C, Caselli D, Giraldi E, Tucci F, Tridello G, Rossi MR, Castagnola E. Safety and efficacy of a caspofungin-based combination therapy for treatment of proven or probable aspergillosis in pediatric hematological patients. BMC Infect Dis 2007;7:28-30.
39. Groll AH, Attarbaschi A, Schuster FR, Herzog N, Grigull L, Dworzak MN, Beutel K, Laws HJ, Lehrnbecher T. Treatment with caspofungin in immunocompromised paediatric patients: a multicentre survey. J Antimicrob Chemother 2006;57:527-35.
40. Patterson TF, Boucher HW, Herbrecht R, Denning DW, Lortholary O, Ribaud P, Rubin RH, Wingard JR, DePauw B, Schlamm HT, Troke P, Bennett JE. European Organization for Research and Treatment of Cancer (EORTC) Invasive Fungal Infections Group (IFIG); Pfizer Global Aspergillus Study Group. Strategy of following voriconazole versus amphotericin B therapy with other licensed antifungal therapy for primary treatment of invasive aspergillosis: impact of other therapies on outcome. Clin Infect Dis 2005;41:1448-52.
41. Blyth CC, Palasanthiran P, O'Brien TA. Antifungal therapy in children with invasive fungal infections: a systematic review. Pediatrics 2007;119:772-84.
42. Schuster F, Moelter C, Schmid I, Graubner UB, Kammer B, Belohradsky BH, Führer M. Successful antifungal combination therapy with voriconazole and caspofungin. Pediatr Blood Cancer 2005;44:682-5.
43. Wisplinghoff H, Seifert H, Wenzel RP, Edmond MB. Current trends in the epidemiology of nosocomial bloodstream infections in patients with hematological malignancies and solid neoplasms in hospitals in the United States. Clin Infect Dis 2003;36:1103-10.
44. 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.
45. Grigull L, Beier R, Schrauder A, Kirschner P, Loening L, Jack T, Welte K, Sykora KW, Schrappe M. Invasive fungal infections are responsible for one-fifth of the infectious deaths in children with ALL. Mycoses. 2003;46:441-6.
46. Riley LC, Hann IM, Wheatley K, Stevens RF. Treatment-related deaths during induction and first remission of acute myeloid leu kaemia in children treated on the Tenth Medical Research Council acute myeloid leukaemia trial (MRC AML10). The MCR Childhood Leukaemia Working Party. Br J Haematol. 1999;106:436-44.

APA	BAYTAN B, GÜNEŞ A, Celebi S, GÜNAY Ü (2009). Invasive fungal diseases in children with hematologic disorders. , 190 - 196.
Chicago	BAYTAN Birol,GÜNEŞ Adalet Meral,Celebi Solmaz,GÜNAY Ünsal Invasive fungal diseases in children with hematologic disorders. (2009): 190 - 196.
MLA	BAYTAN Birol,GÜNEŞ Adalet Meral,Celebi Solmaz,GÜNAY Ünsal Invasive fungal diseases in children with hematologic disorders. , 2009, ss.190 - 196.
AMA	BAYTAN B,GÜNEŞ A,Celebi S,GÜNAY Ü Invasive fungal diseases in children with hematologic disorders. . 2009; 190 - 196.
Vancouver	BAYTAN B,GÜNEŞ A,Celebi S,GÜNAY Ü Invasive fungal diseases in children with hematologic disorders. . 2009; 190 - 196.
IEEE	BAYTAN B,GÜNEŞ A,Celebi S,GÜNAY Ü "Invasive fungal diseases in children with hematologic disorders." , ss.190 - 196, 2009.
ISNAD	BAYTAN, Birol vd. "Invasive fungal diseases in children with hematologic disorders". (2009), 190-196.

APA	BAYTAN B, GÜNEŞ A, Celebi S, GÜNAY Ü (2009). Invasive fungal diseases in children with hematologic disorders. Turkish Journal of Hematology, 26(4), 190 - 196.
Chicago	BAYTAN Birol,GÜNEŞ Adalet Meral,Celebi Solmaz,GÜNAY Ünsal Invasive fungal diseases in children with hematologic disorders. Turkish Journal of Hematology 26, no.4 (2009): 190 - 196.
MLA	BAYTAN Birol,GÜNEŞ Adalet Meral,Celebi Solmaz,GÜNAY Ünsal Invasive fungal diseases in children with hematologic disorders. Turkish Journal of Hematology, vol.26, no.4, 2009, ss.190 - 196.
AMA	BAYTAN B,GÜNEŞ A,Celebi S,GÜNAY Ü Invasive fungal diseases in children with hematologic disorders. Turkish Journal of Hematology. 2009; 26(4): 190 - 196.
Vancouver	BAYTAN B,GÜNEŞ A,Celebi S,GÜNAY Ü Invasive fungal diseases in children with hematologic disorders. Turkish Journal of Hematology. 2009; 26(4): 190 - 196.
IEEE	BAYTAN B,GÜNEŞ A,Celebi S,GÜNAY Ü "Invasive fungal diseases in children with hematologic disorders." Turkish Journal of Hematology, 26, ss.190 - 196, 2009.
ISNAD	BAYTAN, Birol vd. "Invasive fungal diseases in children with hematologic disorders". Turkish Journal of Hematology 26/4 (2009), 190-196.