Management of Invasive Fungal Infections in Pediatric Acute Leukemia and the Appropriate Time for Restarting Chemotherapy

Simsek, Erdem; YILMAZ BENGOA, Şebnem; Karapınar, Tuba Hilkay; Tüfekçi, Özlem; YENİGÜRBÜZ, Fatma Demir; İRKEN, Gülersu; ÖREN, Hale

Management of Invasive Fungal Infections in Pediatric Acute Leukemia and the Appropriate Time for Restarting Chemotherapy

Özlem TÜFEKÇİ, (Dokuz Eylül Üniversitesi, Tıp Fakültesi, Pediatrik Hematoloji Anabilim Dalı, İzmir, Türkiye)

Şebnem YILMAZ BENGOA, (Dokuz Eylül Üniversitesi, Tıp Fakültesi, Pediatrik Hematoloji Anabilim Dalı, İzmir, Türkiye)

Fatma Demir YENİGÜRBÜZ, (Dokuz Eylül Üniversitesi, Tıp Fakültesi, Pediatrik Hematoloji Anabilim Dalı, İzmir, Türkiye)

Erdem ŞİMŞEK, (Dokuz Eylül Üniversitesi, Tıp Fakültesi, Pediatri Anabilim Dalı, İzmir, Türkiye)

Tuba Hilkay KARAPINAR, (Dokuz Eylül Üniversitesi, Tıp Fakültesi, Pediatrik Hematoloji Anabilim Dalı, İzmir, Türkiye)

Gülersu İRKEN, (Dokuz Eylül Üniversitesi, Tıp Fakültesi, Pediatrik Hematoloji Anabilim Dalı, İzmir, Türkiye)

Hale ÖREN (Dokuz Eylül Üniversitesi, Tıp Fakültesi, Pediatrik Hematoloji Anabilim Dalı, İzmir, Türkiye)

Turkish Journal of Hematology

3 0

Yıl: 2015 Cilt: 32 Sayı: 4 Sayfa Aralığı: 329 - 337 Metin Dili: Türkçe İndeks Tarihi: 29-07-2022

Management of Invasive Fungal Infections in Pediatric Acute Leukemia and the Appropriate Time for Restarting Chemotherapy

Öz:

Amaç: Lösemili hastalarda invaziv fungal enfeksiyonların (İFE) çabuk ve etkin tedavisi sağkalım için önemlidir. Bu çalışmada akut lösemi (AL) ve İFE olan çocuklarda klinik bulgular, tedavi şekilleri, tekrar kemoterapiye başlama zamanı ve tedavi sonucu gibi değişkenleri değerlendirmeyi amaçladık. Gereç ve Yöntemler: Kliniğimizde 2001-2013 yılları arasında izlenmiş tüm AL'lı çocukların hastane kayıtları retrospektif olarak tarandı. Tüm hastalara kemoterapi süresince proflaktik flukonazol tedavisi verildi.Bulgular: İFE, 174 AL hastasından 25'inde (%14) saptandı. Çoğu konsolidasyon tedavisi sırasında gelişmişti ve hastalar ağır nötropenikti. Lösemi tanısı ve İFE gelişme arasındaki ortanca süre 122 gündü. Hastaların 24'ünde pulmoner İFE vardı. Bilgisayarlı tomografi tetkikinde en sık izlenen bulgu parenkimal nodüllerdi. İFE epizodları 4 (%16) olguda kanıtlanmış, 7 (%28) olguda olası, 14 (%56) olguda muhtemel olarak değerlendirildi. Kemoterapiye ara verme süresi ortanca 27 gündü. İFE voriconazole, amphotericin B, caspofungin, posaconazole tekli veya kombine tedavileri ile başarıyla tedavi edildi. Olguların %50'sinde kemoterapiye 4 haftadan önce başlandı ve hiçbirinde İFE reaktivasyonu saptanmadı. Tümüne ikincil proflaksi verildi. Antifungal tedavi ve sekonder proflaksi ortanca süresi sırayla 26 ve 90 gündü. Hastalardan hiçbiri İFE ile kaybedilmedi. Sonuç: Verilerimiz AL ve İFE olan çocuklarda erken ve etkin rasyonel antifungal tedavi ile ölüm oranının azaltılabileceğini ve birkaç hafta içinde kemoterapiye güvenle başlanabileceğini göstermektedir

Anahtar Kelime:

Konular: Hematoloji Pediatri

Çocukluk Çağı Akut Lösemisinde İnvaziv Fungal Enfeksiyonların Tedavisi ve Kemoterapiye Başlamanın Uygun Zamanı

Öz:

Objective: Rapid and effective treatment of invasive fungal infection (IFI) in patients with leukemia is important for survival. In this study, we aimed to describe variations regarding clinical features, treatment modalities, time of restarting chemotherapy, and outcome in children with IFI and acute leukemia (AL). Materials and Methods: The charts of all pediatric AL patients in our clinic between the years of 2001 and 2013 were retrospectively reviewed. All patients received prophylactic fluconazole during the chemotherapy period. Results: IFI was identified in 25 (14%) of 174 AL patients. Most of them were in the consolidation phase of chemotherapy and the patients had severe neutropenia. The median time between leukemia diagnosis and definition of IFI was 122 days. Twenty-four patients had pulmonary IFI. The most frequent finding on computed tomography was typical parenchymal nodules. The episodes were defined as proven in 4 (16%) patients, probable in 7 (28%) patients, and possible in 14 (56%) patients. The median time for discontinuation of chemotherapy was 27 days. IFI was treated successfully in all patients with voriconazole, amphotericin B, caspofungin, or posaconazole alone or in combination. Chemotherapy was restarted in 50% of the patients safely within 4 weeks and none of those patients experienced reactivation of IFI. All of them were given secondary prophylaxis. The median time for antifungal treatment and for secondary prophylaxis was 26 and 90 days, respectively. None of the patients died due to IFI. Conclusion: Our data show that rapid and effective antifungal therapy with rational treatment modalities may decrease the incidence of death and that restarting chemotherapy within several weeks may be safe in children with AL and IFI

Anahtar Kelime:

Konular: Hematoloji Pediatri

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

Bow EJ. Infection risk and cancer chemotherapy: the impact of the chemotherapeutic regimen in patients with lymphoma and solid tissue malignancies. J Antimicrob Chemother 1998;(Suppl 41):1-5.
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;117:711-716.
Mor M, Gilad G, Kornreich L, Fisher S, Yaniv I, Levy I. Invasive fungal infections in pediatric oncology. Pediatr Blood Cancer 2011;56:1092-1097.
Kurosawa M, Yonezumi M, Hashino S, Tanaka J, Nishio M, Kaneda M, Ota S, Koda K, Suzuki N, Yoshida M, Hirayama Y, Takimoto R, Torimoto Y, Mori A, Takahashi T, Iizuka S, Ishida T, Kobayashi R, Oda T, Sakai H, Yamamoto S, Takahashi F, Fukuhara T. Epidemiology and treatment outcome of invasive fungal infections in patients with hematological malignancies. Int J Hematol 2012;96:748-757.
Chamilos G, Luna M, Lewis RE, Bodey GP, Chemaly R, Tarrand JJ, Safdar A, Raad II, Kontoyiannis DP. Invasive fungal infections in patients with hematologic malignancies in a tertiary care cancer center: an autopsy study over a 15-year period (1989-2003). Haematologica 2006;91:986-989.
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;27:135-140.
Wiley JM, Smith N, Leventhal BG, Graham ML, Graham ML, Strauss LC, Hurwitz CA, Modlin J, Mellits D, Baumgardner R, Corden BJ. Invasive fungal disease in pediatric acute leukemia patients with fever and neutropenia during induction chemotherapy: a multivariate analysis of risk factors. J Clin Oncol 1990;8:280-286.
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;32:344-348.
Kaya Z, Gürsel T, Koçak U, Aral YZ, Kalkancı A, Albayrak M. Invasive fungal infections in pediatric leukemia patients receiving fluconazole prophylaxis. Pediatr Blood Cancer 2009;52:470-475.
Hale KA, Shaw PJ, Dalla-Pozza L, MacIntyre CR, Isaacs D, Sorrell TC. Epidemiology of paediatric invasive fungal infections and a case-control study of risk factors in acute leukaemia or post stem cell transplant. Br J Haematol 2010;149:263-272.
Cesaro S, Pagano L, Caira M, Carraro F, Luciani M, Russo D, Colombini A, Morello W, Viale P, Rossi G, Tridello G, Pegoraro A, Nosari A, Aversa F; Hema-e-chart Group. A prospective, multicentre survey on antifungal therapy in neutropenic paediatric haematology patients. Mycoses 2013;56:21-25.
Baytan B, Güneş AM, Çelebi S, Günay Ü. Invasive fungal diseases in children with hematologic disorders. Turk J Hematol 2009;26:190-196.
Dvorak CC, Steinbach WJ, Brown JM, Agarwal R. Risks and outcomes of invasive fungal infections in pediatric patients undergoing allogeneic hematopoietic cell transplantation. Bone Marrow Transplant 2005;36:621-629.
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;30:886-890.
Dini G, Castagnola E, Comoli P, van Tol MJ, Vossen JM. Infections after stem cell transplantation in children: state of the art and recommendations. Bone Marrow Transplant 2001;28(Suppl 1):18-21.
Castagnola E, Cesaro S, Giacchino M, Livadiotti S, Tucci F, Zanazzo G, Caselli D, Caviglia I, Parodi S, Rondelli R, Cornelli PE, Mura R, Santoro N, Russo G, De Santis R, Buffardi S, Viscoli C, Haupt R, Rossi MR. Fungal infections in children with cancer: a prospective, multicenter surveillance study. Pediatr Infect Dis J 2006;25:634-639.
Castagnola E, Rossi MR, Cesaro S, Livadiotti S, Giacchino M, Zanazzo G, Fioredda F, Beretta C, Ciocchello F, Carli M, Putti MC, Pansini V, Berger M, Licciardello M, Farina S, Caviglia I, Haupt R. Incidence of bacteremias and invasive mycoses in children with acute non-lymphoblastic leukemia: results from a multi-center Italian study. Pediatr Blood Cancer 2010;55:1103-1107.
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;41:1439-1445.
Cornely OA, Böhme A, Reichert D, Reuter S, Maschmeyer G, Maertens J, Buchheidt D, Paluszewska M, Arenz D, Bethe U, Effelsberg J, Lövenich H, Sieniawski M, Haas A, Einsele H, Eimermacher H, Martino R, Silling G, Hahn M, Wacker S, Ullmann AJ, Karthaus M; Multinational Case Registry of the Infectious Diseases Working Party of the German Society for Hematology and Oncology. Risk factors for breakthrough invasive fungal infection during secondary prophylaxis. J Antimicrob Chemother 2008;61:939-946.
Bow EJ, Kilpatrick MG, Scott BA, Clinch JJ, Cheang MS. Acute myeloid leukemia in Manitoba. The consequences of standard "7 + 3" remission-induction therapy followed by high dose cytarabine postremission consolidation for myelosuppression, infectious morbidity, and outcome. Cancer 1994;74:52-60.
Dornbusch HJ, Groll A, Walsh TJ. Diagnosis of invasive fungal infections in immunocompromised children. Clin Microbiol Infect 2010;16:1328-1334.
Busca A, Locatelli F, Barbui A, Limerutti G, Serra R, Libertucci D, Falda M. Usefulness of sequential Aspergillus galactomannan antigen detection combined with early radiologic evaluation for diagnosis of invasive pulmonary aspergillosis in patients undergoing allogeneic stem cell transplantation. Transplant Proc 2006;38:1610-1613.
Pfeiffer CD, Fine JP, Safdar N. Diagnosis of invasive aspergillosis using a galactomannan assay: a meta-analysis. Clin Infect Dis 2006;42:1417-1427.
El-Mahallawy HA, Shaker HH, Ali Helmy H, Mostafa T, Razak Abo-Sedah A. Evaluation of pan-fungal PCR assay and Aspergillus antigen detection in the diagnosis of invasive fungal infections in high risk paediatric cancer patients. Med Mycol 2006;44:733-739.
Armenian SH, Nash KA, Kapoor N, Franklin JL, Gaynon PS, Ross LA, Hoffman JA. Prospective monitoring for invasive aspergillosis using galactomannan and polymerase chain reaction in high risk pediatric patients. J Pediatr Hematol Oncol 2009;31:920-926.
Castagnola E, Furfaro E, Caviglia I, Licciardello M, Faraci M, Fioredda F, Tomà P, Bandettini R, Machetti M, Viscoli C. Performance of the galactomannan antigen detection test in the diagnosis of invasive aspergillosis in children with cancer or undergoing haemopoietic stem cell transplantation. Clin Microbiol Infect 2010;16:1197-1203.
Steinbach WJ, Addison RM, McLaughlin L, Gerrald Q, Martin PL, Driscoll T, Bentsen C, Perfect JR, Alexander BD. Prospective Aspergillus galactomannan antigen testing in pediatric hematopoietic stem cell transplant recipients. Pediatr Infect Dis J 2007;26:558-564.
Caillot D, Casasnovas O, Bernard A, Couaillier JF, Durand C, Cuisenier B, Solary E, Piard F, Petrella T, Bonnin A, Couillault G, Dumas M, Guy H. Improved management of invasive pulmonary aspergillosis in neutropenic patients using early thoracic computed tomographic scan and surgery. J Clin Oncol 1997;15:139-147.
Blum U, Windfuhr M, Buitrago-Tellez C, Sigmund G, Herbst EW, Langer M. Invasive pulmonary aspergillosis. MRI, CT, and plain radiographic findings and their contribution for early diagnosis. Chest 1994;106:1156-1161.
Crassard N, Hadden H, Piens MA, Pondarré C, Hadden R, Galambrun C, Pracros JP, Souillet G, Basset T, Berthier JC, Philippe N, Bertrand Y. Invasive aspergillosis in a paediatric haematology department: a 15-year review. Mycoses 2008;51:109-116.
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;33:453-460.
Taccone A, Occhi M, Garaventa A, Manfredini L, Viscoli C. CT of invasive pulmonary aspergillosis in children with cancer. Pediatr Radiol 1993;23:177-180.
Burgos A, Zaoutis TE, Dvorak CC, Hoffman JA, Knapp KM, Nania JJ, Prasad P, Steinbach WJ. Pediatric invasive aspergillosis: a multicenter retrospective analysis of 139 contemporary cases. Pediatrics 2008;121:1286-1294.
Marr KA, Carter RA, Crippa F, Wald A, Corey L. Epidemiology and outcome of mould infections in hematopoietic stem cell transplant recipients. Clin Infect Dis 2002;34:909-917.
Brown JM. Fungal infections in bone marrow transplant patients. Curr Opin Infect Dis 2004;17:347-352.
Marr KA, Patterson T, Denning D. Aspergillosis. Pathogenesis, clinical manifestations, and therapy. Infect Dis Clin North Am 2002;16:875-894.
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;42:431-442.
Blyth CC, Hale K, Palasanthiran P, O'Brien T, Bennett MH. Antifungal therapy in infants and children with proven, probable or suspected invasive fungal infections. Cochrane Database Syst Rev 2010;2:CD006343.
Freifeld AG, Bow EJ, Sepkowitz KA, Boeckh MJ, Ito JI, Mullen CA, Raad II, Rolston KV, Young JA, Wingard JR, Infectious Diseases Society of America. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the infectious diseases society of America. Clin Infect Dis 2011;52:56-93.
Maertens JA, Madero L, Reilly AF, Lehrnbecher T, Groll AH, Jafri HS, Green M, Nania JJ, Bourque MR, Wise BA, Strohmaier KM, Taylor AF, Kartsonis NA, Chow JW, Arndt CA, DePauw BE, Walsh TJ; Caspofungin Pediatric Study Group. A randomized, double-blind, multicenter study of caspofungin versus liposomal amphotericin B for empiric antifungal therapy in pediatric patients with persistent fever and neutropenia. Pediatr Infect Dis J 2010;29:415-420.
Walsh TJ, Anaissie EJ, Denning DW, Herbrecht R, Kontoyiannis DP, Marr KA, Morrison VA, Segal BH, Steinbach WJ, Stevens DA, van Burik JA, Wingard JR, Patterson TF; Infectious Diseases Society of America. Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis 2008;46:327-360.
Queiroz-Telles F, Berezin E, Freire A, van der Vyver A, Chotpitayasunondh T, Konja J, Diekmann-Berndt H, Koblinger S, Groll AH, Arrieta A; Micafungin Invasive Candidiasis Study Group. Micafungin versus liposomal amphotericin B for pediatric patients with invasive candidiasis: substudy of a randomized double-blind trial. Pediatr Infect Dis J 2008;27:820-826.
Katragkou A, Roilides E. Best practice in treating infants and children with proven, probable or suspected invasive fungal infections. Curr Opin Infect Dis 2011;24:225-229.
Maertens J, Groll AH, Cordonnier C, de la Cámara R, Roilides E, Marchetti O. Treatment and timing in invasive mould disease. J Antimicrob Chemother 2011;66(Suppl 1):37-43.
Lass-Flörl C. Invasive fungal infections in pediatric patients: a review focusing on antifungal therapy. Expert Rev Anti Infect Ther 2010;8:127-135.
Tragiannidis A, Dokos C, Lehrnbecher T, Groll AH.Antifungal chemoprophylaxis in children and adolescents with haematological malignancies and following allogeneic haematopoietic stem cell transplantation: review of the literature and options for clinical practice. Drugs 2012;72:685- 704.
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;68:231-236.
Abbasi S, Shenep JL, Hughes WT, Flynn PM. Aspergillosis in children with cancer: a 34-year experience. Clin Infect Dis 1999;29:1210-1219.
Riley LC, Hann IM, Wheatley K, Stevens RF. Treatment-related deaths during induction and first remission of acute myeloid leukaemia 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;106:436-444.
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;46:441-446.

APA	Tüfekçi Ö, YILMAZ BENGOA Ş, YENİGÜRBÜZ F, Simsek E, Karapınar T, İRKEN G, ÖREN H (2015). Management of Invasive Fungal Infections in Pediatric Acute Leukemia and the Appropriate Time for Restarting Chemotherapy. , 329 - 337.
Chicago	Tüfekçi Özlem,YILMAZ BENGOA Şebnem,YENİGÜRBÜZ Fatma Demir,Simsek Erdem,Karapınar Tuba Hilkay,İRKEN Gülersu,ÖREN Hale Management of Invasive Fungal Infections in Pediatric Acute Leukemia and the Appropriate Time for Restarting Chemotherapy. (2015): 329 - 337.
MLA	Tüfekçi Özlem,YILMAZ BENGOA Şebnem,YENİGÜRBÜZ Fatma Demir,Simsek Erdem,Karapınar Tuba Hilkay,İRKEN Gülersu,ÖREN Hale Management of Invasive Fungal Infections in Pediatric Acute Leukemia and the Appropriate Time for Restarting Chemotherapy. , 2015, ss.329 - 337.
AMA	Tüfekçi Ö,YILMAZ BENGOA Ş,YENİGÜRBÜZ F,Simsek E,Karapınar T,İRKEN G,ÖREN H Management of Invasive Fungal Infections in Pediatric Acute Leukemia and the Appropriate Time for Restarting Chemotherapy. . 2015; 329 - 337.
Vancouver	Tüfekçi Ö,YILMAZ BENGOA Ş,YENİGÜRBÜZ F,Simsek E,Karapınar T,İRKEN G,ÖREN H Management of Invasive Fungal Infections in Pediatric Acute Leukemia and the Appropriate Time for Restarting Chemotherapy. . 2015; 329 - 337.
IEEE	Tüfekçi Ö,YILMAZ BENGOA Ş,YENİGÜRBÜZ F,Simsek E,Karapınar T,İRKEN G,ÖREN H "Management of Invasive Fungal Infections in Pediatric Acute Leukemia and the Appropriate Time for Restarting Chemotherapy." , ss.329 - 337, 2015.
ISNAD	Tüfekçi, Özlem vd. "Management of Invasive Fungal Infections in Pediatric Acute Leukemia and the Appropriate Time for Restarting Chemotherapy". (2015), 329-337.

APA	Tüfekçi Ö, YILMAZ BENGOA Ş, YENİGÜRBÜZ F, Simsek E, Karapınar T, İRKEN G, ÖREN H (2015). Management of Invasive Fungal Infections in Pediatric Acute Leukemia and the Appropriate Time for Restarting Chemotherapy. Turkish Journal of Hematology, 32(4), 329 - 337.
Chicago	Tüfekçi Özlem,YILMAZ BENGOA Şebnem,YENİGÜRBÜZ Fatma Demir,Simsek Erdem,Karapınar Tuba Hilkay,İRKEN Gülersu,ÖREN Hale Management of Invasive Fungal Infections in Pediatric Acute Leukemia and the Appropriate Time for Restarting Chemotherapy. Turkish Journal of Hematology 32, no.4 (2015): 329 - 337.
MLA	Tüfekçi Özlem,YILMAZ BENGOA Şebnem,YENİGÜRBÜZ Fatma Demir,Simsek Erdem,Karapınar Tuba Hilkay,İRKEN Gülersu,ÖREN Hale Management of Invasive Fungal Infections in Pediatric Acute Leukemia and the Appropriate Time for Restarting Chemotherapy. Turkish Journal of Hematology, vol.32, no.4, 2015, ss.329 - 337.
AMA	Tüfekçi Ö,YILMAZ BENGOA Ş,YENİGÜRBÜZ F,Simsek E,Karapınar T,İRKEN G,ÖREN H Management of Invasive Fungal Infections in Pediatric Acute Leukemia and the Appropriate Time for Restarting Chemotherapy. Turkish Journal of Hematology. 2015; 32(4): 329 - 337.
Vancouver	Tüfekçi Ö,YILMAZ BENGOA Ş,YENİGÜRBÜZ F,Simsek E,Karapınar T,İRKEN G,ÖREN H Management of Invasive Fungal Infections in Pediatric Acute Leukemia and the Appropriate Time for Restarting Chemotherapy. Turkish Journal of Hematology. 2015; 32(4): 329 - 337.
IEEE	Tüfekçi Ö,YILMAZ BENGOA Ş,YENİGÜRBÜZ F,Simsek E,Karapınar T,İRKEN G,ÖREN H "Management of Invasive Fungal Infections in Pediatric Acute Leukemia and the Appropriate Time for Restarting Chemotherapy." Turkish Journal of Hematology, 32, ss.329 - 337, 2015.
ISNAD	Tüfekçi, Özlem vd. "Management of Invasive Fungal Infections in Pediatric Acute Leukemia and the Appropriate Time for Restarting Chemotherapy". Turkish Journal of Hematology 32/4 (2015), 329-337.