Central Nervous System Fungal Infections in Children With Leukemia and Undergoing Hematopoietic Stem Cell Transplantation: A Retrospective Multicenter Study

被引：2

作者：

Karaman, Serap ^{[1
]}

Kebudi, Rejin ^{[2
]}

Kizilocak, Hande ^{[3
]}

Karakas, Zeynep ^{[1
]}

Demirag, Bengu ^{[10
]}

Evim, Melike S. ^{[14
]}

Yarali, Nese ^{[16
]}

Kaya, Zuhre ^{[17
]}

Karagun, Barbaros S. ^{[18
]}

Aydogdu, Selime ^{[4
]}

Caliskan, Umran ^{[19
]}

Ayhan, Aylin C. ^{[5
]}

Bahadir, Aysenur ^{[6
]}

Cakir, Betul ^{[20
]}

Guner, Burcak T. ^{[11
]}

Albayrak, Canan ^{[21
]}

Karapinar, Deniz Y. ^{[12
]}

Kazanci, Elif G. ^{[15
]}

Unal, Ekrem ^{[22
]}

Turkkan, Emine ^{[8
]}

Akici, Ferhan ^{[7
]}

Bor, Ozcan ^{[23
]}

Vural, Sema ^{[9
]}

Yilmaz, Sebnem ^{[13
]}

Apak, Hilmi ^{[3
]}

Baytan, Birol ^{[14
]}

Tahta, Neryal M. ^{[10
]}

Guzelkucuk, Zeliha ^{[16
]}

Kocak, Ulker ^{[17
]}

Antmen, Bulent ^{[18
]}

Tokgoz, Huseyin ^{[19
]}

Fisgin, Tunc ^{[4
]}

Ozdemir, Nihal ^{[7
]}

Gunes, Adalet M. ^{[14
]}

Vergin, Canan ^{[10
]}

Unuvar, Aysegul ^{[1
]}

Ozbek, Namik ^{[16
]}

Tugcu, Deniz ^{[1
]}

Bay, Sema B. ^{[2
]}

Tanyildiz, Hikmet G. ^{[1
]}

Celkan, Tiraje ^{[3
]}

机构：

[1] Istanbul Univ, Istanbul Fac Med, Div Pediat Hematol Oncol, Istanbul, Turkey

[2] Istanbul Univ, Oncol Inst, Div Pediat Hematol Oncol, Istanbul, Turkey

[3] Istanbul Univ Cerrahpasa, Cerrahpasa Fac Med, Div Pediat Hematol Oncol, TR-34098 Istanbul, Turkey

[4] Altinbas Univ, Bahcelievler Med Pk Hosp, Div Pediat Hematol Oncol, Istanbul, Turkey

[5] Medeniyet Univ, Fac Med, Div Pediat Hematol Oncol, Istanbul, Turkey

[6] Bezmialem Vakif Univ, Div Pediat Hematol Oncol, Istanbul, Turkey

[7] Univ Hlth Sci, Okmeydani Training & Res Hosp, Div Pediat Hematol Oncol, Istanbul, Turkey

[8] Univ Hlth Sci, Kanuni Sultan Suleyman Res & Training Hosp, Div Pediat Hematol Oncol, Istanbul, Turkey

[9] Hlth Sci Univ, Istanbul Sariyer Hamidiye Etfal Hlth Practice & R, Div Pediat Hematol Oncol, Istanbul, Turkey

[10] Univ Hlth Sci, Dr Behcet Uz Childrens Hosp, Div Pediat Hematol Oncol, Istanbul, Turkey

[11] Izmir Univ Hlth Sci, Tepecik Training & Res Hosp, Div Pediat Hematol Oncol, Izmir, Turkey

[12] Ege Univ, Fac Med, Div Pediat Hematol Oncol, Izmir, Turkey

[13] Dokuz Eylul Univ, Fac Med, Div Pediat Hematol Oncol, Izmir, Turkey

[14] Uludag Univ, Fac Med, Div Pediat Hematol Oncol, Bursa, Turkey

[15] Hlth Sci Univ, Bursa High Specialist Training & Res Hosp, Div Pediat Hematol Oncol, Bursa, Turkey

[16] Univ Hlth Sci, Ankara Child Hlth & Dis Hematol Oncol Training &, Div Pediat Hematol Oncol, Ankara, Turkey

[17] Gazi Univ, Fac Med, Div Pediat Hematol Oncol, Ankara, Turkey

[18] Acibadem Adana Hosp, Div Pediat Hematol Oncol, Adana, Turkey

[19] Meram Univ, Fac Med, Div Pediat Hematol Oncol, Konya, Turkey

[20] Karadeniz Tech Univ, Fac Med, Div Pediat Hematol Oncol, Trabzon, Turkey

[21] Ondokuz Mayis Univ, Fac Med, Div Pediat Hematol Oncol, Samsun, Turkey

[22] Erciyes Univ, Fac Med, Div Pediat Hematol Oncol, Kayseri, Turkey

[23] Eskisehir Osmangazi Univ, Fac Med, Div Pediat Hematol Oncol, Eskisehir, Turkey

来源：

JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY | 2022年 / 44卷 / 08期

关键词：

central nervous system; fungal infections; leukemia; pediatrics; PEDIATRIC-PATIENTS; MOLD INFECTIONS; MANAGEMENT; ASPERGILLOSIS; CANCER; NEUTROPENIA; DIAGNOSIS;

D O I：

10.1097/MPH.0000000000002499

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: Central nervous system fungal infections (CNSFI) are seen in patients with hematologic malignancies and have high morbidity and mortality. Because of their rarity, there is limited data on CNSFI in children with no established treatment protocols or guidelines. Materials and Methods: In this multicenter retrospective study. 51 pediatric patients with leukemia. 6 of whom had undergone bone marrow transplantation, with proven or probable CNSFI were evaluated. Fungal infections were defined as proven or probable based on European Organisation for Research and Treatment of Cancer criteria. Proven CNSFI was diagnosed by appropriate central nervous system (CNS) imaging or tissue sample findings in combi-nation with positive microbiological results of cerebrospinal fluid. A positive culture, microscopic evidence of hyphae, a positive result of the galactomannan assays are defined as positive microbiological evidence. Probable CNSFI was defined as appropriate CNS imaging findings together with proven or probable invasive fungal infections at another focus without CNS when there is no other explanatory condition. Data was collected by using the questionnaire form (Supplemental Digital Content 1, http://links lww.com/JPHO/A541). Results: Seventeen patients had proven, 34 patients had probable CNSFI. Headaches and seizures were the most common clinical findings. The median time between the onset of fever and diagnosis was 5 days. The most common fungal agent identified was Aspergillus. Sixteen patients received single-agent. 35 received combination antifungal therapy. Surgery was performed in 23 patients. Twenty-two patients (43%) died. 29 of the CNSFI episodes recovered with a 20% neurological sequelae. Conclusion: CNSFIs should be considered in the differential diagnosis in patients with leukemia and refractory/recurrent fever, headache, neurologicalocular symptoms, and a radiologic-serological evaluation should be performed immediately. Early diagnosis and prompt management, both medical and surgical, are essential for improving clinical outcomes.

引用

页码：E1039 / E1045

页数：7

共 45 条

[1] Microbiologically Documented Fungal Infections in Pediatric Patients With Acute Myeloid Leukemia: 12.5-Year Experience at a Single Institution [J].

Agarwal, Vibhuti ;

Joyce, Michael .

JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY, 2014, 36 (08) :E528-E532

[2] Utility of the serum galactomannan assay for the diagnosis of invasive aspergillosis in children with acute lymphoblastic leukemia [J].

Avcu, Gulhadiye ;

Karapinar, Deniz Yilmaz ;

Akinci, Ayse Burcu ;

Sivis, Zuhal Onder ;

Sahin, Akkiz ;

Bal, Zumrut Sahbudak ;

Polat, Suleyha Hilmioglu ;

Metin, Dilek Yesim ;

Vardar, Fadil ;

Aydinok, Yesim .

INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES, 2017, 54 :8-12

[3] Fungal infections in pediatric neurosurgery [J].

Caceres, Adrian ;

Avila, Maria Luisa ;

Herrera, Marco Luis .

CHILDS NERVOUS SYSTEM, 2018, 34 (10) :1973-1988

[4] Fungal infections of the central nervous system and paranasal sinuses in onco-haematologic patients. Epidemiological study reporting the diagnostic-therapeutic approach and outcome in 89 cases [J].

Candoni, A. ;

Klimko, N. ;

Busca, A. ;

Di Blasi, R. ;

Shadrivova, O. ;

Cesaro, S. ;

Zannier, M. E. ;

Verga, L. ;

Forghieri, F. ;

Calore, E. ;

Nadali, G. ;

Simonetti, E. ;

Muggeo, P. ;

Quinto, A. M. ;

Castagnola, C. ;

Cellini, M. ;

Del Principe, M. I. ;

Fracchiolla, N. ;

Melillo, L. ;

Piedimonte, M. ;

Zama, D. ;

Farina, F. ;

Giusti, D. ;

Mosna, F. ;

Capelli, D. ;

Delia, M. ;

Picardi, M. ;

Decembrino, N. ;

Perruccio, K. ;

Vallero, S. ;

Aversa, F. ;

Fanin, R. ;

Pagano, L. .

MYCOSES, 2019, 62 (03) :252-260

[5] Medical Management of Invasive Fungal Infections of the Central Nervous System in Pediatric Cancer Patients [J].

Carter, John H. ;

Lenahan, Jennifer L. ;

Ishak, Gisele E. ;

Geyer, J. Russell ;

Pollard, Jessica ;

Englund, Janet A. .

PEDIATRIC BLOOD & CANCER, 2015, 62 (06) :1095-1098

[6] Fungal infections in children with cancer - A prospective, multicenter surveillance study [J].

Castagnola, Elio ;

Cesaro, Simone ;

Giacchino, Mareva ;

Livadiotti, Susanna ;

Tucci, Fabio ;

Zanazzo, Giulio ;

Caselli, Desire ;

Caviglia, Ilaria ;

Parodi, Stefano ;

Rondelli, Roberto ;

Cornelli, Pier Emilo ;

Mura, Rossella ;

Santoro, Nicola ;

Russo, Giovanna ;

De Santis, Raffaella ;

Buffardi, Salvatore ;

Viscoli, Claudio ;

Haupt, Riccardo ;

Rossi, Mario R. .

PEDIATRIC INFECTIOUS DISEASE JOURNAL, 2006, 25 (07) :634-639

[7]

Celkan T, 2019, J PEDIAT HEMATOL ONC, V41, P256, DOI [10.1097/mph.0000000000001431, 10.1097/MPH.0000000000001431]

[8] Central nervous system aspergillosis in children: a systematic review of reported cases [J].

Dods, John ;

Losifidis, Elias ;

Roilides, Emmanuel .

INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES, 2007, 11 (05) :381-393

[9] Revision and Update of the Consensus Definitions of Invasive Fungal Disease From the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium [J].

Donnelly, J. Peter ;

Chen, Sharon C. ;

Kauffman, Carol A. ;

Steinbach, William J. ;

Baddley, John W. ;

Verweij, Paul E. ;

Clancy, Cornelius J. ;

Wingard, John R. ;

Lockhart, Shawn R. ;

Groll, Andreas H. ;

Sorrell, Tania C. ;

Bassetti, Matteo ;

Akan, Hamdi ;

Alexander, Barbara D. ;

Andes, David ;

Azoulay, Elie ;

Bialek, Ralf ;

Bradsher, Robert W., Jr. ;

Bretagne, Stephane ;

Calandra, Thierry ;

Caliendo, Angela M. ;

Castagnola, Elio ;

Cruciani, Mario ;

Cuenca-Estrella, Manuel ;

Decker, Catherine F. ;

Desai, Sujal R. ;

Fisher, Brian ;

Harrison, Thomas ;

Heussel, Claus Peter ;

Jensen, Henrik E. ;

Kibbler, Christopher C. ;

Kontoyiannis, Dimitrios P. ;

Kullberg, Bart-Jan ;

Lagrou, Katrien ;

Lamoth, Frederic ;

Lehrnbecher, Thomas ;

Loeffler, Jurgen ;

Lortholary, Olivier ;

Maertens, Johan ;

Marchetti, Oscar ;

Marr, Kieren A. ;

Masur, Henry ;

Meis, Jacques F. ;

Morrisey, C. Orla ;

Nucci, Marcio ;

Ostrosky-Zeichner, Luis ;

Pagano, Livio ;

Patterson, Thomas F. ;

Perfect, John R. ;

Racil, Zdenek .

CLINICAL INFECTIOUS DISEASES, 2020, 71 (06) :1367-1376

[10]

Dworsky ZD, 2018, PEDIATR INFECT DIS J, V37, P555, DOI [10.1097/INF.0000000000001839, 10.1097/inf.0000000000001839]

← 1 2 3 4 5 →