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. 2022 Jun 1;39(2):94-102.
doi: 10.4274/tjh.galenos.2021.2021.0203. Epub 2021 Nov 18.

Invasive Fungal Infections in Children with Leukemia: Clinical Features and Prognosis

Melike Sezgin Evim  1 , Özlem Tüfekçi  2 , Birol Baytan  1 , Hale Ören  2 , Solmaz Çelebi  3 , Beyza Ener  4 , Kevser Üstün Elmas  5 , Şebnem Yılmaz  2 , Melek Erdem  2 , Mustafa Kemal Hacımustafaoğlu  3 , Adalet Meral Güneş  1
Affiliations

Invasive Fungal Infections in Children with Leukemia: Clinical Features and Prognosis

Melike Sezgin Evim et al. Turk J Haematol. .

Abstract
in English, Turkish

Objective: The incidence of invasive fungal infections (IFIs) has increased due to intensive chemotherapy in childhood leukemia. The aim of this study was to evaluate the incidence, risk factors, causative pathogens, and impact on survival of IFIs among pediatric leukemia patients.

Materials and methods: The hospital records of 307 children with acute lymphoblastic leukemia (ALL, n=238), acute myeloid leukemia (AML, n=51), and relapsed leukemia (n=18) between January 2010 and December 2015 were retrospectively evaluated.

Results: A total of 1213 febrile neutropenia episodes were recorded and 127 (10.4%) of them were related to an IFI. Of 307 children, 121 (39.4%) developed IFIs. The mean age was significantly older in the IFI group compared to children without IFIs (p<0.001). IFIs were defined as possible, probable, and proven in 73.2%, 11.9%, and 14.9% of the attacks, respectively. Invasive aspergillosis (81.9%) was the most frequent infection, followed by invasive candidiasis (13.4%) and rare fungal diseases (4.8%). The majority of IFI attacks in both ALL and AML occurred during the induction phase. In total, the death rate was 24% and the IFI-related mortality rate was 18%. The mortality rate among children with IFIs was found to be significantly higher than that of children without IFIs (p<0.001). Overall and event-free survival rates at 5 years were also found to be significantly lower in the IFI group (p<0.001). Relapse (odds ratio: 8.49) was the most effective risk factor for mortality, followed by developing an IFI episode (odds ratio: 3.2) and AML (odds ratio: 2.33) according to multivariate regression analysis.

Conclusion: Our data showed that IFIs were more common in older children. Although proven and probable IFI episodes were more frequently diagnosed in cases of relapse and AML, children with ALL and AML had similar frequencies of experiencing at least one episode Conclusion: Our data showed that IFIs were more common in older children. Although proven and probable IFI episodes were more frequently diagnosed in cases of relapse and AML, children with ALL and AML had similar frequencies of experiencing at least one episode

Amaç: Çocukluk çağı lösemisinde yoğun kemoterapi nedeniyle invaziv mantar enfeksiyonlarının (IFI) insidansı artmıştır. Bu çalışmanın amacı, pediatrik lösemi hastalarında IFI’nın insidansını, risk faktörlerini, nedensel patojenleri ve sağkalım üzerindeki etkisini değerlendirmektir.

Gereç ve yöntemler: Ocak 2010 ile Aralık 2015 tarihleri arasında akut lenfoblastik lösemili (ALL, n=238), akut myeloid lösemili (AML, n=51) ve relaps lösemili (n=18) 307 çocukların hastane kayıtları geriye dönük olarak değerlendirildi.

Bulgular: Toplam 1213 febril nötropeni atağı kaydedildi ve bunların 127’si (%10,4) IFI ile ilgiliydi. Bu 307 çocuğun 121’i (%39,4) IFI geliştirdi. Ortalama yaş, IFI grubunda IFI olmayan çocuklara kıyasla anlamlı olarak daha büyük bulundu (p<0,001). IFI, atakları sırasıyla; %73,2, %11,9 ve %14,9’unda olası, yüksek olası ve kanıtlanmış olarak tanımlandı. İnvazif aspergilloz (%81,9) en sık görülen enfeksiyondu, bunu invaziv kandidiyazis (%13,4) ve nadir mantar hastalıkları (%4,8) izledi. Hem ALL hem de AML’deki IFI ataklarının çoğu indüksiyon aşamasında görüldü. Toplamda ölüm oranı %24 ve IFI bağlantılı ölüm oranı %18 olarak bulundu. IFI’lı çocuklarda ölüm oranı, IFI olmayan çocuklarda anlamlı olarak daha yüksek bulundu (p<0,001). Beş yılda genel ve olaysız sağkalım, IFI grubunda önemli ölçüde daha düşük bulundu (p<0,001). Relaps (odds oranı, 8,49), mortalite üzerinde en etkili risk faktörü oldu ve bunu, çok değişkenli regresyon analizi ile bir IFI epizodu geçirmek (odds oranı, 3,2) ve AML olmak (odds oranı, 2,33) izledi.

Sonuç: Çalışmamız, IFI’nın büyük yaştaki çocuklarda daha yaygın olduğunu gösterdi. Kanıtlanmış ve olası IFI epizodlarının nüks ve AML’de daha sık saptanmasına karşın, ALL ve AML’li çocukların da benzer sıklıkta en az bir IFI atağı geçirdiği görüldü. Nadir mantar hastalıkları önemli bir sorun olarak tanımlandı. Tedavideki başarıya rağmen, IFI’nın akut lösemili çocuklarda ölüm oranını artırdığı saptandı.

Keywords: Fungal infections; Pediatric leukemia; Acute lymphoblasticleukemia; Acute myeloid leukemia; Febrile neutropenia.

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Conflict of interest statement

Conflicts of Interest: No conflicts of interest were declared by the authors.

Figures

Figure 1
Figure 1
The rate and causes of mortality.
Figure 2
Figure 2
a). Event-free survival, b) Overall survival. IFI: Invasive fungal infection
See this image and copyright information in PMC

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