Hematolojik maligniteli hastalarda invaziv fungal enfeksiyonların prognoza etkisi
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Date
2018
Authors
Elmas, Kevser Üstün
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Publisher
Uludağ Üniversitesi
Abstract
İnvaziv fungal enfeksyonlar (İFE) tanı ve tedavideki gelişmelere karşın immün sistemi baskılanmış kanserli çocuklarda mortalite ve morbiditenin önemli bir nedenidir. Bu çalışmada akut lösemili olgularda; İFE insidansı, sınıflandırılması, risk faktörleri, mortalite, morbidite ve 5 yıllık sağ kalıma etkisi araştırılmıştır. Bu amaçla; Uludağ ve Dokuz Eylül Üniversitesi Tıp Fakültesi Çocuk Hematoloji Klinik'lerinde, 1 Ocak 2010- 31 Aralık 2015 tarihleri arasında akut lösemi ve relaps lösemi tanısı ile tedavi edilen toplam 307 hastanın 1213 febril nötropeni atağı (FNP) incelendi. Bu hastaların 121'inin 127 atağında EORTC/MSG 2008 kriterlerine göre İFE saptandı. İFE insidansı tüm çalışma grubunda %10.4 bulundu. İFE geçiren hastaların yaş ortalaması 105±65 ay, geçirmeyen hastaların ise 81±60 ay idi. İFE'li hastaların yaş ortalaması diğerlerine göre anlamlı olarak yüksek bulundu (p<0.001). İFE'li ve İFE'siz hastalar arasında cinsiyet ve mevsimsel dağılım açısından farklılık yoktu (p>0.05). Lösemi tanılarına göre en sık relaps lösemi olgularda İFE saptandı (p<0.001). İFE ataklarının çoğunluğu olası (%73.7), %14.2'si kanıtlanmış, %12'si ise yüksek olasılıklı olarak sınıflandırıldı. Ataklarda en sık invaziv aspergillozis (%81.9), daha az sıklıkta ise invaziv kandidiyazis (%13.4) ve nadir mantar enfeksiyonu (%4.8) saptandı. Ataklardaki akciğer görüntüleme tetkikleri değerlendirildiğinde, en sık rastlanan bulgu buzlu cam (%58.8) ve nodül (%49) idi. Toplam 307 hastada 1213 FNP atağının %92'sinde (n=1119) serum galaktomannan değerleri ölçüldü. Duyarlılık %17.9, özgüllük %99.7, pozitif prediktif değer %84 ve negatif prediktif değer %99.3 bulundu. Tüm hastaların %24'ü (n=72) kaybedildi. İFE geçiren 121 hastada mortalite %34 (n=41) iken, İFE geçirmeyen 186 hastada mortalite %16.6 (n=31) olarak saptandı (p=0.001). İFE geçiren hastalarda; İFE'ye bağlı ölüm %18'dir (n=22/121). İFE geçiren hasta grubunda 5 yıllık genel sağkalım %67.5 ve olaysız sağkalım %61.7 olup, İFE geçirmeyen hasta grubuna göre anlamlı olarak düşük bulundu (p<0.001). İFE geçiren grupta mortalite için en önemli risk faktörleri; nötropeni süresi ve relaps lösemi idi (p<0.001). Çalışmamızda mortalitede en etkili bağımsız risk faktörleri ise; relaps olmak, İFE geçirmek ve akut myeloid lösemi (AML) tanısı almak olarak saptandı. Relaps olma durumu mortaliteyi 8.4 kat, İFE geçirme 3.2 kat, AML 2.3 kat artırmaktadır. Bu nedenle çalışmamızda; hematolojik maligniteli hastalarda İFE geçirmek kötü bir prognostik belirteç olarak bulunmuştur.
Invasive fungal infections (IFI) remain a major cause of mortality and morbidity in immunosuppressed children with hematologic malignancies despite of the developments in diagnosis and treatment. In this study, the incidence, classification, risk factors, mortality, morbidity and 5-year survival rates of IFI in acute leukemia cases were investigated. For this goal; 1213 febrile neutropenic attacks were evaluated in a population of 307 patients who were diagnosed as de-novo acute and relapsed leukemia treated in Pediatric Hematology Clinics at Medical Faculties of Uludağ and Dokuz Eylül Universities between January 1, 2010 and December 31, 2015. According to EORTC/MSG 2008 criteria, IFI was detected in 127 episodes in 121 patients. The incidence of IFI was 10.4% in total study group. The mean ages of the patients with IFI and without IFI were 105±65 months and 81± 60 months, respectively. The difference was found significant (p<0.001). No significant difference was obtained between the children with and without IFI in terms of gender and seasonal distribution (p>0.05). IFI was identified most frequently in relapsed leukemia cases. Of the IFI attacks; 14.2% was proven, as 12% was classified as probable and 73.7% were classified as possible. The majoritiy of the attacks was identified as invasive aspergillosis (81.9%) of which was followed by invasive candidiasis (13.4%) and rare fungal infections (4.8%). Evaluation of the pulmonary high resolution computed tomography imaging showed that the most frequent findings were ground-glass opacity (58.8%) and nodules (49%). Serum galactomannan values were measured in 92% (n=1119) of 1213 febrile neutropenic attacks. It showed sensitivity of 17.9%, specificity of 99.7%. Positive and negative predictive value were 84% and 99.3%, respectively. Overall mortality rate was found 24% (n=72) in total population. Mortality rates in IFI group (n=121) and non-IFI group (n=186) were found 34% and 16.6%, respectively. IFI. IFI-related mortality in IFI grup was 18% (n=22/121). The 5-year overall and event-free survival rates in the IFI group were 67.5% and 61.7%, respectively. These rates were significantly different from the corresponding rates of the patients without IFI (p<0.001). The significant mortality risk factors in IFI group (n=121) were defined as duration of neutropenia and relapsed leukemia. For the total study group (n=307), the significant independent risk factors on mortality were found as having relapse, diagnosed as IFI and acute myeloid leukemia. Having a relapse increased the mortality rate by 8.4 times, while IFI by 3.2 times and acute myeloid leukemia by 2.3 times. Therefore, we conclude that IFI is an independent negative risk factor for the prognosis of children with hematologic malignancies.
Invasive fungal infections (IFI) remain a major cause of mortality and morbidity in immunosuppressed children with hematologic malignancies despite of the developments in diagnosis and treatment. In this study, the incidence, classification, risk factors, mortality, morbidity and 5-year survival rates of IFI in acute leukemia cases were investigated. For this goal; 1213 febrile neutropenic attacks were evaluated in a population of 307 patients who were diagnosed as de-novo acute and relapsed leukemia treated in Pediatric Hematology Clinics at Medical Faculties of Uludağ and Dokuz Eylül Universities between January 1, 2010 and December 31, 2015. According to EORTC/MSG 2008 criteria, IFI was detected in 127 episodes in 121 patients. The incidence of IFI was 10.4% in total study group. The mean ages of the patients with IFI and without IFI were 105±65 months and 81± 60 months, respectively. The difference was found significant (p<0.001). No significant difference was obtained between the children with and without IFI in terms of gender and seasonal distribution (p>0.05). IFI was identified most frequently in relapsed leukemia cases. Of the IFI attacks; 14.2% was proven, as 12% was classified as probable and 73.7% were classified as possible. The majoritiy of the attacks was identified as invasive aspergillosis (81.9%) of which was followed by invasive candidiasis (13.4%) and rare fungal infections (4.8%). Evaluation of the pulmonary high resolution computed tomography imaging showed that the most frequent findings were ground-glass opacity (58.8%) and nodules (49%). Serum galactomannan values were measured in 92% (n=1119) of 1213 febrile neutropenic attacks. It showed sensitivity of 17.9%, specificity of 99.7%. Positive and negative predictive value were 84% and 99.3%, respectively. Overall mortality rate was found 24% (n=72) in total population. Mortality rates in IFI group (n=121) and non-IFI group (n=186) were found 34% and 16.6%, respectively. IFI. IFI-related mortality in IFI grup was 18% (n=22/121). The 5-year overall and event-free survival rates in the IFI group were 67.5% and 61.7%, respectively. These rates were significantly different from the corresponding rates of the patients without IFI (p<0.001). The significant mortality risk factors in IFI group (n=121) were defined as duration of neutropenia and relapsed leukemia. For the total study group (n=307), the significant independent risk factors on mortality were found as having relapse, diagnosed as IFI and acute myeloid leukemia. Having a relapse increased the mortality rate by 8.4 times, while IFI by 3.2 times and acute myeloid leukemia by 2.3 times. Therefore, we conclude that IFI is an independent negative risk factor for the prognosis of children with hematologic malignancies.
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Keywords
İnvaziv fungal enfeksiyon, Akut lösemi, Risk faktörleri, Invasive fungal infections, Acut leukamia, Risk factors
Citation
Elmas, K. Ü. (2018). Hematolojik maligniteli hastalarda invaziv fungal enfeksiyonların prognoza etkisi. Yayınlanmamış uzmanlık tezi. Uludağ Üniversitesi Tıp Fakültesi.