Tesis

Uji Diagnostik Interleukin-6, Prokalsitonin dan C-Reactive Protein sebagai Penanda Awal Bakteremia Pada Pasien Leukemia Akut Dewasa Yang Mengalami Neutropenia Berat Selama Menjalani Kemoterapi Standar di Rumah Sakit Tersier di Jakarta = Interleukin-6, Procalcitonin and C-Reactive Protein as Early Markers of Bacteremia in Adult Acute Leukemia Patients With Severe Neutropenia During Standard Chemotherapy at a Tertiary Hospital in Jakarta.

Latar Belakang : Pasien leukmia akut (LMA, LLA, dan MPAL) memiliki defisit granulosit dan limfosit secara kuantitatif kualitatif sehingga menjadi predisposisi infeksi. Rejimen kemoterapi pada leukemia akut bersifat agresif sehingga memperberat defisit imun sehingga menyebabkan neutropenia berat serta gangguan fungsi sawar mukosa dan meningkatkan risiko infeksi. Berbagai studi menemukan bahwa kadar IL-6 dan CRP di dalam darah dapat meningkat 24-48 jam sebelum terjadinya onset demam. Dalam beberapa tahun terakhir, banyak upaya telah diarahkan pada identifikasi penanda inflamasi seperti IL-6, PCT dan CRP yang dapat membantu dalam diagnosis klinis awal bakteremia untuk memastikan tatalaksana yang cepat dan efektif pada pasien leukemia akut dengan demam neutropenia. Tujuan: Mengetahui performa diagnostik delta IL-6, delta PCT, dan delta CRP sebagai penanda awal kejadian bakteremia pada pasien leukemia akut dewasa sebelum menjalani kemoterapi standar sampai dengan neutropenia berat selama menjalani kemoterapi standar. Metode: Penelitian ini dilakukan dengan desain potong lintang dan konsekutif sampling. Penelitian mengambil semua pasien leukemia akut (LMA, LLA, dan MPAL) dewasa yang mengalami neutropenia berat selama menjalani kemoterapi standar di ruang rawat inap RSUPN Cipto Mangunkusumo dan RS Kanker Dharmais, kemudian dilakukan pengambilan sampel darah IL-6, PCT dan CRP sebelum mulai kemoterapi dan dalam 24 jam saat mulai mengalami neutropenia berat serta kultur darah aerob. Data yang diperoleh diolah menggunakan STATA versi 14. Hasil: Hasil penelitian mendapatkan performa diagnostik delta IL-6, delta PCT, dan delta CRP lemah dan tidak berbeda bermakna sebagai penanda bakteremia dengan AUC 0,6703 (IK95% 0,507-0,833); 0,6821 (IK 95% 0,521 -0,844); dan 0,694 (IK 95% 0,532-0,856) serta nilai p=0,9681. Nilai titik potong delta IL-6 ialah penurunan 24,33% akan memberikan sensitivitas 79,31% (IK95% 60,28-92,01) serta spesifisitas 56,25% (IK95% 29,88-80,25). Nilai titik potong delta PCT ialah penurunan 5,06% akan memberikan sensitivitas 79,31% (IK95% 60,28-92,01) serta spesifisitas 50,00% (IK95% 24,65 -75,35). Nilai titik potong delta CRP ialah penurunan 44,29% akan memberikan sensitivitas 665,52% (IK95% 45,67-92,06) dan spesifisitas 50,0% (IK95% 24,65-75,35). Prevalensi bakteremia pada studi ini kami temukan sebanyak 64,44% (29/45). Bakteri terbanyak yang tumbuh dari hasil kultur darah berupa bakteri gram positif 77,42% (24/31) dengan spesies terbanyak ialah Staphylococcus Epidermidis 41,67% (10/24). Sedangkan sisanya merupakan gram negatif 22,58% (7/31) dengan spesies terbanyak adalah Acinetobacter baumannii 42,86% (3/7). Kesimpulan: Performa diagnostik delta Il-6, delta PCT, dan delta CRP lemah sebagai penanda awal bakteremia pada pasien leukemia akut dengan neutropenia berat selama menjalani kemoterapi standar.
Kata kunci: Leukimia akut, Neutropenia, Bakteremia IL-6, PCT, CRP


Background: Acute leukemia patients (AML, ALL, and MPAL) have quantitative and qualitative deficits in granulocytes and lymphocytes, thus predisposing to infection. Chemotherapy regimens in acute leukemia are aggressive, thereby aggravating the immune deficit, causing severe neutropenia and impaired mucosal barrier function and increasing the risk of infection. Various studies have found that IL-6 and CRP levels in the blood can increase 24-48 hours before the onset of fever. In recent years, much effort has been directed at identifying inflammatory markers such as IL-6, PCT and CRP that can aid in the early clinical diagnosis of bacteremia to ensure prompt and effective management of acute leukemia patients with febrile neutropenia. Objective: To determine the diagnostic performance of delta IL-6, delta PCT, and delta CRP as early markers of bacteremia in adult acute leukemia patients before undergoing standard chemotherapy up to severe neutropenia during standard chemotherapy. Methods: This research was conducted using a cross-sectional method and consecutive sampling. The study took all adult acute leukemia patients (AML, ALL, and MPAL) who experienced severe neutropenia while undergoing standard chemotherapy in the inpatient ward of Cipto Mangunkusumo National Central General Hospital and Dharmais Cancer Center Hospital, then took IL-6, PCT and CRP blood samples before starting chemotherapy. and within 24 hours of starting to experience severe neutropenia and aerobic blood culture. The data was processed using STATA version 14. Results: The results of the study showed that the diagnostic performance of delta IL-6, delta PCT, and delta CRP was weak and not significantly different as markers of bacteremia with an AUC of 0.6703 (95% CI 0.507-0.833); 0.6821 (95% CI 0.521-0.844); and 0.694 (95% CI 0.532-0.856) and p value = 0.9681. The IL-6 delta cut point value is a decrease of 24.33% which will provide a sensitivity of 79.31% (95%CI 60,28-92,01) and a specificity of 62.50% (95%CI 29,88-80,25. The PCT delta cut point value is a decrease of 5.06% which will provide a sensitivity of 79.31% (95% CI 60,28-92,01)and a specificity of 50.00% (95% CI 24,65 -75,35. The cut point value for delta CRP is a decrease of 44.29%, which will provide a sensitivity of 65.52% (95% CI 45,67-92,06) and a specificity of 50.0% (95% CI 24,65 -75,35). We found the prevalence of bacteremia in this study to be 64.44% (29/45). The most bacteria that grew from blood culture results were gram positive bacteria 77.42% (24/31) with the largest species being Staphylococcus epidermidis 41.67% (10/24). Meanwhile, the rest were gram negative 22.58% (7/31) with the largest species being Acinetobacter baumannii 42.86% (3/7). Conclusions : The diagnostic performance of delta Il-6, delta PCT, and delta CRP is weak as early markers of bacteremia in acute leukemia patients with severe neutropenia during standard chemotherapy.
Key words: Acute leukemia, Neutropenia, Bacteremia, IL-6, PCT, CRP