Tesis

Hubungan Massa Otot dan Faktor-Faktor Lain Dengan Kejadian Neutropenia Berat Pasca Kemoterapi R-CHOP pada Pasien Diffuse Large B-Cell Lymphoma.

Pendahuluan: Kejadian neutropenia berat pasca kemoterapi R-CHOP pada Diffuse large Bcell lymphoma (DLBCL) di Indonesia mencapai 51,5%. Faktor-fakor prediktor dari studi terdahulu tidak dapat menjelaskan tingginya angka ini. Massa otot dicurigai berhubungan dengan toksisitas pasca kemoterapi. Tujuan: Mengetahui hubungan massa otot dan faktor-faktor lain dengan kejadian neutropenia berat. pasca kemoterapi R-CHOP. Metode: Penelitian ini merupakan studi kohort retrospektif dengan data sekunder pasien DLBCL di Rumah Sakit Umum Pusat Nasional (RSUPN) dr. Cipto Mangunkusumo dari tahun 2020 – 2024. Pengukuran massa otot dilakukan dengan menghitung luas penampang otot dibanding kuadrat tinggi pasien pada penampang aksial CT Scan level L3. Analisis statistik dilakukan dengan piranti lunak IMB SPSS versi 25. Titik potong massa otot ditentukan lewat analisis kurva ROC sesuai jenis kelamin. Analisis bivariat dilakukan dengan Pearson chi square untuk variabel kategorikal. Analisis multivariat dilakukan dengan regresi logistik. Dari model regresi disusun sistem skoring. Uji kalibrasi dilakukan dengan uji Hosmer Lemeshow dan uji diskriminasi dengan menghitung area under curve AUC). Nilai positive predictive value (PPV) dan negative predictive value (NPV) model juga dilaporkan. Hasil: Dari 156 subyek yang dianalisis, proporsi neutropenia berat mencapai 40,4%. Titik potong untuk laki-laki ialah 41,96 cm2/m2 dan untuk perempuan 37,87 cm2/m2. Massa otot OR 6,483 (IK95% 2,761-15,218), dosis kemoterapi OR 6,536 (IK95% 1,305 -32,741), dan status performa OR 6,658 (IK95% 2,702-16,406) berhubungan bermakna dengan neutropenia berat pada analisis multivariat. Model ini memiliki kalibrasi yang baik (Hosmer Lemeshow p = 0.102) dan kemampuan diskriminasi yang baik dengan AUC = 0,792 (IK95%, 0,722-0,862) serta nilai PPV 76,0% (IK95%, 57% - 90%) dan NPV 66,4% (IK95%, 58% -74%). Kesimpulan: Massa otot, status performa dan dosis kemoterapi berhubungan dengan kejadian neutropenia pasca kemoterapi R-CHOP.
Kata Kunci: limfoma, massa otot, toksisitas, neutropenia, sarkopenia


Introduction: Diffuse large B-cell lymphoma (DLBCL) is the most prevalent subtype of nonHodgkin lymphoma (NHL) in Indonesia, with R-CHOP chemotherapy remains as the first-line treatment. Severe post R-CHOP neutropenia in Indonesia was found to be as high as 51,5% in previous study. Factors identified in previous studies could not fully explain this high rate. Low muscle mass is a novel determinant linked with chemotherapy toxicity. Objective: To investigate the link between muscle mass and other factors and the occurrence of severe neutropenia following R-CHOP chemotherapy. Methods: This cohort retrospective study analyzed secondary data from medical records of DLBCL patient in RSUPN dr. Cipto Mangunkusumo from 2020 to 2024. Muscle mass was measured by calculating skeletal muscle area adjusted by height from single axial CT Scan slice at L3. Statistical analysis was performed using IBM SPSS ver 25. Gender-specific cut-off determination for muscle mass was performed through ROC analysis. Bivariate and multivariate analysis were conducted with Pearson chi square test and binary logistic regression test respectively. A scoring system was derived from the regression model. Calibration was tested using the Hosmer-Lemeshow test, and discrimination was assessed by calculating the area under the curve (AUC). The positive predictive value (PPV) and negative predictive value (NPV) of the model were also reported. Results: There were 40,4% subject with severe neutropenia post 1 cycle of chemotherapy from the total of 156 subject. Cut-off for muscle mass were 41.96 cm2/m2 and 37.87 cm2/m2 for male and female, respectively. Proportion of subjects with low muscle mass was 57,6%. In multivariate analysis, muscle mass (OR 6.483, 95% CI 2.761 -15.218), chemotherapy dose (OR 6.536, 95% CI 1.305-32.741), and performance status (OR 6.658, 95% CI 2.702-16.406) were significantly associated with severe neutropenia. The model showed good calibration (HosmerLemeshow p = 0.102) and discrimination ability with an AUC of 0.792 (95% CI, 0.722-0.862). The PPV was 76.0% (95% CI, 57% - 90%) and the NPV was 66.4% (95% CI, 58% - 74%). Conclusions: Muscle mass, performance status, and chemotherapy dose are strong predictors of severe neutropenia following R-CHOP chemotherapy.
Keywords: lymphoma, muscle mass, toxicity, neutropenia, sarcopenia