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Latar belakang: Peran utama matriks metalloproteinase-9 (MMP-9) adalah mendegradasi matriks ekstraseluler sehingga menyebabkan terjadinya invasi dan infiltrasi sel tumor. Tujuan utama penelitian ini adalah menilai kadar MMP-9 pada pasien leukemia limfoblastik akut-L1 (LLA-L1). Metode: Penelitian dengan metode kohort prospektif telah di lakukan di RSUP Dr Wahidin Sudirohusodo, Makassar dari bulan Augustus sampai Desember 2014. Jumlah pasien LLA sebanyak 20 orang yang dikelompokkan menjadi risiko tinggi (RT) dan risiko biasa (RB). Luaran pasien di kelompokkan menjadi remisi dan tidak remisi setelah kemoterapi fase induksi. Hasil: Pada kelompok LLA dengan RT dan RB masing-masing terdiri dari 6(30%) dan 14(70%). Hasil analisis statistik menunjukkan tidak terdapat perbedaan bermakna kadar MMP-9 antara kelompok RT dan RB sebelum dan sesudah kemoterapi fase induksi dengan nilai p=0.216 dan 0.68, perubahan kadar MMP-9 antara RT dan RB sebelum dan sesudah kemoterapi fase induksi dengan nilai p=0.60 dan 0.975, kadar MMP-9 sebelum kemoterapi fase induksi antara kelompok remisi dan yang tidak remisi dengan nilai p=0.614 dan kadar MMP-9 sebelum kemoterapi fase induksi antara kelompok RT dan RB dengan nilai p=0.402 (p>0.05). Kesimpulan: Tidak terdapat perbedaan bermakna kadar MMP-9 antara kelompok RT dan RB sebelum dan sesudah kemoterapi fase induksi, perubahan kadar MMP-9 pada kelompok RT dan RB sebelum dan sesudah kemoterapi fase induksi, kadar MMP-9 sebelum kemoterapi fase induksi anrata kelompok remisi dan tidak remisi, kadar MMP-9 pada yang remisi antara kelompok RT dan RB.

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ABSTRACT
Back ground: The main role of matrix metalloproteinase-9 (MMP-9) in invasive and infiltration is degradation of extracellular matrix. The objective of this study was to evaluate the serum level of MMP-9 in children with acute lymphoblastic leukemia-L1 (ALL-L1) as prognostic marker. Methods: A prospective cohort study was conducted in Dr Wahidin Sudirohusodo General Hospital, Makassar from August to December to 2014. Twenty patients were enrolled and devided into high risk (HR) and standard risk (SR) ALL group. In terms of outcome, patients were classified into remission and non-remission induction phase of chemotherapy. Result: High risk and SR ALL group consisted of 6(30%) and 14(70%) patients respectively. Statistical analysis showed no significant differences levels of MMP-9 between HR and SR groups before and after induction phase of chemotherapy with p=0.216 and 0.68, changes levels of MMP-9 between HR and SR groups before and after induction phase of chemotherapy with p=0.60 and 0.975, levels of MMP-9 before induction phase of chemotherapy between remission and non-remission groups with p=0.614 and levels of MMP-9 before induction phase chemotherapy in remission between HR and SR groups with p=0.402 (p>0.05). Conclusion: MMP-9 expression was no significant difference in HR and SR groups before and after induction phase of chemotherapy, changes MMP-9 expression between HR and SR before and after induction phase of chemotherapy, MMP-9 expression between remission and non-remission groups and MMP-9 expression in remission between HR and SR groups.;

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Latar Belakang: Angka kesintasan LLA pada anak di negara berkembang masih tertinggal dibanding negara maju. Ketepatan diagnosis dan stratifikasi risiko pasien LLA merupakan hal penting yang perlu dievaluasi sebagai langkah awal untuk meningkatkan kesintasan. Di negara maju ketepatan diagnosis dan stratifikasi risiko didasarkan atas hasil pemeriksaan morfologi, imunofenotiping, sitogenetik, dan molekular. Di Indonesia, hal tersebut belum dapat dilakukan sepenuhnya karena keterbatasan biaya dan fasilitas. Untuk itu, perlu kriteria stratifikasi berdasarkan klinis dan laboratorium sederhana tetapi mampu mendekati stratifikasi molekular. Respons steroid merupakan faktor prognostik kuat dalam memprediksi kejadian relaps dan memengaruhi angka kesintasan. Penambahan variabel respons steroid pada stratifikasi RSCM (stratifikasi modifikasi) diharapkan dapat mendekati kemampuan stratifikasi molekular sebagai baku emas. Metode: Penelitian kohort prospektif selama 6 bulan dilakukan di Departemen Ilmu Kesehatan Anak FKUI-RSCM pada Januari 2013 - September 2014. Subjek adalah pasienbaruterdiagnosis LLAkemudiandikelompokkanmenjadirisikobiasa(RB)danrisiko tinggi (RT) berdasarkan kriteria stratifikasi RSCM (usia, jumlah leukosit, massa mediastinum dan infiltrasi SSP). Subjek dengan RB mendapat prednison (60 mg/kgBB/hari) dan RT mendapat deksametason (6 mg/kgBB/hari) selama 7 hari. Respons steroid dievaluasi pada hari ke-8, dengan menghitung blas di darah tepi. Respons baik bila jumlah blas < 1.000/μL dan respons buruk bila jumlah blas > 1.000/μL. Subjek dengan respons buruk dikelompokkan RT sesuai stratifikasi risiko yang baru (stratifikasi modifikasi). Evaluasi remisi fase induksi dilakukan setelah 6 minggu pemberian kemoterapi berdasarkan persentase blas dan minimal residual disease (MRD) sumsum tulang. Kriteria risiko tinggi pada stratifikasi molekular bila terdapat fusi gen E2A-PBX1, MLL-AF4, dan BCR-ABL, sedangkan risiko biasa bila terdapat fusi gen TEL-AML1. Hasil Penelitian: Pada penelitian ini diikutsertakan 73 subjek dengan rerata usia subjek 5,5 (SB ± 3,8) tahun. Subjek lelaki (65,8%) lebih banyak dibanding perempuan (34,2%). Gejala klinis yang sering ditemukan adalah pucat sebanyak 65 (89%), demam 53 (72,6%), nyeri tulang 51 (70%), dan hepatomegali 51 (70%) subjek. Hasil pemeriksaan imunofenotiping mendapatkan 77,1% sel B, 17,1% sel T, dan 5,7% sel campuran. Ketidaksesuaian remisi fase induksi berdasarkan morfologi dan MRD sebesar 15,2%. Stratifikasi RSCM maupun modifikasi tidak berkorelasi dengan stratifikasi molekular (r = 1,1; p = 0,6). Angka kesintasan berdasarkan stratifikasi molekular (79%) lebih tinggi dibandingkan stratifikasi RSCM (68,5%) maupun modifikasi (69,6%). Simpulan: Stratifikasi modifikasi menunjukkan kemampuan yang sama dengan stratifikasi RSCM dibandingkan stratifikasi molekular. Angka kesintasan berdasarkan stratifikasi molekular lebih tinggi dibandingkan stratifikasi RSCM dan modifikasi.;

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ABSTRACT
Introduction: Survival rate of children with ALL in developing countries remains lower compared to developed countries. Diagnosis and risk stratification are important to determine survival rates. Diagnosis and risk stratification in developed countries are based on morphology, immunophenotyping, cytogenetic, and molecular examination of bone marrow while in Indonesia most of those examinations are not available due to financial and facilities limitation. Therefore, we need to develop stratification criteria based on clinical and laboratory assessment which is comparable to molecular stratification. Response to steroid is a strong predictor of relapse and survival rates in ALL. The aim of the study is to develop new stratification to improve accuracy in predicting relapse rate and increase survival rate, by adding steroid response variable to current CMH stratification, in comparison with molecular stratification as gold standard. Methods: A prospective study was conducted at Pediatric Hematology-Oncology Division, Department of Child Health, FMUI-CMH on January 2013 ? September 2014. Morphology, immunophenotyping, cytogenetic and molecular assessment were performed. Patient was stratified into standard risk (SR) and high risk (HR) based on CMH stratification criteria (based on age, WBC, mediastinal mass and CNS infiltration) and given steroid (prednisone or dexamethasone) for 7 days. Steroid response was evaluated at day 8, good response if peripheral blast count < 1,000/μL and poor response if > 1,000/μL. Poor responders were moved to HR group in new stratification (modified stratification). Bone marrow aspiration and minimal residual disease (MRD) detection were perfomed after induction phase to evaluate remission and patient was observed for 6 months. High risk criteria based on molecular stratification are E2A-PBX1, MLL-AF4 and BCR-ABL fusion genes, while standard risk is TEL-AML1. Results: A total of 73 newly diagnosed ALL patients were enrolled in this study. The mean age was 5.5 (SD ± 3.8) years. Incidence in male (65.8%) is higher than female (34.2%). Clinical characteristics are pale (89%), fever (72.6%), bone pain (70%), hepatomegaly (70%), bleeding (42.5%), lymphadenopathy (49.0%), and splenomegaly (46.6%). Immunophenotyping result was 77.1% for B-lineage; 17.1% T-lineage; and 5.7% mixed lineage. Minimal residual disease detection from 33 patients showed no difference in remission between CMH and modified stratification. Four patients were moved to HR after evaluation of steroid response. We found discrepancy of remission induction results based on morphology and MRD in 15.2% subjects. Survival rate for CMH, modified, and molecular stratification were 68.5%, 69.6%, and 75.5%, respectively. Cipto Mangunkusumo Hospital and modified stratification were not correlated with molecular stratification as the gold standard (r = 1.1 ; p = 0.6). Conclusions: Modified stratification had similar accuracy with CMH stratification compare to molecular stratification in predicting survival rate of ALL children. Remission based on MRD detection between the two stratification was also similar. Survival rate by molecular stratification was higher compared to CMH or modified stratification.;Introduction: Survival rate of children with ALL in developing countries remains lower compared to developed countries. Diagnosis and risk stratification are important to determine survival rates. Diagnosis and risk stratification in developed countries are based on morphology, immunophenotyping, cytogenetic, and molecular examination of bone marrow while in Indonesia most of those examinations are not available due to financial and facilities limitation. Therefore, we need to develop stratification criteria based on clinical and laboratory assessment which is comparable to molecular stratification. Response to steroid is a strong predictor of relapse and survival rates in ALL. The aim of the study is to develop new stratification to improve accuracy in predicting relapse rate and increase survival rate, by adding steroid response variable to current CMH stratification, in comparison with molecular stratification as gold standard. Methods: A prospective study was conducted at Pediatric Hematology-Oncology Division, Department of Child Health, FMUI-CMH on January 2013 ? September 2014. Morphology, immunophenotyping, cytogenetic and molecular assessment were performed. Patient was stratified into standard risk (SR) and high risk (HR) based on CMH stratification criteria (based on age, WBC, mediastinal mass and CNS infiltration) and given steroid (prednisone or dexamethasone) for 7 days. Steroid response was evaluated at day 8, good response if peripheral blast count < 1,000/μL and poor response if > 1,000/μL. Poor responders were moved to HR group in new stratification (modified stratification). Bone marrow aspiration and minimal residual disease (MRD) detection were perfomed after induction phase to evaluate remission and patient was observed for 6 months. High risk criteria based on molecular stratification are E2A-PBX1, MLL-AF4 and BCR-ABL fusion genes, while standard risk is TEL-AML1. Results: A total of 73 newly diagnosed ALL patients were enrolled in this study. The mean age was 5.5 (SD ± 3.8) years. Incidence in male (65.8%) is higher than female (34.2%). Clinical characteristics are pale (89%), fever (72.6%), bone pain (70%), hepatomegaly (70%), bleeding (42.5%), lymphadenopathy (49.0%), and splenomegaly (46.6%). Immunophenotyping result was 77.1% for B-lineage; 17.1% T-lineage; and 5.7% mixed lineage. Minimal residual disease detection from 33 patients showed no difference in remission between CMH and modified stratification. Four patients were moved to HR after evaluation of steroid response. We found discrepancy of remission induction results based on morphology and MRD in 15.2% subjects. Survival rate for CMH, modified, and molecular stratification were 68.5%, 69.6%, and 75.5%, respectively. Cipto Mangunkusumo Hospital and modified stratification were not correlated with molecular stratification as the gold standard (r = 1.1 ; p = 0.6). Conclusions: Modified stratification had similar accuracy with CMH stratification compare to molecular stratification in predicting survival rate of ALL children. Remission based on MRD detection between the two stratification was also similar. Survival rate by molecular stratification was higher compared to CMH or modified stratification.;Introduction: Survival rate of children with ALL in developing countries remains lower compared to developed countries. Diagnosis and risk stratification are important to determine survival rates. Diagnosis and risk stratification in developed countries are based on morphology, immunophenotyping, cytogenetic, and molecular examination of bone marrow while in Indonesia most of those examinations are not available due to financial and facilities limitation. Therefore, we need to develop stratification criteria based on clinical and laboratory assessment which is comparable to molecular stratification. Response to steroid is a strong predictor of relapse and survival rates in ALL. The aim of the study is to develop new stratification to improve accuracy in predicting relapse rate and increase survival rate, by adding steroid response variable to current CMH stratification, in comparison with molecular stratification as gold standard. Methods: A prospective study was conducted at Pediatric Hematology-Oncology Division, Department of Child Health, FMUI-CMH on January 2013 ? September 2014. Morphology, immunophenotyping, cytogenetic and molecular assessment were performed. Patient was stratified into standard risk (SR) and high risk (HR) based on CMH stratification criteria (based on age, WBC, mediastinal mass and CNS infiltration) and given steroid (prednisone or dexamethasone) for 7 days. Steroid response was evaluated at day 8, good response if peripheral blast count < 1,000/μL and poor response if > 1,000/μL. Poor responders were moved to HR group in new stratification (modified stratification). Bone marrow aspiration and minimal residual disease (MRD) detection were perfomed after induction phase to evaluate remission and patient was observed for 6 months. High risk criteria based on molecular stratification are E2A-PBX1, MLL-AF4 and BCR-ABL fusion genes, while standard risk is TEL-AML1. Results: A total of 73 newly diagnosed ALL patients were enrolled in this study. The mean age was 5.5 (SD ± 3.8) years. Incidence in male (65.8%) is higher than female (34.2%). Clinical characteristics are pale (89%), fever (72.6%), bone pain (70%), hepatomegaly (70%), bleeding (42.5%), lymphadenopathy (49.0%), and splenomegaly (46.6%). Immunophenotyping result was 77.1% for B-lineage; 17.1% T-lineage; and 5.7% mixed lineage. Minimal residual disease detection from 33 patients showed no difference in remission between CMH and modified stratification. Four patients were moved to HR after evaluation of steroid response. We found discrepancy of remission induction results based on morphology and MRD in 15.2% subjects. Survival rate for CMH, modified, and molecular stratification were 68.5%, 69.6%, and 75.5%, respectively. Cipto Mangunkusumo Hospital and modified stratification were not correlated with molecular stratification as the gold standard (r = 1.1 ; p = 0.6). Conclusions: Modified stratification had similar accuracy with CMH stratification compare to molecular stratification in predicting survival rate of ALL children. Remission based on MRD detection between the two stratification was also similar. Survival rate by molecular stratification was higher compared to CMH or modified stratification., Introduction: Survival rate of children with ALL in developing countries remains lower compared to developed countries. Diagnosis and risk stratification are important to determine survival rates. Diagnosis and risk stratification in developed countries are based on morphology, immunophenotyping, cytogenetic, and molecular examination of bone marrow while in Indonesia most of those examinations are not available due to financial and facilities limitation. Therefore, we need to develop stratification criteria based on clinical and laboratory assessment which is comparable to molecular stratification. Response to steroid is a strong predictor of relapse and survival rates in ALL. The aim of the study is to develop new stratification to improve accuracy in predicting relapse rate and increase survival rate, by adding steroid response variable to current CMH stratification, in comparison with molecular stratification as gold standard. Methods: A prospective study was conducted at Pediatric Hematology-Oncology Division, Department of Child Health, FMUI-CMH on January 2013 – September 2014. Morphology, immunophenotyping, cytogenetic and molecular assessment were performed. Patient was stratified into standard risk (SR) and high risk (HR) based on CMH stratification criteria (based on age, WBC, mediastinal mass and CNS infiltration) and given steroid (prednisone or dexamethasone) for 7 days. Steroid response was evaluated at day 8, good response if peripheral blast count < 1,000/μL and poor response if > 1,000/μL. Poor responders were moved to HR group in new stratification (modified stratification). Bone marrow aspiration and minimal residual disease (MRD) detection were perfomed after induction phase to evaluate remission and patient was observed for 6 months. High risk criteria based on molecular stratification are E2A-PBX1, MLL-AF4 and BCR-ABL fusion genes, while standard risk is TEL-AML1. Results: A total of 73 newly diagnosed ALL patients were enrolled in this study. The mean age was 5.5 (SD ± 3.8) years. Incidence in male (65.8%) is higher than female (34.2%). Clinical characteristics are pale (89%), fever (72.6%), bone pain (70%), hepatomegaly (70%), bleeding (42.5%), lymphadenopathy (49.0%), and splenomegaly (46.6%). Immunophenotyping result was 77.1% for B-lineage; 17.1% T-lineage; and 5.7% mixed lineage. Minimal residual disease detection from 33 patients showed no difference in remission between CMH and modified stratification. Four patients were moved to HR after evaluation of steroid response. We found discrepancy of remission induction results based on morphology and MRD in 15.2% subjects. Survival rate for CMH, modified, and molecular stratification were 68.5%, 69.6%, and 75.5%, respectively. Cipto Mangunkusumo Hospital and modified stratification were not correlated with molecular stratification as the gold standard (r = 1.1 ; p = 0.6). Conclusions: Modified stratification had similar accuracy with CMH stratification compare to molecular stratification in predicting survival rate of ALL children. Remission based on MRD detection between the two stratification was also similar. Survival rate by molecular stratification was higher compared to CMH or modified stratification.]

Abstrak :
Latar belakang: Leukemia limfoblastik akut LLA merupakan jenis kanker tersering pada anak. Faktor penyakit dan kemoterapi dapat menyebabkan ketidakseimbangan nutrisi makro maupun mikro. Zinc adalah salah satu nutrien mikro yang memiliki banyak peran fisiologis dalam tubuh, namun kadarnya berkurang pada penyakit limfoproliferatif. Defisiensi zinc cenderung meningkatkan morbiditas pada anak LLA, salah satunya infeksi. Tujuan: Penelitian ini bertujuan untuk mencari proporsi defisiensi zinc pada LLA anak serta hubungannya dengan kejadian infeksi. Pasien dan metode: Disain penelitian potong lintang deskriptif-analitik, tempat pelaksanaan di Departemen Patologi Klinik dan Departemen Ilmu Kesehatan Anak RSUPN Dr. Cipto Mangunkusumo, Jakarta. Jumlah subjek 81 anak LLA, yang terdiri dari 26 pasien baru dan 55 pasien pada berbagai fase kemoterapi. Kadar zinc diukur menggunakan prinsip kolorimetri dengan alat spektrofotometer otomatis. Hasil: Proporsi defisiensi zinc pada pasien yang baru terdiagnosis sebesar 65.4 n= 26 dan pada pasien kemoterapi sebesar 49 n= 55 . Terdapat hubungan bermakna antara defisiensi zinc dengan kejadian infeksi p= 0.003; RR= 3.2, 95 CI 1.33 ndash; 7.69 Kesimpulan: Defisiensi zinc ditemukan pada anak dengan LLA sebelum kemoterapi dimulai, maupun pada berbagai fase kemoterapi. Risiko infeksi lebih besar pada anak LLA yang mengalami defisiensi zinc. Suplementasi zinc dapat dipertimbangkan untuk meningkatkan prognosis, namun perlu dilakukan penelitian lebih lanjut mengenai efektivitasnya. ...... Background: Acute lymphoblastic leukemia ALL is a most common malignancy in children. Disease factors and chemotherapy effects may cause both macro or micro nutritional imbalance. Zinc is one of the micro nutrients that has many physiological roles in the body, but the levels may decrease in ALL. Zinc deficiency tend to increase morbidity in children with ALL, including infection. Objective: The present study was done in order to find the proportion of zinc deficiency in pediatric ALL patients and to identify its relationship with the incidence of infection. Patients and methods: This cross sectional study was carried out in the Departement of Clinical Pathology and Department of Paediatric Health, RSUPN Dr. Cipto Mangunkusumo, Jakarta. We conducted 81 paediatric ALL patients, consisted of 26 newly diagnosed and 55 in various phases of chemotherapy. Zinc levels were measured using colorimetric method by an automatic spectrophotometer. Results: The proportion of zinc deficiency is 65.4 in newly diagnosed patients and 49 in children with various chemotherapy phases. There is a significant association between zinc deficiency and the incidence of infection p 0.003 RR 3.2, 95 CI 1.33 ndash 7.69. Conclusion: zinc deficiency was found in children with LLA, and has significant association with the risk of infection. Zinc supplementation may be considered to improve the prognosis, however futher study of safety and side effect is necessary.

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Tesis ini membahas mengenai enzim L-asparaginase dimana enzim tersebut termasuk kedalam golongan agen antineoplastik yang digunakan dalam pengobatan Leukemia Limfoblastik Akut LLA . Hingga saat ini enzim L-asparaginase masih diperoleh dari bakteri Escherichia coli dan Erwina carotovora. Penggunaan enzim ini sebagai obat secara berkelanjutan diketahui sebagai penyebab timbulnya alergi pada pengguna, sehingga dibutuhkan enzim L-asparaginase dengan karakteristik yang berbeda dari sebelumnya.Hakophilic archaea yang merupakan mikroorganisme yang dapat hidup dalam kondisi lingkungan dengan kadar garam yang tinggi, kemungkinan juga mempunyai kemampuan untuk menghasilkan enzim L-asparaginase dengan karakteristik yang berbeda dari mikroorganisme lainnya.Pada penelitian ini proses skrining secara kualitatif dilakukan terhadap 71 isolat Halophilic archaea. Proses identifikasi terhadap isolat yang menghasilkan enzim L-asparaginase dilakukan secara molekular melalui pendekatan 16S rRNA. Pengujian aktivitas enzim dilakukan dengan metoda spektrofotometri Nessler dengan panjang gelombang 400 nm.Hasil dari penelitian ini telah diperoleh 9 isolat Halophilic archaea yang memiliki aktivitas enzim L-asparaginase. Hasil identifikasi dan pengujian aktivitas enzim dari 9 isolat diperoleh aktivitas tertinggi dimiliki oleh Halobaculum sp. 0.3033 U/mL , kemudian diikuti dengan Halostagnicola kamekurae 0.2134 U/mL , Halogranum rubrum 0.0927 U/mL , Haloferax, sp 0.0916 U/mL , Halococcus thailandensis 0.0808 U/mL , Halogranum, sp 0.0646 U/mL , Halococcus, sp 0.0326 U/mL , Halalkalicoccus paucihalaphilus 0.0200 U/mL dan Halococcus hamelinensis 0.0056 U/mL Kata kunci : Archaea, L-Asparaginase, Halophilic archaea, Leukemia Limfoblastik Akut

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L asparaginase enzyme that uses for treatment of acute lymphoblastic leukemia ALL is still produced from Escherichia coli dan Erwina carotovora. The use of L asparaginase enzyme for medicine in a sustainable way is thought as the most common cause the allergies to the user, so it needs an L asparaginase enzyme with different characteristics than before.Halophilic archaea is a microorganism that can live in extreme environmental condition and probablility have the capability to produce L asparaginase enzyme with different characteristics than another microorganism.Screening process on this research were using qualitative method have been done for 71 isolates of Halophilic archaea. The identification process for the isolates that produce L asparaginase enzyme were using molecular method based on 16S rRNA identification. The activity of enzyme have been done by using spectrophotometry by Nessler with wavelength 400 nm.The result of qualitative screening, 9 isolates of Halophilic archaea have a L asparaginase enzyme activity. The identification and enzyme activity for 9 isolates of Halophilic archaea shown that Halobaculum sp. Has the highest activity 0.3033 U mL and then followed by Halostagnicola kamekurae 0.2134 U mL , Halogranum rubrum 0.0927 U mL , Haloferax, sp 0.0916 U mL , Halococcus thailandensis 0.0808 U mL , Halogranum, sp 0.0646 U mL , Halococcus, sp 0.0326 U mL , Halalkalicoccus paucihalaphilus 0.0200 U mL and Halococcus hamelinensis 0.0056 U mL Keyword Archaea, L Asparaginase, Halophilic archaea, acute lymphoblastic Leukemia

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Latar belakang: Peningkatan enzim transaminase sering ditemukan pada anak dengan leukemia limfoblastik akut LLA dalam kemoterapi fase pemeliharaan. Belum ada penelitian terkait pemberian vitamin E pada anak LLA dengan kondisi tersebut di Indonesia. Tujuan: Mengetahui prevalens, karakteristik, dan pengaruh pemberian vitamin E terhadap perbaikan kadar enzim transaminase pada anak LLA dalam kemoterapi fase pemeliharaan. Metode: Uji klinis acak tersamar tunggal, membandingkan vitamin E dosis antioksidan dengan plasebo pada anak LLA yang mengalami peningkatan enzim transaminase bulan Agustus-Desember 2017 di Poliklinik Hematologi dan Onkologi Rumah Sakit Cipto Mangunkusumo. Enzim transaminase dievaluasi setelah 3 dan 5 minggu intervensi dan perbaikan didefinisikan bila menurun ge;20 . Hasil: Terdapat 33 kejadian peningkatan enzim transaminase, 17 vitamin E dan 16 plasebo. Prevalens 41,2 , karakteristik pasien predominan laki-laki, usia 2,5-5x. Vitamin E dibandingkan plasebo setelah 3 minggu P=0,601; RR=0,93; IK 95 0,73-1,16 dan 5 minggu P= 0,103; RR= 0,81; IK 95 0,64-1,03 . Kesimpulan: Pemberian Vitamin E dibandingkan plasebo pada anak LLA dalam kemoterapi fase pemeliharaan setelah 3 dan 5 minggu tidak berbeda bermakna, namun kelompok vitamin E terdapat kecenderungan perbaikan kadar enzim transaminase.

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ABSTRACT
Background Aminotransferase enzyme rsquo s elevation is a common complication associated maintenance chemotherapy in pediatric acute lymphoblastic leukemia ALL . Vitamin E is used as therapy but none research has been done on this issue in Indonesia. Objectives To identify the prevalence, characteristics of patients and the effect of vitamin E on aminotransferase enzyme rsquo s improvement in pediatric ALL during maintenance chemotherapy. Methods A randomized single blind controlled trial of antioxidant dose vitamin E versus placebo in pediatric ALL during maintenance chemotherapy with aminotransferase enzyme rsquo s elevation was conducted on August December 2017 at Hematology and Oncology clinic Cipto Mangunkusumo hospital. Aminotransferase enzymes were evaluated after intervention for 3 and 5 weeks. Improvement was defined as a decrease ge 20 of baseline. Results There were 33 events, 17 vitamin E and 16 placebo. Prevalence was 41,2 , characteristics were predominated boys, 2,5 5x. There were no statistical difference in aminotranferase enzyme rsquo s improvement after 3 weeks intervention P 0,601 RR 0,93 CI 95 0,73 1,16 and 5 weeks intervention P 0,103 RR 0,81 CI 95 0,64 1,03 . Conclusion Antioxidant dose of vitamin E tends to decrease aminotransferase enzyme but not statistically significant.

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Kemoterapi fase induksi merupakan fase pertama tahap pengobatan pada anak dengan LLA dan dilakukan hampir segera setelah diagnosis ditegakkan, dimulai dan berlansung selama 4-6 minggu (28-42 hari). Hasil yang dicapai pada fase ini akan menentukan prognosis dan fase kemoterapi selanjutnya. Penelitian ini bertujuan untuk mengidentifikasi faktor-faktor yang berhubungan dengan lama rawat kemoterapi fase induksi pada anak penderita LLA. Desain yang digunakan dalam penelitian ini adalah desain cross sectional, dengan jumlah sampel 94 melalui consecutive sampling. Analisis yang digunakan dengan uji Spearman. Hasil menunjukan terdapat hubungan yang signifikan antara riwayat neutropenia (p value = 0,003) dan riwayat infeksi (p value = 0,000) dengan lama rawat kemoterapi fase induksi. Perawatan atau intervensi yang tepat selama kemoterapi fase induksi perlu menjadi perhatian untuk mencegah atau menurunkan kejadian neutropenia dan infeksi pada anak dengan LLA. ...... Induction chemotherapy phase is the first stage of the treatment in children with ALL and carried out immediately after been diagnosed, started and occurred at 4 to 6 weeks (28-42 days). The results achieved in this phase will determine the prognostic and the next chemotherapy phase. This study aimed to identified factors related to the length of stay of induction chemotherapy phase in children with ALL. The design used in this study is a cross-sectional design, with 94 samples got through consecutive sampling. The Spearman test is used for analysis. Result showed a significant relationship between a history of neutropenia (p value = 0.003) and infection history (p value = 0.000) with the length of stay of induction chemotherapy phase. Appropriate treatment or intervention during the induction phase of chemotherapy needs to be concern to prevent or decrease the incidence of neutropenia and infection in children with ALL.

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Nama : Holong MangasahProgram Studi : Pendidikan KedokteranJudul Tugas Akhir : Perbandingan Kadar Trigliserida Plasma pada Penggunaan Deksametason dan Prednison sebagai Terapi Induksi Leukemia Limfoblastik Akut pada Anak-anak Latar Belakang: Leukemia limfoblastik akut LLA merupakan penyakit keganasan pada sel-sel prekursor limfoid yang sering terjadi anak-anak. Pengobatan terhadap LLA terdiri dari tiga fase, fase induksi, konsolidasi, dan pemeliharaan. Terapi fase induksi merupakan tahap pemusnahan sel-sel kanker dan fase ini bertujuan untuk mencapai remisi. Obat yang digunakan dalam fase ini adalah obat kortikosteroid karena sifat sitotoksiknya. Obat kortikosteroid memiliki efek samping peningkatan lipogenesis yang dapat meningkatkan trigliserida plasma. Deksametason dan prednison saat ini sering dipakai dalam pengobatan fase induksi sebagai obat kortikosteroid pilihan.. Hingga saat ini, belum ada penelitian mengenai tingkat efek samping kedua obat diukur dari kadar trigliserida. Tujuan: Tujuan penelitian ini adalah mengetahui tingkat peningkatan kadar trigliserida dari kedua obat. Metode: Penelitian ini menggunakan desain penelitian potong lintang. Sampel yang diambil sebanyak 21 sampel dari rekam medik Rumah Sakit Cipto Mangunkusumo. Teknik pengambilan sampel yang digunakan adalah consecutive sampling. Hasil: Persebaran data dari kadar trigliserida yang diperoleh tidak normal. Perbandingan kadar trigliserida dari deksametason dan prednison disajikan dalam bentuk median yaitu 108 mg/dL untuk deksametason dan 146 mg/dL untuk prednison. Analisis dilakukan menggunakan Uji Mann-Whitney dan menunjukkan hasil yang tidak bermakna Kesimpulan: Nilai median pada kadar trigliserida dari penggunaan deksametason dan prednison tidak menunjukkan hasil yang bermakna.

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ABSTRACT
ABSTRACT Name Holong MangasahStudy program MedicineTitle of Paper Comparison of Plasma Triglycerides Level in Dexamethasone and Prednisone Usage as Induction Therapy of Acute Lymphoblastic Leukemia in Children Background Acute lymphoblastic leukemia ALL is a malignant disease that affect lymphoid precursors cell and often happen in children. Therapy for ALL consists of three phases, induction phase, consolidation phase, and maintenance phase. During induction phase, malignant cells are destroyed and therefore, this phase is important to achieve remission. Corticosteroid drug is used in induction therapy because of its cytotoxic effect. Meanwhile, one of corticosteroids adverse effect is increasing lipogenesis which may elevate plasma triglycerides level. Dexamethasone and prednisone currently served as the drug of choice for induction phase. There has been no research comparing dexamethasone and prednisone in elevating plasma triglycerides level in ALL patients. Objective The purpose of this study is to know the level of elevated triglycerides after dexamethasone and prednisone usage in ALL patients Method The design of this study is cross sectional. This study uses 21 samples which are obtained from medical records in Rumah Sakit Cipto Mangunkusumo by consecutive sampling. Results The obtained data of triglycerides level shows an uneven distribution. Dexamethasone group has a median of 106 mg dL and prednisone group has a median of 146 mg dL. Comparison between both groups shows an insignificant result. Conclusion The difference in median value of dexamethasone group and prednisone group is not significant.

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Acute lymphoblastic leukemia has been known as the most common cancer to occur in childhood. Along the treatment process of ALL, hematologic toxicities including thrombocytopenia has been identified as one of the side effects which may occur in patients during the maintenance phase of chemotherapy. This may cause the treatment to be discontinued and lead to a higher risk of relapse. To prevent a worse prognosis, it is essential to analyze factors which may induce thrombocytopenia. This study aimed to identify association between the occurrence of thrombocytopenia with several factors including gender, age, nutritional status, risk group, and serum albumin level. The research was conducted with a cross sectional retrospective analytical approach towards 101 subjects from Rumah Sakit Cipto Mangunkusomo within the year of 2014 – 2016. This study revealed that there were 26.7% of patients that experienced thrombocytopenia, with grade 1 thrombocytopenia accounted for most of the case. These patients with thrombocytopenia were mostly male and there were similar proportions between patients with high risk and standard risk. They had a younger age (median of 3.33 years old), had a good nutritional status, and normal serum albumin level. The result of this study revealed a significant association between age with the occurrence of thrombocytopenia (p=0.003). While, no significant association was found between the occurrence of thrombocytopenia with the other factors including gender (p=0.575), nutritional status (p=1.000), risk group (p=0.799) and serum albumin level (p=0.809). In conclusion, age is the only significant factor that influence the occurrence of thrombocytopenia. ......Leukemia limfoblastik akut (LLA) merupakan jenis kanker yang paling sering ditemukan pada anak. Angka kelangsungan hidup pasien semakin meningkat seiring dengan berkembangnya kemoterapi dalam tatalaksana penyakit ini. Namun, terdapat risiko untuk pasien mengalami trombositopenia sebagai salah satu efek samping toksisitas dalam fase pemeliharaan kemoterapi. Hal ini menjadi salah satu penyebab penghentian dini terapi yang dapat meningkatkan risiko untuk mengalami relaps. Untuk menghindarinya, dibutuhkan pengkajian terhadap faktor -faktor yang dapat memicu terjadinya trombositopenia pada pasien LLA. Penelitian ini bertujuan untuk mengetahui asosiasi antara kejadian trombositopenia yang dialami oleh pasien pada fase pemeliharaan kemoterapi, dengan berbagai faktor meliputi jenis kelamin, umur, status gizi, stratifikasi risiko dan kadar serum albumin. Studi ini dilaksanakan menggunakan metode potong lintang dengan pendekatan retrospektif analitik terhadap 101 data anak dengan diagnosis LLA di Rumah Sakit Cipto Mangunkusumo pada tahun 2014 sampai tahun 2016. Dalam penelitian ini, ditemukan bahwa 26.7% pasien mengalami trombositopenia selama fase pemeliharaan kemoterapi, dengan grade 1 trombositopenia berdasarkan klasifikasi ECOG sebagai kasus terbanyak. Diantara pasien yang mengalami trombositopenia, terdapat lebih banyak pasien laki – laki, dengan proporsi seimbang antara pasien dengan risiko standar dan risiko tinggi. Mayoritas pasien trombositopenia memiliki umur yang lebih muda (median 3.3 tahun), mempunyai status gizi yang baik, dengan kadar serum albumin yang normal. Penelitian ini menunjukan adanya hubungan signifikan antara umur dan kejadian trombositopenia (p=0.003). Sementara, kejadian trombositopenia tidak berhubungan dengan faktor lain seperti; jenis kelamin (p=0.575), status gizi (p=1.000), stratifikasi risiko (p=0.799), dan kadar serum albumin (p=0.809). Umur merupakan satu-satunya faktor yang mempengaruhi kejadian trombositopenia pada pasien.

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Leukemia limfoblastik akut adalah penyakit keganasan hematologi yang paling sering ditemukan pada anak. Perubahan metabolisme pasien kanker dan pengobatan kemoterapi menyebabkan pasien mengalami anoreksia sehingga dapat mengakibatkan pasien mengalami malnutrisi. Kondisi tersebut dapat menurunkan respons terhadap terapi, rendahnya kualitas hidup, dan tingginya mortalitas. Terapi medik gizi yang adekuat diperlukan untuk mendukung proses penyembuhan anak dengan pasien kanker. Asam amino rantai cabang (AARC) merupakan salah satu zat gizi spesifik yang dapat memperbaiki asupan makan dengan cara berkompetisi dengan triptofan pada transporter di otak pada mekanisme lapar-kenyang sehingga menurunkan efek anoreksigenik. Penelitian sebelumnya menunjukkan efek positif pemberian AARC terhadap asupan makan dan menurunkan kadar triptofan bebas di otak pada pasien kanker. Serial kasus ini memaparkan tiga pasien laki-laki dan satu pasien perempuan, berusia 8-14 tahun dengan malnutrisi, mengalami penurunan asupan makan, dan peningkatan kadar inflamasi. Seluruh pasien mendapatkan terapi medik gizi sejak awal perawatan hingga sebelum pulang dari rumah sakit. Pemberian energi dan protein sesuai fase pada penatalaksanaan gizi buruk dan AARC yang berasal dari bahan makanan sumber serta makanan cair. Asupan energi tertinggi pasien kasus sebesar 54-140 kkal/kgBB dan asupan protein tertinggi sebesar 2-4,7 g/kgBB dengan AARC tertinggi sebesar 8,9-23,4 g. Terdapat penurunan kadar inflamasi pada seluruh pasien kasus. Skala lapar-kenyang terendah sebelum makan 2 dan setelah makan 5, perbaikan tingkat lapar-kenyang pada seluruh pasien kasus diikuti dengan peningkatan jumlah asupan. Satu orang pasien mengalami penurunan berat badan, dua orang tetap, dan satu orang mengalami peningkatan berat badan. Terapi medik gizi yang adekuat dengan pemberian AARC dapat menunjang keberhasilan pengobatan pasien anak malnutrisi dengan lekemia limfoblastik akut yang menjalani kemoterapi. ......Acute lymphoblastic leukemia is the most common hematological malignancy in children. Metabolic changes in cancer patients and chemotherapy cause patients to experience anorexia which can increase the risk of malnutrition. These conditions can reduce the response to therapy, lower quality of life, and high mortality. Adequate nutritional management is needed to support the healing process of children with cancer patients. Branched-chain amino acids(BCAA) are specific nutrients that can improve calorie intake by competing with tryptophan on transporters in the brain on the hunger-satiety center, thereby reducing anorexigenic effects. Previous research has shown a positive effect of BCAAs on improving calorie intake and reducing levels of free tryptophan in the brain in cancer patients. This case series describes three male and one female patient, aged 8-14 years, malnutrition, decreased calorie intake, and inflammation. All patients received medical nutrition therapy from early treatment until before leaving the hospital. Provision of energy and protein according to the phase in the management of malnutrition and specific nutrients, BCAAs derived from food and liquid food. The highest energy intake of patients in the case of 54-140 kcal/kg BW, and the highest protein intake of 2-4.7 g/kg BW with the highest AARC of 8.9-23.4 g. All patients experienced a reduction in inflammation. The level of hunger-satiety is 2 before eating, and it is 5 thereafter. In all cases, patients increase their intake after experiencing improvements in their hunger-satiation levels. Two patients' weights remained the same, one gained weight, and one patient lost weight. Adequate nutritional therapy and AARC supplementation can support the successful treatment of malnourished pediatric patients with acute lymphoblastic leukemia on chemotherapy.

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Latar Belakang: Di Indonesia diperkirakan terdapat 4100 kasus baru kanker anak setiap tahunnya. Kejadian paling banyak adalah leukemia limfoblastik akut LLA sebesar 80 . Permasalahannya adalah angka kejadian kekambuhan pasien anak cukup tinggi sekitar 20-40 . Data pasien anak di Bagian Hematologi/Onkologi Departemen Ilmu Kesehatan Anak RSCM/FKUI periode tahun 2005-2011 kejadian kambuh mencapai 40 . Tujuan penelitian ini adalah mengetahui apakah ada hubungan kekambuhan pasien anak LLA terkait terapi vinkristin dengan polimorfisme gen MDR1. Metode: Studi dilakukan di Departemen Ilmu Kesehatan Anak RSCM/FKUI selama periode Februari 2014 sampai Januari 2015 dengan disain penelitian cohort. Kriteria pasien dengan LLA berusia lebih dari satu tahun hingga usia kurang dari 18 tahun. Sampel adalah pasien baru didiagnosis LLA dan pasien sedang menjalani kemoterapi fase induksi. Pemeriksaan sensitifitas obat in vitro dari sampel darah metode flow cytometry dengan menghitung Leukemia Cell Survival Index LCSI . Penelitian pendahuluan gen MDR1 dengan RFLP dan polimorfisme dengan Multiplex PCR. Data klinis pasien dilihat secara retrospektif dari catatan medis. Inform consent diperoleh dari pasien atau orang tua pasien. Hasil: Sampel memenuhi kriteria inklusi sebanyak 101 pasien terdiri dari 63 62.4 laki-laki dan 38 37.6 perempuan. Kekambuhan pasien anak LLA dipengaruhi oleh faktor usia,kelompok risiko dan jumlah lekosit p

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Background There are an estimated 4100 new cases of childhood cancer each year in Indonesia. The most common cancer in children is acute lymphoblastic leukemia ALL which is approximately 80 . The problem faced is the incidence of relapse in children is quite high, about 20 40 . Data from Hematology Oncology Division of Child Health Department RSCM FKUI period 2005 2011, showed that the incidence of relapse reached 40 . The purpose of this study is to investigate whether there is an association of polymorphism related to vincristine therapy. Methods The study was conducted in the Child Health Department RSCM FKUI with cohort design from February 2014 to January 2015. The number of patients with ALL included in the study was 101. The patients participated in the study were 1 18 years old, newly diagnosed of ALL, and undergoing chemotherapy induction phase. In vitro examination of drug sensitivity from blood samples was conducted using flow cytometry to determine leukemia cell survival index LCSI . The preliminary study was done by RFLP and polymorphism by Multiplex PCR. Clinical data of patients were obtained retrospectively from medical records.The informed consent was obtained from the patient or the patient 39 s parents. Results From 101 patients, there were 63 male 62.4 and 38 female 37.6 . The occurence of relapse of ALL patients was affected by age, risk group and leukocyte count p