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"Latar belakang. Anak dan remaja dengan leukemia limfoblastik akut (LLA) berisiko mengalami osteoporosis sekunder, salah satunya karena pemberian obat kemoterapi metotreksat dan steroid. Saat ini belum terdapat data prevalens osteoporosis sekunder pada anak dengan LLA di Indonesia dan bukti keterkaitan dosis kumulatif metotreksat dan steroid terhadap kejadian osteoporosis sekunder pada anak dengan LLA.Tujuan. Mengetahui ada tidaknya kaitan antara dosis kumulatif metotreksat dan/atau steroid terhadap kejadian osteoporosis sekunder pada anak dan remaja dengan LLA.Metode. Penelitian ini merupakan studi potong lintang terhadap 52 anak dan remaja dengan LLA yang sedang menjalani kemoterapi di Rumah Sakit dr. Cipto Mangunkusumo (RSCM). Pengambilan darah dan foto polos tulang belakang dilakukan untuk menilai parameter kesehatan tulang, serta pemeriksaan dual energy X-ray absorptiometry (DEXA) untuk menilai densitas mineral tulang. Analisis regresi logistik digunakan untuk menganalisis keterkaitan dosis kumulatif metotreksat dan steroid terhadap kejadian osteoporosis sekunder.Hasil. Median usia subyek adalah 10 (7-14) tahun dengan lelaki 54% (n=52). Didapatkan kejadian osteoporosis sekunder 6/52 (11,5%) dan densitas mineral tulang rendah 11/52 (21,2%). Tidak didapatkan kaitan antara dosis kumulatif steroid (adjusted RP 0,474 [0,057-3,935], p = 0,489) dan dosis kumulatif metotreksat (adjusted RP 0,083 [0,006-1,126], p = 0,061)  dengan kejadian osteoporosis sekunder. Pasien berusia di bawah 10 tahun, memiliki kadar vitamin D rendah, dan status prepubertas memiliki kecenderungan mengalami osteoporosis sekunder.Kesimpulan. Tidak didapatkan hubungan yang bermakna secara statistik antara dosis kumulatif steroid dan/atau metotreksat terhadap osteoporosis sekunder pada anak dan remaja dengan LLA.

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Background. Children and adolescents with acute lymphoblastic leukemia (ALL) are at risk of secondary risk, one of which is the administration of chemotherapy drugs (methotrexate and steroids). Currently, there are no data on the prevalence of secondary osteoporosis in children with ALL in Indonesia and evidence about association between methotrexate and steroids with the incidence of secondary osteoporosis with ALL.

Objective. To determine whether there is an association between the cumulative dose of methotrexate and/or steroids on the incidence of secondary osteoporosis in children and adolescents with ALL.

Methods. This study was a cross-sectional study of 52 children and adolescents with ALL who were undergoing chemotherapy at the Cipto Mangunkusumo Hospital (CMH). Blood sampling and plain radiographs of the spine were performed to assess bone health parameters, as well as dual energy X-ray absorptiometry (DEXA) examination to assess bone mineral density. Logistic regression analysis was used to analyze the association between the cumulative dose of methotrexate and steroids on the incidence of secondary osteoporosis.

Result. The median age of the subjects was 10 (7-14) years with 54% men (n=52). The incidence of secondary osteoporosis was 6/52 (11.5%) and low bone mineral density 11/52 (21.2%). There was no association between the cumulative dose of steroids (adjusted PR 1.501 [0.124-18.124], p=0.75) and the cumulative dose of methotrexate (adjusted PR 0.071 [0.005-0.951], p=0.05) and the incidence of secondary osteoporosis. None of the confounding factors (pubertal status, vitamin D levels, income level, age, and sex) were associated with secondary osteoporosis. Patient aged below 10 years old, have prepubertal status, and with low vitamin D serum tends to have osteoporosis more likely.

Conclusion. There was no statistically significant relationship between the cumulative dose of steroids and/or methotrexate on secondary osteoporosis in children and adolescents with ALL."

"ABSTRAK Hiperglikemia adalah efek samping yang umum kombinasi steroid dan L-asparaginase, terjadi paling sering selama kemoterapi fase induksi LLA. Sampai saat ini di Indonesia, belum didapatkan data mengenai kejadian hiperglikemia pada pasien anak dengan LLA pada fase induksi dan bagaimana peranan perbedaan kombinasi L-asparaginase dan jenis steroid yang digunakan.Tujuan penelitian ini adalah untuk mengetahui angka kejadian hiperglikemia pada anak LLA fase induksi, perbedaan prednison dan deksametason dalam kombinasinya dengan L-asparaginase dalam menyebabkan hiperglikemia pada anak dengan LLA dan hubungan faktor-faktor lain dengan kejadian hiperglikemia pada fase induksi LLA.Penelitian ini merupakan studi prospektif analitik dengan desain pre-post test, dilakukan di RSCM, RS Kanker ldquo;Dharmais rdquo; dan RSPAD Gatot Soebroto. Pasien yang akan menjalani kemoterapi fase induksi LLA diperiksa kadar gula darah sewaktu pada minggu ke-3 pretest , minggu ke-4, minggu ke-5 dan minggu ke-6 protokol post test .Dari 57 pasien yang berasal dari 3 Rumah Sakit yang berbeda berhasil dikumpulkan, terbanyak berasal dari RSCM 57,9 disusul RS Kanker ldquo;Dharmais rdquo; 24,6 dan RSPAD Gatot Soebroto 17,5 . Rentang umur pasien berkisar antara 1,4 tahun sampai 15,8 tahun dengan rerata 6,7 tahun. Tidak terdapat perbedaan rerata kadar gula darah sewaktu sebelum dan sesudah kombinasi steroid dan L-asparaginase. Tidak didapatkan hubungan antara umur, infiltrasi SSP, leukositosis, sindrom Down, status gizi, riwayat DM pada keluarga, infeksi dan stratifikasi LLA dengan kejadian hiperglikemia. Pemberian deksametason memiliki peluang 10,68 x didapatnya angka di atas rerata perubahan kadar gula darah sewaktu dibandingkan pemberian prednison.Kesimpulan: kejadian hiperglikemia pada penelitian ini adalah 5,2 . Walaupun tidak terdapat perbedaan antara prednison dan deksametason dalam kombinasinya dengan L-asparaginase dalam menyebabkan hiperglikemia, namun deksametason memiliki risiko angka di atas rerata perubahan kadar gula darah sewaktu dibandingkan prednison.

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ABSTRACTHyperglycaemia is a common side effect of steroid and L asparaginase combinations, occurring most often during LLA induction phase. To date in Indonesia, it has not been obtained data on the incidence of hyperglycemia in children with LLA in the induction phase and how the role of combinations of L asparaginase and different type of steroid used.The purpose of this study is to determine the incidence of hyperglycemia in children LLA induction phase, knowing the difference between prednisone and dexamethasone in combination with L asparaginase in causing hyperglycemia in children with LLA and determine the relationship of other factors related to hyperglycaemia.This study is a prospective analytic study with pre post test design, conducted in RSCM, National Cancer Hospital Dharmais and RSPAD Gatot Soebroto. When undergoing chemotherapy induction phase LLA, blood sugar levels were checked at the 3rd pretest , 4th, 5th and 6th week of protocol post test .Of the 57 patients from three different hospitals that had been gathered, mostly came from RSCM 57.9 followed by the Cancer Hospital Dharmais 24.6 and RSPAD 17.5 . The patient age ranged from 1.4 years to 15.8 years with a mean of 6.7 years. There was no difference in mean blood sugar levels before and after combination of steroids and L asparaginase. There were no relationship between age, CNS infiltration, leukocytosis, Down syndrome, nutritional status, family history of diabetes, infections and LLA stratification with the incidence of hyperglycemia. Dexamethasone has a 10.68 x chance of obtaining a rate above the mean change in blood sugar levels compared to prednisone.Conclusion The incidence of hyperglycemia in this study is 5.26 . Despite no difference between prednisone and dexamethasone in combination with L asparaginase in causing hiperglycaemia, but dexamethasone has a risk to have value above the mean change in blood sugar levels when compared to prednisone."

"Obesitas adalah salah satu masalah kesehatan kronik yang dialami oleh sebagian besar survivor LLA. Deksametason digunakan dalam terapi LLA dan memiliki efek samping peningkatan berat badan sehingga diduga memiliki hubungan terdahap risiko obesitas pada anak dengan ALL yang mendapatkan terapi. Data penelitian diambil dari 149 subjek, 43 kasus dan 106 kontrol. Analisis Odds Ratio menunjukkan bahwa dosis kumulatif deksametason berhubungan dengan angka kejadian obesitas pada setiap kelompok dosis dengan nilai paling besar pada dosis 100-200 mg (OR = 4,961 CI = 1,812-13,536). Analisis multivariat menujukan bahwa stratifikasi risiko merupakan faktor risiko obesitas (OR = 7,839 CI = 2,559-24,009), sedangkan usia merupakan faktor protektif (OR = 0,041 CI = 0,008 0,220).

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Obesity is one of chronic health conditions that affect a majority of ALL survivors. Corticosteroid is used in the treatment of ALL and has the side effect of weight gain. Hence, the usage of corticosteroid in the treatment of ALL is suspected to be the cause of obesity in ALL survivors. The study was done on 149 subjects, consisted of 43 cases and 106 controls. Odds ratio analysis shows correlation between high corticosteroid dose and obesity in all dose ranges with highest value at 100-200 mg range (OR = 4,961 CI = 1,812-13,536). Multivariate analysis shows that risk stratification is a risk factor for obesity (OR = 7,839 CI = 2,559-24,009) whereas age is protective for obesity (OR = 0,041 CI = 0,008-0,220).

"

"ABSTRAKLatar belakang : Prevalens terjadinya malnutrisi bervariasi pada berbagai siklus kemoterapi LLA. Penelitian di Malaysia mendapatkan anak LLA pasca-kemoterapi fase induksi cenderung mengalami obesitas atau status gizi lebih. Penyebab malnutrisi pada anak LLA dapat dipengaruhi oleh berbagai faktor. Perubahan status gizi selama kemoterapi dapat memengaruhi luaran kemoterapi.Tujuan: mengetahui faktor-faktor yang memengaruhi perbaikan status gizi anak LLA setelah kemoterapi fase konsolidasi, serta pengaruhnya terhadap luaran kemoterapi, sehingga dapat dipakai sebagai masukan untuk upaya mengatasi malnutrisi pada anak LLA.Metode : Penelitian ini dengan uji retrospektif, di Rumah sakit Cipto Mangunkusumo, selama tahun 2016-2018. Total sampling pada pasien leukemia limfoblastik akut yang terdiagnosis, dan menjalani kemoterapi di RSCM hingga fase konsolidasi.Hasil : Seratus empat puluh satu subyek pasien anak LLA diikutsertakan dalam penelitian ini. Terdapat 69,5% subyek mengalami perbaikan status gizi, dan 30,5% mengalami perburukan status gizi, dengan 60% perburukan ke arah overnutrition pasca-kemoterapi fase konsolidasi. Faktor risiko independen terhadap terjadinya perbaikan status gizi pasca-kemoterapi fase konsolidasi ialah tidak timbulnya efek samping kemoterapi (RR 1,36, 95% IK 1,02 - 1,81). Jenis makanan dan cara pemberian makan tidak memengaruhi perubahan status gizi anak LLA pasca-fase konsolidasi. Terdapat hubungan antara perbaikan status gizi anak LLA pasca-fase konsolidasi dengan kejadian remisi (RR 1,24, 95% IK 1,03 - 1,5).Simpulan : Status gizi pasca-kemoterapi fase konsolidasi mengalami perbaikan dibandingkan sebelum kemoterapi, sedangkan yang mengalami perburukan status gizi cenderung mengalami overnutrition. Perbaikan status gizi anak LLA pasca-kemoterapi fase konsolidasi dipengaruhi oleh tidak timbulnya efek samping kemoterapi. Terdapat hubungan antara perbaikan status gizi anak LLA pasca-kemoterapi fase konsolidasi dengan kejadian remisi.

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ABSTRACTBackground: Acute lymphoblastic leukemia (ALL) is the most common malignancy in childhood. The prevalence of malnutrition varies in phase of ALL chemotherapy. Study in Malaysia showed ALL children after induction phase of chemotherapy tended to be obese or overweight. The causes of malnutrition in ALL children can be influenced by various factors. Changes in nutritional status during chemotherapy can affect the outcome of chemotherapy.Aim: To investigate factors that influence nutritional status improvement of ALL children after consolidation phase, as well as the effect on the outcomes of chemotherapy, so it can be used as an input to overcome malnutrition in ALL children.Method: A retrospective design was performed in Cipto Mangunkusumo Hospital from 2016 until 2018. Total sampling in patients with acute lymphoblastic leukemia who was diagnosed and started chemotherapy at Cipto Mangunkusumo Hospital until the consolidation phase.Result: A total of 141 subjects were included in this study. After consolidation phase, 69.5% of subjects experienced nutritional status improvements, and 30.5% worsened, of which 60% become over nutrition post-consolidation phase. Independent risk factor for the improvement of nutritional status after consolidation phase was the absence of chemotherapy side effects (RR 1.36, 95% CI 1.02 - 1.81). There were no association between type of food and route of feeding with nutritional status improvement of ALL children after consolidation phase. There was association between improvement in nutritional status of ALL children after consolidation phase with the incidence of remission (RR 1.24, 95% CI 1.03 - 1.5).Conclusion: Nutritional status at post-consolidation phase has improved compared to pre- chemotherapy, while those who worsening nutritional status tend to overnutrition. The absence of chemotherapy side effects affects nutritional status improvement of ALL children after consolidation phase. There is a relationship between nutritional status improvement of ALL children after consolidation phase with the incidence of remission."

"[ABSTRAKLatar 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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ABSTRACTIntroduction: 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.]"

"Latar belakang: Anak yang menderita Leukemia Limfoblastik Akut LLA menunjukkan peningkatan sistem imun pada akhir perawatan kemoterapi. sIgA merupakan hasil dari sistem imun yang ada pada saliva. Tujuan: Menganalisis perbedaan kadar sIgA saliva antara anak LLA fase pemeliharaan dengan gingivitis dan anak sehat dengan gingivitis. Metode Penelitian: Saliva diambil dari anak LLA dan anak sehat. selanjutnya kadar sIgA saliva diukur dengan metode ELISA. Hasil: Signifikansi Mann-Whitney menunjukkan besar 0.157 p>0.05 . Kesimpulan: Terdapat perbedaan kadar sIgA saliva antara anak LLA fase pemeliharaan dengan gingivitis dan anak sehat dengan gingivitis, namun tidak signifikan.

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Background: Acute Lymphoblastic Leukemia ALL children shows an increasing of immune system in the late phase of chemotherapy. sIgA is a product of immune system in saliva.

Aim: To analyze salivary sIgA difference between ALL children in maintenance phase and healthy children with gingivitis.

Method: Saliva was collected from ALL and healthy children. The salivary sIgA level was then measured with ELISA method.

Results: Mann Whitney significance shows the number 0.157 p 0.05 .

Conclusion There is a difference in salivary sIgA levels among ALL children in the maintenance phase and healthy children with gingivitis, but the difference is not significant."

"ABSTRAK Latar Belakang Leukemia limfoblastik akut LLA adalah keganasan paling sering pada anak di sebagian besar dunia insiden bervariasi di berbagai daerah mulai 15 sampai 40 Keberhasilan pengobatan pada LLA dapat dilihat berdasarkan angka kesintasan Rumah Sakit Sanglah telah merawat pasien leukemia anak akan tetapi sampai saat ini belum pernah dilakukan penilaian terhadap kesintasan pada kasus leukemia akut Tujuan Untuk mengetahui angka kesintasan pasien LLA serta faktor faktor yang memengaruhi LLA di bawah umur 12 tahun di RSUP Sanglah dari tahun 2010 2012 Metode Penelitian kohort retrospektif dilakukan di RS Sanglah dengan menggunakan data sekunder dari catatan medis pasien LLA dari Januari 2010 ndash Desember 2012 Sampel adalah pasien berusia 0 12 tahun terdiagnosis LLA kemudian dikelompokkan menjadi risiko biasa dan risiko tinggi berdasarkan nilai leukosit awal usia dan protokol LLA tahun 2006 Hasil Penelitian Terdapat 33 subjek pasien LLA Didapatkan perbedaan bermakna faktor prognostik usia 1 9 tahun dengan usia 9 tahun dan jumlah leukosit 50 000 mL dengan leukosit 50 000 mL memengaruhi angka kesintasan dengan nilai masing masing p 0 023 dan p 0 013 Angka kesintasan hidup secara keseluruhan pasien LLA adalah 30 3 didapatkan perbedaan bermakna angka kesintasan antara RT dan RB dengan nilai masing masing adalah 11 8 43 8 dan p ABSTRACT Background Acute lymphoblastic leukemia ALL is the most common hildhood cancer in the world Incidence rate found various in several countries from 15 to 40 A successful theraphy of ALL be evaluated by the survival rate Sanglah hospital has been treated children with ALL but however a research of survival rate in children with ALL has never been done before Objective To know the survival rate of children with ALL and factors that affect ALL in children under 12 years old that has been treated in Sanglah Hospital from 2010 2012 Method A retrospective cohort study run in Sanglah Hospital using secondary data from medical record of children with ALL between January 2010 December 2012 Sample is ALL patients aged 0 12 years old with diagnosis ALL will be separated into normal risk group and high risk group based on early number of leucosyte age and therapy protokol year 2006 Results There are 33 subjects of children with ALL Significant difference of prognostic factors were found between the age of 1 9 years old and at the age 9 years old as well as between leucocyte count 50 000 mL and those with leucocyte count 50 000 mL affect the survival rate with each p value of p 0 023 and p 0 013 The Overall survival rate of ALL patients was 30 3 There were significant difference of survival rate between RT and RB valued 11 8 43 8 with p;Background Acute lymphoblastic leukemia ALL is the most common hildhood cancer in the world Incidence rate found various in several countries from 15 to 40 A successful theraphy of ALL be evaluated by the survival rate Sanglah hospital has been treated children with ALL but however a research of survival rate in children with ALL has never been done before Objective To know the survival rate of children with ALL and factors that affect ALL in children under 12 years old that has been treated in Sanglah Hospital from 2010 2012 Method A retrospective cohort study run in Sanglah Hospital using secondary data from medical record of children with ALL between January 2010 December 2012 Sample is ALL patients aged 0 12 years old with diagnosis ALL will be separated into normal risk group and high risk group based on early number of leucosyte age and therapy protokol year 2006 Results There are 33 subjects of children with ALL Significant difference of prognostic factors were found between the age of 1 9 years old and at the age 9 years old as well as between leucocyte count 50 000 mL and those with leucocyte count 50 000 mL affect the survival rate with each p value of p 0 023 and p 0 013 The Overall survival rate of ALL patients was 30 3 There were significant difference of survival rate between RT and RB valued 11 8 43 8 with p;Background Acute lymphoblastic leukemia ALL is the most common hildhood cancer in the world Incidence rate found various in several countries from 15 to 40 A successful theraphy of ALL be evaluated by the survival rate Sanglah hospital has been treated children with ALL but however a research of survival rate in children with ALL has never been done before Objective To know the survival rate of children with ALL and factors that affect ALL in children under 12 years old that has been treated in Sanglah Hospital from 2010 2012 Method A retrospective cohort study run in Sanglah Hospital using secondary data from medical record of children with ALL between January 2010 December 2012 Sample is ALL patients aged 0 12 years old with diagnosis ALL will be separated into normal risk group and high risk group based on early number of leucosyte age and therapy protokol year 2006 Results There are 33 subjects of children with ALL Significant difference of prognostic factors were found between the age of 1 9 years old and at the age 9 years old as well as between leucocyte count 50 000 mL and those with leucocyte count 50 000 mL affect the survival rate with each p value of p 0 023 and p 0 013 The Overall survival rate of ALL patients was 30 3 There were significant difference of survival rate between RT and RB valued 11 8 43 8 with p"

"Pengobatan pada anak Leukemia limfoblastik akut terus dikembangkan, saat ini di Indonesia ada beberapa protokol yang lazim digunakan yaitu protokol Nasional Jakarta, protokol WK-LLA 2000, protokol LLA 2006 dan protokol LLA 2013. Tujuan studi ini untuk mengetahui probabilitas kesintasan hidup 3 tahun pada anak leukemia limfoblastik akut antara protokol 2006 dan 2013. Studi ini menggunakan mix method yaitu kohort retrosfektif dan wawancara mendalam. Populasi dalam penelitian ini adalah anak LLA usia 1-15 tahun yang mendapatkan protokol 2006 dan 2013 di RSKD Jakarta dari tahun 2008 ndash; 2016 sebanyak 68 anak dengan waktu penelitian dari April 2016 sampai Juni 2016. Data dianalisis dengan menggunakan Cox Regression. Hasil studi ini didapatkan probabilitas kesintasan 3 tahun anak LLA berdasarkan protokol pengobatan 2006 dan 2013 HR 1,57 CI 90 0,577 ndash; 4,299, namun perbedaan antara kedua protokol ini tidak bermakna secara statistik dengan p-value 0,456. Hasil wawancara mendalam juga didapat pada protokol 2006 dan 2013 secara prinsip sama namun tetap ada beberapa perbedaan diantara keduanya seperti jadwal pengobatan dan dosis secara kumulatif meningkat. Kesimpulan yang didapat ada interaksi waktu pada variabel trombosit, kedua protokol ini secara prinsip sama dan tidak terdapat banyak perbedaan dalam hal input dan proses.

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Treatment of children with Acute lymphoblastic leukemia was developing, currently in Indonesia there are several commonly used protocols such as National protocol Jakarta, WK LLA 2000 protocol, LLA protocol 2006 and protocol LLA 2013. The purpose of this study to determine the probability of survival 3 years In children with acute lymphoblastic leukemia between protocols 2006 and 2013. This study used a mix method of retrospective cohorts and in depth interviews. The population in this study were LLA children aged 1 15 years who received protocol 2006 and 2013 in RSKD Jakarta from 2008 2016 is 68 children with research time from April 2016 until June 2016. Data were analyzed using Cox Regression.

The result of this study shows the probability of 3 year survival of LLA children based on treatment protocol 2006 and 2013 HR 1,57 CI 90 0,577 ndash 4,299, but the difference between these two protocols was not statistically significant with p value 0.456. The results of in depth interviews were also obtained in protocols 2006 and 2013 in the same principle but there remain some differences between the both of the treatment schedule and doses are cumulatively increased. The conclusion is that there is time interaction on platelet variable, these two protocols are in principle the same and there is not much difference in input and process."

"Hematotoksisitas pada leukemia limfoblastik akut (LLA) anak selama terapi fase pemeliharaan, merupakan hal penting, karena dapat menyebabkan kondisi mengancam jiwa dan penghentian dini terapi, yang dapat meningkatkan risiko relaps. Untuk menghindari hematotoksisitas, American Society for Clinical Pharmacology and Therapeutics merekomendasikan penyesuaian dosis awal merkaptopurin (6MP) berdasarkan genotip enzim pemetabolisme 6MP yaitu thiopurine S-methyl transferase (TPMT), berdasarkan studi-studi sebelumnya polimorfisme enzim tersebut memengaruhi kadar metabolit aktif 6MP dan hematotoksisitas. Penelitian ini bertujuan untuk mengetahui prevalensi hematotoksisitas dan melihat hubungannya dengan genotip TPMT, fenotip TPMT, dan karakteristik pada pasien LLA anak di Indonesia. Studi potong lintang dilakukan di RS Cipto Mangunkusumo dan RS Kanker Dharmais pada bulan Juni 2017–Oktober 2018 terhadap 106 pasien LLA anak yang sedang mendapatkan 6MP minimal 1 bulan pada terapi fase pemeliharaan. Prevalensi hematotoksisitas pada fase pemeliharaan pasien LLA anak di Indonesia 71,7%, dengan neutropenia 51,9%, anemia 44,3%, dan trombositopenia 6,6%. Neutropenia tingkat 3–4 sebesar 9,4%. Alel mutan yang ditemukan hanya TPMT*3C dengan frekuensi 0,95%. Kadar 6TGN, 6MeMP dan rasio kadar 6MeMP/6TGN sangat bervariasi, yaitu 6–234,04 pmol/8x10⁸ eritrosit, 3,5–3167,01 pmol/8x10⁸ eritrosit, dan 0,06–100,64 pmol/8x10⁸ eritrosit, secara berurutan. Sebesar 76,4% pasien berusia antara 1–10 tahun dan > 95% pasien memiliki status gizi dan kadar albumin normal. Proporsi pasien berdasarkan stratifikasi risiko dan dosis harian 6MP sebanding. Tidak terdapat hubungan antara hematotoksisitas dengan genotip TPMT, usia, status gizi, kadar albumin, stratifikasi risiko, cara pemberian dosis harian 6MP, dan pemberian bersama kotrimoksazol. Faktor yang berhubungan dengan hematotoksisitas adalah fenotip TPMT: kadar 6MeMP (p = 0,004) dan rasio kadar 6MeMP/6TGN (p = 0,010). IMT ≤ 16,6 kg/m2 berhubungan dengan anemia dan kadar albumin serum ≤ 4,2 g/dL berhubungan dengan trombositopenia. Tidak terdapat hubungan antara genotip dengan fenotip TPMT pada pasien LLA anak di Indonesia. Kesimpulan: Hematotoksisitas tidak berhubungan dengan genotip TPMT dan karakteristik pasien. Fenotip TPMT berhubungan dengan hematotoksisitas, namun kurang kuat untuk memprediksi hematotoksisitas.

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Hematotoxicity in acute lymphoblastic leukemia (ALL) children during maintenance phase therapy is important, because it can cause life-threatening conditions and it is the major cause of drug discontinuation, which can increase the risk of relapse. To reduce hematotoxicity, American Society for Clinical Pharmacology and Therapeutics recommended to adjust starting dose of mercaptopurine (6MP) based on patient's genotype of thiopurine S-methyl transferase (TPMT), that affected 6MP active metabolite levels and hematotoxicity.

The aim of the study was to determine the prevalence of hematotoxicity and factors that affecting hematotoxicity, focus on genotype and phenotype of TPMT. A cross-sectional study was conducted at Cipto Mangunkusumo Hospital and Dharmais Cancer Hospital in June 2017–October 2018 for 106 LLA patients who were receiving at least 1 month of 6MP during maintenance therapy.

The prevalence of neutropenia, anemia, and thrombocytopenia were 51.9%, 44.3%, and 6.6%, respectively. We found only TPMT *3C with a frequency of 0.95%. Erythrocyte levels of 6TGN, 6MeMP, and ratio of 6MeMP/6TGN levels vary greatly, 6–234,04 pmol/8x10⁸ RBC, 3,5–3167,01 pmol/8x10⁸ RBC, and 0,06–100,64 pmol/8x10⁸ RBC. About 76.4% of patients aged 1–10 years, and > 95% of patients had normal nutritional status and serum albumin levels. The proportion of patients based on risk stratification and daily dose of 6MP were comparable. There was no association between hematotoxicity and genotype TPMT, age, nutritional status, serum albumin levels, risk stratification, daily dose of 6MP, and co-administration of cotrimoxazole. The factor associated with hematotoxicity was the TPMT phenotype: 6MeMP levels (p = 0.004) and the ratio of 6MeMP/6TGN levels (p = 0.010). BMI ≤ 16.6 kg/m2 was associated with anemia and serum albumin level ≤ 4.2 g/dL was associated with thrombocytopenia. There was no relationship between genotype and the TPMT phenotype in pediatric LLA patients in Indonesia.

Conclusion: Hematotoxicity is not associated with TPMT genotype and patient characteristics. The TPMT phenotype is associated with hematotoxicity but is not strong enough at predicting hematotoxicity."

"Leukemia limfoblastik akut (ALL) adalah jenis kanker yang paling umum pada anak-anak. Nyeri dan kelelahan berhubungan dengan faktor-faktor kanker dan perawatannya. Tujuan dari penelitian ini adalah untuk menemukan hubungan antara kualitas nyeri dan kelelahan pada anak-anak dengan ALL 1-3 hari setelah kemoterapi. Penelitian ini menggunakan desain cross sectional dan menggunakan teknik consequtive sampling. Total sampel adalah 44 anak-anak dengan ALL (7-18 tahun) di Jakarta. Alat ukur yang digunakan dalam penelitian ini adalah kuesioner Simple Pain Inventory (BPI) untuk mengukur kualitas nyeri dan Kelelahan Onkologi Anak-Allen (FOA-A) untuk mengukur kelelahan. Nilai rata-rata kualitas nyeri adalah 1,63932 dan nilai rata-rata kelelahan adalah 9,25. Hasil penelitian ini menunjukkan bahwa ada hubungan yang signifikan antara kualitas nyeri dan kelelahan (p = 0,006), status kambuh dan kelelahan (p = 0,058), dan antara seseorang yang menemani anak-anak dan kelelahan (p = 0,016). Hasil penelitian ini merekomendasikan pentingnya penilaian nyeri lebih lanjut dan pengobatan kombinasi antara farmakologi dan nyeri non-farmakologi setelah kemoterapi untuk mengurangi kelelahan pada anak-anak dengan kanker.

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Acute lymphoblastic leukemia (ALL) is the most common type of cancer in children. Pain and fatigue are related to cancer factors and their treatments. The aim of this study was to find an association between pain quality and fatigue in children with ALL 1-3 days after chemotherapy. This research uses cross sectional design and uses consequtive sampling technique. The total sample was 44 children with ALL (7-18 years) in Jakarta. The measuring instrument used in this study was a Simple Pain Inventory (BPI) questionnaire to measure the quality of pain and Fatigue Oncology of Children-Allen (FOA-A) to measure fatigue. The average value of pain quality is 1.63932 and the average value of fatigue is 9.25.

The results of this study indicate that there is a significant relationship between quality of pain and fatigue (p = 0.006), relapse and fatigue status (p = 0.058), and between someone who accompanies children and fatigue (p = 0.016). The results of this study recommend the importance of further pain assessment and combination treatment between pharmacology and non-pharmacological pain after chemotherapy to reduce fatigue in children with cancer."