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"[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 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 Latar belakang: Minimal residual disease MRD adalah faktor prediktor yang sensitif pada leukemia limfoblastik akut LLA dengan menggunakan flowsitometri. Minimal residual disease dapat mendeteksi 1 sel blas diantara 10.000 sel normal 0,01 . Pemerikasaan MRD dapat digunakan untuk menyempurnakan status remisi induksi pada LLA. Metode: Penelitian uji potong lintang selama 4 bulan dilakukan di bagian Onkologi Anak RSKD, Departemen Ilmu Kesehatan Anak RSAB Harapan Kita; divisi Hematologi-Onkologi RS Kramat 128 pada Febuari ndash; Juni 2017. Subjek adalah pasien yang terdiagnosis LLA yang menyelesaikan kemoterapi pasca fase induksi. Pemeriksaan morfologi sumsum tulang, imunofenotiping leukemia dan MRD untuk evaluasi pasca fase induksi dilakukan dilakukukan di bagian Patologi Klinik RSKD.Hasil penelitian: Pada penelitian ini diikutsertakan 52 subjek dengan usia rerata 6.4 tahun. Subjek lelski 62 lebih banyak dibanding perempuan 38 . Semua pasien dengan leukemia sel B. Stratifikasi Risiko Biasa RB 46 adalah lebih sedikit dibandingkan Risiko Tinggi RT 54 . Minimal residual disease 0,01 42,3 dengan morfologi yang juga remisi. Stratifikasi RB dengan pemeriksaan MRD kuantitatif ABSTRACT Introduction Minimal residual disease MRD is the most powerful predictor of outcome in acute leukemia and is useful in therapeutic stratification for acute lymphoblastic leukemia ALL protocols. Nowadays, the most reliable methods for studying MRD in ALL are multiparametric flow cytometry. It provides a MRD level of 0,01 of normal cells, that is, detection of one leukemic cell in up to 10.000 normal nucleated cells. Evaluation after induction phase, is the most informative time to predict danger of relapse.Methods A cross sectional study was conducted at Pediatric Hematology Oncology Division, Department of Child Health, Pediatric Oncology Division of ldquo Dharmais rdquo Cancer Hospital Women and Children Harapan Kita Hospital Pediatric Hematology Oncology Division Kramat 128 Hospital on February June 2017. Morphology, immunophenotyping, MRD assessment was performed. Bone marrow aspiration and MRD detection performed after induction phase to evaluate remission.Results A total of 52 diagnosed ALL patients enrolled in this study. The mean age was 6.4 years. Incidence in male 62 is higher than female 38 . All patients are B lineage. Standard risk SR patients 46 is less than high risk HR patients 54 . Minimal residual disease 0,01 1 42,3 and morphological remission. Standard risk stratification with quantitative minimal residual disease "

"Leukemia limfoblastik akut (LLA) adalah jenis kanker yang disebabkan oleh akumulasi limfoblas di sumsum tulang yang mempengaruhi banyak anak. Keberhasilan pengobatan pada pasien leukemia dapat dinilai berdasarkan tingkat kelangsungan hidup pasien LLA. Tujuan dari penelitian ini adalah untuk mengidentifikasi kelangsungan hidup 5 tahun, faktor-faktor yang mempengaruhinya, dan nilai skor prediktor kelangsungan hidup pada anak usia 1-18 tahun yang didiagnosis dengan leukemia limfoblastik akut (LLA) di RSAB Harapan Kita. Penelitian ini adalah penelitian observasional analitik yang menggunakan desain penelitian kohort retrospektif. Sampel adalah 130 pasien LLA yang didiagnosis pada tahun 2013-2014 yang diperoleh dari teknik pengambilan sampel non-probabilitas jenis consecutive sampling. Data dikumpulkan dengan melacak rekam medis pasien. Data dianalisis menggunakan analisis Kaplan-Meier dan Regresi Cox. Hasil penelitian menunjukkan bahwa probabilitas tingkat kelangsungan hidup pasien LLA tahun 2013-2014 adalah 92,25% dengan tingkat kelangsungan hidup rata-rata 60 bulan. Berdasarkan analisis multivariat menggunakan model interaksi regresi Cox, faktor yang paling berpengaruh pada tingkat kelangsungan hidup pasien LLA adalah komorbiditas (p = 0,002; HR = 10,76 CI; 2,38-48,55), remisi (p = 0,001; HR = 13,28 CI2,98- 59,73) dan kambuh (p = 0,014; HR = 7,92 CI; 1,53-41,12).

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Acute lymphoblastic leukemia (LLA) is a type of cancer caused by the accumulation of lymphoblasts in the bone marrow that affects many children. The success of treatment in leukemia patients can be assessed based on the survival rate of LLA patients. The aims of this study were to identify 5-year survival, the factors that influence it, and the scoring value of predictors of survival in children aged 1-18 years diagnosed with acute lymphoblastic leukemia (LLA) in RSAB Harapan Kita. This study is an analytic observational study that used retrospective cohort study design. The sample was 130 LLA patients diagnosed in 2013-2014 who were obtained from a non-probability sampling technique consecutive sampling. Data were collected by tracking the patient's medical records. Data were analyzed using Kaplan- Meier analysis and Cox Regression. The results show that the LLA patient's survival rate probability from 2013-2014 was 92.25% with a median survival rate of 60 months. Based on multivariate analysis using Cox regression interaction models, the most influential factors on survival rate of LLA patients were comorbidity (p = 0.002; HR = 10.76 CI; 2.38-48.55), remission (p = 0.001; HR = 13.28 CI2.98-59.73) and relapse (p = 0.014; HR = 7.92 CI; 1.53- 41.12)"

"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."

"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."

"Kemoterapi memiliki dampak terjadinya kelelahan pada anak yang menderita leukemia limfoblastik akut. Kelelahan pada anak dapat diperberat oleh masalah tidur yang dialami anak. Penelitian ini bertujuan untuk menganalisis hubungan masalah tidur dengan kelelahan pada anak dengan leukemia limfoblastik akut yang menjalani satu siklus kemoterapi fase induksi. Desain penelitian ini adalah deskriptif analitik dengan pengukuran berulang masalah tidur dan kelelahan pada anak berumur 7-18 tahun (n=62). Pengambilan data dilakukan selama 7 hari yaitu, satu hari sebelum, lima hari selama, dan satu hari setelah kemoterapi. Hasil analisis data menggunakan uji korelasi Pearson dengan tingkat kemaknaan 95% menunjukkan hubungan yang signifikan (p<0,001) antara masalah tidur dengan kelelahan. Kesimpulannya masalah tidur menjadi penyebab beratnya kelelahan pada anak sehingga penting untuk dilakukan pengkajian dan memberikan intervensi mengatasi masalah tidur untuk mengurangi kelelahan pada anak. Pelatihan manajemen masalah tidur dan kelelahan menjadi penting untuk meningkatkan pengetahuan dan kemampuan perawat dalam mengatasi kelelahan pada anak leukemia limfoblastik akut yang menjalani kemoterapi fase induksi.

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Chemotherapy had an impact of disruption in sleep patterns and fatigue in children who suffer from acute lymphoblastic leukemia. Fatigue in children can be exacerbated by sleep problems experienced by children. This study aimed to analyze the relationship of sleep problems with fatigue in children with acute lymphoblastic leukemia who underwent a cycle of induction phase chemotherapy. The design of this research used descriptive analytic with repeated measurements of sleep problems and fatigue in children aged 7-18 years (n = 62). The data were taken for 7 days, consist of one day before, five days during, and one day after chemotherapy.

The result of data analysis using Pearson correlation test with significance level 95% showed significant relationship (p <0.001) between sleep problems with fatigue. The conclusion were sleep problems cause severe fatigue in children so it is important to do the assessment and provide intervention to overcome sleep problems to reduce fatigue in children. Training on sleep problems and fatigue management becomes important to improve knowledge and abilities of nurses in overcoming fatigue in children with acute lymphoblastic leukemia undergoing chemotherapy on induction phase."

"Leukemia limfoblastik akut (LLA) adalah keganasan yang paling sering terjadi pada anak-anak. Angka kesembuhan yang besar terjadi akibat terapi kanker saat ini, namun respon toksik yang terkait dan pembentukan radikal bebas meningkatkan angka kematian akibat pengobatan daripada kematian akibat penyakitnya itu sendiri. Komplikasi kemoterapi meningkatkan rasa ingin tahu dokter untuk mempelajari penggunaan antioksidan sebagai pengobatan tambahan pada kanker. Penelitian ini bertujuan untuk mengevaluasi peran N-asetilsistein ​​(NAS) sebagai terapi antioksidan pada anak-anak dengan LLA SR (standard risk) selama fase induksi kemoterapi, dan kemungkinan peran mereka dalam pencegahan dan pengendalian komplikasi hati terkait dengan penggunaan agen kemoterapi. Sebuah uji klinis acak tersamar tunggal NAS dibandingkan dengan plasebo yang dilakukan pada pasien anak Departemen Ilmu Kesehatan Anak Divisi Hematologi dan Onkologi di Rumah Sakit Cipto Mangunkusumo, Jakarta. Penelitian ini dilakukan pada 11 pasien anak-anak usia mereka berkisar antara 2 dan 10 tahun dengan LLA SR yang menjalani kemoterapi fase induksi dan memenuhi kriteria inklusi. Pasien secara acak dialokasikan ke dalam dua kelompok, NAS atau kelompok plasebo. Mereka dievaluasi secara klinis untuk terjadinya komplikasi dan sampel darah dikumpulkan sebagai parameter laboratorium (plasma malondialdehid (MDA), enzim transaminase, dan bilirubin). Sebanyak 11 subjek dilakukan analisis yang terdiri dari 6 pada kelompok n-asetilsistein dan 5 pada kelompok plasebo. Karakteristik subjek didominasi oleh anak laki-laki dengan status gizi kurang. Kadar rerata MDA cenderung mengalami penurunan, sebanyak tiga subjek dari enam subjek pada kelompok perlakuan dan tiga subjek dari lima subjek pada kelompok plasebo. Insidens peningkatan kadar enzim transaminase sebesar 25%. Tidak terjadi kejadian kolestasis pada subjek penelitian. Pengobatan NAS ​​berdasarkan dosis antioksidan cenderung menurunkan kadar MDA, dan mencegah peningkatan enzim transaminase, dan bilirubin.

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Acute lymphoblastic leukemia (ALL) is the most commonly malignancy in children. Cancer therapies have experienced great success nowadays, yet the associated toxic response and free radicals formation have resulted in significant number of treatment-induced deaths rather than disease-induced fatalities. Complications of chemotherapy increases physicians curiosity to study antioxidant use as adjunctive treatment in cancer. This study aims to evaluate the role of N-acetylcysteine (NAC) as antioxidant therapy in children with ALL during the induction phases of chemotherapy, and their possible role in prevention and control of hepatic complications associated with the use of chemotherapic agents. A randomized single-blind clinical trial of NAC in comparison with placebo conducted in hematology and oncology pediatric patient of Cipto Mangunkusumo Hospital, Jakarta. The study was performed in 11 pediatric patients with ALL with their ages ranging between 2 and 10 years, undergoing induction phase chemotherapy that fulfilled the inclusion criteria consecutively. Patient were randomly allocated into of two groups, NAC or placebo group. They were evaluated clinically for the occurance of complications and blood samples were collected as the laboratory parameters (plasma malondyaldehide (MDA), transaminase enzyme, and bilirubin). A total 11 participants were included in analysis consisted of 6 in n-acetylcysteine group and 5 in placebo group. Characteristics of subject were predominated by boys and moderate malnourished. Mean MDA levels tended to decrease, as many as three subjects from six subjects in the NAC group and three subjects from five subjects in the placebo group. Incidence of increased levels of the transaminase enzyme by 25%. There was no cholestasis events in the study subjects. NAS treatment based on antioxidant doses tends to reduce MDA levels, and prevent the increase in the transaminase enzyme and bilirubin."

"Latar Belakang & Tujuan: Leukemia limfoblastik akut (LLA) adalah jenis kanker yang sering ditemukan pada pasien anak. Selama terapi, pasien akan menerima fase maintenance untuk mencegah remisi dengan diberikan obat utama 6-merkaptopurin. Ada beberapa faktor yang dapat mempengaruhi berjalannya fase maintenance, diantaranya kejadan anemia. Studi ini bertujuan untuk memperoleh prevalensi, karakteristik, dan faktor risiko dari pasien yang mengalami anemia selama fase maintenance diperlukan untuk membantu mengantisipasi dan mencegah diberhentikannya fase maintenance yang dapat berakibat pada kejadian relaps. Metode: Penelitian ini menggunakan studi observational cross sectional. Sebanyak 101 rekam medis pasien anak di Rumah Sakit Cipto Mangunkusumo yang memenuhi kriteria inklusi digunakan sebagai sampel. Hasil: Usia (p = 0.0025) dan jenis kelamin (p=0.004) memiliki hubungan yang signifikan dengan terjadinya anemia selama fase maintenance terapi ALL dengan 6-merkaptopurin. IMT (p = 0.052), kelompok risiko (p = 0.067), dan kadar serum albumin (p = 0.21) tidak menunjukkan hubungan yang signifikan. Kesimpulan: Prevalensi kejadian anemia pada pasien LLA yang menjalankan fase maintenance terapi adalah 79.2% dengan karakteristik dimana pasien didominasi oleh pasien laki-laki, median usia 4 tahun, median BMI 16.10 kg/m², mayoritas tergolong pasien LLA risiko standard, dan median kadar albumin dalam serum 4.50 g/dL. Faktor-faktor yang mempengaruhi terjadinya anemia selama fase maintenance terapi LLA mencakup usia dan jenis kelamin.

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Background & Aim: Acute lymphoblastic leukemia (ALL) is the most common form of malignancies among children. During the therapy, ALL patients undergo maintenance phase therapy at the end of the protocol with 6-mercaptopurine as the main drug to prevent relapse. However, maintenance phase therapy may be interrupted in several conditions (i.e. anemia) increasing the risk of relapse. This study is done to obtain the prevalence, characteristics and contributing factors to anemia to prevent treatment interruptions and lower the risk of relapse.

Method: This research utilizes observational cross-sectional study. A total of 101 medical records of children patients in Rumah Sakit Cipto Mangunkusumo (RSCM) that fulfil the inclusion criteria were used as samples.

Result: Age (p = 0.0025) and gender (p = 0.004) have significant relationship with the occurrence of anemia during the maintenance phase of ALL treatment with 6-mercaptopurine. BMI (p = 0.052), risk groups (p = 0.067), and serum albumin level (p = 0.21) do not show significant relationship to anemia in this population.

Conclusion: The prevalence of anemia in ALL patients that underwent maintenance phase therapy is 79.2%, with the several characteristics, including domination by male children patients, median age of 4 years old, median BMI of 16.10 kg/m², categorized as standard risk group, and median serum albumin level of 4.50 g/dL. The contributing factors to anemia during maintenance phase therapy include age and gender."