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Enhancing Pediatric Cancer Survival in Indonesia: The Role of CAR T Cell Therapy Azhar, Muhammad Al; Aisyi, Mururul
Indonesian Journal of Cancer Vol 18, No 2 (2024): June
Publisher : http://dharmais.co.id/

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.33371/ijoc.v18i2.1238

Abstract

Pediatric cancer poses a major health challenge globally, especially in low-middle-income countries like Indonesia. The survival rate of pediatric cancer in many high-income countries (HICs) reaches 90%, while it only ranges from 5 to 60% in LMICs. Over 80% of children with cancer live in low-middle-income countries, indicating the urgency to improve the survival rate of pediatric cancer in LMICs [1]. In Indonesia, the prevalence of pediatric cancer was 43.5% in 2020, making it the highest among Southeast Asian countries [2]. According to Dharmais Cancer Hospital (2024), the national cancer referral center for all of Indonesia, the 5-year survival rate of high-risk pediatric acute lymphoblastic leukemia is only 48.8% (unpublished data).One key factor contributing to the low survival rate of pediatric cancer in Indonesia is the lack of effective therapy options, especially for high-risk and relapsed or refractory patients. Several therapeutic approaches, such as immunotherapy, have been widely used in HICs but are still not very popular in Indonesia. CAR (Chimeric Antigen Receptor) T-cell therapy is one of the most promising immunotherapeutic approaches to treat pediatric cancer. Implementing CAR T Cell therapy in Indonesia offers promising prospects for improving the survival rates of pediatric cancer patients.CAR T cell therapy utilizes the body's immune system to specifically target and eliminate cancer cells. This innovative therapy entails extracting a patient's T cells, genetically modifying them to express chimeric antigen receptors specific to tumor-associated antigens, and then reinfusing them into the patient. Once infused, these engineered T cells recognize and eliminate cancer cells bearing the targeted antigen, thereby offering a highly targeted and potentially curative treatment option [3]. This innovative therapy has demonstrated remarkable success in treating certain hematologic malignancies, including pediatric leukemia. The most extensively studied case in childhood patients involves CAR T cells that target CD19, a B cell surface receptor [4].CAR T cell therapy holds great promise for improving survival rates among pediatric cancer patients in Indonesia. Children with refractory or relapsed leukemia, such as B-cell acute lymphoblastic leukemia (B-ALL), who have exhausted standard treatment options, can benefit from CAR T cell therapy. Most relapsed or refractory pediatric cancer patients in Indonesia do not have effective therapy options to treat the disease. CAR T cell therapy emerges as a novel therapy that can significantly improve the survival of this subset of patients. Numerous studies have documented high remission rates (ranging from 70% to 90%) in adults and children diagnosed with refractory B-ALL [4]. A study by Maude et al. [5] reported high remission rates and durable responses in young adults and children with refractory or relapsed B-ALL treated with CAR T cells. Similarly, Park et al. [6] demonstrated long-term remissions and improved survival in pediatric leukemia patients receiving CAR T cell therapy. Several groups also have observed the persistence of CAR T cells and sustained remission lasting over six months in the majority of patients examined [4]. Efforts have been made to implement CAR T cells in Indonesia. Dharmais Cancer Hospital, as a National Cancer Center in Indonesia, has initiated this effort by collaborating with iCarTAB Biomed Inc., a China-based CAR T cell manufacturer with one of its manufacturing sites located in Malaysia. However, this approach involves sending patients' blood samples that have been processed through leukapheresis to Malaysia for CAR T cell manufacturing, followed by the shipment of the manufactured cells back to Indonesia for administration to patients. This process is impractical and incurs intangible costs such as transportation and cryopreservation, ultimately making it more expensive for patients. Regulatory issues related to the shipment of cells across borders in the region and early preparation of patients for CAR T cell therapy soon after relapse before they succumb to treatment-related mortality or relapse-related complications are also challenges that need to be addressed [7]. Reflecting on the abovementioned issue, CAR T cell therapy adoption in Indonesia faces significant challenges. Limited healthcare infrastructure, including specialized facilities for cell therapy manufacturing and administration, poses logistical hurdles. Moreover, cost remains a major barrier, as CAR T cell therapy is often expensive and inaccessible to many patients in Indonesia. Furthermore, the lack of local expertise in cellular immunotherapy may impede the successful implementation of CAR T cell therapy programs.Efforts to address these challenges and maximize the potential of CAR T cell therapy in Indonesia are essential. This requires a multi-faceted approach involving investment in healthcare infrastructure, including establishing specialized centers equipped for CAR T cell therapy manufacturing and administration. Two alternative models have been proposed for manufacturing CAR-T cell therapy: centralized and de-centralized models [8]. In the centralized manufacturing model, point of manufacturing and point of care are located in different geographical areas, while decentralized manufacturing focuses on establishing point of care and manufacturing in close proximity. A decentralized manufacturing model might be the best approach to be implemented in LMICs like Indonesia. Building hospital-based cellular therapy manufacturing reduces the need for transportation and cryopreservation. The decentralized system's geographic proximity improves communication between manufacturing and treatment teams, facilitating the creation of customized products based on a patient's phenotype. This setup also reduces administration time and the risk of delays and mix-ups compared to centralized manufacturing, making hospital-based cellular therapy manufacturing a potentially more cost-effective option [8].In addition, initiatives to reduce the cost of therapy through partnerships with pharmaceutical companies, government subsidies, or philanthropic endeavors can improve affordability and access. Furthermore, capacity-building initiatives aimed at training local healthcare professionals in cellular immunotherapy techniques are essential for ensuring the successful implementation and sustainability of CAR T cell therapy programs in Indonesia. Collaboration between local institutions, international organizations, and industry stakeholders can facilitate knowledge transfer and technology transfer, fostering indigenous expertise in this cutting-edge treatment modality.CAR T cell therapy represents a transformative approach to improving survival rates among pediatric cancer patients in Indonesia. By harnessing the power of immunotherapy, specifically tailored to target cancer cells, CAR T cell therapy offers hope for children with refractory or relapsed leukemia who have limited treatment options. Through continued research, collaboration, and investment in healthcare infrastructure, CAR T cell therapy potentially could greatly improve the prognosis and quality of life for pediatric cancer patients in Indonesia.
Unveiling the Survival Gap: Addressing the Challenges of Acute Lymphoblastic Leukemia in Adolescents Aisyi, Mururul; Kosasih, Agus Susanto; Utomo, Ahmad Rusdan Handoyo; Saputra, Fahreza; Sari, Teny Tjitra; Sjakti, Hikari Ambara; Dwijayanti, Fifi; Harimurti, Kuntjoro; Andriastuti, Murti
Indonesian Journal of Cancer Vol 19, No 2 (2025): June
Publisher : http://dharmais.co.id/

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.33371/ijoc.v19i2.1396

Abstract

Background: Acute Lymphoblastic Leukemia (ALL) remains the most common pediatric cancer, yet survival outcomes vary widely across age groups. In Indonesia, comprehensive data on ALL survival rates are sparse, particularly for adolescents who often fare worse than younger children. The underlying factors contributing to the difference in adolescent survival rates still need to be fully understood. This study aimed to evaluate and compare the survival rates of children and adolescents with ALL treated at Dharmais Cancer Hospital.Method: We conducted a retrospective cohort analysis of 94 ALL patients, including 37 adolescent patients and 71 patients with B-lineage ALL. All patients with ALL from 2021 to 2023 were identified. Children aged 1–18 years, diagnosed with ALL based on bone marrow results and not yet treated, are included in the study. Patients were stratified by risk stratification (Standard Risk [SR] vs. High Risk [HR]), lineage (B-lineage vs. T-lineage), and age group (children under 10 vs. adolescents 10 years and above). The survival curve was analyzed using the KaplanMeier method, and the log-rank test was used to assess and compare survival across groups.Results: The overall survival (OS) rate for ALL patients was 49.5%. Adolescents had a significantly lower OS rate of 23.2% compared to children. SR patients exhibited an OS rate of 95.7%, while HR patients had a 33.3%. B-cell lineage had a higher OS rate (59.8%) than T-cell lineage (15.9%). In B-cell ALL, OS was 61.4% in children but only 28.1% in adolescents. Conclusion: The survival rate for adolescents with acute lymphoblastic leukemia (ALL) is significantly lower than that of children, influenced by risk stratification, lineage, and age. Further research is needed to identify these risk factors through genetic and molecular analyses.Conclusion: The survival rate for adolescents with acute lymphoblastic leukemia (ALL) is significantly lower than that of children, influenced by risk stratification, cell type, and age. Unexplained factors, including lineage differences, remain a challenge in adolescents. Further research into genetic and molecular factors is essential to enhance treatment precision and improve survival rates for ALL patients in Indonesia, especially adolescents.Keywords: Overall Survival, Leukemia, Adolescent ALL, Stratification
Associations between genomic copy number alterations and clinical and laboratory results in pediatric B-cell acute lymphoblastic leukemia Aisyi, Mururul; Andriastuti, Murti; Kosasih, Agus Susanto; Utomo, Ahmad Rusdan Handoyo; Saputra, Fahreza; Sari, Teny Tjitra; Sjakti, Hikari Ambara; Dwijayanti, Fifi; Harimurti, Kuntjoro
Paediatrica Indonesiana Vol. 65 No. 2 (2025): March 2025
Publisher : Indonesian Pediatric Society

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14238/pi65.2.2025.89-95

Abstract

Background Copy Number Alterations (CNAs) are changes in DNA structure that lead to gain or loss of copies of DNA sections in the genome. They correlate with unfavorable prognostic outcomes in pediatric leukemia, influencing treatment resistance, relapse rates, and overall survival. Identifying high-risk patients with a likelihood of CNA positivity is essential for understanding its association with clinical characteristics and laboratory findings. Since routine CNA testing is costly, recognizing simple clinical and laboratory markers that predict CNA presence can help focus screening efforts, enabling more efficient risk stratification and prognosis assessment in acute leukemia Objective To describe the characteristics and analyze for associations between CNA, clinical characteristics, and laboratory findings in pediatric ALL patients. Methods This cross-sectional observational study included B-cell acute lymphoblastic leukemia (ALL) patients from three hospitals, excluding those above 18 years. Data collected encompassed demographics, clinical features, and laboratory results. We performed multiplex ligation-dependent probe amplification (MLPA) testing to identify CNA positivity. Results From January to December 2019, there were 74 pediatric ALL patients incuded in our study; 26 of them had positive results and the remaining 48 had negative results. CNA-positive status was commonly found in subjects aged ? 5 years (38.6%), while CNA-negative status was highest in patients aged ? 10 years (72.7%). CNA-positive status was significantly higher in patients with lymphadenopathy, lower hemoglobin level (7.73 g/dL), and lower platelet level (52,019/µL) (P<0.05). Conclusion Patients with lymphadenopathy, lower hemoglobin, and lower platelet levels are more likely to test positive for CNA. However, more research is needed to fully understand the implications of this finding and its potential impact on patient care.
EVALUASI PENGGUNAAN ANTIBIOTIKA PADA PASIEN PEDIATRI LEUKIMIA LIMFOBLASTIK AKUT DENGAN FEBRILE NEUTROPENIA SELAMA PEMBERIAN KEMOTERAPIDI RUMAH SAKIT KANKER DHARMAIS JAKARTA Muliyani, Muliyani; Perwitasari, Dyah Aryani; Andalusia, Rizka; Aisyi, Mururul
Media Farmasi: Jurnal Ilmu Farmasi Vol. 11 No. 1: Maret 2014
Publisher : Universitas Ahmad Dahlan

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.12928/mf.v11i1.1402

Abstract

Pemilihan  terapi  antibiotika  harus  berdasarkan  hasil  kultur,  pola  resistensi  serta guideline  yang  ada  karena  mikroorganisme  dan  sensitivitasnya  terhadap antibiotika  senantiasa  berubah.  Penelitian  ini  bertujuan  untuk mengevaluasi penggunaan  antibiotika  pada  pasien  pediatri  dengan  leukimia  limfoblastik  akut yang  mengalami  febrile  neutropenia  selama  pemberian  kemoterapi  kanker  di RSKD  Jakarta.  Penelitian  ini  merupakan  penelitian  non-eksperimental  dengan pengambilan data secara retrospektif dan prospektif di periode bulan  Maret -April 2014.  Data  diambil  dari  rekam  medik  pasien  kemudian  dianalisis  dengan dekskriptif.  Subyek  yang  memenuhi  kriteria  inklusi  adalah  pasien  pediatri  ≤  18 tahun  yang  mengalami  febrile  neutropenia  yang  mendapat kemoterapidan Absolute Neutrophile Count(ANC) <  1500 sel/mm3 Suhu oral ≥ 38,3 °C atau 2-3x terukurnya  suhu  ≥  38°C  selama  lebih  dari  1  jam.  Pengumpulan  data  dilakukan dengan  melakukan  pencatatan  pada   form  pengambilan  data  yang  diambil  dari mediacal record.  Pada penelitian ini terdapat 25 episode pasien pediatri dengan febrile neutropenia  yang sesuai dengan kriteria inklusi. Tingkat keparahan  febrile neutropenia  yang  terjadi  sebanyak  (72  %)  severe,  (24  %)  moderate  dan  (4  %) mild. Penggunaan antibiotik paling banyak cefotaxime (56 %), ceftazidime (28 %) dan berdasarkan hasil kultur (28 %). Keberhasilan terapi antibiotik empirik yang digunakan  (88   %)  dan  kegagalan  terapi  sebesar  (12  %).  Pemilihan  terapi antibiotika  pada  pasien  pediatri  leukimia  limfoblastik  akut  yang  mengalami febrile  neutropenia  sudah  sesuai  dengan  guideline  dan  pola  kuman  di  RSKD Jakarta.Kata Kunci : febrile neutropenia, antibiotika, keberhasilan terapi