Faktor Risiko dan Luaran Klinis Hiperglikemia pada Anak dengan Leukemia Limfoblastik Akut Selama Fase Induksi Kemoterapi: Tinjauan Naratif
DOI:
https://doi.org/10.57218/jkj.Vol5.Iss1.2319Kata Kunci:
asparaginase, hiperglikemia, kortikosteroid, leukemia limfoblastik akutAbstrak
Hiperglikemia merupakan komplikasi metabolik yang sering terjadi selama fase induksi kemoterapi pada anak dengan Leukemia Limfoblastik Akut (LLA), yang terutama berkaitan dengan efek diabetogenik kortikosteroid dan asparaginase. Pemahaman mengenai faktor-faktor yang memengaruhinya penting untuk deteksi dini, pencegahan komplikasi, dan optimalisasi luaran terapi. Tinjauan ini merupakan narrative review yang merangkum bukti dari uji klinis dan studi observasional pada pasien anak (0–18 tahun) dengan LLA selama fase induksi. Pencarian literatur dilakukan melalui PubMed, Scopus, Ovid, Wiley, dan Google Scholar menggunakan kata kunci terkait LLA, terapi induksi, hiperglikemia, dan faktor risiko. Artikel full-text yang melaporkan kejadian atau faktor penentu hiperglikemia diikutsertakan dalam analisis. Sebanyak sembilan studi memenuhi kriteria inklusi, dengan prevalensi hiperglikemia yang dilaporkan berkisar antara 7% hingga 52%. Faktor risiko yang paling menonjol adalah usia >10 tahun, terutama pada masa pubertas akibat resistensi insulin fisiologis. Faktor lain yang turut berkontribusi meliputi overweight atau obesitas, riwayat keluarga diabetes melitus, serta Down syndrome. Faktor terkait terapi, khususnya penggunaan kortikosteroid dan native L-asparaginase, juga berhubungan dengan peningkatan risiko. Hiperglikemia dikaitkan dengan peningkatan angka infeksi dan luaran terapi yang lebih buruk. Oleh karena itu, identifikasi dini pasien berisiko tinggi serta pemantauan glukosa yang lebih ketat penting dilakukan untuk meningkatkan luaran klinis.
Referensi
Aisyi, M., Andriastuti, M., & Kurniati, N. (2019). The effect of combination of steroid and L-asparaginase on hyperglycemia in children with acute lymphoblastic leukemia (ALL). Asian Pacific Journal of Cancer Prevention, 20(9), 2619–2624. https://doi.org/10.31557/APJCP.2019.20.9.2619
Alasiri, A., Alamoudi, A., Albalawi, A., Almatrafi, S., Ameen, M., & Alkanhal, K. (2025). The Incidence of Steroid-Induced Hyperglycemia in Pediatric Patients With Acute Lymphocytic Leukemia. Cureus. https://doi.org/10.7759/cureus.90556
Andria, N., Moelyo, A. G., & Riza, M. (2020). During induction phase chemotherapy in childhood acute lymphoblastic leukemia. Paediatrica Indonesiana (Paediatrica Indonesiana), 60(4), 192–197. https://doi.org/10.14238/pi60.4.2020.192-7
Awwad, S., Abu Alnasr, R., Almanjomi, F., Al Sultan, M., Howaidi, J., Almotairi, M., & AlFayyad, I. (2024). Peg-asparaginase associated toxicities in children with acute lymphoblastic leukemia: A single-center cross-sectional study. Pediatric Hematology Oncology Journal, 9(1), 54–62. https://doi.org/10.1016/j.phoj.2024.03.001
Aziz Eghbali, R. R. A. (2023). The effect of hyperglycemia during induction chemotherapy on the prognosis of pediatric acute lymphoblastic leukemia (ALL). Canon Journal of Medicine, 4, 50–54. https://doi.org/10.30477/CJM.2023.363122.1050
Dare, J. M., Moppett, J. P., Shield, J. P., Hunt, L. P., & Stevens, M. C. (2013). The impact of hyperglycemia on risk of infection and early death during induction therapy for acute lymphoblastic leukemia (ALL). Pediatric Blood and Cancer, 60(12). https://doi.org/10.1002/pbc.24689
Demedis, J., Scarbro, S., Suresh, K., Maloney, K., & Forlenza, G. P. (2023). Hyperglycemia and Other Glycemic Measures Throughout Therapy for Pediatric Acute Lymphoblastic Leukemia and Lymphoma. Journal of Pediatric Hematology/Oncology, 45(2). https://journals.lww.com/jpho-online/fulltext/2023/03000/hyperglycemia_and_other_glycemic_measures.12.aspx
Drucis, M., Irga-Jaworska, N., & Myśliwiec, M. (2018). Steroid-induced diabetes in the paediatric population. Pediatric Endocrinology, Diabetes and Metabolism, 24(3), 135–139. https://doi.org/10.5114/pedm.2018.80995
Ersan, F. G., Yilmaz, H., Coskun, C., Cilsaat, G., Vuralli Karaoglan, D., Kuskonmaz, B., Özön, Z. A., Unal, S., Aytac, S., & Gonc, E. N. (2024). Drug-Induced Diabetes during Treatment of ALL in Children: Who Is at Risk and When? Blood, 144(Supplement 1), 5853–5853. https://doi.org/10.1182/blood-2024-199258
Gatzioura, I., Papakonstantinou, E., Dimitriadou, M., Kourti, M., Sidi, V., Triantafyllou, P., Koliouskas, D., & Christoforidis, A. (2016). Glucose Levels Before the Onset of Asparaginase Predicts Transient Hyperglycemia in Children With Acute Lymphoblastic Leukemia. Pediatric Blood and Cancer, 63(7), 1181–1184. https://doi.org/10.1002/pbc.25956
Gregoriou, K., Craigie, I., Gibson, B., Mason, A., & Shaikh, M. G. (2020). Risk factors and management of corticosteroid-induced hyperglycaemia in paediatric acute lymphoblastic leukaemia. In Pediatric Blood and Cancer (Vol. 67, Number 2). John Wiley and Sons Inc. https://doi.org/10.1002/pbc.28085
Hill, R., Hamby, T., Levitt, M., Siebert, G., Diaz, M., & Mohamed, A. (2023). Proactive Glucose Screening Tool Effective for Time-sensitive Identification of Hyperglycemia in Childhood Cancer Patients. Journal of Pediatric Hematology/Oncology, 45(6), E695–E701. https://doi.org/10.1097/MPH.0000000000002674
Koltin, D., Sung, L., Naqvi, A., & Urbach, S. L. (2012). Medication induced diabetes during induction in pediatric acute lymphoblastic leukemia: Prevalence, risk factors and characteristics. Supportive Care in Cancer, 20(9), 2009–2015. https://doi.org/10.1007/s00520-011-1307-5
Maloney, K. W., & Gore, L. (2018). Agents in Development for Childhood Acute Lymphoblastic Leukemia. In Pediatric Drugs (Vol. 20, Number 2, pp. 111–120). Springer International Publishing. https://doi.org/10.1007/s40272-017-0268-7
McCormick, M. C., Sharp, E., Kalpatthi, R., Zullo, J., Gurtunca, N., Zhang, J., Krafty, R., & Raman, S. (2020). Hyperglycemia requiring insulin during acute lymphoblastic leukemia induction chemotherapy is associated with increased adverse outcomes and healthcare costs. Pediatric Blood and Cancer, 67(9). https://doi.org/10.1002/pbc.28475
Panigrahi, M., Swain, T., Jena, R., & Panigrahi, A. (2016). L-asparaginase-induced abnormality in plasma glucose level in patients of acute lymphoblastic leukemia admitted to a tertiary care hospital of Odisha. Indian Journal of Pharmacology, 48(5), 595–598. https://doi.org/10.4103/0253-7613.190762
Pollock, N. I., Flamand, Y., Zhu, J., Millington, K., Stevenson, K., Silverman, L. B., Vrooman, L. M., & Cohen, L. E. (2022). Hyperglycemia during induction therapy for acute lymphoblastic leukemia is temporally linked to pegaspargase administration. Pediatric Blood and Cancer, 69(7). https://doi.org/10.1002/pbc.29505
Popov, A., Henze, G., Roumiantseva, J., Bydanov, O., Belevtsev, M., Verzhbitskaya, T., Movchan, L., Tsaur, G., Lagoyko, S., Zharikova, L., Myakova, N., Litvinov, D., Khlebnikova, O., Streneva, O., Stolyarova, E., Ponomareva, N., Novichkova, G., Fechina, L., Aleinikova, O., & Karachunskiy, A. (2023). A Single Dose of PEG-Asparaginase at the Beginning of Induction Not Only Accelerates MRD Clearance but Also Improves Long-Term Outcome in Children with B-Lineage ALL. Cancers, 15(23). https://doi.org/10.3390/cancers15235547
Silva, L. C. O. E., Siviero-Miachon, A. A., Sousa, A. V. L., & Spinola-Castro, A. M. (2025). When and why do children develop hyperglycemia during acute lymphoblastic leukemia therapy? Revista Da Associacao Medica Brasileira (1992), 71(9), e20240953. https://doi.org/10.1590/1806-9282.20240953
Taher, Y. Y. , L. L. , Z. M. , M. A. H. , R. H. , A. A. A. , S. I. , & E.-H. A. (2026). Risk factors and clinical implications of hyperglycemia during induction therapy in pediatric acute lymphoblastic leukemia. International Journal of Cancer, 158, 163–171.
Tamaddoni, A., Alijanpour, M., Mahmoodi, H., Miladi, B., Bijani, A., Assadollahi, E., & Aghajanpour, F. (2019). The incidence of hyperglycemia during the induction phase of chemotherapy in patients with acute lymphoblastic leukemia. Iranian Journal of Pediatric Hematology and Oncology, 9(2), 66–72. https://doi.org/10.18502/IJPHO.V9I2.605
Vu, K., Busaidy, N., Cabanillas, M. E., Konopleva, M., Faderl, S., Thomas, D. A., O’Brien, S., Broglio, K., Ensor, J., Escalante, C., Andreeff, M., Kantarjian, H., Lavis, V., & Yeung, S. C. J. (2012). A randomized controlled trial of an intensive insulin regimen in patients with hyperglycemic acute lymphoblastic leukemia. Clinical Lymphoma, Myeloma and Leukemia, 12(5), 355–362. https://doi.org/10.1016/j.clml.2012.05.004
Wu, Y., Deng, Y., Wei, B., Xiang, D., Hu, J., Zhao, P., Lin, S., Zheng, Y., Yao, J., Zhai, Z., Wang, S., Lou, W., Yang, S., Zhang, D., Lyu, J., & Dai, Z. (2022). Global, regional, and national childhood cancer burden, 1990–2019: An analysis based on the Global Burden of Disease Study 2019. Journal of Advanced Research, 40, 233–247. https://doi.org/10.1016/j.jare.2022.06.001
Yeshayahu, Y., Koltin, D., Hamilton, J., Nathan, P. C., & Urbach, S. (2015). Medication-induced diabetes during induction treatment for ALL, an early marker for future metabolic risk? Pediatric Diabetes, 16(2), 104–108. https://doi.org/10.1111/pedi.12138
Yoshida, H., Imamura, T., Saito, A. M., Takahashi, Y., Suenobu, S., Hasegawa, D., Deguchi, T., Hashii, Y., Kawasaki, H., Endo, M., Hori, H., Suzuki, N., Kosaka, Y., Kato, K., Yumura-Yagi, K., Hara, J., Oda, M., Sato, A., & Horibe, K. (2015). Protracted administration of L-asparaginase in maintenance phase is the risk factor for hyperglycemia in older patients with pediatric acute lymphoblastic leukemia. PLoS ONE, 10(8). https://doi.org/10.1371/journal.pone.0136428
Yoshida, H., Nishimura, Y., Suzuki, M., Hayashi, K., Yoshida, T., Takita, M., Morikawa, D., Fujii, S., Kawaguchi, T., Shimizu, N., Hokuto, I., Suzuki, N., & Fujitani, S. (2026). Case-specific optimal extracorporeal membrane oxygenation configuration for cardiogenic shock in the peripartum period: a case report. Journal of Artificial Organs, 29(1), 19. https://doi.org/https://dx.doi.org/10.1007/s10047-026-01546-x
Zhang, B. H., Wang, J., Xue, H. M., & Chen, C. (2014). Impact of chemotherapy-related hyperglycemia on prognosis of child acute lymphocytic leukemia. Asian Pacific Journal of Cancer Prevention, 15(20), 8855–8859. https://doi.org/10.7314/APJCP.2014.15.20.8855.
