Objective: To assess the predictors of treatment-related mortality (TRM) among pediatric acute lymphoblastic leukemia (ALL) cases in Pakistan.
Methodology: This retrospective study was conducted in the Pediatric Oncology department at Combined Military Hospital Rawalpindi, Pakistan. All newly diagnosed ALL cases between the ages of one and 18 years from 1st January 2013, to 31st December 2022 were included in the study. Physical and demographic data of all subjects were obtained and treatment outcome in terms of any complications or mortality were recorded during the above mentioned period. All data were analyzed using SPSS software.
Results: Among 1004 cases of ALL 636(63.3%) were males and 368(36.7%) were females. The mean age during the diagnosis was 5.76±3.60 years. Overall Mortality was 295 (29.4%) including 191/295(64.7%) TRM and 104(35.3%) relapse-related mortality. Among the TRM cases, 124/191(64.9%) expired during induction. The usual complication during induction was Neutropenic fever. In univariate analysis, malnutrition (P=0.043), high WBC count (P=0.011), reduced hemoglobin level (P=0.005), low platelet count (P=0.002), neutropenic sepsis (P=0.001), and hepatotoxicity (P=0.001), were found to be related to high induction mortality. On multivariate analysis, infection was the most significant predictor of mortality during the induction and post-induction period. Infection followed by bleeding was the most common cause of mortality. After a median follow-up of 49.94+34.04 months, the overall Survival and Disease-Free Survival rates at five years were 70.6% and 68.4% respectively.
Conclusion. The main causes of TRM in pediatric ALL are Neutropenic fever and bleeding. Malnutrition, high WBC count, neutropenic sepsis, and hepatotoxicity are the main predictors of high TRM.
Key Words: Pediatric, Acute Lymphoblastic Leukemia, Mortality, Treatment Related Mortailty
Pui CH. Precision medicine in acute lymphoblastic leukemia. Front Med. 2020 Dec 1;14(6):689–700.
Rodriguez-Galindo C, Friedrich P, Morrissey L, Frazier L. Global challenges in pediatric oncology. Curr Opin Pediatr [Internet]. 2013 Feb [cited 2022 Aug 13];25(1):3–15. Available from: https://pubmed.ncbi.nlm.nih.gov/23295716/
Fadoo Z, Nisar I, Yousuf F, Lakhani LS, Ashraf S, Imam U, et al. Clinical features and induction outcome of childhood acute lymphoblastic leukemia in a lower/middle income population: A multi-institutional report from Pakistan. Pediatr Blood Cancer [Internet]. 2015 Oct 1 [cited 2022 Aug 13];62(10):1700–8. Available from: https://pubmed.ncbi.nlm.nih.gov/25982135/
Nisar I, Shahid S, Yousuf F, Lakhani LS, Ashraf S, Imam U, et al. Treatment outcomes and prognostic factors of childhood acute lymphoblastic leukemia in a low-middle income population: A multi-institutional report from Pakistan. Pediatr Blood Cancer [Internet]. 2022 Aug 3 [cited 2022 Aug 13]; Available from: https://pubmed.ncbi.nlm.nih.gov/35920528/
Jabeen K, Ashraf MS, Iftikhar S, Belgaumi AF. The Impact of Socioeconomic Factors on the Outcome of Childhood Acute Lymphoblastic Leukemia (ALL) Treatment in a Low/Middle Income Country (LMIC). J Pediatr Hematol Oncol [Internet]. 2016 Nov 1 [cited 2022 Aug 13];38(8):587–96. Available from: https://pubmed.ncbi.nlm.nih.gov/27467375/
Abdelmabood S, Fouda AE, Boujettif F, Mansour A. Treatment outcomes of children with acute lymphoblastic leukemia in a middle-income developing country: high mortalities, early relapses, and poor survival. J Pediatr (Rio J) [Internet]. 2020 Jan 1 [cited 2020 Nov 12];96(1):108–16. Available from: https://pubmed.ncbi.nlm.nih.gov/30240631/
Gupta S, Antillon FA, Bonilla M, Fu L, Howard SC, Ribeiro RC, et al. Treatment-related mortality in children with acute lymphoblastic leukemia in Central America. Cancer [Internet]. 2011 Oct 15 [cited 2022 Aug 19];117(20):4788–95. Available from: https://pubmed.ncbi.nlm.nih.gov/21446043/
Rahat-Ul-Ain, Faizan M, Shamim W. Treatment-related mortality in children with acute lymphoblastic leukaemia in a low-middle income country. J Pak Med Assoc [Internet]. 2021 Oct 1 [cited 2023 Jan 24];71(10):2373–7. Available from: https://pubmed.ncbi.nlm.nih.gov/34974574/
Asim M, Zaidi A, Ghafoor T, Qureshi Y. Death analysis of childhood acute lymphoblastic leukaemia; experience at shaukat khanum memorial cancer hospital and research centre, pakistan. J Pak Med Assoc [Internet]. 2011 Jul [cited 2020 Nov 12];61(7):666–70. Available from: https://pubmed.ncbi.nlm.nih.gov/22204242/
Ghafoor T, Khalil S, Farah T, Ahmed S, Sharif I. Prognostic Factors in Childhood Acute Myeloid Leukemia; Experience from A Developing Country. Cancer Rep (Hoboken) [Internet]. 2020 Oct 1 [cited 2022 Aug 13];3(5). Available from: https://pubmed.ncbi.nlm.nih.gov/33085844/
UKALL2011 trial protocol - Google Search [Internet]. [cited 2023 Jan 25]. Available from: https://www.google.com/search?client=firefox-b-d&q=UKALL2011+trial+protocol+
Malvezzi M, Santucci C, Alicandro G, Carioli G, Boffetta P, Ribeiro KB, et al. Childhood cancer mortality trends in the Americas and Australasia: An update to 2017. Cancer [Internet]. 2021 Sep 15 [cited 2023 Feb 8];127(18):3445–56. Available from: https://pubmed.ncbi.nlm.nih.gov/34043810/
Fadoo Z, Nisar I, Yousuf F, Lakhani LS, Ashraf S, Imam U, et al. Clinical Features and Induction Outcome of Childhood Acute Lymphoblastic Leukemia in a Lower/Middle Income Population: A Multi-Institutional Report From Pakistan. Pediatr Blood Cancer. 2015;62:1700–8.
Pribnow AK, Ortiz R, Báez LF, Mendieta L, Luna-Fineman S. Effects of malnutrition on treatment-related morbidity and survival of children with cancer in Nicaragua. Pediatr Blood Cancer [Internet]. 2017 Nov 1 [cited 2022 Aug 20];64(11). Available from: https://pubmed.ncbi.nlm.nih.gov/28449403/
Barr RD, Gomez-Almaguer D, Jaime-Perez JC, Ruiz-Argüelles GJ. Importance of Nutrition in the Treatment of Leukemia in Children and Adolescents [Internet]. Vol. 47, Archives of Medical Research. Elsevier Inc.; 2016 [cited 2020 Nov 21]. p. 585–92. Available from: https://pubmed.ncbi.nlm.nih.gov/28476186/
Brinksma A, Huizinga G, Sulkers E, Kamps W, Roodbol P, Tissing W. Malnutrition in childhood cancer patients: a review on its prevalence and possible causes. Crit Rev Oncol Hematol [Internet]. 2012 Aug [cited 2022 Aug 20];83(2):249–75. Available from: https://pubmed.ncbi.nlm.nih.gov/22264939/
T G, I S, F B, S A, T A, S K, et al. Mortality in paediatric acute myeloid leukaemia. J Pak Med Assoc [Internet]. 2020 Dec 1 [cited 2021 Jul 13];70(12(B)):2316–22. Available from: https://pubmed.ncbi.nlm.nih.gov/33475535/
Oskarsson T, Söderhäll S, Arvidson J, Forestier E, Frandsen TL, Hellebostad M, et al. Treatment-related mortality in relapsed childhood acute lymphoblastic leukemia. Pediatr Blood Cancer [Internet]. 2018 Apr 1 [cited 2023 Feb 8];65(4). Available from: https://pubmed.ncbi.nlm.nih.gov/29230958/
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