Differences in induction phase outcomes of acute lymphoblastic leukemia between well-nourished and malnourished pediatric patients

Meilani Puspasari Simarmata; Nelly Rosdiana; Arlinda Sari Wahyuni

doi:10.14238/pi63.3.2023.146-51

Meilani Puspasari Simarmata FK USU
Nelly Rosdiana Department of Child Health, Universitas Sumatera Utara Medical School, Medan, North Sumatera
Arlinda Sari Wahyuni Department of Child Health, Universitas Sumatera Utara Medical School, Medan, North Sumatra

DOI: https://doi.org/10.14238/pi63.3.2023.146-51

Keywords: acute lymphoblastic leukemia; malnutrition; induction phase outcomes

Abstract

Background Leukemia is the most common malignancy in childhood. Malnutrition is the main nutritional disorder occurring in children with cancer. Nutritional supportive care is a medical modality that has been associated with improved tolerance to chemotherapy, survival, and quality of life, as well as decreased risk of infection in children undergoing cancer therapy.

Objective To examine differences in induction phase outcomes in well-nourished and malnourished pediatric acute lymphoblastic leukemia (ALL) patients.

Methods This prospective study was conducted in newly-diagnosed ALL patients aged 1 to 18 years who underwent induction phase chemotherapy at Haji Adam Malik General Hospital, Medan, North Sumatera. Mid-upper arm circumference (MUAC) was used to determine nutritional status. Patient characteristics such as complete blood count (CBC) at the time of diagnosis, occurrence of febrile neutropenia, duration of induction, length of hospital stay, and remission status were collected. We analyzed differences in CBC, frequency of febrile neutropenia, as well as duration of induction and hospital stay between well-nourished and malnourished patients. We also assessed the difference in remission attainment between the two groups.

Results There were 21 subjects in each group. Compared to well-nourished subjects, malnourished ones had a higher median incidence of febrile neutropenia [1 (range 0 to 30) vs. 3 (range 0 to 4); P=0.04], longer mean induction duration [64.2 (SD 11.5) vs. 71.2 (SD 10.6) days; P=0.046], and longer median hospital stay [30 (range 19 to 56) vs. 36 (range 22 to 49) days; P=0.001] compared to well-nourished subjects. There was no significant difference in CBC parameters and remission status after induction between the two groups.

Conclusion Malnourished pediatric ALL patients had a significantly higher incidence of febrile neutropenia, duration of induction phase, and duration of hospital stay compared to well-nourished ALL patients.

References

1. Permono B, Ugrasena IDG, Supriyadi E. Leukemia akut. In: Windiastuti E, Nency YM, Mulatsih S, Sudarmanto B, Ugrasena IDG, editors. Buku Ajar Hematologi-Onkologi Anak, 2018. Jakarta: BP IDAI;2018. p. 276-8, 282.
2. Howard MR, Hamilton PJ. Haematology: an illustrated colour text. 3rd ed. London: Churcill Livingstone Elsevier; 2008. p.42.
3. Herintya F, Mulatsih S, Prawirohartono EP. Association between nutritional status and outcome of childhood acute lymphoblastic leukemia treated with Wijaya Kusuma Protocol. Paediatr Indones. 2008;48:28-31. DOI: https://doi.org/10.14238/pi48.1.2008.28-32.
4. Maldonado-Alcazar A, Carlos J, Alberto C, Fajardo-Gutierrez A, Manuel J. Alterations of nutritional status in childhood acute leukemia. Clinical Epidemiology of Acute Lymphoblastic Leukemia - From the Molecules to the Clinic. InTech; 2013. DOI: https://doi.org/10.5772/52715.
5. Athifah A, Hidayati SN, Sulistiawati. Correlative study between nutritional status and remission outcome in childhood acute lymphoblastic leukemia in Dr. Soetomo General Hospital Surabaya. Biomol Health Sci J. 2019;2:27-30. DOI: https://doi.org/10.20473/bhsj.v2i1.12723.
6. Yazbeck N, Samia L, Saab R, Abboud MR, Solh H, Muwakkit S. Effect of malnutrition at diagnosis on clinical outcomes of children with acute lymphoblastic leukemia. J Pediatr Hematol Oncol. 2016;38:107-10. DOI: https://doi.org/10.1097/MPH.0000000000000428.
7. Kadir RAA, Hassan JG, Aldorky MK. Nutritional assessment of children with acute lymphoblastic leukemia. Arch Can Res. 2017;5:1-9. DOI: https://doi.org/10.21767/2254-6081.1000128
8. Hafiz MG, Mannan MA. Nutritional status at initial presentation in childhood acute lymphoblastic leukemia and its effect on induction of remission. Mymensingh Med J. 2008;17(2 Suppl):S46-51. PMID: 18946451.
9. Frisancho AR, Tracer DP. Standards of arm muscle by stature for the assessment of nutritional status of children. Am J Phys Anthropol. 1987;73:459-65.
10. Mejia-Arangure JM, Fajardo-Gutierrez A, Reyes-Ruiz NI, Bernaldez-Rios R, Mejia-Dominguez AM, Navarette-Navarro S, et al. Malnutrition in childhood lymphoblastic leukemia: a predictor of early mortality during the induction-to-remission phase of the treatment. Arch Med Res. 1999;30:150–3. DOI: https://doi.org/10.1016/s0188-0128(98)00026-8.
11. Tandon S, Moulik NR, Kumar A, Mahdi AA, Kumar A. Effect of pre-treatment nutritional status, folate and vitamin B12 levels on induction chemotherapy in children with acute lymphoblastic leukemia. Indian Pediatr. 2015;52:385-9. DOI: https://doi.org/10.1007/s13312-015-0642-x.
12. Nency YM. Perbedaan kebutuhan transfusi darah selama fase induksi pada leukemia limfoblastik akut. Sari Pediatri. 2011;13:271-4. DOI: https://doi.org//10.14238/sp13.4.2011.271-4.
13. Agnes M, Widjajanto PH, Damayanti W. Impact of malnutrition on febrile neutropenia in children with acute lymphoblastic leukemia during induction phase chemotherapy. Paediatr Indones. 2018;58:298-304. DOI: https://doi.org/10.14238/pi58.6.2018.298-304.
14. Mihalea C, Despina B, Adrienne H, Diana M. Nutritional parameters in children with acute leukemia. Acta Med Marisiensis. 2011;57:12-15.
15. Perdani RRW, Sudarmanto B. Hematological parameters and remission induction of childhood acute lymphoblastic leukemia. Paediatr Indones. 2018;58:71-4. DOI: https://doi.org/10.14238/pi58.2.2018.71-4.
16. Widiaskara IM, Bambang P, Ugrasena IDG, Ratwita M. Luaran pengobatan fase induksi pasien leukemia limfoblastik akut pada anak di Rumah Sakit Umum Dr. Soetomo Surabaya. Sari Pediatri. 2010;12:128-134. DOI: https://doi.org/10.14238/sp12.2.2010.128-34
17. Lobato-Menzibal E, Ruiz-Arguelles GJ, Marin-Lopez A. Leukaemia and nutrition. I: Malnutrition is an adverse prognostic factor in the outcome of treatment of patients with standard risk acute lymphoblastic leukemia. Leuk Res. 1989;13:899–906. DOI: https://doi.org/10.1016/0145-2126(89)90043-x
18. Linga VG, Shreedhara AK, Rau ATK, Rau A. Nutritional Assessment of children with hematological malignancies and their subsequent tolerance to chemotherapy. Ochsner J. 2012;12:197-201.
19. Co-Reyes E, Li R, Huh W, Chandra J. Malnutrition and obesity in pediatric oncology patients: causes, consequences, and interventions. Pediatr Blood Cancer. 2012;59:1160-7. DOI: https://doi.org/10.1002/pbc.24272.
20. Bakhsi S, Padmanjali KS, Arya LS. Infections in childhood acute lymphoblastic leukemia: an analysis of 222 febrile neutropenic episodes. Pediatr Hematol Oncol. 2008;25:385-92. DOI: https://doi.org/10.1080/08880010802106564.
21. Khalid A. Evaluation of the nutritional status in children with acute lymphoblastic leukemia and its effect on the outcome of induction in a developing country. J Clin Oncol. 2017;35:e22004. DOI: https://doi.org/10.1200/JCO.2017.35.15_suppl.e22004.
22. Warrick K, Althouse SK, Rahrig A, Rupenthal J, Batra S. Factors associated with a prolonged hospital stay during induction chemotherapy in newly diagnosed high risk pediatric acute lymphoblastic leukemia. Leuk Res. 2018;71:36-42. DOI: https://doi.org/10.1016/j.leukres.2018.06.013.
23. Roy A, Saha A, Chakraborty S, Chattopadhyay S, Sur P. Effects of pre-existing undernutrition on treatment-related complications and treatment outcomes in children with acute lymphoblastic leukemia: a tertiary care center experience. Clin Cancer Investig J. 2013;2:143-8. DOI: https://doi.org/10.4103/2278-0513.113637.
24. Barr RD, Gomez-Almaguer D, Jaime-Perez JC, Ruiz-Arguelles GJ. Importance of nutrition in the treatment of leukemia in children and adolescents. Arch Med Res. 2016;47:585-92. DOI: https://doi.org/10.1016/j.arcmed.2016.11.013.
25. Al Ani M. Nutritional status of acute childhood lymphoblast leukemia (ALL) pre & post induction chemotherapy. Iraqi J Comm Med. 2008;3:198-203.
26. Antillon F, Rossi E, Molina AL, Sala A, Pencharz P, Valsecchi MG, et al. Nutritional status of children during treatment for acute lymphoblastic leukemia in Guatemala. Pediatr Blood Cancer. 2013;60:911-5. DOI: https://doi.org/10.1002/pbc.24377.
27. Owens JL, Hanson SJ, McArthur JA, Mikhailoy TA. The need for evidence based nutritional guidelines for pediatric acute lymphoblastic leukemia patients: acute and long-term following treatment. Nutrients. 2013;5:4333-46. DOI: https://doi.org/10.3390/nu5114333.
28. Pramanik R, Sheng X, Ichihara B, Heisterkamp N, Mittelman SD. Adipose tissue attracts and protects acute lymphoblastic leukemia cells from chemotherapy. Leuk Res. 2013;37:503–9. DOI: https://doi.org/10.1016/j.leukres.2012.12.013.