Aims and Objectives: Our aim was to document the toxicity profile in Acute Lymphoblastic Leukemia in pediatric patients who received only chemotherapeutic agent i.e. High Dose Methotrexate in their consolidation phase of their treatment plan.

Method: A Retrospective study was carried out in the inpatient department of Aware Gleneagles Global Hospital, Hyderabad, India. A total of 100 pediatric in patients  with  Acute Lymphoblastic Leukemia  from the age of 1-18 years  in their  Consolidation phase consisting of 4 cycles each containing a course of HDMTX from 2017-2018 were included in the study. All information significant to the study was collected from the Patient case sheets and Electronic medical records in the designed patient’s proforma or data collection form which includes Patient demographic details, Laboratory values etc. The information was also retrieved by the telephonic conversation with the patient or patient’s representative.

Results: In our study mean age was found to be 7.07 ± 4.520.We found that there was high incidence rate in males (67%) than females (33).We observed pediatric patients effected with adverse effects such as nausea and Vomiting (25%), Mucositis (13%), Neutropenia (5%), Anemia (55%), Thrombocytopenia (27%) and Leucopenia (44%).

Conclusion: Thus from our study we have concluded that toxicity of High Dose Methotrexate can be minimized to great extent by adequate hydration/ Alkalinization, Leucovorin doses, accurate dose of Anti emetics and frequent monitoring of Urine pH, Serum Creatinine, Complete Blood Count as to detect any toxicity and acute management of the toxicity.

Keywords: Acute Lymphoblastic Leukemia, Methotrexate, Toxicity, Febrile Neutropenia, Mucositis.

1. Pui CH, Jeha S: New therapeutic strategies for the treatment of acute lymphoblastic leukaemia. Nat Rev Drug Discov 6 (2): 149-65, 2007.
2. Peterson LC, Bloomfield CD, Brunning RD: Blast crisis as an initial or terminal manifestation of chronic myeloid leukemia: a study of 28 patients. Am J Med 60(2): 209-220, 1976.
3. Pui CH, Yang JJ, Hunger SP, Pieters R, Schrappe M, Biondi A, et al. Childhood ALL: Progress through collaboration. J ClinOncol. 2015;33:2938–48.
4. Dipiro. Chapter 142: Acute leukemia. Gary C. Yee Editor. In: pharmacotherapy A pathophysiologic approach; 8^th Edition .P.2384.

5. Perez-Andreu V, Roberts KG, Harvey RC, et al. Inherited GATA3 variants are associated with Ph-like childhood ALL and risk of relapse. Nat Genet2013; 45:1494-1498
6. Mantadakis E, Cole PD, Kamen BA. High‐dose methotrexate in ALL: where is the evidence for its continued use?. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy. 2005 May;25(5):748-55.
7. Tripathi KD. Essentials of MEDICAL PHARMACOLOGY. 2013;7:862

8. Vaishnavi K, Bansal D, Trehan A, Jain R, Attri SV. Improving the safety of high‐dose methotrexate for children with hematologic cancers in settings without access to MTX levels using extended hydration and additional leucovorin. Pediatric blood & cancer. 2018 Dec;65(12):e27241.
9. Traivaree C, Likasitthananon N, Monsereenusorn C, Rujkijyanont P. The effect of intravenous hydration strategy on plasma methotrexate clearance during intravenous high-dose methotrexate administration in pediatric oncology patients. Cancer Management and Research. 2018;10:4471.
10. Warrier AR, Rejiv R, Biswajit D, Ramanan SG, Sagar TG. High-dose methotrexate in the treatment of ALL: Toxicity profile and comparison of tolerability betwen two dosage schedules. Journal of Clinical Oncology. 2010 May 20;28(15_suppl):9573-.
11. Fisgin T, Yarali N, Kara A, Bozkurt C, Birgen D, Erten U, Duru F. Hemostatic side effects of high-dose methotrexate in childhood ALL. 2004;21(1):77-83.
12. Siddique R, Hafiz MG, Jamal CY, Karim MA, Islam A, Alia RA. Randomized Double Blind Trial to Compare the Efficacy of Granisetron And Ondansetron in Controlling Emesis in Children with ALL. Bangladesh Journal of Child Health. 2012;36(3):115-21.
13. Rask C, Albertioni F, Bentzen SM, Schroeder H, Peterson C. Clinical and pharmacokinetic risk factors for high-dose methotrexate-induced toxicity in children with ALL: a logistic regression analysis. Acta Oncologica. 1998 Jan 1;37(3):277-84.

Shaik Ruman

Department of Pharmacy Practice, Sree Dattha Institute of Pharmacy, Hyderabad, India