High Dose Methotrexate in Acute Lymphoblastic Leukemia without monitoring drug levels: Indain Experience

Date 24 November 2018
Event ESMO Asia 2018 Congress
Session Poster display - Cocktail
Topics Leukaemia
Presenter Deepak Yadlapalli
Citation Annals of Oncology (2018) 29 (suppl_9): ix87-ix93. 10.1093/annonc/mdy437
Authors D.C. Yadlapalli, P. Ankur, V. Gumdal, M. Renu, S. Runu, B.S. Ankit, P.G. Chitalkar
  • Medical Oncology, SAIMS-Sri Aurobindo Institute of Medical Sciences, 453555 - Indore/IN



High Dose Methotrexate (HDMTX) is a therapeutic armamentarium in oncology since last four decades. While monitoring methotrexate levels was a established standard during HDMTX administration, its not always possible in rural setting due to logistical and cost constraints. When we search the literature, there is little discussion on HDMTX administration without monitoring levels across the world. We report our experience of HDMTX use with leucovorin rescue without drug monitoring in patients of ALL at a rural tertiary center in Central India.


Ours was a retrospective study of 24 patients with ALL from January 2015 to February 2018.All were treated based on risk stratified BFM-2002 protocol. After pre-treatment evaluation of hematological and biochemical parameters, HDMTX (2-5 gm/m2) was given over 18 hour after 2 consecutive urine pH readings were more than 7.5, with adequate hydration with sodium bicarbonate and urinary alkalinization. Leucovorin rescue (15mg/m2, IV) started 10 hours after completion, for total of 6 doses every 4th hourly. Toxicities were recorded based on CTCAE Version 4.03.


There were 24 patients (18 males and 6 females), with median age of 7 years. One patient was in standard risk (SR),18 in intermediate (IR) and 5 in high risk (HR) category. SR and IR received 4 cycles, HR patients received 2 cycles. Total HDMTX cycles were 86. Serum transaminases elevation occurred in 14% cycles, bilirubin rise in 3%, with highest value of 2.4mg%. Nausea and vomiting in 32%, oral mucositis in 28%, mostly grade 2. Transient elevation in serum creatinine noted in 18%. Hematological toxicity occurred in 32% and encephalopathy in 1.2%. Morbilliform rash observed in 7%. Toxicities were mostly grade 2-3 and managed conservatively. During follow up, relapse was documented in one in IR with isolated testicular and one in HR with marrow, testicular and CNS relapse.


HDMTX is a vital component in ALL regimen. The unavailability of in-house testing of MTX levels, delayed turn around timing and maintaining cold chain of outsourced samples is difficult. The use of HDMTX with careful pretreatment evaluation, with adequate hydration, alkalanization and leucovorin, appears possible with manageable toxicities.

Editorial acknowledgement

Legal entity responsible for the study

Sri Aurobindo Institute of Medical Sciences, Indore, India.


Has not received any funding.


All authors have declared no conflicts of interest.