Administration of high dose methotrexate monitoring a single serum methotrexate level at 72 hours

Abstract

Background

When administering high dose Methotrexate (HD-MTX), in children with high-risk Acute lymphoblastic leukemia (ALL), serial monitoring of serum Methotrexate (MTX) levels till they are less than <0.4 μmol/L at 42 hrs is regarded as standard of care in avoiding HD-MTX toxicity. We studied the feasibility of administering HD-MTX in children with high-risk Acute lymphoblastic leukemia (ALL), with a single monitoring level of serum MTX level at 72 h.

Materials and methods

This is a retrospective study from patients treated at the Department of Paediatric Oncology from January to December 2019 at a regional cancer centre in South India. Patients aged <15 years with diagnosis of B (high risk) or T lineage Acute lymphoblastic leukemia (ALL) and Lymphoblastic Non-Hodgkin lymphoma (NHL) who received HDMTX were included in the study. A solitary serum MTX level was done at 72 h after starting the infusion. The most common side effects of HD-MTX were noted and correlated with age, sex, grade of nutrition, dose of Methotrexate (3g versus 5g) and Methotrexate levels at 72 h (<0.05 versus >/ = 0.05 μmol/L). Data was entered in excel sheet and analyzed by appropriate statistical tests. P < 0.05 was taken as significant.

Results

Children who received higher dose of MTX (5g/m²) were found to have significantly more episodes of diarrhea, thrombocytopenia and hyperbilirubinemia as opposed to 3g/m2 (p = 0.02,0.043 and 0.035 respectively). There was no significant difference in clinical toxicities in those whose 72-h serum MTX levels were </>0.05 μmol/L. However, patients with delayed excretion had significantly higher levels of serum transaminases and increase in creatinine.

Conclusion

The results of our study showed that prolonged hydration along with extended leucovorin rescue with single level of serum MTX at 72 h is feasible, but the impact on efficacy is unknown and this way of HD-MTX administration needs to be validated in larger studies along with comparisons with levels at other time points.