Dataset MTX - Eryfolate.csv

This is a dataset of 43 pediatric acute lymphoblastic leukemia patients in which we analysed consecutive methotrexate and folate levels.

Background After
High-Dose Methotrexate (HD-MTX), folinic acid rescue therapy (Leucovorin) is
administered to reduce side effects in pediatric acute lymphoblastic leukemia
(ALL) patients. Leucovorin and MTX are structural analogues, possibly competing
for cellular transport and intracellular metabolism. We hypothesize that
Leucovorin accumulates during consecutive courses, which might result in a
lower MTX uptake.

Methods We prospectively
measured red blood cell (RBC) folate and MTX levels during four HD-MTX and
Leucovorin courses in 43 patients treated according the DCOG ALL-11 protocol with
2-weekly HD-MTX (5 g/m2/dose) and Leucovorin (15 mg/m2/dose)
using LC-MS/MS. We estimated a linear mixed model to assess the relationship
between these variables over time.

Results Both
RBC MTX-PG and folate levels increased
significantly during protocol M. MTX-PG2-5 levels increased most
substantially after the first two HD-MTX courses (until median 113.0 nmol/L,
IQR 76.8-165.2) after which levels plateaued during the 3d and 4th
course (until median 141.3 nmol/L, IQR 100.2-190.2). In parallel, folate levels
increased most substantially after the first two HD-MTX courses (until median
401.6 nmol/L, IQR 163.3-594.2) after which levels plateaued during the 3d
and 4th course (until median 411.5 nmol/L, IQR 240.3-665.6). The
ratio folate/MTX-PG decreased significantly over time, which was mostly due to
the relatively higher increase (delta) of MTX-PG.

Conclusion These
results suggest that the increase in RBC folate levels does not seem to have a
large effect on RBC MTX levels. Future
studies, assessing competition of Leucovorin and MTX on other cellular
mechanisms which might negatively affect treatment efficacy, are necessary.