Patient Selection and Evaluation of Clinical Data
This study was approved by the Johns Hopkins Institutional Review Board
(IRB00282395). Data were extracted from EPIC, the electronic medical
record (EHR) used by Johns Hopkins Hospital. We retrospectively reviewed
an existing database of pediatric ALL patients treated at Johns Hopkins
Hospital from January 2012 to March 2021. From this database, we first
searched the EHR to identify individuals who had MTHFR genetic testing
sent and further categorized based upon result. Patients were grouped as
not tested, wildtype, heterozygous 677CT, homozygous 677TT, compound
heterozygous 677CT/1298AC, heterozygous 1298AC, and homozygous 1298CC.
We then examined each individual EHR for basic demographic information
including age at diagnosis, ALL phenotype, treatment protocol utilized,
and outcome (remission, relapsed/refractory disease, death). Patients
whose disease relapsed or progressed before receiving standard of care
MTX were excluded from further analysis. For each remaining individual,
we examined the record to best determine causal reason for sending MTHFR
genetic testing which was further generalized to broader categories for
comparison. We also identified patients who received Capizzi MTX (C-MTX)
and/or HDMTX dosing to record maximum dose achieved and/or clearance
time with those treatment regimens respectively. We also examined
maximum tolerated dose for oral agent 6-MP and MTX given during
maintenance therapy. Here, we defined maximum tolerated dose for oral
agents as stable dosing for > 12 weeks after at least 6
months of therapy. In addition to the above, we also collected
information regarding the occurrence of thrombosis or MTX
leukoencephalopathy anytime during their treatment course.