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.