Safety evaluation for less restrictive discharge criteria for patients receiving high dose methotrexate

Abstract

Abstract Introduction: High Dose Methotrexate (HD MTX) is commonly given either as a single agent or in combination to treat patients with various hematologic malignancies. Due to its potential toxicity to the kidneys, liver and bone marrow, drug levels are monitored to ensure appropriate clearance. Historically, the standard for safe discharge is a MTX level less than 0.10 Umol/L. The goal of our study is to validate the safety of discharging patients with a MTX level greater than 0.10 Umol/L, specifically <0.30 Umol/L. Methods: This was a single center, retrospective review of all encounters for patients receiving inpatient HD MTX with doses ranging from 1,000 mg/m2 to 3,500 mg/m2 between April 29, 2024, to June 30, 2025. Diagnoses include Primary CNS Lymphoma, Diffuse Large B-cell Lymphoma, Acute Lymphocytic Leukemia and Burkitt Lymphoma. Patients received HD MTX alone or in combination with Cytarabine, R-CHOP, Blinatumomab, Vincristine or CODOX-M/IVAC. We recorded outcomes per encounter. Therefore, if patients were admitted for multiple cycles of HD MTX, they were recorded as separate encounters. Patients were eligible for early discharge (MTX 0.1< x <0.30) if they presented with a normal creatinine on admission and did not develop acute kidney injury (AKI) while admitted (AKI definition; creatinine level increase of >0.30 mg/dL), ECOG PS of ≤ 2, normal or improving liver function tests at discharge, ability to take oral supportive medications after discharge, ability to pay out of pocket for supportive medications, and have bloodwork completed within 7 days of discharge. Chi Squared testing was performed to detect differences in toxicity (hepatic and cytopenias) between those who met criteria for early discharge and those that did not. Results: The review analyzed a total of 117 patient encounters. Seventy-two (62%) patient encounters met criteria for early discharge. Of this group, the median age was 63 years old (range 21-77), 38% female, and 54% received single agent HD MTX. Forty-five (38%) were not eligible for early discharge. Of this group, the median age was 64 (range 32-78), 38% female, and 73% received single agent chemotherapy. Of the 72 encounters eligible for early discharge, 49 (68%) were discharged with a MTX 0.11- 0.30 Umol/L. One patient developed AKI five days after discharge which improved without intervention in labs the following day. No other renal injuries occurred. Hepatic toxicity occurred in 57% of patient encounters: 30 (78%) Grade 1, 9 (24%) Grade 2, and 2 (4%) Grade 3. All improved or resolved on follow up labs. Cytopenias occurred in 99% of patient encounters 23 (32%) Grade 1, 34 (48%) Grade 2, 13 (18%) Grade 3, and 1 (1%) Grade 4. No one was admitted due to complications of cytopenias. Of the group who were not eligible for discharge, 51% developed AKI- all which were grade 1, either on admission or after receiving HD MTX. Hepatic toxicity occurred in 62% of encounters: 22 (79%) Grade 1, 5 (18%) Grade 2, and 1 (4%) Grade 3. Cytopenias occurred in 87% of encounters: 4 (10%) Grade 1, 22 (54%) Grade 2, 9 (24%) Grade 3, and 5 (14%) Grade 4. There was no statistically significant difference in hepatic toxicity in the between the two groups chi2 0.318 (p-value: 0.572). The early discharge group did have significantly increased rate of cytopenias, chi2 7.023 (p-value: 0.008), although it was mostly Grade 1 and 2. Median LOS for patients who met criteria for early discharge (MTX 0.11- 0.30 Umol/L) was 3 days (range 3-4 days) compared to 4 days for the whole group (range 3-14 days) and 5 days (range 4-14 days) for those that did not meet criteria for early discharge. Of the patients who were discharged early but their MTX level was <0.10, the level drawn the day before ranged from 0.41-0.80 Umol/L. Conclusion: Our study shows that it is safe to discharge patients w/ MTX < 0.30 Umol/L compared to our prior standard of 0.10 Umol/L or less with leucovorin and sodium bicarbonate for three days after discharge. Patients discharged early had stable renal function on discharge as well as on follow up labs, no difference in LFTs and no readmissions. While there was a higher incidence of cytopenias, it was mostly grade 1 and 2 and did not result in treatment delays or other complications. The less restrictive discharge criteria resulted in decreased length of stay, which is meaningful for both bed utilization and for patients who spend a frequent amount of time in the hospital receiving therapy.