Abstract 5671: Folinic Acid Rescue after Methotrexate GVHD Prophylaxis to Reduce Mucositis and Improve the Probability of Day +11 Methotrexate Administration - Role of the Hematopoietic Cell Transplant Pharmacist in Development of Program Guidelines

Background: Methotrexate (MTX) is routinely utilized for prophylaxis of graft versus host disease (GVHD). MTX may contribute to mucositis and delayed engraftment. Severe mucositis results in MTX dose reduction, holding day +6 and/or day + 11, addition of folinic acid (FA), or the use of dexamethasone. Delivery of day +11 MTX has been reported to be important in reducing the risk of aGVHD. FA administration after MTX doses has been shown to reduce MTX toxicity. In an effort to reduce the incidence of mucositis to improve the likelihood of administering day +11 MTX and to provide a consistent treatment guideline, the Hematopoietic Cell Transplant (HCT) program director enlisted the help of the HCT pharmacist to review the data and recommend guidelines.

Methods:  A review of the literature for post-MTX FA use was performed and presented at an HCT program education session. FA dosing, time of initiation post MTX, schedule and number of doses were discussed. The HCT providers agreed to follow the HCT pharmacist recommendation of FA 10mg/m² IV every 6 hours x 3 doses starting 12 hours after each MTX dose (day +1, +3, +6 and +11) with myeloablative (MA) conditioning regimens. All patients received tacrolimus. Data was retrospectively collected in 2013 after the FA guideline was adopted and compared to consecutive patients receiving MA regimens from a control group in 2012. The primary endpoint was administration of full dose day +11 MTX.  Secondary endpoints were rates of aGVHD, cGVHD, total parenteral nutrition (TPN) use, patient controlled analgesia (PCA) use, transplant-related mortality (TRM), relapse and overall survival (OS).

Results: The FA group consisted of 27 patients while there were 31 in the control. Patients in the FA group were more likely to receive full dose day +11 MTX as compared to control, 85.2% vs 48.4% (p=0.0025) and were less likely to require PCA, 63% vs. 87.1% (p=0.03). There was no significant difference in rates of TPN use (48.2% vs. 58.1%), grade II-IV aGVHD at day 100 (50.4% vs. 30.5%), cGVHD (19.9% vs. 27.7%), cumulative incidence of relapse (10.8% vs. 8.6%), TRM at 1 year (13.1% vs. 19.5%) and OS at 1 year (77.9% vs. 75.9%) for the FA group and control, with a median follow-up of 465 days and 670 days, respectively.

Discussion:  Patients experienced less mucositis and were more likely to receive full dose day + 11 MTX after implementation of the FA guideline. This was also supported by a statistically significant decrease in PCA use. Other endpoints trended in a favorable direction, but did not reach statistical significance.  The development and utilization of the program guideline improved consistency of care, improved staff satisfaction and decreased patient discomfort. HCT pharmacists play an important role in the review of literature and development of program guidelines.