Simplified Technique for Administration of High Dose Melphalan

High dose IV melphalan is widely used in preparative regimens for hematopoietic cell transplantation.  Package insert recommendations state to prepare doses to a concentration of </= 0.45 mg/mL in Normal Saline (NS) and to infuse within 60 minutes of reconstitution.  When using these recommendations, many doses must be prepared in volumes of 1000 mL or more which results in infusion rates of up to 2 liters/hour over 30 minutes.  Available infusion pumps have maximum infusion rate of 999 mL/hour, often requiring doses be prepared in multiple bags and infused simultaneously using 2 pumps to ensure a 30 minute infusion time.  Melphalan was found to have 90% or greater stability at 60 and 90 minutes when diluted in NS polyolefin bags to concentrations from 0.45 mg/mL to 2 mg/mL – personal communication on National Cancer Institute in-house data.  This, in combination with available package insert data, supports a wider range of options for preparation.  In December 2011 we implemented a simpler technique for administration of melphalan by preparing all doses in a total volume of 250 mL NS.  This method yields concentrations between 0.45 to 2 mg/mL for patients of a BSA from 0.81 to 3.56 m² for 140 mg/m² doses and 0.57 to 2.5 m² for 200 mg/m² doses.  In a review of the first 30 autologous HCT patients who received melphalan 200 mg/m² via this method, median engraftment was on days 12 and 16 for neutrophils and platelets, respectfully, which is the same as our historical data for this transplant regimen.  To date this method has been used for over 350 transplant patients.  This practice change simplified both pharmacy and nursing procedures such that all doses are dispensed in a single bag with a total volume of 250 mL and infused via one infusion pump at a standard rate of 500 mL/hour.  This simplified compounding and administration of doses decreases time spent by both pharmacy and nursing for treatments using melphalan.  The use of a single bag and one standard infusion rate also reduces the likelihood of administration errors by eliminating the need to calculate infusion rates and coordinate the use of multiple pumps.