Oral Loading of Tacrolimus and Sub-Therapeutic Levels on the Day of Transplant Do Not Predict the Incidence of Acute Graft Versus Disease or Survival After Allogeneic Stem Cell Transplant

Abstract 4543

Tacrolimus is proven to be effective in the prophylaxis of acute graft versus host disease (aGVHD) after allogeneic stem cell transplantation (ASCT). Published studies that initiate tacrolimus loading intravenously indicate that levels should be between 5 and 20ug/L on the day of transplant. Our institution often performs ASCT in the outpatient setting and therefore we developed a process for oral loading of tacrolimus. We retrospectively reviewed our experience in 94 consecutive patients (pts) who received ASCT from 10/10 HLA matched donors, 47 were matched sibling donors (MSD) and 47 were matched unrelated donors (MUD) with a median age of 50 and 52 respectively. Preparative regimens were IV busulfan based in 68 pts (BuFlu n=44, BuCY n=24), TBI based in 19pts, and other in 7 pts. All pts received GVHD prophylaxis with tacrolimus started orally between day -3 and -1 at a dose of 0.06 mg/kg/day divided twice daily. Standard short course methotrexate (MTX) was prescribed for all pts (D1 dose 15mg/m2, D3, 6, and 11 dose 10mg/m2). Pts who had sub-therapeutic tacrolimus levels (less than 5ug/L) on the day of transplant (Day 0) were compared to pts who had therapeutic tacrolimus levels (greater than 5ug/L) for incidence of any aGVHD and overall survival. Sixty nine patients had tacrolimus levels less than 5 ug/L on day 0 and 25 patients had tacrolimus levels of 5 ug/L or greater. There was no difference in incidence of any GVHD or survival between the groups (Table 1). Thirty one pts did not receive the entire MTX dose prescribed (most commonly because of withholding day 11 MTX dose), but there was no significant difference in the incidence of aGVHD in these pts despite the level of tacrolimus on D0. With a median follow up of 441 days 54/94 pts (57%) survive; 40/69 pts (58%) with day 0 tacrolimus levels that were less than 5 ug/L, and 14/25 pts (56%) with day 0 tacrolimus levels that were greater than or equal to 5 ug/L. In conclusion, oral loading of tacrolimus prior to ASCT at our institution results in sub-therapeutic levels on the day of transplant in the majority of patients, however, this does not appear to impact the overall incidence of aGVHD or survival. This study was limited by its retrospective nature, small size, and single center experience. Prospective randomized studies will be needed to determine if oral loading of tacrolimus impacts outcomes of ASCT.

Tacro; tacrolimus, OS; overall survival, MUD; matched unrelated donor, SIB; sibling. Survival determined in mean months from date of transplant.