177: Combined tacrolimus (FK-506) and mycophenolate mofetil (MMF) for graft-versus-host disease (GVHD) prophylaxis in children undergoing cord blood transplantation (CBT)

Background: Effectiveness of FK-506 and MMF combination as prophylaxis for GVHD is still under investigation. We studied the feasibility and effectiveness of this regimen in preventing GVHD in children undergoing matched unrelated donor (MUD) CBT to avoid methotrexate and methylprednisone toxicity. Patients and Methods: Between 5/1/04-9/1/06, 11 children undergoing MUD CBT have received FK-506 and MMF combination as prophylaxis for GVHD. Thymoglobulin (Rabbit ATG, 2.5-5mg/kg total) was used as part of the conditioning regimen. Both myeloablative (n=9) and non-myeloablative (n=2) preparative regimens were used and majority of the children (n=7) have received one antigen mismatch (Class I/II-antigen disparate) CBT. FK-506, 0.015mg/kg IV every 12 hours (infused over 6 hours) was started on day-2 (trough level maintained 5-15 ng/ml),rather than as a continuous infusion. MMF was started on day +1 at 15mg/kg /dose IV q 8-12 hours and stopped on day +30, if there were no signs of GVHD. Both were converted to PO formulation at the time of discharge. MMF levels (active MPA) were monitored weekly. Results: The regimen was well tolerated. Only major side-effect noted was hypertension in the first 2 patients, which was controlled with prophylactic anti-hypertensive use in subsequent patients. Tremors occurred in 2 patients and responded to MMF taper. No major neuro- or nephrotoxicity was noted. All children have engrafted (median=16 days). No patient has developed >Grade II GVHD (Glucksberg staging criteria). 6/11 patients (54.5%) had developed Grade I/II GVHD, limited only to skin and gut (1 pt.) that was steroid-responsive. Only 1/6 patients continued to have limited chronic GVHD of the skin (median follow-up: 255days ; range: 62-725 days). Immune-reconstitution was not delayed. MMF levels ranged from <0.5-5.7 mcg/ml. No correlation was seen between the MMF levels and the incidence of GVHD in this study. Conclusion: FK-506/MMF combination is well tolerated, does not affect engraftment kinetics or immune-reconstitution and is efficacious in preventing GVHD in CBT.