337: Double umbilical cord blood transplantation with reduced intensity conditioning and sirolimus-based GVHD prophylaxis

Abstract

Umbilical cord blood (UCB) is an alternative for patients without related or unrelated donors. Single-unit UCB transplantation in adults is associated with high transplant related mortality, largely due to delayed engraftment and infection, so we studied the value of double unit umbilical cord blood (DUCB) transplantation. Methods: Reduced-intensity conditioning consisted of fludarabine 30mg/m2 x 6 days, melphalan 100mg/m2 x 1 day, and rabbit ATG 1.5 mg/kg x 4 days. DUCB units were ≥4/6 HLA-A, B, DRβ1 matched with each other and the recipient, and contained a minimum combined dose of 3.7 × 107 TNC/kg (pre-cryopreservation). GVHD prophylaxis consisted of tacrolimus (serum conc. 5-10 ng/ml) and sirolimus (serum conc. 3-12 ng/ml), which is effective in PBSC transplantation. Results: 18 patients (median age 48.5 years, range 19-64) with >100 day follow-up are reported. Diagnoses include NHL(6), AML(5), MDS(3), HD(3), and CML(1). The total cell doses infused were 4.23 × 107 TNC/kg (range 3.51–6.74 × 107) and 2.11 × 105 CD34+cells/kg (range 0.48–5.67 × 105). Subjects engrafted neutrophils at 22 (median, range 15–75) and platelets at 46 (median, range 24-69) days from transplantation. Two subjects did not attain platelet transfusion independence and there was 1 late graft failure. 100-day treatment-related mortality was 16.7%. 3 patients developed Gr II-IV acute GVHD (2 Gr. II and 1 Gr. III) and 2 patients developed chronic GVHD at a median of 30 and 203 days from transplantation respectively. The median follow up is 6.5 months (range 3-12 months) and overall survival at 1 year is 64.3%. Causes of death include sepsis(4), relapse(1), and EBV-associated PTLD(1). Chimerism analysis (n=14) at day 30 revealed complete single cord chimerism in 3, mixed cord chimerism in 10, and persistent host hematopoiesis with single or double cord chimerism in 1. By day 100, 5/9 patients demonstrated complete single cord chimerism and 3/9 demonstrated persistent double cord chimerism. Conclusions: This study demonstrates excellent engraftment after DUCB transplantation in adult recipients after a reduced-intensity conditioning regimen. Using sirolimus and tacrolimus as GVHD prophylaxis, the risk of acute and chronic GVHD is low when compared to our prior experience with cyclosporine and MMF, and survival is comparable to other unrelated donor cohorts. Long-term follow-up on an expanded patient cohort will be presented at ASBMT.