Double-Unit Cord Blood Transplantation (DCBT) for Acute Leukemia: High Disease-Free Survival in Adults and Children with Comparable Survival in European and Minority Patients

Background: Given DCBT may improve engraftment & protect against relapse, we have adopted DCBT for both children & adults with acute leukemia, myelodysplasia (MDS), & myeloproliferative diseases (MPD). However, determinants of disease-free survival (DFS) after DCBT have yet to be established. Methods: We analyzed the DFS of 92 DCBT recipients with acute leukemia in morphologic remission or aplasia (n = 83), & MDS/MPD with ≤ 5% blasts at work-up (n = 9) transplanted from 10/2005-5/2012. Nearly all patients had high-risk disease. Results: Children [n = 27, median age 7 years (range 0.9-15), median weight 30 kg (range 8-72)] were 33% European & 26% CMV sero-positive with diagnoses of AML (or biphenotypic) in 44%, ALL in 52%, MDS/MPD in 4%, & all received high-dose conditioning. Their grafts had a median infused TNC x 10⁷/kg of 4.4 (larger unit) & 2.9 (smaller unit), & 4% of units were 6/6 HLA-A,-B antigen,-DRB1 allele matched, 61% 5/6, & 35% 4/6. Adults [n = 65, median age 47 years (range 16-69), median weight 69 kg (range 45-105)] were 48% European & 68% CMV sero-positive. Diagnoses in adult patients were AML (or biphenotypic) in 62%, ALL in 26%, & MDS/MPD in 12%. Forty-two percent of adults received high-dose & 58% reduced intensity conditioning. Their units had a median infused TNC/kg of 2.7 & 2.0, respectively, & 3% were 6/6 HLA-matched, 44% 5/6, & 53% 4/6. All patients received calcineurin-inhibitor/ mycophenolate mofetil immunosuppression. Sustained donor neutrophil engraftment was seen in 93% of children (median neutrophil recovery at 20 days) & 97% of adults (median 25 days). Platelet engraftment was seen in 85% of children (median recovery at 50 days) & 83% of adults (median 48 days). The incidence of day 180 grade II-IV acute GVHD was 41% in children & 60% in adults. Day 100 TRM was 7% in children & 15% in adults. The 2-year relapse incidence was 17% in children & 7% in adults. With a median 33 month (range 3-84) follow-up of survivors, the 2-year DFS is 72% in children & 65% in adults. Univariate analysis of variables potentially influencing 2-year DFS (Table) demonstrated there were no differences according to patient age, ancestry, remission status, conditioning intensity, engrafting unit-recipient HLA-match, or engrafting unit infused TNC dose/kg. However, patients who were CMV seronegative had a higher 2-year DFS (81% vs 53%, p = 0.01). Multivariate analysis revealed recipient CMV serostatus was a predictor of DFS independent of patient age, & its effect was mediated by an influence on TRM. Conclusions: DCBT can achieve high & comparable DFS in both European & non-European patients with acute leukemia with a low rate of relapse. While the mechanism of the mortality risk associated with CMV seropositivity requires further investigation, our findings support DCBT as an immediate alternative therapy for high-risk acute leukemia in patients without suitable unrelated volunteer donors.