Outcomes After Double Cord Blood Transplantation Compared to Single Cord Blood Transplantation in Adults with Acute Leukemia Given a Reduced Intensity Conditioning Regimen

Unrelated cord blood (UCB) is an alternative source of allogeneic hematopoietic stem cell transplantation (HSCT) for adults with acute leukemia lacking a HLA matched donor. Double cord blood unit (dUCBT) has been increasingly used over single CB unit (sUCBT) after reduced intensity conditioning regimen (RIC). We analyzed 360 adults with ALL (n= 77) or AML (n=238) in CR1 (n=212) and CR2 (n=148) transplanted with a sUCBT (n=131) or a dUCBT (n=229) after RIC. Only patients (pts) transplanted with a sUCBT with a minimum of 2.5x10⁷/kg total nucleated cells (TNC) were included. Pts were transplanted from 2005-2011 in EBMT centers. Comparing the recipients of sUCBT and dUCBT in CR1, there were no statistical differences according to age, diagnosis (AML or ALL), weight, CMV serostatus, cytogenetic risk, number of HLA incompatibilities. However, dUCBT were performed more recently (2009 vs 2008), the time from CR1 to transplant was longer (142 days vs 121 days), more frequently transplanted with CY+FLU+TBI2Gy (87% vs 68%), lower frequency of ATG use (21% vs 35%) and they received higher number of TNC collected (5x10⁷/kg vs 3.9x10⁷/kg) or infused (4x10⁷/kg vs 3.1x10⁷/kg). Median follow-up was 23 months in both groups.

Cumulative incidence (CI) of 60 days neutrophil recovery was 82% for dUCBT and 76% for sUCBT (p=0.86); frequency of full donor chimerism at day 100 was not statistically different between dUCBT (81%) and sUCBT (86%). At day 100, CI of acute GVHD (grade II-IV) was 35% in both groups, however there was a trend of increased incidence of grade III-IV after sUCBT (19%) compared to dUCBT (10%, p=0.06) but increased incidence of grade II aGVHD after dUCBT (28%) compared to 17% after sUCBT (p=0.05). CI of chronic GvHD at 2 years was 21% after dUCBT and 12% after sUCBT (p=0.15). At 2 years, CI of non relapse mortality (NRM) was 28% after dUCBT and 30% after sUCBT (p=0.87). CI of 2y RI was 21% after dUCBT whereas it was 38% after sUCBT (p=0.03). In a multivariate analysis adjusting for the differences between the 2 groups, dUCBT was associated with lower RI compared to sUCBT (HR=0.74, p=0.01). Therefore, there was an improved 2-y LFS after dUCBT (51%) compared to sUCBT (32%; p=0.03). This was confirmed in a multivariate analysis (HR=0.64, p=0.04).  

Concerning pts transplanted in CR2 (n=148), there were no differences of outcomes after dUCBT (n=93) or sUCBT (n=55). At 2y, LFS was 40% after dUCBT and 48% after sUCBT (p=0.32).  In a subgroup analysis of dUCBT (n=118) and sUCBT (n=51) recipients using the same conditioning regimen (CY+FLU+TBI2Gy), 2 y LFS were 54% and 33% respectively (p=0.05).

In this retrospective comparative based registry analysis, in AL pts transplanted in CR1, neutrophil recovery, GVHD and NRM were not statistically different after RIC-dUCBT or RIC-sUCBT, however, dUCBT recipients had decreased RI and improved LFS. For AL pts transplanted in CR2, there was no benefit of using dUCBT when compared to sUCBT.