Chronic Graft Versus Host Disease and Immunosuppression Burden Is Significantly Lower Following Adult Cord Blood Transplantation Versus Matched Unrelated Donor Transplantation

Adult umbilical cord blood (UCB) transplant has emerged as an important option for patients lacking matched related (MRD) and matched unrelated donors (MUD).  Numerous studies have demonstrated comparable overall survival (OS) between these donor sources as well as decreased classic chronic GVHD (cGVHD) following UCB transplantation as compared to MUD.  We compared cGVHD incidence and immunosuppression burden in consecutive patients undergoing UCB (n=29) versus peripheral blood MUD transplant (n=51) at our center between June 2009 and February 2013.  NIH consensus criteria were used to grade cGVHD.   Among UCB patients, median age at transplant was 49 (range 22-71) versus 55 (range 18-72) among MUDs.  Twelve UCB patients underwent myeloablative conditioning and 17 patients underwent non-myeloablative (NMA) conditioning for acute leukemia (n=17), MDS (n=5), CLL (n=2), NHL (n=4), and CML (n=1).  GVHD prophylaxis was CSA and MMF.  Forty-eight MUD patients were 10/10 matched and three patients were 8/8 matched (DQ mismatched).  Seventeen patients underwent myeloablative conditioning (TAC/MTX GVHD prophylaxis) and 34 patients underwent NMA conditioning (TAC/MMF GVHD prophylaxis) for acute leukemia (n=19), NHL (n=15), MDS (n=6), CLL (n=4), Other (n=6).  At two years post-transplant, cumulative incidence (CI) of moderate to severe cGVHD was 30% following MUD versus 7% following UCB (p=0.02).  Among patients not experiencing competing risks of relapse or transplant related mortality (TRM) prior to onset of cGVHD, median time to being off immunosuppression was 307 days among UCB patients (n=15) versus not reached among MUD patients (n=33) (p<0.001).  Among 15 UCB patients, one patient remains on immunosuppression (227 days post-transplant).  Two patients restarted immunosuppression due to recrudescent symptoms, but both patients subsequently tapered again and remain off immunosuppression. All 15 patients remain alive. Among 33 MUD patients, seven patients stopped immunosuppression and four subsequently restarted for recrudescent GVHD symptoms.   All four remain on immunosuppressive therapy.  Five of the 33 patients subsequently died of complications related to GVHD.  One year OS is not significantly different between UCB and MUD patients (65% UCB versus 67% MUD).   Cumulative incidence of relapse and TRM are also non-significant comparing UCB and MUD patients (one year CI relapse 21% UCB versus 17% MURD, CI TRM 11% UCB versus 17% MUD).  These data confirm the low incidence of classic cGVHD following CBT.  We demonstrate a markedly lower immunosuppression burden following UCB versus MUD transplant without decreased OS, increased relapse, or TRM.  Combined with the rapid availability of UCB, this finding has led our center to move primarily to UCB when a MRD is not available.  Assessment of early and late costs of transplant using this donor selection approach is ongoing.