Unrelated Cord Blood Transplantation: Comparison After Single Unit Cord Blood Intrabone Injection and Double Unit Cord Blood Transplantation In Patients with Hematological Malignant Disorders. A Eurocord-EBMT Analysis

Abstract 223

The use of single cord blood unit for transplantation in adult patients is limited due to the high risk of graft failure and delayed neutrophil and platelet recoveries. The limited hematopoietic progenitors in UCB grafts and their homing after IV injection, have prompted investigators to study the design of delivering CB grafts directly into the bone marrow (BM) space (IBCBT) or to use double cord blood transplantation (dUCBT) to improve engraftment. To evaluate the impact of IBCBT, we made a retrospective based registry comparison with dUCBT performed in the same time period (2006-2010) and reported to Eurocord-EBMT. We included 87 and 149 patients who received either IBCBT or dUCBT, respectively, after a myeloablative conditioning regimen for malignant disorders. IBCBT was performed in 8 EBMT centers whereas dUCBT was performed in 56 EBMT centers. Majority of patients in both groups had acute leukemia. IBCBT patients were older (p<0.001), more frequently received an autologous graft (p<0.001) and had positive CMV serology (p<0.001), and importantly had more advanced disease at transplantation (p=0.04). Median number of infused (after thawing) nucleated cells injected intrabone was 2.5×10⁷/kg and it was 3.9×10⁷/kg in dUCBT (p<0.001). In 72% of both groups, CB grafts were HLA 4/6 (the highest HLA disparity was taken into consideration in dUCBT). Other differences were regarding GVHD prophylaxis that was based on CSA+MMF in 100% of IBCBT and in 62% of dUCBT cases; ATG was used in all IBCBT and 40% of dUCBT. Median follow-up time was 18 months in IBCBT and 17 months in dUCBT. At day 30, cumulative incidence (CI) of neutrophil recovery (ANC >500) was 83% after IBCBT and 63% after dUCBT, and at day 60, it was 90% in both groups; the median time to reach ANC>500 was 23 and 28 days after IBCBT and after dUCBT (p=0.001) respectively. At Day-180 CI of platelets recovery was 81% after IBCBT and 65% after dUCBT (p<0.001) with a median time of 36 days and 49 respectively (p=0.002). At day 100, CI of acute GVHD (II-IV) was 19% and 47% (p<0.001) and chronic GVHD 34% and 37% respectively (p=NS) respectively. Unadjusted 2 years-CI of NRM and RI were 31% and 23% after IBCBT and 35% and 28% after dUCBT, respectively (p=NS). Unadjusted 2 y-DFS estimation was 47% after IBCBT and 37% after dUCBT (p=NS). In multivariate analysis adjusting for statistical differences between 2 groups (such as status of the disease at transplant, age, CMV, previous transplants, GVHD prophylaxis), recipients of IBCBT had improved DFS (HR: 1.64, p=0.035), faster platelet recovery (HR:2.13, p<0.001) and decreased acute GVHD (HR:0.31; p<0.001) compared to dUCBT recipients. We did not find a cut-off value of number of nucleated cells after IBCBT or dUCBT that could be associated with outcomes after both approaches. In conclusion, both strategies have extended the use of CB transplants to adults in need of cord blood transplantation. Therefore, IBCBT is an option to transplant adult patients with single CB units after myeloablative conditioning regimen and may impact the total costs of cord blood transplantation. Based on these results, intra-bone technique may disclose new transplant potentialities also with other HSC sources.