Reduced Intensity Allogeneic Transplant In Patients Older Than 55 Years: Unrelated Umbilical Cord Blood Is Safe And Effective For Patients Without A Matched Related Donor

摘要

The lower morbidity and mortality of reduced-intensity conditioning (RIC) regimens have allowed allogeneic hematopoietic cell transplantation (HCT) in older patients. Unrelated umbilical cord blood (UCB) has been investigated as an alternative stem cell source to suitably HLA matched related (MRD) and adult volunteer unrelated donors. We hypothesized that RIC HCT using UCB would be safe and efficacious in older patients and compared the transplant related mortality (TRM) and overall survival of RIC HCT in patients older than 55 years using either MRD (n=47) or, in patients with no 5/6 or 6/6 HLA compatible related donors, UCB (n=43). RIC regimen consisted of total-body irradiation (200 cGy) and either cyclophosphamide and fludarabine (n=69), or busulfan and fludarabine (n=16) or busulfan and cladribine (n=5). The median age of MRD and UCB cohorts was 58 (range, 55-70) and 59 (range, 55-69) years, respectively. AML/MDS (50%) was the most common diagnosis. All MRD grafts were 6 of 6 HLA matched to the recipient. Among patients undergoing UCB HCT, 88% received two UCB units to optimize cell dose and 93% received 1-2 HLA mismatched grafts. The median followup for survivors was 27 (range, 12-61) months. The 3-year probabilities of progression-free survival (30% vs. 34%, p=0.98) and overall survival (43% vs. 34%, p=0.57) were similar for recipients of MRD and UCB. The cumulative incidence of grade 2-4 acute graft-versus-host disease (42% vs. 49%, p=0.20) and TRM at 180-days (23% vs. 28%, p=0.36) were comparable. However, UCB recipients had a lower incidence of chronic graft-versus-host disease at 1-year (40% vs. 17%, p=0.02). On multivariate analysis, graft type had no impact on TRM or survival and HCT comorbidity index score was the only factor independently predictive for these endpoints. Our study supports the use of HLA mismatched UCB as an alternative graft source for older patients who need a transplant but do not have a MRD. The use of RIC and UCB extends the availability of transplant therapy to older patients previously excluded on the basis of age and lack of a suitable MRD. A careful review of existing comorbidities is necessary when considering older patients for HCT.