Unrelated Umbilical Cord Blood Grafts Research Articles

Clinical Outcomes of Unrelated Umbilical Cord Blood Graft vs. Haploidentical Donor Transplantation: Critical Issues for an Adequate Comparison.

Unrelated umbilical cord blood (UCB) and haploidentical grafts have been used for allogeneic hematopoietic stem and progenitor cell (HSPC) transplantation in patients without a related or non-related human leukocyte antigen (HLA)-matched donor. The less stringent HLA-matching requirement in both sources raises an important possibility for patients in need of urgent transplantation to treat any hematological disease. Selection of the best alternative donor is a difficult task that will depend on donor criteria, center experience, patient disease conditions, and risk, among others. Most comparisons available in scientific publications between both graft sources are obtained from retrospective analysis in wide time windows and a heterogeneous number of patients, types of disease, disease stages, previous treatments, graft source, conditioning regimen, graft vs. host disease (GVHD) approach, and evaluable endpoints. There is also an evident impact of the economic traits since low-income countries must consider less expensive treatments to satisfy the needs of the patients in the most effective possible path. Therefore, haploidentical transplantation could be an appealing option, even though it has not been completely established if any chronic treatment derived from the procedure could become a higher cost. In Colombia, there is a huge experience in UCB transplantation especially in units of pediatric transplantation where benign indications are more common than in adults. Due to the availability of a public UCB bank and HLA high-resolution typing in Colombia, there is a wider inventory of cord blood donors. Unfortunately, we do not have an unrelated bone marrow donor registry, so UCB is an important source along with haploidentical transplantation to consider in decision-making. This minireview focuses on comparing the main issues associated with the use of both HSCP sources and provides tools for physicians who face the difficult decision between these alternative donor sources.

Unrelated cord blood compared with haploidentical grafts in patients with hematological malignancies.

Alternative donors, such as unrelated umbilical cord blood (UCB) and related haploidentical (haplo) donors, are more and more frequently searched for and used for patients who are candidates for allogeneic hematopoietic stem cell transplantation but are without a suitable related or unrelated donor. The aim of the current retrospective study was to compare the outcome of patients after haplo and UCB grafts prepared using a nonmyeloablative conditioning regimen. A total of 150 adult patients with high-risk hematologic diseases who underwent allogeneic hematopoietic stem cell transplantation from alternative donors at 2 centers (Paoli-Calmettes Institute [Marseille, France] and Humanitas Cancer Center [Milan, Italy]) were analyzed. Sixty-nine patients had haplo donors and 81 patients had UCB donors. The cumulative incidence of nonrecurrence mortality at 1 year was 23% in the UCB group versus 17% in the haplo group (P = .39). The incidence of grade 2 to 4 acute graft-versus-host disease and extensive chronic graft-versus-host disease in the UCB group versus the haplo group was 52% versus 29% (P = .05) and 12% versus 6% (P<.0001), respectively. The overall survival rate at 2 years was 45% in the UCB group (95% confidence interval [95% CI], 34%-56%) versus 69% in the haplo group (95% CI, 58%-80%) (P = .10). The progression-free survival rate at 2 years was 36% in the UCB group (95% CI, 25%-47%) versus 65% in the haplo group (95% CI, 53%-77%) (P = .01). The results of the current study suggest that for patients with high-risk hematological diseases without a related or unrelated donor, haploidentical transplants are a promising alternative option that deserves further investigation.

Risk Factor Analysis of Outcomes after Unrelated Cord Blood Transplantation in Patients with Hurler Syndrome

Allogeneic stem cell transplantation (SCT) is considered effective in preventing disease progression in patients with Hurler syndrome (HS). Unrelated umbilical cord blood (UCB) grafts are suggested as an alternative to bone marrow (BM) or peripheral blood stem cells (PBSC). We studied 93 HS patients receiving an UCB graft to analyze risk factors for outcomes. The median time from diagnosis to transplant was 4.6 months, median follow-up was 29 months, and median number of nucleated CB cells infused was 7.6 × 10 7/kg. Most of the patients received 1 or 2 HLA disparate grafts, and the most frequently used conditioning regimen was cyclophosphamide + busulfan (Bu/Cy). All patients received anti-T cell antibody. At post transplant day +60, the cumulative incidence of neutrophil engraftment was 85%. A younger age at transplant and a higher CD34 + dose at infusion were favorably associated with engraftment. With the exception of 2 patients, all engrafted patients achieved full and sustained donor chimerism. The 3-year event-free survival (EFS) and 3-year overall survival (OS) rates were 70% and 77%, respectively. In a multivariate analyses, use of Bu/Cy and a shorter interval from diagnosis to transplant were predictors for improved EFS rate (82% for patients transplanted within 4.6 months after diagnosis compared to 57% for the rest). Improved outcomes from early transplantation and immediate availability of CB unit lead us to conclude that CB transplantation is a beneficial option, which should be considered expediently for children with HS.

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.

The lower morbidity and mortality of reduced-intensity conditioning (RIC) regimens has allowed allogeneic hematopoietic cell transplantation (HCT) in older patients. Unrelated umbilical cord blood (UCB) has been investigated as an alternative stem cell source because of insufficient availability of 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 (OS) after 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, 38 (88%) received two UCB units to optimize cell dose and 40 (93%) received 1–2 HLA mismatched grafts. The median total nucleated cell dose was 9.2 × 108/kg (range, 3.0–21.2) for MRD grafts and 0.4 × 108/kg (range, 0.2–0.8) for UCB grafts. The median followup for survivors was 27 (range, 12–61) months. The probability of progression-free survival (PFS) at 3-years for recipients of MRD and UCB was 30% (95% confidence intervals [CI], 16–44%) and 34% (95% CI, 19–48%)(p=0.98) and OS was 43% (95% CI, 29–58%) and 34% (95% CI, 17–50%)(p=0.57), respectively. The cumulative incidence of sustained donor engraftment at 6 weeks was 100% for MRD and 89% (95% CI, 80–99%) for UCB recipients (p=0.05). The cumulative incidence of grade 2–4 acute graft-versus-host disease (GVHD, 42% vs. 49%, p=0.20) and TRM at 180-days (23% vs. 28%, p=0.36) was comparable between the MRD and UCB groups; however, UCB recipients had a lower incidence of chronic GVHD at 1-year (40% vs. 17%, p=0.02). On multivariate analysis, graft type (MRD vs. UCB) had no impact on TRM, PFS or OS; only HCT comorbidity index score was independently predictive for these endpoints. For the whole cohort, 180-day TRM for patients with HCT comorbidity index scores of 0, 1–2 and ≥ 3 was 14% (95% CI, 0–28%), 19% (95% CI, 5–32%) and 44% (95% CI, 26–62%), respectively. Compared to patients with a higher score, patients with a score of 0–2 had lower TRM (hazard ratio [HR] 0.3 [95% CI, 0.1–0.7]) as well as better PFS (HR 0.5 [95% CI, 0.3–0.9]) and OS (HR 0.5 [95% CI, 0.2–0.9]). 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. Older HCT candidates with limited comorbidity have a low and acceptable risk of TRM and a careful review of existing comorbidities is necessary when considering older patients for HCT.

Hematopoietic recovery after unrelated umbilical cord-blood allogeneic transplantation in adults treated with in vivo stem cell factor (R-MetHuSCF) and filgrastim administration

Transplantation with unrelated umbilical cord blood (UCB) is marked by delayed hematologic recovery. This report summarizes two adults with chronic myelogeneous leukemia (CML), who received myeloablative conditioning followed by infusion of a non-expanded single UCB graft. These CML patients were enrolled in a clinical trial incorporating concomitant in vivo administration of stem cell factor (R-MetHuSCF) and filgrastim from day of UCB infusion until attained hematopoietic recovery. Each patient engrafted fully with donor UCB, with days to absolute neutrophil count (ANC) >500/μl being 13 and 29 days, respectively. Both patients remain in cytogenetic remission at 28 months follow-up. ‘In vivo UCB expansion’ with administration of concomitant R-MetHuSCF and filgrastim may facilitate prompt hematologic engraftment.