Outcomes of Hematopoietic Stem Cell Transplantation (HCT) From Umbilical Cord Blood (UCB) Units in Patients With Malignant and Non-Malignant Disorders

Abstract

HCT is a curative treatment option for high risk malignant and non-malignant diseases. HLA-identical donors are the preferred graft sources. Matched unrelated donors have been utilized successfully for the last two decades. However, in about 30% of all patients neither an HLA-matched sibling nor a MUD donor is available; for these patients UCB has become an acceptable stem cell source. UCB offers several advantages: rapid availability, the possibility of using HLA-mismatched units and a decreased risk of GVHD. We analyzed the treatment outcomes in patients who have undergone HCT using UCB at City of Hope. 45 patients with malignant (82%) and non-malignant (18%) hematological disorders received 46 HCT using allogeneic or autologous UCB from January 1, 1997 through June 31, 2007. 29 patients (66%) carried a diagnosis of acute leukemia. 36 patients received single cord unit (including 2 autologous transplants), 10 patients received two UCB units. 80% of patients were alive at day 100. 1 year and estimated 5-year overall survival (0S) was 53% (95% CI 38%–89%) and 43% (95% CI 28%–64%) respectively with median follow up of patients alive at date of analysis of 4.2 years. Estimated 5-year survival for single (excluding autologous), double and autologous UCB transplant was 44% (95% CI 27%–60%), 28% (95% CI 4%–59%) and 100% respectively. Degree of HLA mismatch impacted OS – patients receiving UCB mismatched at 0 or 1 loci had significantly better 5-year survival (61%, 95% CI 40%–77%) compared to patients transplanted with 2 to 3 antigen mismatched units (17% 95% CI 4%–36%) p = 0.005. Neutrophil engraftment occurred at median 26 days (89% of patients engrafted by day 53). The incidence and time to platelet engraftment to 20K and 50K was 76% (median 50.5 days) and 67% (median 69 days) respectively. 62% of patients receiving single UCB developed acute GVHD (44% grade 1–2; 18% grade 3–4). 23% of these patients developed chronic GVHD (20% limited, 3% severe). All patients who received two UCB units developed acute GVHD (80% grade 1–2, 20% grade 3–4; and later chronic GVHD). 14 patients (30%) developed CMV infection (4 prior to day 30, 7 within days 30–100, 3 post day 100). 26% of patients had culture proven viral infections. In conclusion, for patients with high risk disease lacking HLA-matched sibling donor, UCB can offer a rapidly available alternative source of stem cells with transplant outcomes comparable to the results achieved using matched unrelated donors. HCT is a curative treatment option for high risk malignant and non-malignant diseases. HLA-identical donors are the preferred graft sources. Matched unrelated donors have been utilized successfully for the last two decades. However, in about 30% of all patients neither an HLA-matched sibling nor a MUD donor is available; for these patients UCB has become an acceptable stem cell source. UCB offers several advantages: rapid availability, the possibility of using HLA-mismatched units and a decreased risk of GVHD. We analyzed the treatment outcomes in patients who have undergone HCT using UCB at City of Hope. 45 patients with malignant (82%) and non-malignant (18%) hematological disorders received 46 HCT using allogeneic or autologous UCB from January 1, 1997 through June 31, 2007. 29 patients (66%) carried a diagnosis of acute leukemia. 36 patients received single cord unit (including 2 autologous transplants), 10 patients received two UCB units. 80% of patients were alive at day 100. 1 year and estimated 5-year overall survival (0S) was 53% (95% CI 38%–89%) and 43% (95% CI 28%–64%) respectively with median follow up of patients alive at date of analysis of 4.2 years. Estimated 5-year survival for single (excluding autologous), double and autologous UCB transplant was 44% (95% CI 27%–60%), 28% (95% CI 4%–59%) and 100% respectively. Degree of HLA mismatch impacted OS – patients receiving UCB mismatched at 0 or 1 loci had significantly better 5-year survival (61%, 95% CI 40%–77%) compared to patients transplanted with 2 to 3 antigen mismatched units (17% 95% CI 4%–36%) p = 0.005. Neutrophil engraftment occurred at median 26 days (89% of patients engrafted by day 53). The incidence and time to platelet engraftment to 20K and 50K was 76% (median 50.5 days) and 67% (median 69 days) respectively. 62% of patients receiving single UCB developed acute GVHD (44% grade 1–2; 18% grade 3–4). 23% of these patients developed chronic GVHD (20% limited, 3% severe). All patients who received two UCB units developed acute GVHD (80% grade 1–2, 20% grade 3–4; and later chronic GVHD). 14 patients (30%) developed CMV infection (4 prior to day 30, 7 within days 30–100, 3 post day 100). 26% of patients had culture proven viral infections. In conclusion, for patients with high risk disease lacking HLA-matched sibling donor, UCB can offer a rapidly available alternative source of stem cells with transplant outcomes comparable to the results achieved using matched unrelated donors.