HLA-identical sibling allogeneic hematopoietic stem cell transplantation (HSCT) is the best therapeutic option for high-risk hematological disease, but it is limited by lack of availability of a suitable donor for most candidate patients. At our institution our center, unrelated cord blood transplantation (UCBT) was used as the first alternative option for patients who lack an HLA-matched related donor in the last decade. We retrospectively analyzed the clinical outcomes of UCBT versus HLA-identical sibling HSCT for adult patients with hematologic malignancies.
Between April 2000 and May 2012, 194 consecutive adult patients with malignant hematological diseases received UCBT (77 patients; median age 21y, r 14–46; male 49) and related bone marrow transplantation (BMT) and/or peripheral blood stem cells transplantation (PBSCT) (117 patients; median age 30y, r 14–53; male 75). Diagnoses in two groups (UCBT/Sibling) included de novo AML (n = 23/32), ALL (n = 30/26), CML (n = 17/47), MDS/AML (n = 3/8), mixed phenotype acute leukemia (MPAL) (n = 3/1), NHL (n = 1/2), and MM (n = 0/1)). Overall rates of high-risk patients were 84.4% for UCBT recipients and 50.4% for BMT/PBSCT recipients(P<0.05). 11.6 percent of UCB grafts and 100% sibling grafts were HLA-identical (antigen level for HLA-A and B, allelic for DRB1, respectively). All patients received myeloablative conditioning regimens and CsA plus mycophenolate mofetil as GVHD prophylaxis.
The median number of nucleated cells and CD34+ cells infused were 0.36 (r 0.19–0.69)×108 and 0.21(r 0.06–0.52)×106 per kilogram of the recipient's body weight for UCBT recipients, and 5.68 (r 2.02–12)×108 and 3.63(r 0.67∼14.99)×106 per kilogram for BMT/PBSCT recipients (P=0.000). The primary engraftment rate was 96.1% (UCBT) and 100% (BMT/PBSCT). The median time to 0.5×109/L ANC was 19 days (r 12–35) and 12 days(r 10–18)(P = 0.000) and the median time to 20×109/L platelets was 36 days(r 14–90)and 15 days(r 11–17)(P = 0.001); hematopoietic recovery was significantly delayed after UCBT. The cumulative incidence of total acute GVHD (47.3% vs.22.2%, P = 0.001), early transplantation-related mortality (TRM) before day +100 (13.0% vs.3.4%, P<0.05), and infection (58.4%vs. 12.0%, P<0.05) was higher in UCBT recipients. Median follow-up was 42.2 months (range, 4.5–123.2 months) for BMT/PBSCT recipients and 22.2 months (range, 3.0–110.2 months) for UCBT recipients. There was no significant difference in cumulative incidence of grades ?to ? acute GVHD (9.4% vs. 5.0% P = 0.247), relapse rate (14.3% vs. 14.5%, P=0.962), and 3 year over survival (OS) (59.6% vs. 64.1%, P=0.123). But the cumulative incidence of chronic GVHD (18.8% vs. 44.1%) and extensive chronic GVHD (0% vs. 18%) was lower in UCBT recipients (P<0.05). The estimated 9-M CI of discontinuing immunosuppressive therapy (IST) while alive was 80%, and long-term survivors of UCBT had better quality of life.
Our data shows similar survival, but better quality of life after myeloablative transplantation using UCB versus identical sibling hematopoietic cells in adults with hematologic malignancies. HLA-mismatched cord blood should be considered an acceptable source of hematopoietic stem-cell grafts for adults in the absence of an HLA-matched adult donor.
Sun:Anhui Provincial “115” Industrial Innovation Program (2009): Research Funding; the Fund of the Key Medical Project of Anhui Provincial Healthy Department (2010A005): Research Funding; Key Scientific and Technological Project of Anhui province “Twelfth Five-Year Plan” (11010402164): Research Funding.
Asterisk with author names denotes non-ASH members.