Juliet N. Barker

Reduced-intensity conditioning may reduce transplantation-related mortality in high-risk adults undergoing hematopoietic transplantation. We investigated unrelated donor umbilical cord blood (UCB) transplantation after such conditioning in 43 patients (median age, 49.5 years; range, 22-65 years) with a primary end point of donor engraftment. The first 21 patients received busulfan 8 mg/kg, fludarabine 200 mg/m², and 200 cGy of total body irradiation (Bu/Flu/TBI). Subsequent patients (n = 22) received cyclophosphamide 50 mg/kg, fludarabine 200 mg/m², and 200 cGy TBI (Cy/Flu/TBI). UCB grafts (93%) were 1-2 HLA antigen–mismatched with the recipient and contained a median cryopreserved cell dose of 3.7 × 10⁷ (range, 1.6 × 10⁷-6.0 × 10⁷) nucleated cells per kilogram of recipient body weight (NC/kg). Graft versus host disease (GVHD) prophylaxis was cyclosporin A to day 180 plus mycophenolate mofetil to day 30. The cumulative incidence of sustained donor engraftment was 76% (95% confidence interval [CI], 56%-96%) for Bu/Flu/TBI recipients and 94% (95% CI, 84%-100%) for Cy/Flu/TBI recipients. The median day of neutrophil recovery (at least 0.5 × 10⁹/L) for engrafting Bu/Flu/TBI recipients was 26 days (range, 12-30 days) and for Cy/Flu/TBI recipients was 9.5 days (range, 5-28 days). Incidence of grades III-IV acute GVHD was 9% (95% CI, 1%-17%), and survival at 1 year was 39% (95% CI, 23%-56%). These data demonstrate that 0-2 antigen mismatched UCB is sufficient to engraft most adults after reduced-intensity conditioning and is associated with a low incidence of severe acute GVHD.

Allogeneic bone-marrow transplantation is the best treatment for patients with haematological cancers. This procedure, however, is limited by lack of suitable donors, as well as the complications of graft-versus-host disease (GVHD) and opportunistic infection. Umbilical-cord blood is an excellent source of haematopoietic stem cells. It has the advantages of speedy availability and reduced incidence of causing GVHD. This allows for transplantation of grafts with limited HLA disparity, and thereby extends the donor pool. The main determinants of successful umbilical-cord blood transplant are the number of cells that are available for transplantation and HLA matching. Cord blood transplantation has been validated as an alternative to bone-marrow transplantation for the treatment of leukaemia in children. A number of approaches are being developed to improve the efficacy of cord blood transplantation in adults, such as multiple-unit transplantation and reduced intensity of chemo-radiation therapy.

Human leukocyte antigen-matched sibling donor umbilical cord blood transplantation, or 0–2 human leukocyte antigen mismatched unrelated donor umbilical cord blood, is now considered an acceptable alternative to the use of bone marrow as a source for hematopoietic stem cells for pediatric hematopoietic stem cell transplantation, and is being investigated in adults. Major advantages of umbilical cord blood include the speed of availability compared with unrelated donor bone marrow, and tolerance of 1–2 human leukocyte antigen mismatch, which offers the opportunity to extend the donor pool. Umbilical cord blood transplantation is associated with durable engraftment and low incidence of severe graft-versus-host disease, even in the 1–2 human leukocyte antigen mismatched setting. Clinical experience has established the importance of graft cell dose in determining engraftment and survival in unrelated donor umbilical cord blood transplantation. More recently, the influence of human leukocyte antigen on outcome has become apparent. This review outlines the state of the art of umbilical cord blood transplantation, with emphasis on practical considerations in umbilical cord blood selection, and describes current research directions for this hematopoietic stem cell source.

Umbilical cord blood (UCB) is being increasingly used for hematopoietic stem cell transplantation and has been associated with a reduced incidence of severe graft-versus-host disease (GVHD). To further investigate the relative merits of unrelated donor UCB versus bone marrow (BM), a matched-pair analysis comparing the outcomes of recipients of 0 to 3 human leukocyte antigen (HLA)–mismatched UCB and HLA-A, B, DRB1-matched BM was performed. UCB patients, who received cyclosporine (CSA) and methylprednisolone (MP), were matched for age, diagnosis, and disease stage with BM patients, who received either methotrexate (MTX) and CSA (26 pairs) or T-cell depletion (TCD) and CSA/MP (31 pairs). Patients were predominantly children (median age, 5 years) undergoing transplantation for malignancy, storage diseases, BM failure, and immunodeficiency syndromes between 1991 and 1999. Although neutrophil recovery was significantly slower after UCB transplantation, the probability of donor-derived engraftment at day 45 was 88% in UCB versus 96% in BM-MTX recipients (P = .41) and 85% in UCB versus 90% in BM-TCD recipients (P = .32), respectively. Platelet recovery was similar in UCB versus BM pairs. Furthermore, incidences of acute and chronic GVHD were similar in UCB and BM recipients, with 53% of UCB versus 41% of BM-MTX recipients alive (P = .40) and 52% of UCB versus 56% of BM-TCD recipients alive at 2 years (P > .80), respectively. These data suggest that despite increased HLA disparity, probabilities of engraftment, GVHD, and survival after UCB transplantation are comparable to those observed after HLA-matched BM transplantation. Therefore, UCB should be considered an acceptable alternative to HLA-matched BM for pediatric patients.