IMMUNOLOGICAL RECONSTITUTION AFTER UNRELATED CORD BLOOD (CB) TRANSPLANTATION.† 953

Umbilical CB from term neonates contains increased numbers of committed progenitor cells compared to adult peripheral blood (Broxmeyer, et al,Proc Natl Acad Sci USA 86:3828, 1989). However, the neonatal immune system is developmentally immature at birth. Since 1988, CB has been used as a source of hematopoietic stem cells in young patients with sibling donors(Gluckman, et al, N Engl J Med 321:1174, 1989). Recently, we have demonstrated the feasibility of unrelated HLA-identical or 1 or 2 antigen mismatched cord blood transplantation (CBT) (Sweetman, et al, Blood 86:388a, 1995). We evaluated immune reconstitution following unrelated CBT. Five patients (median 4 years, range 0.9-21 years) received unrelated CBT for malignant (n=4, 1 ANLL, 2 ALL, 1 MDS in transformation) or non-malignant (n=1) conditions. Evaluation of immune reconstitution included the following: 1) B-cells (CD19), T cells (CD3), T-helper cells (CD3/CD4), T-suppressor cells(CD5/CD8) and natural killer (NK) cells (CD56); 2) mitogen responses to PHA, Con A, and PWM;3) quantitative immune globulin levels; 4) expression of C3bi. Three patients are alive (306, 260, and 159 days post transplant), one patient died of multi-organ failure on day + 19, and one pt died of grade IV GvHD. The number of B cells (CD19+) exceeded normal levels after day +75, with a mean at day +90 of 321/mm³ and 718/mm³ at day +120. T-helper and T-suppressor cells remained low even at day +180 with mean values of 414/mm³ and 256/mm³ respectively. The number of natural killer cells were within normal range throughout the first 180 days with day +30 -+180 means ranging from 252-518/mm³. Mean IgG levels were normal throughout the study period with mean day +120 levels of 845 mg/dl. IgA levels revealed a decreasing trend and most patients had low levels at day +120. IgM showed a similar trend but levels at day +120 were in the low normal range with a mean level of 44mg/dl. Mitogen response studies revealed low blastogenesis to PHA, Con A, and PWM from day of transplant through day +180. C3bi expression (CD11b) was within normal range throughout the study period with 70-96% of neutrophils and monocytes demonstrating C3bi expression. While reconstitution of B cells and NK cells is not impaired, recovery of both helper and cytotoxic T cell subpopulations is delayed in patients receiving CBT. This delay may play a role in reducing the incidence of GvHD as well as attenuating graft-versus-leukemia effect in patients undergoing CBT.