Impact of viable CD45 cells infused on lymphocyte subset recovery after unrelated cord blood transplantation in children

Abstract

We studied lymphocyte recovery in 88 children who consecutively underwent unrelated cord blood transplantation for malignant (n = 64) or nonmalignant (n = 24) diseases. All children but 3 received myeloablative conditioning regimens with pretransplant antithymocyte globulin. Median age was 5.6 years (0.1-18 years) and median follow-up was 40 months (10-136 months). The median dose of infused viable CD45(+) cells (vCD45) was 3.35 × 10(7)/kg with a ratio infused vCD45/collected total nucleated cell at 0.46. Immunologic endpoints were: time to achieve CD3(+) >500 and 1500/mm(3), CD4(+) >500/mm(3), CD8(+) >250/mm(3), CD19(+) >200/mm(3), natural killer >100/mm(3). These endpoints were analyzed through the use of cumulative curves for estimating incidence over time in the context of competing risks, and through Fine and Gray models to assess prognostic factors. The median time to reach these endpoints was 33, 97, 214, and 340 days for natural killer, B, CD8, and CD4 cells, respectively. In multivariate analysis, a high infused vCD45 cell dose improved CD3 (P = .014) and CD4 (P = .032) reconstitutions. A young recipient age also favored CD3 recovery (P = .013). With patients grouped according to vCD45 cell dose quartiles, the threshold for a better recovery was 3.35 × 10(7)/kg. Considering the ratio vCD45/TNC, this "immune recovery based" threshold corresponds to a higher cell dose than the minimum usually recommended dose for myelogenous engraftment. This may have important implication for UCB selection.