Transplantation of adult and pediatric cancer patients with ex vivo expanded cord blood

Cord blood (CB) cells are being used increasingly as a source of allogeneic hematopoietic support, but have been associated with delays in engraftment. In this study we evaluated ex vivo expansion of CB from unrelated donors in 29 patients (21 adult, 8 children) with AML (n = 5), ALL (n = 8), CML (n = 3), CLL (n = 3), NHL (n = 5), HD (n= 2), and breast ca (n = 3). The patients received high-dose melphalan and ATG plus TBI (n = 17) or busulfan (n = 4), or TBI-cytoxan-ARA-C (n = 8 children). Strata A patients (n = 22) had CB frozen in one fraction (fx). On day 0 to transplant, the CB was thawed and 60% of the CB was infused without manipulation. The CD34+ cells in the remaining 40% of the CB were isolated and expanded in teflon bags in 800 ml of media containing 100 ng/ml each of rhSCF, rhG-CSF and rhMGDF. After 10 days in culture the expanded product was harvested, washed and reinfused. Strata B patients (n = 7), whose CB was frozen in two fx, had the 40% fx thawed on day −10 and cultured for 10 days as described above. Both the expanded and the unmanipulated CB were infused on day 0. The cultures generated a median 89 (range 42-270) fold expansion of cells and 4 (range 2-13) fold expansion of CD34+ cells. To date, all 19 of 20 (95%) patients, evaluable for engraftment, achieved recovery of neutrophils (ANC ≥500/mm 3 ) in a median of 26 (range 15–45) days. Fourteen of 15 (93%) patients engrafted platelets (≥20,000/mm 3 , unsupported) in a median of 58 (range 27–380) days. All patients tested at day +60 (n = 11) have been 98–100% donor. Eight of 13 patients (62%) experienced acute and 7/10 (70%) extensive chronic GVHD. Preliminary analysis suggests that the neutrophil engraftment failure rate of 5% in our patients may be lower than the 15–60% failure rate reported for recipients of unexpanded CB transplants. The median time to neutrophil and platelet engraftment rates in adult patients appears to be comparable to that in smaller pediatric patients despite significantly lower CB cell doses.