Transplantation of adult and pediatric cancer patients with cord blood progenitors expanded ex vivo
Cord blood (CB) cells are used increasingly as allogeneic hematopoietic support, but have been associated with delays in engraftment. We evaluated the ex vivo expansion of CB from unrelated donors in 37 patients (25 adults, 12-children) with AML (n=7), ALL (n=13), CML (n=3), CLL (n=3), NHL (n=5), HD (n=3), and breast ca (n=3). The patients received high-dose melphalan and ATG, plus TBI (n=20) or busulfan (n=5), or TBIcytoxan-ARA-C (n=12). Cohort 1 (n=25) had 40% and Cohort 2 (n=12) 60% of their CB expanded; the unexpanded CB fractions were thawed and infused without further manipulation on Day 0 following high-dose therapy. The CD34+ cells were isolated from the remaining CB using the Isolex-300i device (Nexell), and cultured in teflon bags in l L of media containing 100 ng/ml each of rhSCF, rhG-CSF and rhMGDF (Amgen Inc). After 10 days in culture at 37°C in 5% CO2, the expanded CB was harvested, washed and reinfused. The cultures generated a median 111 (range 26-270) fold expansion of cells and 4.5 (range 2-20) fold expansion of CD34+ cells. To date, all but two of 33 patients évaluable for neutrophil engraftment (followed 45 days) achieved recovery (ANC 500 /mm1) in a median of 26 (range 15-45) days; platelets engrafted (20,OOQ/mm3, unsupported) in a median of 59 (range 27-370) days. Initial patients (n=l 1) tested at day +100 for chimerism have been 98-100% donor. 16/32 patients (50%) experienced grade I-II (n=8) or III-IV (n=8) acute GVHD; 10/15 (67%) followed for lOOdays had limited (n=l) or extensive (n=9) chronic GVHD. Preliminary analysis suggests that the neutrophil engraftment failure rate of 6% (2/33 patients with extensive marrow relapse) 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 pédiatrie patients despite lower CB cell doses. Accrual continues to fully assess the efficacy and toxicity of expanded CB.
Shpall, EJ; Quinones, R; Giller, R; Jones, RB
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