Katherine Evans

Donor-recipient allele-level HLA matching of unrelated cord blood units reveals high degrees of mismatch and alters graft selection.

The feasibility of selecting cord blood (CB) units at high-resolution HLA match has not been investigated. We analyzed the high-resolution donor–recipient HLA match of 100 double-unit 4–6/6 HLA-A,-B antigen, -DRB1 allele-matched CB grafts (units 1a and 1b) and their back-up units (n=377 units in total). The median cryopreserved graft dose was 2.9 × 107/kg/unit, and at high resolution these units had a median donor–recipient HLA-allele match of 5/8 (range 2–8/8) and 6/10 (range 2–9/10), respectively. We then evaluated how often use of high-resolution HLA-match criteria would change the original graft selection to substitute one or both of the back-up units for units 1a and/or 1b. On using a model in which both a higher eight-allele HLA match and a cell dose ⩾2.0 × 107/kg/unit were required, graft selection changed in 33% of transplants with minimal effect on cell dose (8.3% reduction). In summary, while units chosen based on HLA-A,-B antigen and -DRB1 allele match have substantial mismatch at higher resolution, CB selection based on high-resolution HLA match is possible in a significant proportion of patients without compromise in cell dose.

“No Wash” Albumin-Dextran Dilution for Double-Unit Cord Blood Transplantation is Safe with High Rates of Sustained Donor Engraftment

Washing cord blood (CB) grafts involves product manipulation and may result in cell loss. We investigated double-unit CB transplantation (CBT) using red blood cell (RBC)-depleted units diluted with albumin-dextran in patients with hematologic malignancies. One-hundred thirty-six patients (median age, 43 years; range, 4 to 71; median weight, 69 kilograms (kg); range, 24 to 111) underwent transplantation with a 4/6 to 6/6 HLA-matched graft. Patients ≤ 20 kg were excluded, as they only received washed units. Units were diluted a median of 8 fold to a median volume of 200 mL/unit. The median infused total nucleated cell doses were 2.7 (larger unit) and 2.0 (smaller unit) x 10(7)/kg, respectively, and the median post-thaw recovery was 86%. Units were infused consecutively (median, 45 minutes/unit). While only 17 patients (13%) had no infusion reactions, reactions in the remaining 119 patients were almost exclusively mild-moderate (by CTCAE v4 criteria 12 grade 1, 43 grade 2, 63 grade 3) with only 1 patient (< 1%) having a severe (grade 4) reaction. Moreover, most were easily treated. Grade 2 to 3 hypertension was the most common in 101 (74%) patients. The cumulative incidence of sustained donor-derived neutrophil engraftment was high: 95% in myeloablative and 94% in nonmyeloablative CBT recipients. With appropriate supportive care, double-unit CBT with RBC-depleted grafts infused after albumin-dextran dilution is safe with high rates of engraftment in patients > 20 kg.