Graft-versus-host disease after double-unit cord blood transplantation has unique features and an association with engrafting unit-to-recipient HLA match

Abstract

Manifestations of and risk factors for graft-versus-host disease (GVHD) after double-unit cord blood transplantation (DCBT) are not firmly established. We evaluated 115 DCBT recipients (median age, 37 years) who underwent transplantation for hematologic malignancies with myeloablative or nonmyeloablative conditioning and calcineurin inhibitor/mycophenolate mofetil immunosuppression. Incidence of day 180 grades II to IV and III to IV acute GVHD (aGVHD) were 53% (95% confidence interval, 44 to 62) and 23% (95% confidence interval, 15 to 31), respectively, with a median onset of 40 days (range, 14 to 169). Eighty percent of patients with grades II to IV aGVHD had gut involvement, and 79% and 85% had day 28 treatment responses to systemic corticosteroids or budesonide, respectively. Of 89 engrafted patients cancer-free at day 100, 54% subsequently had active GVHD, with 79% of those affected having persistent or recurrent aGVHD or overlap syndrome. Late GVHD in the form of classic chronic GVHD was uncommon. Notably, grades III to IV aGVHD incidence was lower if the engrafting unit human leukocyte antigen (HLA)-A, -B, -DRB1 allele match was >4/6 to the recipient (hazard ratio, 0.385; P = .031), whereas engrafting unit infused nucleated cell dose and unit-to-unit HLA match were not significant. GVHD after DCBT was common in our study, predominantly affected the gut, and had a high therapy response, and late GVHD frequently had acute features. Our findings support the consideration of HLA- A,-B,-DRB1 allele donor-recipient (but not unit-unit) HLA match in unit selection, a practice change in the field. Moreover, new prophylaxis strategies that target the gastrointestinal tract are needed.

Figure 1. Cumulative incidence of grade II–IV and III–IV aGVHD at day 180

The incidence is reported at day 180 to include the 2 patients that had late onset aGVHD between days 100–180 after DCBT, and the 3 patients who developed aGVHD prior to day 100 but peaked at grade III–IV disease after day 100. These latter 3 patients, although grade II at onset, are included in the III–IV curve.

Figure 2. Cumulative incidence of GVHD in engrafted and disease-free at 100 days after transplantation

Figure 2A shows the cumulative incidence of any active GVHD after day 100, and 2B shows exclusively cGVHD (classical and overlap) after day 100 in this patient population.

Figure 3

Cumulative incidence of day 180 grade III–IV aGVHD by engrafting unit-recipient match at HLA-A,-B,-DRB1 (3A) and HLA-A,-B,-C,-DRB1,-DQ (3B) alleles.