Acute Graft-Versus-Host Disease: Clinical Presentation and Response to Therapy Following Umbilical Cord Blood Transplant.

Abstract

The nature of aGVHD after umbilical cord blood transplant (UCBT) has not been well characterized. We analyzed acute graft-versus-host disease (aGVHD) incidence and response to therapy in 136 recipients of unrelated UCBT. aGVHD developed in 72 receiving myeloablative (MA) (n=39) and non ablative stem cell transplant conditioning (NST) (n=33) (indicated if age >45 years, prior transplant and major co-morbidity). MA transplant recipients were significantly younger (median age 14 years, range 0.8–50) than NST transplant recipients (median 48 years, range 0.7–59), p < 0.0001 and had fewer advanced malignant disease at transplant (8% versus 24%), p = 0.09. At diagnosis of aGVHD, the clinical grades and organ involvement were similar in the 2 groups. Grade II–IV aGVHD developed in 34% of MA transplant recipients and 45% (p = 0.1) of NST transplant recipients at a median of 35 days (12–137) and 30 days (15–96) post transplant whereas grade III–IV aGVHD developed in 9% and 13% (p=0.6), respectively. 87% of MA vs. 85% of NST recipients (p=0.8) had skin involvement; 39% vs. 49% had GI disease (p=0.4); and 10% vs.9% (p=0.9) had liver GVHD, respectively. Response to therapy was assessed at 28 and 56 days after diagnosis of aGVHD. A high frequency of complete response (CR) was seen across all grades at day 28 (47%, 48% and 43% CR in grades I, II and III–IV, respectively). At day 56, CR was more frequent in grade I aGVHD (68% vs 64% and 50% in patients with grade II and III–IV disease, respectively, p 0.08). Response rates were similar in MA and NST transplant recipients (CR in 49% vs 46% by day 28, p=0.1, and 64% vs 61% by day 56, p=0.5. Age < 20 years (CR or PR 82% vs 64%, p = 0.09) and single organ GVHD (81% vs 52%, p=0.01) were associated with a higher response. A higher response rate was seen in patients with skin GVHD (85%) vs GI disease (63%) vs skin + GI (56%) vs liver involvement with skin/GI (43%), p=0.04. After a median follow up of 1.0 year (0.8–7 years) in both groups, 67% (95% CI 52%–81%) of MA versus 45% (95% CI 28%–62%) of NST patients survive (p=0.05). Higher 1 year survival of 70% (95% CI 58%–83%) was seen in patients with day 28 CR or PR to treatment versus non responders (24%, 95% CI 6%–42%), p<0.0001.This data suggests that among unrelated UCBT recipients using either MA or NST preparative regimens, similar incidence, clinical presentation and response to therapy of aGVHD was seen. Early identification of high risk group (age >20, multiorgan disease, GI or liver GVHD) should facilitate timely assignment of intensified therapy.