Single Versus Double Umbilical Cord Blood Transplantation (UCBT): Higher Risk of Acute Graft-Versus-Host Disease (GVHD) but Lower Transplant Related Mortality (TRM) in Recipients of Double UCBT.

Abstract

Transplantation of 2 partially HLA matched UCB units has been shown to be a safe and effective means to overcome the cell-dose barrier in adolescents and adults. In addition, preliminary data suggest that double UCBT is associated with a greater graft-versus-leukemia effect (Blood 2005: 106:93a). To date, there has been no comparative analysis on the risk of acute GVHD in this population of patients. Therefore, we compared rates of acute GVHD in recipients of single (n=210) versus double (n=169) UCBT. Double UCB recipients were more likely to be older, transplanted in recent years, treated with a non myeloablative therapy, received mycophenolate mofetil as GVHD prophylaxis, and less likely to receive antithymocyte globulin (ATG) as part of the conditioning. Incidences of grades II–IV and III–IV acute GVHD were higher in recipients of double than single UCBT recipients (60% vs 33%, p.01) and (21% vs 11%, p=.01), respectively. Adjusting for differences between groups, two factors were associated with the development of grade II–IV acute GVHD in Cox regression: use of 2 UCB units (RR 2.0 vs 1.0 [95% CI, 1.3–3.2, p.01]) and absence of ATG in the preparative regimen (RR 1.0 vs 0.5 [95% CI, 0.3–0.8, p.01]). Other factors that were tested in the model but not determined to be significantly associated with acute GVHD were recipient age, gender, weight, diagnosis, time from diagnosis to UCBT, HLA disparity, total and CD3 cell dose, CMV serostatus, conditioning regimen, and GVHD prophylaxis. Despite increased risk of acute GVHD, TRM 1 year was significantly lower in recipients of double UCBT (17%, 95% CI, 5–29%) as compared to recipients of a single UCBT (47%, 95% CI, 26–68%; p =.02) (Figure 1) among those that developed grade III–IV acute GVHD. Survival at 1 year among those with grade III–IV acute GVHD was significantly higher after double UCBT (67%, 95% CI, 51–83%) than after single UCBT (41%, 95% CI 21–61%; p=.04) (Figure 2). [Display omitted] [Display omitted] In conclusion, risk of acute GVHD is significantly higher in recipients of two partially HLA matched UCB units, yet it does not appear to adversely effect TRM or survival. ATG in the preparative therapy, however, does not appear to reduce TRM despite its favorable association with reduced GVHD. Impact of GVHD on immune recovery and infection risk in recipients of single and double UCBT is under investigation.