Engraftment kinetics and graft failure after single umbilical cord blood transplantation using a myeloablative conditioning regimen

Abstract

Umbilical cord blood transplant recipients are exposed to an increased risk of graft failure, a complication leading to a higher rate of transplant-related mortality. The decision and timing to offer a second transplant after graft failure is challenging. With the aim of addressing this issue, we analyzed engraftment kinetics and outcomes of 1268 patients (73% children) with acute leukemia (64% acute lymphoblastic leukemia, 36% acute myeloid leukemia) in remission who underwent single-unit umbilical cord blood transplantation after a myeloablative conditioning regimen. The median follow-up was 31 months. The overall survival rate at 3 years was 47%; the 100-day cumulative incidence of transplant-related mortality was 16%. Longer time to engraftment was associated with increased transplant-related mortality and shorter overall survival. The cumulative incidence of neutrophil engraftment at day 60 was 86%, while the median time to achieve engraftment was 24 days. Probability density analysis showed that the likelihood of engraftment after umbilical cord blood transplantation increased after day 10, peaked on day 21 and slowly decreased to 21% by day 31. Beyond day 31, the probability of engraftment dropped rapidly, and the residual probability of engrafting after day 42 was 5%. Graft failure was reported in 166 patients, and 66 of them received a second graft (allogeneic, n=45). Rescue actions, such as the search for another graft, should be considered starting after day 21. A diagnosis of graft failure can be established in patients who have not achieved neutrophil recovery by day 42. Moreover, subsequent transplants should not be postponed after day 42.

Figure 1.

Probability density to engraftment. The curve shows the ratio between engrafted patients and subjects at risk for each 5-day interval from UCBT.

Figure 2.

(A) Impact of engraftment time on transplant-related mortality (TRM); (B) Impact of engraftment time on overall survival. Solid line means engraftment within 21 days of transplantation; dashed line means engraftment between 22 and 30 days after transplantation; Dotted line means engraftment between 31 and 42 days after transplantation; Dotted-dashed line means engraftment more than 42 days after transplantation.