Umbilical Cord Blood Transplantation after Graft Failure from a Previous Hematopoietic Stem Cell Transplantation

Graft failure (GF) is a life-threatening complication after allogeneic hematopoietic stem cell transplantation (HCT). The incidence of GF after HCT using human leukocyte antigen (HLA) matched donors is lower than 5%; however, a higher incidence is observed when considering HLA mismatched donors or alternative donor sources and the use of reduced intensity conditioning (RIC) regimens.

In the absence of autologous recovery, a second HCT is necessary to attempt preventing death due to prolonged pancytopenia. Previous studies describing outcomes of second HCT performed after a GF with different types of donor sources report a wide range of overall survival (OS) and transplant related mortality (TRM), however studies including a large number of patients receiving a second transplant with umbilical cord blood (UCB) are scarce.

In this retrospective study, using registry data from Eurocord and the European Society for Blood and Marrow Transplantation (EBMT), we report the outcomes of 247 umbilical cord blood transplants (UCBT) performed after GF following a previous HCT. Data were analyzed separately for patients with malignant (n=141) and non-malignant diseases (n=106). UCB was the most frequent stem cell source that resulted in GF (65.0% and 68.9%, for malignant and non-malignant diseases, respectively), and most of the reported GF occurred within 100 days after HCT (92.3% and 85.9%). The most frequent diagnosis in malignant diseases was acute leukemia (64.5%), mainly acute myeloid leukemia (AML). In non-malignant diseases, the diagnoses most often reported were inborn error of metabolism (IEM) (37.7%), followed by bone marrow failure syndrome (BMF) (34.0%) and primary immune deficiency (PID) (21.7%). In malignant and non-malignant diseases, we observed a similar cumulative incidence of neutrophil engraftment of 59.1% (95% CI 51.4- 67.9%) and 60.4% (95% CI 51.7- 70.6%), in a median time of 23 and 24 days, and a 3-year OS of 28.9% (95% CI 21.8- 37.3%) and 49.1% (95% CI 39.5- 58.8%). TRM at 100 days and at 3 years for malignant diseases was 39.9% (95%CI 32.5 - 49.1%), and 57.5% (95%CI 49.4 - 66.8%). In multivariate analyses, none of the characteristics were statistically significantly associated with engraftment or overall survival.

Although survival for patients requiring a second transplant is not optimal, UCB remains a valid life-saving option for some patients with GF as it is an immediately available source of stem cells in severely ill patients. The most appropriate stem cell source for salvage transplants remains controversial, as it depends on multiple factors including center choice, donor availability, underlying disease and existing comorbidities.