Late Effects in Infants and Young Children Following Umbilical Cord Blood Transplant Using Busulfan-Based, Myeloablative Non-TBI Conditioning Regimens

Background:It has been 20 years since the first unrelated cord blood transplant (CBT) and many CBTs that followed, particularly early on, were performed in young children.  Improved donor selection, management of transplant-related complications, and supportive care have led to increasing numbers of long-term survivors of CBT. Infants and young children who undergo allogeneic CBT are at increased risk for certain late effects due to organ immaturity at the time of transplantation, particularly if radiation is used. Myeloablative regimens using Busulfan (Bu) have been employed to eliminate radiation exposure and associated consequences. In this single center retrospective review, late effects in young children receiving CBT following myeloablative, Bu-based conditioning regimens are reported.

Methods:The records of 215 consecutive patients from 1993 to 2008 who received Bu containing conditioning regimens for allogeneic CBT at < 2 years of age were reviewed. Of these, 105 patients who survived at least 5 years post-CBT were identified. A database was created to capture information regarding patient demographics, diagnosis, cord blood unit (CBU) characteristics, graft-related outcomes, and incidence and severity of organ system-specific late effects.

Results:  Of the 182 patients who underwent CBT at least 5 years prior, 58% were alive at 5 years post-CBT (n = 105). Median time from transplant was 10.8 years (range 5.1–19.9 years). Sixty-four percent of these patients were male and 83% were Caucasian. Diagnoses included inherited metabolic disease (58%, majority were Krabbe disease and Hurler syndrome), leukemia (20%), immune deficiency (16%), bone marrow failure/myelodysplastic syndrome (4%), and hemoglobinopathy (2%). Median age at time of CBT was 1.04 years (range 0.06-1.96 years). All patients received Bu containing regimens. Most received Bu/Cyclophosphamide/ATG (71%) or Bu/Melphalan/ATG (17%). CBUs were human leukocyte antigen (HLA) matched at 4/6 (43%), 5/6 (45%), and 6/6 (12%). Of the 112 patients who underwent CBT at least 10 years prior, 57 and 54% were alive at 5 and 10 years post-CBT, respectively. There were no deaths after 10 years post-CBT. The most commonly observed late effects included dental problems, short stature, and pubertal delay/gonadal failure. Pulmonary dysfunction was less common, and the majority of cases were mild. We will describe the characteristics of this cohort and where possible, compare these with existing data regarding late effects after allogeneic transplantation using TBI containing regimens.

Conclusions: This is the first report of late effects of Bu-based conditioning in a large cohort of patients who were very young at time of CBT. These results will inform clinical care and guidelines for long-term follow-up, as well as add to the growing information regarding late effects of HSCT in general.