Directed Donor Cord Blood Transplantation for Hematological Disorders.

The Sibling Donor Cord Blood Program was initiated in 1998 as a resource to collect, characterize, and to release for transplantation cord blood units (CBU) from families affected by malignant and non-malignant disorders. Currently, 1686 CBUs from 1587 families have been collected among referrals from all 50 US States. The categories of participation include malignant disorders (50%), sickle cell disease (29%), thalassemia (6%), and other hereditary or rare hematological conditions (15%). The mean cell volume collected was 102 ml (range, 31–284) with a mean total nucleated cell count (TNC) of 9.5 x 10⁸ (range, 0.6–53.6) and mean CD 34+ cell count of 3.6 x 10⁶ (range, 0.1–88.1). The post-thaw viability of CBU released for transplantation was 94.4 % (SD ±8.7%) and only 4.4% of CBUs were not processed due to having inadequate volume.

To date, 54 children have been treated by sibling donor cord blood transplantation (CBT), 38 using the cord blood unit as the sole source of stem cells. There was a very high rate of CBU utilization, particularly among thalassemia families where 18 of 105 (17%) of CBUs collected have been released for CBT. CBT recipients had hematological malignancies (N=20), thalassemia major (N=18), sickle cell anemia (N=8) or other non-malignant disorders (N=8), and all but 6 received HLA-identical allografts. The median total nucleated (TNC) and CD34+ cell dose was 3.1 x 10⁷ TNC/kg and 0.7 x 10⁵/kg recipient weight, respectively. The median time to ANC >500 and platelet >20,000/mm³ was 22 and 45 days, respectively. One of 52 (2%) evaluable patients had graft failure accompanied by autologous reconstitution. With a median follow-up of 9.6 (range, 0.1 – 94) months, 45 of 54 (83%) patients survive, and 9 patients (17%) died of relapse (N=6) or transplant-related causes (N=3) after CBT. Among the hemoglobinopathy patients, 23 of 26 (88%) survive, and 22 (85%) survive disease-free. Overall, the Kaplan-Meier probabilities of survival and event-free survival after sibling CBT are 79% and 72%, respectively.

These results confirm the feasibility of remote site, directed donor cord blood collection and subsequent transplantation for hematological disorders. The ability to combine cord blood collections with a marrow harvest from the sibling donor effectively reduced the incidence of graft rejection when CBU cell doses were judged to be insufficient. Transplantation of sibling CBUs in lieu of bone marrow may be particularly advantageous when there is urgency for transplantation and in non-malignant disorders where graft-versus-host disease, in particular, has a negative impact upon outcome.