How Much Is Enough? Ethical Consideration for the Depletion of Large Public Cord Blood Units (CBU)

Background:  The Be The Match Registry® provides access to over 230,000 CBU with a median pre-freeze Total Nucleated Cell (TNC) count of 105 x 10^7 TNC.  Prior studies have established an acceptable dose threshold of at least 2.5 x 10^7 for the treatment of hematological malignancies. Pediatric patients often only require a single CBU to achieve suitable cell dose for transplant (Tx) and some have received cell doses per patient weight in excess of 20 x 10^7 TNC/kg. Meanwhile adults may require multiple units to achieve the recommended minimal dose.  This study evaluated whether CBU Tx in peds achieving a cell dose >20 x 10^7 TNC/kg deplete a unit that may be suitable for an adult patient when another potentially acceptable unit is available for the child.

Methods:  We identified 74 single CBU Tx of patients age 0-12 years old, facilitated through the Be The Match Registry from Sept 2009 to Aug 2012 with a Tx cell dose >20 x 10^7 TNC/kg. The CBU searches were reviewed to determine whether another suitable CBU (10-20 x 10^7 TNC/kg and equivalent or better low resolution HLA-A, B, C, high resolution -DRB1) was available for that patient.  A TNC threshold for CBU suitability for a potential adult patient of 178 x 10^7 was established based on the historical median weight of 71kg for adult CBU Tx recipients. 

Results:  Of the 74 Tx evaluated, 58 (78%) units had a minimum TNC of 178 x 10^7 (range 178-452), large enough for the median weight adult patient.  In 48 of the 58 cases a suitable CBU with 10-20 TNC/kg was available on the search with an equivalent or better HLA match and 23% of the time the lower TNC CBU was a better HLA match. If the lower TNC CBUs had been selected for this cohort, the median cell dose would decrease from 28.7 to 11.5 TNC/kg.    

Conclusions:  The number of CBU in the registry that meet the median adult patient dose of 178 x 10^7 TNC is 16,494 (7%) CBU compared to 234,292 available for peds Tx. Transplant practice is often to take the largest CBU available for a patient, with consideration of HLA match differing between centers. This study shows that CBU used in Tx for children can exceed 20 x 10^7 TNC/kg.  These CBU have a large TNC and could be suitable for adolescent or adult single cord transplantation. Although 74 CBU Tx correspond to a small proportion of total peds (age 12 and under) single CBU Tx during this timeframe (n=951), these units may offer the only opportunity for an adult patient. With a limited number of CBUs achieving high TNC available for adult patients, consideration of the ethics of providing a young patient with an adequate TNC CBU (e.g. 10-20 x 10^7 TNC/kg) vs the largest TNC CBU will continue to confront the community. Centers should consider selecting a CBU with smaller, yet still substantial cell dose, particularly when it’s a better HLA match. Future outcomes research is needed to elucidate the optimal TNC or identify a maximum threshold recommendation for guidance in CBU Tx in small children prior to a policy being implemented.