Use of Aldehyde Dehydrogenase Content to Predict Dominating Cord in Double Cord Blood Transplant.
Authors: Page Kristin M , Gentry Tracy , Shoulars Kevin , Horwitz Mitchell , Herrmann Nicholas , Meadows Norin , Philipps Brittney , Balber Andrew , Kurtzberg Joanne 
Published: October 2019

Abstract
Abstract 2155
Poster Board II-132

Background:
Use of two cord blood units (CBU) for transplantation has increased access to transplantation especially for adult patients who have previously been limited by CBU cell dose. When two cords are used, cell dose can be increased above critical thresholds for engraftment, but typically only one cord confers durable engraftment. To date, it has not been possible to predict which cord will engraft. We have a long-standing interest in hematopoietic progenitor and stem cells that express high levels of the intracellular enzyme aldehyde dehydrogenase [ALDHbr cells]. ALDHbr cells can be enumerated by a rapid flow cytometric assay and we have shown that dosing of ALDHbr cells correlates with CBU potency. We have now tested the hypothesis that the CBU delivering the highest ALDHbr cell dose is the unit that establishes durable engraftment after double cord blood transplantation (CBT).

Methods:
Between 9/25/07 and 3/31/09, 27 consecutive adult and pediatric patients received conventional double cord blood transplants for high risk or relapsed malignancies. Most (n=24) received a myeloablative preparative regimen. We prospectively measured the ALDHbr dose delivered from both CBUs at time of thaw using Aldecount ® (Aldagen, Inc). Patient and graft characteristics were correlated with clinical outcomes. Engraftment was defined as the first of 3 days with an absolute neutrophil count of ≥ 500 donor cells/mm3with >75% donor chimerism which was confirmed by RLFP. The dominating CBU was defined as that with chimerism >75%. The ALDHbr dosing threshold was defined as high if the thawed graft delivered >47,000 ALDHbr cells/kg which preliminary results identified as predictive of engraftment in single CBT.

Results:
Patients had a median age of 28.8 years (range, 3.7-64.8 years) and weight of 68.70 kg (range, 15.2-111.8kg), 17 male, 13 CMV+. The median TNC per individual cord blood unit was 2.17 ×107/kg (range, 1.17-10.30 ×107/kg) with the median combined TNC of 3.93 ×107/kg (range, 2.67-18.00 ×107/kg). Five patients received transplants with two units with high ALDHbr cells, 10 patients received one unit with high ALDHbr and one unit with low cells, and 12 received two units with low ALDHbrcells. Of these patients, 23 were evaluable for engraftment. 10 of 12 patients receiving 1 or 2 high ALDHbrcontaining units engrafted. The other 2 patients died of infection without evidence of engraftment on days 29 and 34 post-transplant, respectively. Conversely, 4 of 9 evaluable patients receiving only low ALDHbr containing units failed to engraft. In the high/low group, only the high ALDHbr units engrafted. The sensitivity and specificity for ALDHbr content is 0.71 and 0.67, respectively. The positive and negative predictive values are 0.86 and 0.44, respectively. The pre-cryopreservation total nucleated cell (TNC) dose and post thaw TNC, CD34, and CFU cell doses were not found to be predictive of the dominating cord.

Conclusion:
ALDHbr dosing in thawed UCB grafts has a high positive predictive value for predicting engraftment in double cord blood transplantation. Further studies are indicated.

Disclosures:
Gentry: Aldagen, Inc: Employment. Herrmann:Aldagen, Inc: Employment. Meadows:Aldagen, Inc: Employment. Philipps:Aldagen, Inc: Employment. Balber:Aldagen, Inc: Employment.