Skeptical UCB Customer: Experiences of University of Rochester/Strong Memorial Transplant Program with Umbilical Cord Blood Units Craig Mullen, MD, PhD Chief, Pediatric Hematology/Oncology/HSC Transplantation University of Rochester
History of HSCT in Rochester 25 years > 2000 transplants FACT accredited
Facilities Inpatient unit has 12 beds Day hospital on same unit: 6 chairs New facility 2012 New pediatric inpatient beds 2015
URMC Blood & Marrow Transplant Program Overall Transplant Volumes
URMC Blood and Marrow Transplant Program
URMC Blood and Marrow Transplant Program
Why are we not UCB enthusiasts?
10 years of allogeneic transplants Graft Number Related BM 36 Related PB 198 Unrelated BM 24 Unrelated PB 163 UCB 33
10 years of allogeneic transplants Graft Number Days to Median ANC500 Related BM 36 16 Related PB 198 13 Unrelated BM 24 18 Unrelated PB 163 13 UCB 33 17
10 years of allogeneic transplants Graft Number Days to Median ANC500 3 rd Quartile Days to ANC500 Related BM 36 16 21 Related PB 198 13 15 Unrelated BM 24 18 24 Unrelated PB 163 13 16 UCB 33 17 34
10 years of allogeneic transplants Graft Number Days to Median ANC500 3 rd Quartile Days to ANC500 Graft Failure Rate Related BM 36 16 21 0 % Related PB 198 13 15 2 % Unrelated BM 24 18 24 4 % Unrelated PB 163 13 16 5.7 % UCB 33 17 34 15.1 %
Autologous graft comparison The problem is not just thawing cells. Graft Number Days to Median ANC500 3 rd Quartile Days to ANC500 Graft Failure Rate Related BM 36 16 21 0 % Related PB 198 13 15 2 % Unrelated BM 24 18 24 4 % Unrelated PB 163 13 16 5.7 % UCB 33 17 34 15.1 % Autologous PB 788 11 12 0 %
Why are we not UCB enthusiasts? Delayed engraftment and graft failure is associated with high degrees of morbidity, mortality, and expense.
How do you pick a good UCB unit?
How do you pick a good UCB unit?
What information is missing? Post-thaw viability 24-48 hour post-thaw viability Post-thaw hematopoietic function
Conventional Evaluation Trypan blue dye exclusion: Identifies cells that are dead and no longer exclude molecules outside the cell membrane Done immediately post-thaw
Dyes like Trypan Blue Do Not Detect Apoptosis
Even sensitive flow dye exclusion viability assays do not detect severe metabolic stress on cells several days post-thaw
Real World UCB Results Graft Characteristic Precryo Post-thaw Median Recovery Post-thaw n Median (Range) n Median (Range) n % Correlation Coefficient of pre/post values TNC, 107/kg 434 6.7 (1.4-67.3) 435 5.7 (0.9-50.3) 434 81.1 0.96 MNC, 107/kg 216 2.8 (0.21-30.3) 383 2.1 (0.2-15.1) 197 82.8 0.83 CD34+, 105/kg 381 2.1 (0.1-29.3) 433 1.7 (0.1-18.3) 379 84.5 0.87 CFU, 104/kg 279 19.1 (0-294.0) 435 3.3 (0-105.3) 279 21.2 0.4 Biol Blood Marrow Transplant. 2011 Sep;17(9):1362-74. doi: 10.1016/j.bbmt.2011.01.011. Epub 2011 Jan 28. Total colony-forming units are a strong, independent predictor of neutrophil and platelet engraftment after unrelated umbilical cord blood transplantation: a single-center analysis of 435 cord blood transplants. Page KM 1, Zhang L, Mendizabal A, Wease S, Carter S, Gentry T, Balber AE, Kurtzberg J.
Page et al., BBMT, 2011 Graft failure occurs in approximately 20% of patients after unrelated umbilical cord blood transplantation (UCBT). Post-thaw recovery of the colony-forming unit (CFU), a biological assay reflecting functional viability of the cord blood cells was the lowest percentage (median 21.2%, mean 36.5%) of the pre-cryo value, regardless of the bank of origin. In multivariate modeling, higher CFU dosing was the only pre-cryo graft characteristic predictive of neutrophil (P =.0024) and platelet engraftment (P =. 0063). Comparatively, CD34 + and total nucleated cell (TNC) were only weakly predictive in post-thaw neutrophil and platelet engraftment models, respectively.
Estimate of National UCB Inventory with Satisfactory CFU s Page et al., BBMT, 2011
Haploidentical Donor Grafts Are An Emerging Option Competition for UCB Newer strategies do not rely on expensive, complex ex vitro cell processing procedures In vivo alloreactive lymphocyte ablation with cyclophosphamide surprisingly effective Apheresis is easy and relatively inexpensive Willing donor remains available for supplemental cell infusions
Marketing to Parents You ve Probably Seen The Ads
Opportunities For Product Differentiation. If you want to be in that business I looked at several snazzy looking web sites this morning..did not see any meaningful quality control data. Probability of family/personal use of the UBC is low. Viacord claims: > 350,000 private units in storage ~ 300 used to date Big business: $1,400,000,000 (Gross revenue, est. using retail pricing) 0.09% probability of use...ethics of marketing to anxious parents?
Enforce best practices on cord blood collection Demonstrate consistent superiority of products from your bank Provide as much HLA information as practical Provide meaningful post-thaw viability and function data Need to demonstrate better outcomes and less total transplant costs vis-a-vis haploidentical donors A Customer s Perspective: Challenges for New Cord Blood Banks