Higher Cell Dose and CD34+ Content Improves Engraftment Following Unrelated Donor Cord Blood Transplantation (CBT): A Report of the National Marrow Donor Program (NMDP) Cord Blood (CB) Experience.

Cord blood has become an important alternative unrelated donor allogeneic hematopoietic stem cell source. The NMDP has developed a comprehensive coordinated network of CB banks, search coordinating center and transplant programs with prospective collection of outcome data coordinated by the NMDP (now CIBMTR). Critical to CBT has been limited cell dose with resultant prolonged engraftment time. The NMDP cord blood inventory has both total nucleated cell count (TNC) and CD34+ quantification on the units, allowing a comparison of the relative utility of either measure in identifying units that would result in rapid engraftment. We report a retrospective review of the NMDP CBT experience, analyzing the impact of graft characteristics with engraftment and survival. Between 03/2000 and 03/2004, 12 NMDP banks (total inventory 31,976 units) released CB units to 144 patients at 44 NMDP transplant programs included in this analysis (median f/u 217 days, 26–1204 days). The median recipient age was 8.2 years (0.2–63.1 years, 38 were ≥ 15 years) and median weight was 27 kg (3–158 kg: 26% > 57 kg). Transplant indications included malignancy in 113 (ALL 36, AML 43, MDS 13, other 21), metabolic disorders (8) immune disorders (9) histiocytic disorders (3), erythrocytic abnormalities (6), platelet abnormality (1), SAA (3) and other nonmalignant disease (1). Most malignancy patients had advanced disease (60 patients (53%) were beyond CR2 or in relapse). The median prefreeze TNC was 4.4 x 10⁷/kg (0.3–433 x 10⁷/kg) and CD34+ cells 7.9 x 10⁵/kg (1.1–68.5 x 10⁵/kg) in units selected for transplantation. Thus the median CB TNC was 142 x 10⁷ cells (54–396 x 10⁷ cells); only 12 units under 80 x 10⁷ cells were used. 114 patients engrafted by day +42 post CBT with median time to neutrophil recovery > 500/mm³ of 21 days (8–62 days) and platelet count > 20,000 x 10⁹/L of 64 days (12–473) respectively. 1-year survival and DFS were 39% ± 9% and 38% ± 9% respectively. Relapse rate was 16% ± 8% in this high risk population. The 100-day TRM rate was 26% ± 7%. For patients > 15 yrs, TRM was 42% ± 16% vs. 21% ± 8% for patients < 15 years. Higher cell dose was associated with faster neutrophil and platelet engraftment. Units with both high TNC/kg and high CD34+/kg were associated with more rapid engraftment vs. those with only high TNC or high CD34+ or neither (p<0.0001). In multivariate analysis, recipient age > 15 years led to poorer survival (RR 3.4 (1.7, 6.7)) and DFS (RR 2.8 (1.5, 5.2)) compared to younger children, especially those < 3 years (p<0.0001). Male grafts into females yielded poorer survival than other gender combinations. These data confirm that CB is a valuable alternative unrelated donor histocompatible stem cell source. Since transplantation using CB units containing both high TNC and CD34+ content resulted in more rapid engraftment, optimal CB inventory should strive for both high cell count (> 80 x 10⁷ cells) and high CD34+ cell content.