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

Abstract

Graft failure occurs in approximately 20% of patients after unrelated umbilical cord blood transplantation (UCBT). This could be because of inadequate potency of the cord blood unit (CBU). To this end, we investigated the impact of graft characteristics on engraftment and survival of 435 primarily pediatric (median age: 5.3 years) patients receiving a single-unit unrelated UCBT after myeloablative conditioning from 2000 to 2008. Pre-cryopreservation (pre-cryo) graft characteristics were provided by the banks. Post-thaw parameters were measured on dextran/albumin-washed grafts. Post-thaw recovery of the colony-forming unit (CFU), a biological assay reflecting functional viability of the cord blood cells was the lowest percent age (median 21.2%, mean 36.5%) of the pre-cryo value, regardless of the bank of origin. The cumulative incidences of neutrophil and platelet engraftment were 76.9% (95%, confidence interval [CI], 71.3%-82.5%) and 55% (95% CI, 49.3%-60.7%), respectively. Univariate and separate multivariate models using pre-cryo and post-thaw datasets including clinical parameters identified predictors of engraftment and survival. In multivariate modeling, higher CFU dosing was the only pre-cryo graft characteristic predictive of neutrophil (P = .0024) and platelet engraftment (P = .0063). In the post-thaw model, CFU dose best predicted neutrophil and platelet engraftment (both P < .0001). Comparatively, CD34(+) and total nucleated cell (TNC) were only weakly predictive in post-thaw neutrophil and platelet engraftment models, respectively. In conclusion, CFU dose is a strong independent predictor of engraftment after unrelated UCBT and should be used to assess potency when selecting CBUs for transplantation.

Early peripheral blood and T-cell chimerism dynamics after umbilical cord blood transplantation supported with haploidentical cells

“…28,29 Various mechanisms have been associated with CB graft failure, including unit cell content, clonogenic capacity of CB progenitors, degree of HLA mismatch, presence of host anti-HLA antibodies, disease status at trasplant and so on. [16][17][18] In our series, poor post-thawing growth of colony forming units was most likely related to CB graft failure in 3 cases, as well as HLA-antibodies directed against CB antigens in one case. Therefore, we believe that both post-thawing CB colony forming units assays and detection of HLA-antibodies should be used as criteria for unit selection, as previously suggested.…”

“…BM chimerism on day þ 30 of these cases showed a median of 100% of CB cells (range 75-100%). Median time to neutrophil engraftment in this group was 19 days (range [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29].…”

“…Median time for neutrophil engraftment in this group was 13 days. [10][11][12][13][14][15][16][17][18][19] There were no significant differences between patients from standard and early engraftment groups regarding age, gender, diagnosis, disease status at transplant, previous therapy, CB-recipient ABO compatibility, CB-recipient HLA mismatch, TPD-recipient HLA mismatch, CB TNC and CD34 þ cells, TPD TNC and CD3 þ cells, CB colony forming units and CB bank origin.…”

“…[13][14][15] From the extensive experience with CB transplantation, various risk factors have been associated with CB graft failure. [16][17][18] Once transplantation has been performed, early detection of graft failure is important to start rapid therapeutic measures such as immunomodulation and to launch a second transplant when appropriate as soon as possible. With this objective, chimerism studies performed in the early post-transplant period have been shown to facilitate prediction of engraftment outcome in different allogeneic SCT settings including CB SCT.…”

Expression of a Surface Antigen (MA6) by Peripheral Blood CD34+Cells Is Correlated with Improved Platelet Engraftment and May Explain Delayed Platelet Engraftment Following Cord Blood Transplantation

“…While clinical data suggest that the time to platelet engraftment is correlated with the dose of CD34 + hematopoietic progenitor cells transplanted [1,2], other measures of hematopoietic progenitors contained within the transplanted tissue have also shown some correlation [3][4][5][6][7][8]. Lineage-committed MK progenitors can be characterized by in vitro colony-forming assays and their generation of burst-and colony-forming units (BFU-MK and CFU-MK, respectively) [9][10][11][12].…”