Post Thaw Colony Forming Units (CFU) Is a Strong Independent Predictor of Engraftment after Unrelated Donor Umbilical Cord Blood Transplantation (UCBT).
Background: Unrelated donor umbilical cord blood is an acceptable graft source for patients lacking related donors. However, a non-engraftment rate of approximately 20% despite adequate total nucleated cell (TNC) dose remains a barrier to the overall success of UCBT. Of various patient and graft characteristics that may influence engraftment, identifying an assay predictive of cord blood unit (CBU) potency and overall engraftment would be beneficial.
Methods: Pre-cryopreservation (pre-cryo) and post-thaw graft characteristics were available on 423 UCBT performed at our institution between 2/11/2000 and 5/1/2007. The units were obtained from 16 US public cord blood banks and were selected by pre-cryo cell dose and HLA matching. Pre-cryo data (TNC, CD34 cells and CFU) was provided by the cord blood bank as part of routine banking practices. All units were thawed in the Duke Stem Cell Laboratory (SCL). Post-thaw testing (TNC, CD34, CFU) was performed by consistent personnel in the SCL after thaw and washing with Dextran/Albumin as described previously by Rubinstein et al. Univariate and multivariate analyses were performed to identify significant pre-cryo, post-thaw, and baseline factors predictive of neutrophil and platelet engraftment.
Results: Of the 423 evaluable patients, 68% had malignancies, 61% were males, 73% were Caucasian and 38% were CMV+. The grafts were HLA (93%), sex (50%) or racially (24%) mismatched with the patients. There was excellent correlation between pre-cryo and post-thaw TNC (r2=0.92) and CD34 (r2=0.68) content, but much weaker correlation for CFUs (r2=0.27). In univariate analysis, age (≤5 years), disease (non-malignant), weight (≤12 kg), CMV status (negative), recipient ethnicity (Caucasian), HLA match (5/6 or 6/6) and pre-cryo/post-thaw TNC (larger), pre-cryo/post-thaw CD34 (larger) and pre-cryo/post-thaw CFU (larger) were predictive of both neutrophil and platelet engraftment. Multivariate analysis of parameters are presented in Table 1. In the overall multivariate analysis of neutrophil engraftment, Male units (p=0.01), 5/6 or 6/6 HLA match (p=0.02), larger post-thaw CD34 (p=0.02) and larger post-thaw CFU (<0.0001) were significant. For platelet engraftment, Caucasian recipients (p=0.006) and larger post-thaw CFU (p=0.002) were the only predictive parameters.
Conclusions: Post-thaw CFUs are a strong independent predictor of neutrophil and platelet engraftment after UCBT. This assay could be tested on a CBU segment and used as a marker of potency for graft selection.
Factors Predictive of Neutrophil and Platelet Engraftment in Multivariate Analysis of Graft/Recipient Characteristics. Neutrophil Engraftment Platelet Engraftment Pre−Cryopreservation Multivariate Model (p−value) CD34+ (0.0046), Recipient CMV (0.0138), CFU (0.0337), Unit Sex (0.0393) Recipient ethnicity (0.0052), TNC (0.0173), CFU (0.0324) Post−Thaw Multivariate Model (p−value) CFU (<0.0001), CD34 (0.0013), HLA match (0.0065) CFU (<0.0001), HLA match (0.0117), Recipient ethnicity (0.0135) Overall Multivariate Model (p−value) Post thaw CFU (<0.0001), Unit Sex (0.0131), HLA match (0.0186), Post thaw CD34 (0.02) Recipient ethnicity (0.0063), Post thaw CFU (0.002)
Page, KM; Mendizabal, A; Waters-Pick, B; Avrutsky, S; Reese, M; Prasad, V; Kurtzberg, J
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