CD34+ Cell Dose Is the Major Cell Dose Determinant of Myeloid Engraftment After Single Umbilical Cord Blood Transplantation (sUCBT) for Adult Patients with High-Risk Hematologic Malignancies

Abstract 1339

There is conflicting data on the capacity of single-unit UD-UCBT to achieve stable engraftment. Moreover, criteria for UCB unit selection in adults with hematologic malignancies undergoing sUCBT are mainly based on registry studies that in most cases lack homogeneity in patient selection and management, analyse pooled data from adults and children with benign conditions and malignant disorders, and lack of specific information on potentially relevant characteristics of the UCB unit. The aim of the present study was to identify by multivariate analysis relevant prognostic factors of myeloid engraftment in a large series of adults with high-risk hematologic malignancies undergoing sUCBT after myeloablative conditioning at a single institution. One hundred and seventy-eight consecutive patients (112 males, 66 females) with median age 32 yr (range, 15–52) who underwent single-unit UD-UCBT after myeloablative conditioning at Hospital Universitario La Fe from 1997 until 2010 were included in the analysis. One hundred and twenty-four patients (70%) had acute leukemia (62 AML, 62 ALL) while the remaining 54 patients (30%) had a variety of high-risk hematological malignancies. Disease stage at transplantation by CIBMTR criteria was early in 75 (42%), intermediate in 44 (25%) and advanced in 59 (33%). Conditioning regimen consisted of thiotepa, busulfan (oral, 43; IV, 135), cyclophosphamide (72) or fludarabine (106), and anti-thymocyte globulin. Cyclosporine and prednisone (128) or cyclosporine and mycophenolate mofetil (50) were used for graft-versus-host disease (GVHD) prophylaxis. Most patients (94%) received an HLA-mismatched single UCB unit with 1 (29%), 2 (64%) or 3 (1%) mismatches with the recipient. The median number of total nucleated cells (TNC) was 2.9 × 10⁷/kg (range, 1–7.5) at cryopreservation and 2.4 × 10⁷/kg (range, 1–5.9) at infusion. Median number of CD34+ cells was 1.6 × 10⁵/kg (range, 0.2–6.6) at cryopreservation and 1.2 × 10⁷/kg (range, 1–5.9) at infusion. Eight patients died early without engraftment and five had primary graft failure. The remaining 165 patients experienced myeloid engraftment with full donor chimerism at a median time of 22 days (range, 11 – 57) and the cumulative incidence (CI) of myeloid engraftment at 57 days was 93%. Disease stage at time of transplantation was the only transplant or patient-related characteristic affecting engraftment. The CI of myeloid engraftment for patients transplanted in advanced and non- advanced stage was 86% and 96%, respectively (P = 0.002). All other variables with an influence on neutrophil recovery were related to UCB unit cell content. Cell dose information at time of freezing offered by UCB banks and that obtained at time of infusion were analyzed separately. For variables considered at time of UCB unit selection (data provided by UCB banks), only CD34⁺ cell dose with a best cut-off at 1.5 × 10⁵/kg had a statistically significant and independent impact on multivariate analysis. CI rates of myeloid engraftment for patients receiving UCB units with CD34⁺ cells above and below 1.5 × 10⁵/kg, were 96% and 90% respectively (P = 0.003). At time of infusion, cell dose measurements showing a significant and independent influence on myeloid engraftment in multivariate analysis were CD34⁺ cell dose with a best cut-off at 1 × 10⁵/kg (P < 0,01), CFU-GM with a best cut-off at 2 × 10⁴/kg (P < 0,01) and lymphocyte dose with a best cut-off at 1 × 10⁷/kg (P < 0,01). Neither TNC dose at cryopreservation or at infusion nor degree of HLA disparity between the UCB unit and the recipient had any impact on myeloid engraftment.These results confirm that sUCBT after busulfan-based myeloablative conditioning offers high rates of myeloid engraftment in adults with hematological malignancies. UCB cell dose, especially CD34+ cell dose, is the most important predictor of engraftment in adults with hematologic malignancies undergoing sUCBT. CD34⁺ cell dose at cryopreservation provided by UCB banks, although not fully standardized, offers more valuable information than TNC dose and should be used for UCB unit selection.