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Grade III - IV Acute GvHD and Treatment-Related Mortality Are Reduced Among Recipients of Larger Numbers of Donor Naïve CD8+ T-cells and Plasmacytoid Dendritic Cell Precursors in Allogeneic BM Grafts from Unrelated Donors: Results from BMT CTN 0201


Conference Paper

Waller, E.K.; Harris, W.A.; Devine, S.; Porter, D.L.; Ferrara, J.; McCarthy, J.M.; Gonzalez, C.E.; Spitzer, T.R.; Krijanovski, O.; Howard, A.; Gurgol, C.; Logan, B.; Confer, D.L.; Anasetti, C.

38th Annual EBMT (European Group for Blood and Marrow Transplantation)

Geneva, Switzerland


{Background: A subset of 161 patients from the 278 subjects randomized to receive BM grafts in the BMT CTN 0201 study had aliquots of the BM allografts analyzed at a central laboratory for the content of CD34+ progenitors and immune cell subsets by flow cytometry. Demographics, disease characteristics, conditioning regimens (all myeloablative) and GvHD immune-prophylaxis of the 161 patients were similar to the entire BMT CTN0201 population. Methods: 46 progenitor and immune cell subsets were selected for study based upon the absence of a strong correlation with another graft subset (Pearson or Spearman correlation >0.8) and a priori interest. Graft characteristics were described separately for survivors and those who died and compared using a nonparametric Mann-Whitney Wilcoxon test. P-values were not adjusted for multiple comparisons, but only covariates for which the false discovery rate (q value) <0.2 are presented. Univariate and multivariable analysis (adjusting for factors known to be associated with transplant outcomes) were used to estimate the association of graft characteristics with transplant outcomes. Results: Numbers of nucleated cells/kg, CD34+ cells/kg, CD8+ T-cells/kg, and CD4+ T-cells/kg were not significantly associated with OS. Two cell subsets in the BM graft were significantly associated with transplant outcomes with univariate p-values <0.01 and q values of <0.2: pre-plasmacytoid dendritic cells (pre-pDC) (median number 0.3 x 10E6/kg; p=0.007), and naïve CD8+ T-cells (CD8N; median number of 1.3 x 10E6/kg; p=0.009). Multivariable analysis including the content of either pre-pDC or CD8N showed better overall survival and decreased transplant-related mortality among patients receiving larger numbers of each donor cell subset. Grade ¾ acute GvHD was lower among recipients of more CD8N . Estimated 3 year OS for patients receiving > 0.3 x 10E6 pre-pDC /kg was 55% versus 35% for recipients of <0.3 x 10E6 pre-pDC /kg (p=0.025) and with 58% estimated 3 year OS for patients receiving > 1.3 x 10E6 CD8N /kg versus 35% for recipients of <1.3 x 10E6 CD8N/kg (p=0.01). Recipients of more than the median number of CD8N w significantly less grade III-IV acute GvHD 0.34 (0.12-0.96)

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