Comparison of two T-cell depletion methods of grafts from alternative donors for allogeneic hematopoietic cell transplantation of patients with fanconi anemia.

Abstract

Background & Aim Our program has used 2 T-cell depleted HSCT approaches for patients with FA for transplants from donors other than HLA matched siblings: 1) the Isolex 300i Magnetic Cell Selection System (Baxter) + sheep RBC depletion (E-) (TCD1) was used to achieve an approximate 5 log10 depletion of CD3+ cells, and (2) the CliniMACS device (Miltenyi; TCD2) was used as a sole TCD method with an approximate 4.5 log10 depletion of CD3+cells. Methods, Results & Conclusion We retrospectively reviewed charts of consecutive patients with FA who received a first HCT from alternative donors. We identified 42 patients with aplastic anemia, MDS or AML, 24 who received TCD1 (1999-2009) and 18 who received TCD2 (2010-present). Most patients in TCD1 received a TBI-based conditioning, while most in TCD2 received busulfan-based conditioning. Donors were matched unrelated, mismatched unrelated, or mismatched related. Because of the differences in the treatment periods, conditioning regimens, and disease breakdown, we analyzed the data specifically related to the T-cell depletion. Distributions of continuous variables were compared using a Mann-Whitney-Wilcoxon test, while binary and categorical variables were compared using a Fisher's exact test. Grafts were G-CSF mobilized peripheral blood progenitor cells. T-cell depletions were performed as described. Table 1 provides demographics, cell doses and hematologic recovery data for TCD1 and TCD2. Median CD34 cell doses of the grafts did not differ significantly while median CD3 dose did (N=0.048). All but one patient engrafted. Two patients receiving grafts from mismatched unrelated donors developed grade 2-4 acute GvHD in TCD1, none in TCD2. Neutrophil engraftment did not significantly differ while platelet engraftment was more rapid with TCD1 (N=0.0045). CD4 recovery (Abs CD4 >200) and PHA recovery (50th%ile) differences were comparable (NS). In conclusion, no difference were noted between the Isolex E- T-cell depletion and the CliniMACS CD34 selection system, except for a more rapid platelet reconstitution for the CliniMACS column. There was no difference in risks of graft rejection and GvHD, and immune reconstitution was comparable in both cohorts. Future plans include the comparison of these methods to the TCR alpha beta depletion in this patient population.