Lineage‐specific engraftment and outcomes after T‐cell‐depleted peripheral blood stem cell transplant with Flu/Cy/TBI conditioning

Abstract

Sixty patients with haematological malignancies received a myeloablative regimen of total body irradiation, cyclophosphamide and fludarabine followed by a T-cell-depleted peripheral blood stem cell transplant from a human leucocyte antigen identical sibling. To improve donor immune function, 1 x 10(7) CD3+ cells/kg were added-back between d 45 and 100. T-cell and myeloid chimaerism were monitored regularly to evaluate the effect of T-cell chimaerism on outcome. The major factor affecting outcome was disease risk, with significantly lower relapse and higher survival in 29 standard risk (SR) patients compared with 31 patients at high risk (HR) for treatment failure (relapse 4.8 +/- 5% vs. 59 +/- 11%, P < 0.0001, and overall survival 93 +/- 5% vs. 39 +/- 10%, P < 0.0001, respectively). Donor myeloid chimaerism reached > or = 95% within 14 d of transplant, but in the first several months, donor T-cell chimaerism was frequently mixed. Full T-cell chimaerism was significantly more frequent in HR vs. SR patients. Landmark analysis at days 30 and 90 in HR patients with mixed versus full T-cell chimaerism, showed relapse probabilities of 50.5 +/- 14% vs. 70 +/- 16% (P = 0.62) and 34.4 +/- 20% vs. 58.8 +/- 15% (P = 0.32) respectively. Early full T-cell engraftment correlated with development of severe acute graft-versus-host disease (GVHD). However, mixed T-cell chimaerism was favourable for reducing GVHD, and did not affect relapse in this small series.