Aldemar Montero

Imatinib synergizes with donor lymphocyte infusions to achieve rapid molecular remission of CML relapsing after allogeneic stem cell transplantation

Summary:Donor lymphocyte infusions (DLI) have been the mainstay of treatment for chronic myeloid leukemia (CML) relapsing after allogeneic stem cell transplantation (allo-SCT). Imatinib mesylate (IM) is also effective in these patients. However, advanced phase relapse (APRel) responds poorly with either treatment. To test the possibility that combinations of DLI and IM might be more effective, 37 patients with CML relapsing after allo-SCT between August 1994 and May 2004 were studied. Ten had molecular relapse (MRel), 14 hematological relapse (HRel) and 13 APRel. Thirteen received DLI, 9 IM and 11 DLI+IM. Four patients received DLI+IM but not concurrently. Thirty (81%) patients responded (actuarial survival and current leukemia-free survival of 80.6±6.7% and 69.1±7.7%). Of 30 patients, 26 are in molecular remission (MR), median follow-up of 1226 days (range 249–3257) since relapse. Ten of 11 patients (including four with APRel) treated with DLI+IM achieved MR in 3 months and all are alive in MR. In contrast, only two of 22 treated with either modality (1/13 DLI and 1/9 IM) achieved MR at 3 months, 15 are alive, 11 in MR. Four patients receiving nonconcurrent DLI+IM are also alive in MR. In conclusion, DLI appears to synergize with IM to induce rapid and durable MR.

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

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 × 107 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 ≥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.