Long Term Follow-up and Matched Pair Analysis of Adjuvant Donor Lymphocyte Transfusions Following Allogeneic Stem Cell Transplantation after Reduced Intensity Conditioning for High-Risk AML.

Adjuvant transfusion of donor lymphocytes (aDLT) may reduce the risk of relapse after allogeneic stem cell transplantation. We report our data on aDLT in high-risk AML. Cells were given within a prospective protocol that contained a sequence of chemotherapy, reduced intensity conditioning for allogeneic transplantation, and aDLT. For aDLT, patients had to be in CR at least 120 days from transplantation, off immunosuppression and free of GvHD. 30% of patients (n=46) alive at day +120 fulfilled the criteria for aDLT. They had been transplanted for refractory (n=11) or relapsed leukemia (n=24) or in CR1 because of unfavourable cytogenetics (n=7) or other unfavourable criteria (n=2) or in CR2 with unfavourable cytogenetics (n=2). 24 patients had an unfavourable karyotype, 10 with complex aberrations. Thirty-one patients with similar disease characteristics and fulfilling similar selection criteria (being alive in CR at d +120, no cGVHD and no history of aGVHD> II°) transplanted during the same time period served as control. Of these, 10 pts. were transplanted at a different center not using aDLT and 21 at the center in Wiesbaden during 2000 and 2002 prior to the introduction of the protocol at this center. The median time from transplant to first aDLT was 160 days (range 71–303). Median follow up of the surviving transfused patients is 3.6 years (range 1.8–7.8). Seven patients received 1, 15 patients received 2, and 24 patients received 3 transfusions in escalating doses, containing a median of 1x10⁶, 5x10⁶ and 1x10⁷ CD3+ cells/kg at aDLT 1, 2 and 3, respectively. Reasons for giving less than 3 transfusions were GvHD, relapse or patient’s refusal. Induction of GvHD was the main complication; grade II/III acute GvHD developed in 4, and chronic GvHD in 8 patients. So far, 9 (19.6%) patients have relapsed despite aDLT, as compared to 52.9% in the control group (Fisher-exact: p=0.004). Of these, 8 pts. finally died despite adoptive immunotherapy and only one patient is now surviving more than 3 years after relapse was treated by a second transplantation. Non relapse mortality post DLT was low with patients dying from infection, severe cGvHD, and secondary solid tumour one each. At the time of analysis, 35/46 patients are alive and all are in CR at a median of 3.2 years post first DLT. The actuarial overall survival four years after transplant is 79% as compared to 34% in the control group and at six years 63% vs. 31%, respectively (p=0.000). In conclusion, aDLT is safe, when given in escalating doses and to a selected group of patients. Results are encouraging, and improved long term leukemia-free survival can be achieved.