Improved Survival with Adjuvant Donor Lymphocyte Transfusions Following Allogeneic Stem Cell Transplantation after Reduced Intensity Conditioning for High-Risk AML.

Albeit clinical experience is limited 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 (24 from matched unrelated donors) 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). Twenty-four 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 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 594 days (range 113–1920). Nine patients received 1, 18 patients received 2, and 19 patients received 3 transfusions in escalating doses, containing a median of 1×10⁶, 5×10⁶ and 1×10⁷ CD3+ cells/kg at aDLT 1, 2 and 3, respectively. Reasons for giving less than 3 transfusions were GvHD, relapse or refusal of the patient. Induction of GvHD was the main complication; grade II/III acute GvHD developed in 4, and chronic GvHD in 8 patients. So far, 8 (17%) patients have relapsed despite aDLT, as compared to 42% in the control group (Chi-square: p=0.018). Two died of refractory leukemia, whereas 5 achieved a secondary CR following adoptive immunotherapy. At the time of analysis (April 2006), 39/46 patients were alive and all but one patient who is actually receiving adoptive immunotherapy are in CR at a median of 441 days post DLT. The actuarial overall survival two years after transplant is 85% as compared to 53% in the control group and at four years 78% vs. 40%, respectively (p=0.005). In conclusion, aDLT is safe, when given in escalating doses and to a selected group of patients. Results are encouraging, and improved long term survival can be achieved.