Adjuvant transfusion of donor lymphocytes (aDLT) may reduce the risk of relapse after allogeneic stem cell transplantation in high-risk AML. We performed a retrospective analysis on the safety and efficacy of aDLT in a cohort of 46 patients. To be eligible for aDLT, patients had to be in CR for at least 120 days from transplantation, off immunosuppression for ⩾ 30 days and free of GvHD. Thirty-four patients with similar disease characteristics and fulfilling the same selection criteria served as controls. Median follow-up among aDLT recipients was 7.2 years. Ten patients (22%) relapsed inspite of aDLT, as compared with 53% in the control group. Induction of GvHD was the main complication. However, non-relapse mortality was low with patients dying from infection (n = 2), severe chronic GvHD (n = 1) and secondary malignancy (n = 2). At the time of analysis, 31/46 aDLT recipients were alive in CR at a median of 5.7 years after first aDLT. Overall survival at 7 years after transplant was 67% as compared with 31% in the control group (P o 0.001). In conclusion, aDLT is safe, when given in escalating doses to a well predefined group of patients. Long-term survival can be achieved. INTRODUCTIONDespite advances in allogeneic transplantation (allogeneic stem cell transplantation; alloSCT), high-risk AML remains a disease with poor outcome, lacking optimal therapeutic strategy. In particular, patients with refractory disease or early relapse still have a poor prognosis. High-risk disease can further be defined by delayed response to chemotherapy, unfavorable karyotype or molecular genetics 1 and by a history of preceding neoplasia and/or chemotherapy.In the era of reduced intensity conditioning (RIC), high rates and a poor outcome of relapse after alloSCT (2 years overall survival (OS) 20%) 2,3 are the main causes for treatment failure in high-risk AML. Thus, effective strategies for preventing post-transplant relapse are urgently needed. As donor lymphocyte transfusion (DLT) enhances the graft-versus-leukemia (GVL) effect, it offers an attractive therapeutic option to decrease relapse-related mortality rates. The GVL potential of donor T-lymphocytes has been described in several preclinical 4,5 and clinical studies. [6][7][8] In particular, their use in the management of post-transplant relapses of chronic myeloid leukemia has been a story of success. However, despite of its desirable GVL effects, DLT may also increase the incidence and severity of GvHD. Thus, DLT protocols have to be optimized to minimize the risk of severe GvHD and maximize the benefit of the GVL effect.The establishment of RIC provided a basis for the employment of DLT in the post-transplantation period of AML therapy. There are several clinical studies supporting the positive role of DLT in the prophylaxis 9 and treatment of post-transplant relapse in AML. 2,10 Despite these encouraging data, the efficacy and the toxicity of DLT in the management of AML is still poorly assessed,

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2254 Poster Board II-231 Chronic graft-versus-host disease (cGVHD) remains a major cause of morbidity and mortality in hematopoietic transplant recipients. The mammalian target of rapamycin inhibitors (mTOR-I) sirolimus and everolimus are immunosuppressants that have activity in the prevention and treatment of acute GVHD. Sirolimus in combination with calcineurininhibitors (CNI) has also been shown to have activity in chronic GVHD, however at the cost of considerable toxicity. Since mTOR-I exert their action by blocking interleukin 2 receptor signaling and thus arresting the cells at G1 phase they are promising candidates for tolerance induction. In addition, they also have antiangiogenic and antiproliferative activity. We hypothesized that treatment of cGVHD with mTOR-I and without CNI would be more effective in inducing tolerance than the combination of both and would have a lower toxicity profile. In this retrospective analysis we report 31 consecutive patients (pts) with severe cGVHD according to the NIH consensus, in whom treatment with mTOR-I (everolimus n=20; sirolimus n=11) was initiated between 2004 and 2006, with a median follow-up after initiation of mTOR-I therapy for surviving pts of 46.5 months. Three pts terminated treatment prematurely (within 3 months after starting therapy) because of adverse events (1xsevere cough; 1xhypertriglyceridemia; 1xmouth ulcers) and they were excluded from further analysis. Of the remaining, 12 pts had de novo or quiescent cGVHD, 5 progressive cGVHD developing from acute GVHD and 11 had cGVHD following donor lymphocyte transfusions. Organ involvement included skin (scleroderma) in 21, lungs in 12, mucous membranes in 9, liver in 6, gut in 2 and eyes in 4 pts. Eighteen pts received mTOR-I in combination with steroids, three received a monotherapy and 7 pts received additional immunomodulatory drugs, no CNI however. To further reduce the risk of adverse events drug trough levels were monitored and the dosing was adjusted to low therapeutical levels (3-8 ng/ml). Eleven pts each had a complete and partial response, respectively, with an overall response rate of 78%. At the time of analysis 6 of the 15 surviving pts were complete off immunosuppression and steroids could be tapered and stopped in 5 additional pts. Best responses were seen in pts with de novo or quiescent cGvHD. Thirteen pts have died. Causes of death were: progressive cGvHD (n=5) relapse of the underlying disease (n=4), infections (n=2), secondary malignancy (n=1), unknown (n=1). No difference was observed in everolimus- and sirolimus-treated pts. With a median treatment time of 24 months (range 3 – 54 mo) the major adverse events possibly related to mTOR-I were hyperlipidaemia and impaired wound healing, especially in pts with ulcerative lesions of skin or mucous membranes. Only one of the pts developed thrombotic microangiopathy (TMA) and infectious complications were rare. In pts treated in combination with steroids frequently a shortened prothrombin time has been observed, suggesting an increased risk for thomboembolic events. Controlled trials comparing this approach with alternative strategies are warranted. Disclosures: Off Label Use:Everolimus and Sirolimus for the treatment of chronic GVHD. Jedlickova:Wyeth: Research Funding.