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<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.

Allogeneic hematopoietic stem cell transplantation is one curative treatment for hematological malignancies, but is compromised by life-threatening complications, such as severe acute graft-versus-host disease (aGvHD). Prediction of severe aGvHD as early as possible is crucial to allow timely initiation of treatment. Here we report on a multicentre validation of an aGvHD-specific urinary proteomic classifier (aGvHD_MS17) in 423 patients. Samples (n=1106) were collected prospectively between day +7 and day +130 and analyzed using capillary electrophoresis coupled on-line to mass spectrometry. Integration of aGvHD_MS17 analysis with demographic and clinical variables using a logistic regression model led to correct classification of patients developing severe aGvHD 14 days before any clinical signs with 82.4% sensitivity and 77.3% specificity. Multivariate regression analysis showed that aGvHD_MS17 positivity was the only strong predictor for aGvHD grade III or IV (P<0.0001). The classifier consists of 17 peptides derived from albumin, β2-microglobulin, CD99, fibronectin and various collagen α-chains, indicating inflammation, activation of T cells and changes in the extracellular matrix as early signs of GvHD-induced organ damage. This study is currently the largest demonstration of accurate and investigator-independent prediction of patients at risk for severe aGvHD, thus allowing preemptive therapy based on proteomic profiling.

Abstract 4573 Patients with acute myeloid leukemia (AML) with FLT-3 mutations have an extremely high risk of relapse after conventional chemotherapy. The role of allogeneic stem cell transplantation (SCT) for this patient cohort has been discussed controversially in recent years. This retrospective analysis reports our cumulative experience in a cohort of 42 consecutive patients (age 17–70, median 51 years) allografted for FLT-3 positive AML in a single centre. In more than 80% a FLAMSA-RIC based conditioning regimen was used, in 5% BCNU/Melphalan/Fludarabine, and in 14% conventional radiation- or Busulfan- based regimens. Most patients received mobilized peripheral blood stem cells as graft and 10 patients had a sibling and 32 an unrelated donor (MUD), respectively. Half of the patients were allografted in complete remission and twenty with active, mostly refractory disease. With a median follow-up for surviving patients of nearly 2 years (range 64 – 1746 days) the Kaplan-Meyer procedure estimates a 48% probability of survival at 2 y after transplantation. Interestingly, there is no difference what so ever in survival if patients had an identical sibling donor or a MUD. Similarly, neither patient age below or above the median, nor the applied conditioning regimen did affect the outcome. The only significant variable for improved survival was being in complete remission at transplantation with a 2-year overall survival probability of 60% as compared to 30% for patients with active disease. Thirteen patients (31%) relapsed after allografting, which is substantially lower as to what is reported after conventional chemotherapy. Three of these patients could be salvaged by a second transplant, whereas 10 patients finally died from leukaemia. Non relapse mortality was 24% with 2 patients dying from acute GVHD, 7 from infections and 1 from suicide, despite being well physically. In conclusion, our data support the notion that allogeneic SCT is a highly effective treatment option for patients with AML and FLT-3 mutations and that, if the patient is eligible, it should be undertaken whenever possible in 1. complete remission. However, even patients with primary induction failure have a reasonable chance to be salvaged by allogeneic SCT. Disclosures: No relevant conflicts of interest to declare.

In AML, a complex aberrant karyotype is associated with poor response to chemotherapy and dismal prognosis. We prospectively studied the concept of allogeneic haematopoietic SCT (HSCT), performed early and regardless of response to induction treatment in patients with complex karyotype AML (CK-AML). The preparative regimen consisted of fludarabine, Ara-C and amsacrine (FLAMSA) chemotherapy, followed by reduced intensity conditioning (RIC) 3 days later. In vivo T-cell depletion by anti-thymocyte globulin was used to protect from early GvHD, and prophylactic donor lymphocyte transfusion was given from day+120 to augment the GvL effect, once tolerance was established. Eighteen consecutive patients with CK-AML (median age: 53 years) received HSCT from related (n=7) or unrelated (n=11) donors. Before FLAMSA–RIC, nine patients each had received one and two induction courses. Stage at start of FLAMSA–RIC was CR/CRi (n=8) or persistent disease (n=10). Following HSCT, 16 patients achieved CR. After a follow-up of 51 months, 11 patients are alive in CR, whereas seven have died in remission (n=3), or from leukaemia (n=4). Cumulative incidence of relapse, non-relapse mortality, acute GvHD⩾II and chronic GvHD were 0.222±0.098, 0.235±0.104, 0.367±0.120 and 0.481±0.123, respectively. Four-year survival from HSCT is 61%. Early HSCT following FLAMSA–RIC may improve the outcome of this unfavourable AML subgroup.

Primary and post-ET/PV-myelofibrosis (MF) is a rare myeloproliferative disorder with a very variable, on the long term always fatal course. After allogeneic hematopoietic cell transplantation (alloHCT) encouraging short term survival has been reported. We present data from 57 consecutive transplants for MF in our institution, demonstrating that close monitoring of the post-transplant course is warranted.

To analyze the outcome of solid organ transplantation (SOT) in patients who had undergone allogeneic hematopoietic stem cell transplantation (HSCT), a questionnaire survey was carried out within 107 European Group of Blood and Marrow Transplantation centers. This study covered HSCT between 1984 and 2007 in Europe. Forty-five SOT in 40 patients were reported. Fifteen liver, 15 renal, 13 lung, 1 heart and 1 skin transplantations were performed in 28 centers. Overall survival (OS) of patients after SOT was 78% at 5 years (95% confidence interval [CI], 64% to 92%). OS at 5 years was 100% for renal, 71% (95% CI, 46% to 96%) for liver and 63% (95% CI, 23% to 100%) for lung transplant recipients. The 2-year-incidence of SOT failure was 20% (95% CI, 4% to 36%) in patients with graft-versus-host disease (GvHD) and 7% (95% CI, 0% to 21%) in patients without GvHD before SOT. The relapse incidence for underlying malignant diseases was 4% at 5 years (95% CI, 0% to 12%). In summary, this study shows that selected patients receiving SOT after HSCT have a remarkably good overall and organ survival. These data indicate that SOT should be considered in selected patients with single organ failure after HSCT.

Abstract Abstract 2348 Stem cell transplantation (SCT) will continue to be a treatment option for patients with chronic myeloid leukemia, despite the introduction of tyrosine kinase inhibitors (TKI). However, many patients will have received prior therapy with TKI, including Nilotinib or Dasatinib at the time of allogeneic SCT. While the use of Imatinib prior to SCT seems to have no adverse impact on the outcome of allogeneic SCT little is known on the impact of prior use of second generation TKI. Therefore we conducted a retrospective registry study and identified 56 patients with CML who received an allotransplant after having been treated with Nilotinib and/or Dasatinib. Best responses to second generation TKI were major molecular response in 11%, complete cytogenetic response in 7%, partial cytogenetic response in 18%, complete hematologic remission in 25% and no response in 34%, respectively. At SCT, 37% of the patients were in accelerated or in blast phase, 36% in CP2 or higher and 27% in first chronic phase. Graft failure occurred in two patients. The median follow-up for surviving patients is 19 months. At 24 months the estimated non-relapse mortality was 33% and the relapse incidence 15%. Probability of survival is more than 85% at 2 years in patients transplanted in CP1. In univariate analysis there was a non significant trend in favor for pretreatment with Nilotinib as compared to the other groups. However, in multivariate analysis only stage of the disease was a predictor for survival. With respect to overall survival no significant differences could be identified for the following variables: patient age, donor type, stem cell source, intensity of the conditioning, time diagnosis to transplant, in or ex vivo T-cell depletion, response to treatment with second generation TKI. Patients transplanted in blast crisis had a significant higher risk of non relapse mortality. In summary, despite the shortcomings of a retrospective study, the data reported clearly show the feasibility and efficacy of allo SCT in patients pretreated with second generation TKI and it should be emphasized that the timing of allogeneic stem cell transplantation remains crucial to avoid unacceptable high treatment related mortality. Disclosures: Ekblom: Bristol-Myers Squibb: Honoraria.