Allogeneic hematopoietic cell transplantation (HCT) offers the chance of cure for patients with non-transformed follicular lymphoma (FL), but is associated with the risk of non-relapse mortality (NRM). The aim of this study was to identify subgroups of FL patients who benefit from HCT. The European Society for Blood and Marrow Transplantation (EBMT) Minimum-Essential-A Data of 146 consecutive patients who received HCT for FL between 1998 and 2008 were extracted from the database of the German Registry 'DRST'. Diagnosis of FL was verified by contact with the reference pathologists. Estimated 1-, 2- and 5-year overall survivals (OS) were 67%, 60% and 53%, respectively. Day 100 NRM was 15%. Thirteen out of 33 patients (40%) with treatment-refractory disease (RD) at the time of transplantation survived long term. Univariate statistical analysis suggested limited chronic GvHD, donor age ⩽42 years and TBI-based conditioning in treatment refractory patients to correlate with favorable OS. Independent prognostic factors for OS were treatment-sensitive disease and limited chronic GvHD for the whole cohort, and additionally TBI-based conditioning for the treatment refractory subgroup. In contrast, patient age ⩾55 years had no impact on outcome. Thus, HCT for FL is associated with acceptable NRM, and offers a substantial chance of cure for patients with RD or advanced age. Donors ⩽42 years should be preferred if available.

Tyrosine kinase inhibitors represent today’s treatment of choice in chronic myeloid leukemia (CML). Allogeneic hematopoietic stem cell transplantation (HSCT) is regarded as salvage therapy. This prospective randomized CML-study IIIA recruited 669 patients with newly diagnosed CML between July 1997 and January 2004 from 143 centers. Of these, 427 patients were considered eligible for HSCT and were randomized by availability of a matched family donor between primary HSCT (group A; N=166 patients) and best available drug treatment (group B; N=261). Primary end point was long-term survival. Survival probabilities were not different between groups A and B (10-year survival: 0.76 (95% confidence interval (CI): 0.69–0.82) vs 0.69 (95% CI: 0.61–0.76)), but influenced by disease and transplant risk. Patients with a low transplant risk showed superior survival compared with patients with high- (P<0.001) and non-high-risk disease (P=0.047) in group B; after entering blast crisis, survival was not different with or without HSCT. Significantly more patients in group A were in molecular remission (56% vs 39%; P=0.005) and free of drug treatment (56% vs 6%; P<0.001). Differences in symptoms and Karnofsky score were not significant. In the era of tyrosine kinase inhibitors, HSCT remains a valid option when both disease and transplant risk are considered.

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.

Introduction Myelofibrosis (MF) is a clonal hematological disorder classified as a myeloproliferative neoplasm (MPN). Bone marrow fibrosis, splenomegaly and extramedullary hematopoiesis are hallmarks of the disease. Symptomatic burden is present in most of the affected patients and can compromise quality of life (QoL) by its severity. Most patients suffer from constitutional symptoms such as fatigue, pruritus, night sweats, bone pain, fever, early satiety and weight loss. Currently allogeneic stem cell transplantation (HSCT) is the only curative therapy but it is associated with a high morbidity and mortality. Infectious complications, acute and chronic GvHD are major complications which influence quality of life after transplantation. Until now, no systematic evaluation of QoL after allogeneic stem cell transplantation for myelofibrosis patients exists. Methods In this cross-sectional study we examined 77 patients (male=37, female=40) with a median age of 61 years (range, 40 to 79 years) who received an allogeneic HSCT with a busulfan-based reduced-intensity conditioning from related (n=20) or unrelated donor (n=54) in the period from 1999 to 2011. Diagnosis was primary myelofibrosis in 47 patients and secondary myelofibrosis in 30 patients. At time of transplantation all patients had advanced disease and were classified by the Lille score as high-risk (n=18), intermediate-risk (n=34) and low-risk (n=12) patients. At time of evaluation, 72 patients were in complete remission, 5 patients were not in complete remission, 25 patients suffered from GvHD (limited=14, extensive=11). The patient population was divided into four groups according to the time between transplantation and evaluation of QoL. First group = 6-36 months (n=24); second group= 36-60 months (n=16); third group = 60-85 months (n=22); fourth group 85-146 months after transplantation (n=15). QoL was measured by using the two validated questionnaires FACT-BMT and MPN-SAF. By means of statistical analysis (SPSS; ANCOVA) it was examined whether there are significant differences between the groups. Results According to the MPN-SAF Total Symptom score (the lower the score the better is the Result: possible range= 0-100, the mean scores of the groups one to four are as followed: group1: 18.9 (SD =11.3), group2: 21.1 (SD=17.9), group 3:19.3 (SD=15.5) and group 4: 18.9 (SD=12.4). There were no significant differences between the groups (p=0,962). Unfortunately no MPN-SAF Total Symptoms score was available before transplantation, but according to the mean value of MPN described in the literature (mean=25.3; SD=17.2) the mean score after transplantation (mean=19.5; SD=14.0) of our study population was lower. The mean scores of the FACT-BMT from group one to four were 115.3 (SD=16.6); 120.9 (SD=17.5); 112.4 (SD=15.5) and 115.3 (SD=20.9) There were also no significant differences between the 4 groups (p=0.541). We investigated whether there are significant differences of the results in both questionnaires regarding gender (male/female), donor (unrelated/related), GvHD (yes/no), HLA (matched/mismatched), primary or secondary MF (post-PV/post-ET/PMF), remission (complete/not complete), but none of the variables did influence QoL significantly. The subscales BMTS, FACT-G, and its subscales Physical Well-Being (PWB), Functional Well-Being (FWB), Emotional Well-Being (EWB), Social Well-Being (SWB), of the FACT-BMT were calculated and analyzed by ANCOVA. No significant differences were found among the groups. Comparing the mean value of the FACT-G (mean=85.7; SD=13,1; range= 60-108)and its subscales PWB (mean=22.7; SD= 4.5), SWB (mean=22.4; SD=4.7), EWB (mean 19.9; SD=3.1), FWB (mean=20.6; SD=4.7) of our entire patient population with the mean value of a normal population FACT-G (mean=80.1; SD=18.1; range= 15.4-108), PWB (mean=22.7; SD= 5.4), SWB (mean= 19.1; SD=6.8), EWB (mean=19.9; SD=4.8) and FWB (mean=18.5; SD=6.8) our population has even the same or higher scores. Conclusion This cross-sectional study shows that after dose reduced allogeneic stem cell transplantation in MF-patients Physical and Emotional Well Being is almost as good as that of the normal healthy population whereas Social and Functional Well Being seem to be classified as even better than that of a normal population. Disclosures: No relevant conflicts of interest to declare.

A total of 20 patients enrolled in a multicenter phase II dose escalation study of radioimmunotherapy (RIT) using yttrium-90-ibritumomab tiuxetan at two dose levels (22 and 30 MBq/kg) in 10 patients, combined with reduced intensity conditioning (RIC) using fludarabine, melphalan and alemtuzumab followed by allogeneic hematopoietic cell transplantation (HCT) from either matched-related (n=5) or matched-unrelated donors (n=15). Postgrafting immunosuppression with cyclosporine was administered. Diagnoses were diffuse large B-cell lymphoma (n=13), transformed CLL (n=4), blastic mantle cell lymphoma (n=2) and follicular lymphoma grade 3 (n=1). Median age was 51 (range, 29–69) years. All patients were high risk with relapsed/refractory disease or relapse after preceding autologous HCT. Median follow-up of patients alive was 1115 (range, 1006–1252) days. No directly RIT-related toxicities were observed. The cumulative incidence of non-relapse mortality was 30%. Incidences of grade II–IV acute and chronic GvHD was 45% and 70%, respectively. Kaplan–Meier estimated 3-year OS and EFS were 20% for both dose levels. In conclusion, dose escalation of RIT and combined use with RIC is feasible with no additional toxicity due to dose escalation. This study is registered on http://clinicaltrials.gov as NCT00302757.

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.