ALBERT

Description: Introduction. Chronic lymphocytic leukemia (CLL) has typically an indolent course but can undergo transformation into a more aggressive lymphoma so called Richter's syndrome. While the advent of novel targeted therapies is transforming the management of patients with CLL, these drugs failed to prevent the risk of RS. RS is associated with a very poor outcome and is thus becoming the main obstacle to long term CLL control. Autologous (auto-) and allogeneic (allo-) hematopoietic stem-cell transplantation (-SCT) have been recommended as the treatment of choice in eligible patients with clonally related RS (Rossi Blood 2018) but previous experience is still limited to less than 50 cases. We here aimed to investigate the safety and efficacy of both auto- and allo-SCT for patients with RS in a large cohort in a period overlapping the advent of novel agents. Methods. We report on a retrospective study of consecutive adult patients with RS who underwent auto- or allo-SCT between 2008 and 2018 in EBMT centers. Results. A total of 197 patients (M/F= 133/64) were included in the present study; 125 patients received allo-SCT and 72 auto-SCT. The main difference between these 2 cohorts was the median age at transplant that was lower in the allo- than in the auto-SCT group (median age 57 [18-71] vs 61 [39-74] years, p = 0.006). Regarding the allo-SCT cohort, median time from RS diagnosis to SCT was 10 months [1.1-322.8] and 54.2% had received 〉2 therapeutic lines for RS. At allo-SCT, 60 (48.4%) were in CR and 53 (42.7%) in PR or SD. Most patients received reduced intensity conditioning (RIC) regimen (n= 90, 72.6%) and peripheral blood (89.6%) as stem cell source. Donors were related (matched, n=40 (33%) or mismatched, n=4 (3%)) or unrelated (matched, n= 76 (61%) and mismatched, n=4 (3%). A total of 41 patients (33.6%) received total body irradiation (TBI). With a median follow-up of 48 months, 2-year OS was 46% (36-55%) and 2-year PFS 38% (28-48%). Two-year cumulative incidence of relapse (CIR) was 31% (22-40%) as was the 2-year NRM (Figure 1). Two-year CIR was significantly reduced in patients with ≤2 therapeutic lines for RS (12% (1-22%) vs 41% (26-55%); p=0.005). Performance status affected 2-y PFS (24% (7-42%) if Karnofsky index

Description: Objectives: In patients with refractory chronic lymphocytic leukemia (CLL), the potential to cure is unique to allogeneic stem cell transplantation (HSCT). Clearance of minimal residual disease by suspected graft-versus-leukemia effects has been described elegantly and documented in several independent patient cohorts. Yet data from large numbers of patients which support the concept of cure by allogeneic transplantation have not been published. With the advent of new targeted therapies for patients with advanced chemo-refractory CLL, this information becomes crucial for clinical decision making and patient counselling. Therefore, we aimed at the description of long-term survival outcomes, and the estimation of excess mortality compared to the age- and sex-matched general population. Patients and Methods: Data from patients with CLL who had received a first allogeneic HSCT from an HLA-identical sibling (SIB) or alternative donor between January 2000 and December 2010, and who were registered with the EBMT database, were analyzed. Patients with Richter's syndrome and with syngeneic donors were excluded from this analysis. Survival probabilities were calculated by means of the Kaplan-Meier estimator both in the total population, and in patients who passed the 2- and 5-year landmark without previous relapse or progression. Excess mortality of the landmark populations compared to an age-, sex- and calendar year-matched general population was estimated with a Cox regression model for relative survival using the R-package relsurv. Results: In total 2589 patients were included into the analysis. The median follow-up of patients alive at the end of follow-up was 4.0 years (range: 1 to 161 months). The median age at HSCT was 55 years (range: 12 to 74 years). One hundred and fifty eight patients (6.1%) were below 40 years of age at the time of transplantation. Seventy-four percent of patients were male. The remission status at the time of transplantation was reported as complete remission in 15%, partial remission in 47%, and stable disease or progressive disease in 32%. Information on the remission status was not available for 6% of the patients. Fifty-one percent of the patients had an HLA-matched sibling donor and seventy-seven percent of patients received reduced-intensity conditioning. For the whole cohort of patients, the 5- and 10-year overall survival (OS), progression-free survival (PFS), and non-relapse mortality (NRM) were 45%, 35%, 36%, and 35%, 28%, 40%, respectively. The cumulative incidence of relapse (CIR) was 21% at two years, 29% at five years, and 32% at ten years. A total of 1023 patients and 394 patients were alive without relapse or progression, and in follow-up at two and five years after HSCT. Five years after patients had passed the 2- and 5-year landmark, OS, CIR and NRM were 73%, 22%, 16%, and 83%, 11%, 10% respectively. Compared to the general population excess mortality of the 5-year landmark population in the subsequent five years was estimated to be 3% for male patients at an age of 45 years, 10% for male patients at an age of 55 years, and 24% for male patients at an age of 65 years (see Figure 1). For female patients in this 5-year landmark population, the corresponding excess mortality rates were 4%, 11%, and 27%. Patients without progression and with CR at any time from HSCT to the two and five-year landmarks had a slightly better outcome than those who had never had CR. Surprisingly, this was not a result of a lower CIR but of a lower NRM. Conclusion: Long-term follow-up data derived from the EBMT registry show a steady decline in hazard of relapse after allogeneic HSCT, yet relapse continues to be a threat. Moreover, even patients alive and disease-free after 5 years are still confronted with substantial NRM. These results show that there is room for improvement of long-term patient care. By comparing mortality of younger patients who passed the 5-year landmark with the general population, only marginal excess mortality was observed, while elderly patients still had substantial excess mortality beyond this landmark. Nevertheless, the results indicate that a significant fraction of patients can be cured by allogeneic HSCT. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Description: Key Points The outcome of HSCT in this large SCN cohort is acceptable. Given the TRM, a careful selection of HSCT candidates should be undertaken.

Description: Introduction:Even in the era of novel targeted therapies for the treatment of Chronic Lymphocytic Leukemia (CLL) patients, such as BTK, PI3K and BCL2 inhibitors, allogeneic hematopoietic stem cell transplantations (alloHCT) will remain an important treatment option for a subset of patients with very high risk CLL. The current study focused on the impact of center and procedure-related factors on outcomes after alloHCT, taking into account the impact of patient- and disease-related risk factors. Patients and Methods:Data of 684 CLL patients who received a first alloHCT between 2000 and 2011 were analyzed. Their data were collected as part of the EBMT CLL Data Quality Initiative. Outcomes of interest were Event-Free Survival (EFS) up to 5 years after transplantation and mortality in the first 100 days after alloHCT. Outcomes were analyzed by means of the Kaplan-Meier method and Cox proportional hazards models with a frailty (random effects) component to take into account unexplained center heterogeneity. The following factors describing center characteristics or the transplant procedure were analyzed: experience in alloHCT in general and, for CLL specifically, accreditation by the Joint Accreditation Committee-ISCT & EBMT (JACIE), Gross National Income (GNI)/capita based on purchasing power parity (PPP) (GNI/cap), donor type, donor-patient sex-match, type of conditioning, stem cell source and T-cell depletion (TCD). Results:Five-year EFS of the whole cohort was 37% (95% Confidence Interval, 33%-42%), Day-100 survival was 90% (88%-92%). Experience of the transplant center was measured by the number of all alloHCTs, and alloHCTs for patients with CLL respectively. The median total number of alloHCTs per center per year was 45 (range 0-169) and the median number of CLL alloHCTs was only 2 per center per year (range 0-19). Greater experience with transplantation of patients with CLL (Hazard Ratio (HR) 0.96 per additional transplant, p=0.002), JACIE accreditation (HR 0.7, p=0.045) and a higher GNI/cap (HR 0.4, 95% CI 0.2-0.96, p=0.04) showed a protective impact on 5-year EFS in the Cox model. In vivo TCD with alemtuzumab (HR 1.5 compared to no TCD, p=0.03) and a female donor for a male patient (HR 1.4 compared to a male donor for a male patient, p=0.02) were the only procedure-related factors significantly associated with EFS. Event-Free Survival after in vivo TCD with Anti-Thymocyte-Globulin or after ex vivo TCD was comparable to EFS without TCD (HR 0.9, 0.7-1.3, p=0.6; HR 0.9, 0.5-1.6, p=0.8). Non-myeloablative conditioning did not have a negative impact on 5-year EFS, and exposed patients to a lower risk of non-relapse mortality. Measured and unmeasured center characteristics did not have a significant impact on 100-day mortality. Even when correcting for patient-, procedure- and center-related characteristics, there was still significant variation in center outcome, expressed by center-specific HRs derived from the frailty models, ranging from 0.6 to 1.2. Their impact is illustrated in a model-based plot for EFS (see Figure) which shows outcomes for three reference patients with the same characteristics who would be transplanted in three centers with the same measured characteristics but with the highest, average and lowest HRs in the dataset. These unexplained center effects likely represent a mixture of differences which could apply to the location of the transplant center, unmeasured characteristics of the patient population transplanted at this center, selection criteria which were not reported and factors determining the success of the transplant procedure which might differ between centers. Conclusion: We have confirmed that both center- and procedure-related factors have a significant impact on the EFS of patients with CLL undergoing alloHCT. Our results may help to interpret outcomes of single or multicenter studies better. Since non-myeloablative conditioning did not have a negative impact on EFS and exposed patients to a lower risk of non-relapse mortality, this approach should be favored for future alloHCT for CLL. Probability of Event-Free Survival up to Five Years Post-HCT for three Reference Patients Contribution: J.S. designed the research and wrote the paper. L.C.d.W conducted the statistical analysis and produced the figure. Figure Figure. Disclosures Schetelig: Sanofi: Honoraria. Gramatzki:Janssen: Other: Travel/Accommodation/Expenses, Research Funding. Dreger:Gilead: Consultancy; Gilead: Speakers Bureau; Janssen: Consultancy; Novartis: Speakers Bureau; Novartis: Consultancy; Roche: Consultancy.

Description: Introduction The number of MDS patients who receive allogeneic stem cell transplantation is steadily increasing. However, the main cause for treatment failure is relapse which exceeds 50%. Post transplant strategies such as novel agents (5-azacytidine, HDAC inhibitor etc.) as well as adoptive immunotherapy (e.g. DLI) are currently under investigation to reduce the risk of relapse. Patients and methods In order to have a valid tool for stratification in phase III studies, the CMWP of EBMT is developing a simplified "Relapse-risk score" for MDS patients. For this purpose 1638 patients with MDS who received an allogeneic stem cell transplantation from HLA-identical sibling or a matched unrelated donor between 1995 and 2012 and reported to EBMT registry were included. The median age of the patients was 54 years (range 18-76) and diagnosis were: RAR/RARS/RCDM-(RS) and RAEB. Variables which were taken into the analysis were: age, classification of MDS, donor source (HLA-identical sibling vs matched unrelated donors), acute and chronic GvHD,stem cell source (PBSC vs bone marrow), T-cell depletion , intensity of the conditioning regimen (reduced intensity vs standard myeloablative), blasts in bone marrow at time of transplant, and cytogenetic: very poor (very poor according to IPSS revised or monosomal karyotype), poor (according to IPSS-revised), and good (according to IPSS-revised) and unclassifiable. To take the different risks of relapse depending on time from transplant into account we developed 4 different prognostic models: 1) relapse between SCT and 6 months after SCT, 2) relapse between 6 and 12 months post-SCT, 3) relapse between 12 and 24 months post-SCT and 4) relapse after 24 months post-SCT. Results Multivariate Fine and Gray regression models were used to assess the impact of risk factors on the cumulative incidence of relapse. Disease status RAEB remains significant in all 4 models (1: HR 1.62 (95% CI 1.14-2.86), 2: HR 2.51 (95% CI 1.49-4.20), 3: HR 2.10 (95% CI 1.19-3.73), and 4: HR 2.97 (95% 1.56-5.60), whereas very poor cytogenetic was significant in model 1: HR 4.33 (95% CI 2.85-6.60), and model 3: HR 3.51 (95% CI 1.69-7.29)), poor cytogenetic only for early relapse: model 1: HR 2.19 (95% CI 1.39-3.27). RIC was significant for model 1: HR 2.04 (95% CI 1.51-2.75 and 2: HR 1.72 (95% CI 1.06-2.77), T-cell depletion for model 2: HR 1.61 (95% CI 1.02-2.56), and 3: HR 2.01 (95% CI 1.19-3.39). The prognostic risk scores are directly obtained by adding up the relevant log-hazard ratios, which allows dividing patients into three risk groups, low, medium, high, defined by tertiles in the study population. Cumulative incidence plots of relapse for each of the three groups are shown. Conclusion Relapse as most common treatment failure of allogeneic SCT in MDS can occur even after 24 months. Several risk factors influence the incidence of relapse, however while RAEB disease status influence early, intermediate and late relapse, other risk factors such as cGvHD influence only late (〉24 months relapse. Therefore, these risk scores may help to stratify patients according to their risk of relapse after stem cell transplantation which can be used for stratification in further prospective trials using post transplant therapies at different time points after stem cell transplantation to reduce the risk of relapse. Figure Figure. Disclosures Kröger: Sanofi: Honoraria, Research Funding. Maertens:Amgen: Consultancy; Merck Sharp & Dohme: Consultancy, Honoraria, Research Funding, Speakers Bureau; Pfizer: Consultancy, Honoraria, Research Funding, Speakers Bureau; Astellas: Consultancy, Speakers Bureau; Gilead: Consultancy, Honoraria, Speakers Bureau. Schetelig:Sanofi: Honoraria.

Description: Objectives: For medically-fit young patients with high-risk chronic lymphocytic leukemia (CLL) BTK-/PI3K-inhibitors or allogeneic stem cell transplantation (alloHCT) are considered. We hypothesized that given the choice between these drugs and transplantation in future only patients with a low risk of treatment failure will be selected for alloHCT. Therefore, we searched for risk factors for 2-year non-relapse mortality (NRM) and 5-year event-free survival (EFS) after alloHCT, the latter as a surrogate for long-term disease-control. Methods: Data from patients with CLL who had received a first alloHCT from a HLA-identical sibling (SIB) or unrelated donor between 2000 and 2011 were updated in an EBMT data quality initiative. Multivariable Cox regression models were fitted to assess the impact of baseline risk factors for NRM and EFS. Results: Data on 694 patients were included into the analysis. The median age of the cohort of patients was 55 years (19 years to 74 years). Seventy-nine percent of patients had a Karnofsky performance status of 90% or higher. A disease history of less than two years was reported in 20% of patients and 44% of patients had a disease history of more than 5 years. The median number of pretreatments was 3 (range, 0-15). Eleven percent of patients had received a previous autologous HCT. Only 9% of patients had never received purine-analogs (PA) during their treatment history. Sixty-three percent of patients had either PA-refractory disease or relapse within 24 months from the last PA-containing chemotherapy at the time of HCT. A deletion 17p had been diagnosed in 28% of patients in this cohort. Information on PA-sensitivity, early relapse after autologous transplantation or PA-combination therapy and del(17p)/TP53 is used to select patients for allogeneic HCT according to the EBMT 2007 consensus. EBMT consensus criteria were met in 76% of evaluable patients. Overall, the majority of patients analyzed in this subset of all registered patients had high-risk CLL. For the whole cohort 2-year NRM was 28% (95%-CI, 24% to 32%). The baseline risk factors age, Karnofsky performance status, donor type, and donor-recipient sex mismatch had a significant impact on 2-year-NRM. With the help of these risk factors the outcome of good risk and poor risk reference patients was predicted whose linear predictors were close to the 10th and the 90th percentile of all patients in the dataset. The good risk male reference patient has an age of 45 years, a Karnofsky performance index of 100%, is in partial remission at HCT and has a matched related male donor. The poor risk male reference patient has 55 years of age a Karnofsky performance index of 80%, SD/PD at HCT, and a matched unrelated female donor. The female reference patients had the same characteristics, apart from the donor sex. Two-year-NRM was predicted to be 11% (12%) for male (female) patients with a favorable risk compared to 40% (32%) with a poor risk profile (see Figure). The same approach was used to analyze risk factors for long-term disease control. Five-year-EFS was 37% (95%-CI, 33% to 41%) for all patients. Age, Karnofsky performance status, history of an autologous HCT, remission status, and donor-recipient sex mismatch had a significant impact. The model-based prediction of 5-year EFS was 54% (64%) for a male (female) patient with a favorable risk profile compared to 15% (30%) with a poor risk profile. Current knowledge suggests that allogeneic HCT can overcome the negative prognostic impact of high risk cytogenetic abnormalities, especially of a deletion(17p) or TP53 -mutation. Even in this large cohort we observed only a trend for a lower incidence of relapse/progression in patients without deletion(17p) CLL within the first two years after HCT with translated into a trend for better EFS at that time. The impact on long-term disease-control and mortality was even smaller. Conclusion: Information on predicted 2-year-NRM and 5-year-EFS for good and poor risk reference patients derived from a large CLL dataset may be instrumental to select patients for future alloHCT. Model-based prediction of non-relapse mortality and relapse/progression. Figure 1. Figure 1. Figure 2. Figure 2. Disclosures No relevant conflicts of interest to declare.

Description: Introduction Multiple myeloma (MM) patients with renal impairment (RI), especially dialysis-dependent (DD) RI, have poorer outcomes than MM patients with normal renal function. Autologous stem cell transplantation (ASCT) is a treatment option, but there is concern at a perceived higher risk of complications which may be limiting consideration of the use of ASCT in this population. The evidence is inconsistent among studies and interpretation is complicated by heterogeneous datasets, some dating to before the availability of novel agents. Finally, the reversibility of RI following ASCT is an important prognostic factor for both survival and quality of life. Aim To evaluate the safety and efficacy of ASCT in MM patients with DD RI transplanted in EBMT centres between 1997 and 2017. Methods Baseline characteristics at diagnosis, patient treatment regimens and clinical outcomes were collected using standardised report forms. OS was defined as the period between the date of ASCT and the date of death or the date of last observation. PFS was defined as the period between the date of ASCT and date of progression/relapse or death of any causes or the date of the last observation. Cox proportional hazard regression analysis was applied to assess risk factors for progression and death. Survival curves were plotted by the Kaplan-Meier method and compared using log-rank test. P140 mg/m2 (n=12, 15%). The times to Neutrophil (〉0.5) and Platelet (〉20) engraftment were 12 (10-37) and 14 (4-128) days, respectively. The 30-day and 100-day transplant-related mortality (TRM) rates were 0.0% and 0.9%, respectively. ASCT was associated with a significant deepening of response (at least VGPR pre- vs post-ASCT: 36/93 (39%) vs 48/93 (52%), p 〈 0.001). The median PFS was 37 months (95% CI: 24-43) and 5-year PFS was 31% (95% CI: 20-41). The median OS was 102 months (95% CI: 67-129). Five-year OS post-ASCT was 62% (52-72) and 10-year OS 36% (17-55). Thirty-one (26%) DD MM patients achieved dialysis independence. There were no differences in PFS or OS when comparing the 1997-2007 and 2008-2017 cohorts: 5-year PFS - 28% (6-49) vs 31% (19-43) (p=0.7) and 5-year OS - 61% (38-84) vs 63% (51-74) (p=0.9), respectively. On univariate analysis of factors affecting PFS, achievement of an Overall Response Rate (ORR) (CR+VGPR+PR vs. Other) pre-ASCT was associated with a lower risk (HR 0.467, p=0.032) and older age (〉55 years) with a higher risk (HR 1.786, p=0.035) of post-ASCT progression. Age higher than 55 (HR 2.033, 95%CI: 0.992 - 4.166, p=0.053) increased and achievement of at least VGPR pre-transplant (HR 0.494, 95%CI: 0.224 - 1.091, p=0.081, on the verge of statistical significance) decreased the risk of death. Conclusion To the best of our knowledge, the DIADEM study is the largest analysis of ASCT in DD MM pts to date. This cohort of 118 unselected patients had an OS comparable to patients without RI. This may reflect patient selection based on younger age, Karnofsky scores and pre-ASCT response. The low TRM and excellent outcomes support consideration of the use of ASCT in pts with DD RI. Notably, more than a quarter of patients became dialysis independent, an outcome likely to confer an improved Quality-of-Life.. These results can also inform the debate around the role of renal transplantation in younger DD MM patients who do not achieve dialysis independence. Disclosures Snowden: IDMC: Honoraria; Kiadis: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria; Mallinckrodt: Honoraria; Jazz: Honoraria; Gilead: Honoraria. Dreger:MSD: Membership on an entity's Board of Directors or advisory committees, Other: Sponsoring of Symposia; AbbVie, AstraZeneca, Gilead, Janssen, Novartis, Riemser, Roche: Consultancy; AbbVie, Gilead, Novartis, Riemser, Roche: Speakers Bureau; Neovii, Riemser: Research Funding. Illés:Takeda, Seattle: Research Funding; Janssen, Celgene, Novartis, Takeda, Roche, Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees. Basak:Teva: Honoraria; Celgene: Honoraria. Gyan:Pfizer: Honoraria. Hayden:Alnylam: Honoraria; Amgen: Honoraria. Beksac:Amgen: Consultancy; Celgene: Consultancy; Janssen&Janssen: Consultancy; Takeda: Consultancy. Schönland:Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Medac: Other: Travel Grant; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Prothena: Membership on an entity's Board of Directors or advisory committees, Research Funding.

Description: Introduction: Optimal HLA matching is associated with clinical outcome of unrelated donor (UD) hematopoietic cell transplantation (HCT)(Pidala, Blood2014, Morishima, Blood2015, Fürst, Blood2013), but a comprehensive analysis addressing this question in European transplant centers has not yet been performed. Within the CTIWP of EBMT, we have addressed this issue in adultsreceiving an UD-HCT from 2000 to 2015. Methods: All consecutive cases of UC-HCT with available 6-loci high resolution (2nd field) HLA-A, -B, -C, -DRB1, -DQB1, -DPB1 typing for both patient and donor and ARD-level matching for at least 7/8 HLA-A,B,C,DRB1 alleles reported to the EBMT were selected. Further inclusion criteria were first allogeneic HCT for hematological malignancies, patient age 〉=18 years, availability of donor age and use of either bone marrow or peripheral blood (PB) as stem cell source. Overall, 9575 patient-donor pairs were included from 29 countries and 198 transplant centers. Median follow-up was of 28.3 months, main diagnosis was acute leukemia (AL)(51.5%), disease stage was early in 44.1% of cases. UD-HCT were performed with PB in 84.7%, in vivo T cell depletion (TCD) in 64.4% and reduced intensity conditioning regimen in 57.3% of cases, and mostly standard graft-versus-host-disease (GvHD) prophylaxis with calcineurin inhibitors. HLA data were validated using the HLAcore library and a haplotype based probability check from the German Donor Registry. Pairs were stratified by: 1) In the overall cohort, according to HLA-A, -B, -C, -DRB1 matching status (8/8 N=7724 and 7/8 N=1851) and 2) in informative 8/8 matched pairs (N=7480), according to HLA-DPB1 matching status as identical (23.7%), permissive (26.6%) or non-permissive (32.9%) by the 3-group T Cell Epitope (TCE3) model, or by the 4-group TCE4 model (Fleischhauer, Blood2017). Primary endpoint was overall survival (OS), secondary endpoints were non-relapse mortality (NRM), relapse and acute GvHD grade II-IV, and relapse free survival (RFS). Results: At 5 years, OS and RFS in the entire cohort were 47% and 40.5%. The cumulative incidence of 5-y NRM, relapse and 1-y grade II-IV aGvHD was 28.1%, 31.4% and 19.4%, respectively. In multivariate analysis, a single mismatch at HLA-A, -B, -C, -DRB1 (7/8) was associated with a significantly higher risk of death compared to full match (8/8; HR 1.16, p

Description: Patients with t-MN have a poor prognosis with median overall survival 〈 1 year due to high risk features of the disease and refractoriness to chemotherapy. HSCT represents the only curative treatment. Outcome after HSCT has progressively improved over time with a last EBMT study showing a 2-year OS at 44% in patients with secondary leukemia (79% post MPN or MDS) (BBMT 2018: 1406). Previous large studies showed survival 〈 30% in patients transplanted for t-MN (Blood. 2010:1850; Haematologica 2009:542). We recently reported in patients transplanted for a leukemia arising from MDS, MPN and CMML that the primary disease impacts the outcome, particularly patients with a previous MPN had the worst outcome (BJH, 2019: 725). We report here outcome of patients who received HSCT for a t-MN (excluding post MDS, MPN and CMML) with the hypothesis that the primary cancer impacts the outcome. From EBMT registry, patients with MDS or AML occurring after a primary cancer who received a HSCT between 01/06 and 12/16 were included. OS and RFS were analyzed using Kaplan Meier curves and log-rank test, relapse and NRM were analyzed as competing risks with cumulative incidence curves and Gray's test. 2334 patients were identified. Primary cancers were CLL in 102, non-Hodgkin lymphoma (NHL) in 668, Hodgkin lymphoma (HL) in 235, plasma cell disease (PCD) in 111, breast cancer in 643 and other solid tumor (ST) in 575. 981 patients had MDS and 1353 had AML at time of transplantation. Performance status by Karnofsky score was 90 or higher in 1376 (59%) patients. 722 (31%) patients were transplanted from HLA matched sibling donor (SIB) and 843 (36%) received a myelo-ablative conditioning regimen (MAC). 1307 patients were in remission at time of transplantation: 29% of MDS and 76% of AML patients. Three-year OS and RFS were 34 and 32% respectively. OS was significantly better in patients with AML in CR (43%) than not in CR (21%). OS and DFS were impacted by the primary cancer: post NHL (30 and 27%), post HL (29 and 28%), post ST (34% for both), post breast cancer (41 and 37%), post CLL (34 and 31%) and post PCD (32 and 25%) (p

Description: Hemophagocytic lymphohistiocytosis (HLH; hemophagocytic syndrome) is a rare syndrome of potentially fatal, uncontrolled hyperinflammation. Allogeneic stem cell transplantation (alloSCT) is indicated in familial, recurrent or progressive HLH. Additional recommendations include central nervous system involvement and unknown triggering factor. While data for alloSCT outcome are available for the pediatric setting, information for adults is very limited. The aim of this study was to retrospectively analyze the information from the EBMT databases about adult HLH patients who underwent allogeneic stem cell transplantation. We obtained data of 67 adult (≥18 years of age) patients transplanted due to HLH. The first reported transplantation was in 1995. Due to the rise of HLH awareness, the number was steadily growing. Until 2006 only 12 transplants were performed, while in the next 10 years it was 55. Median age at transplantation was 28 (range: 18-65). There was a slight male predominance 43/67 (64%). The majority of patients were reported with secondary HLH 33/67 (49%), the familial disease was reported in 29/67 (43%) patients. In two patients triggering factor was attributed to malignancy. The majority of patients received stem cells obtained from the peripheral blood (52/67; 78%) while for the remaining ones it was bone marrow. Reduced intensity conditioning was used since 2004 in 23/63 (37%)of patients. Thirteen (19%) patients received TBI. Donor choice was: matched unrelated 33 (50%), mismatched unrelated 7 (11%), identical sibling 26 (39%). Engraftment was observed in 55/61 (77%); 7/61 (12%) patients suffered from primary and 2/61 (3%) from secondary graft failure. The cumulative incidence of acute graft versus host disease (GvHD) at 100 days was 26% (95% CI 15-37%). The cumulative incidence of chronic GvHD at 1 year after alloSCT was 13% (95% CI 2-23%) and increased to 31% at 3 years (95% CI 16-47%). The overall survival until three years is shown in Fig.1. The median survival time was 8 months. The three year OS was 41% (95% CI 28-55%). For patients who survived until 3 months, this proportion was more favorable with an OS of 62% (95% CI 45-78%) at 3 years after transplantation. Among 19 patients with observation times longer than 15 months, only one patient died (in the 48th month after alloSCT due to relapse which occurred in the 12th month). Main causes of death in the described group were: relapse or progression 10/36 (28%), infection 9/36 (25%) and GvHD 6/36 (17%). After 12 months no more relapses of HLH were recorded - the cumulative incidence reached 19%. The non-relapse mortality reached 42% after 15 months. The familial disease was associated with a better prognosis than secondary HLH (p=0.04). Unlike the pediatric population, where reduced intensity conditioning (RIC) was associated with higher survival, in adult patients there was no difference between the conditioning types. The choice of donor: matched related versus matched unrelated did not alter the survival. To our knowledge, this is the largest group of adult patients with HLH who underwent allogeneic stem cell transplantation. Relatively low relapse incidence shows that alloSCT can effectively cure HLH. Patients who survive the first period after this procedure can expect a long disease-free survival. Figure Overall survival after allogeneic stem cell transplantation for adult HLH patients until 36 months (95% Confidence Intervals are shown in grey). The number of patients at risk is indicated below the time axis at the corresponding time points. Figure. Overall survival after allogeneic stem cell transplantation for adult HLH patients until 36 months (95% Confidence Intervals are shown in grey). The number of patients at risk is indicated below the time axis at the corresponding time points. Disclosures Jedrzejczak: Celgene: Consultancy; Roche: Consultancy, Research Funding; Jansen-Cilag: Consultancy; Novartis: Consultancy, Research Funding; Amgen: Research Funding; BMS: Research Funding; Angelini: Consultancy; Sandoz: Consultancy. Kobbe:Jansen: Honoraria, Other: travel support; Celgene: Honoraria, Other: travel support, Research Funding. Kroeger:Sanofi: Honoraria, Research Funding.