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Contains fulltext : 251601.pdf (Publisher’s version ) (Closed access) Hemophagocytic lymphohistiocytosis (HLH; hemophagocytic syndrome) is a rare syndrome of potentially fatal, uncontrolled hyperinflammation. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is indicated in primary, recurrent or progressive HLH, but information about its outcomes in the adult population is limited. We obtained data about 87 adult (≥18 years of age) patients retrospectively reported to the EBMT. The median survival time was 13.9 months. The three and five-year overall survival (OS) was 44% (95% CI 33-54%). Among 39 patients with a follow-up longer than 15 months, only three died. Relapse rate was 21% (95% CI 13-30%), while NRM reached 36% (95% CI 25-46%). Younger patients (

Contains fulltext : 248798.pdf (Publisher’s version ) (Open Access) Allogeneic hematopoietic cell transplantation (allo-HCT) remains a treatment option for patients with chronic myeloid leukemia (CML) who fail to respond to tyrosine kinase inhibitors (TKIs). While imatinib seems to have no adverse impact on outcomes after transplant, little is known on the effects of prior use of second-generation TKI (2GTKI). We present the results of a prospective non-interventional study performed by the EBMT on 383 consecutive CML patients previously treated with dasatinib or nilotinib undergoing allo-HCT from 2009 to 2013. The median age was 45 years (18-68). Disease status at transplant was CP1 in 139 patients (38%), AP or >CP1 in 163 (45%), and BC in 59 (16%). The choice of 2GTKI was: 40% dasatinib, 17% nilotinib, and 43% a sequential treatment of dasatinib and nilotinib with or without bosutinib/ponatinib. With a median follow-up of 37 months (1-77), 8% of patients developed either primary or secondary graft failure, 34% acute and 60% chronic GvHD. There were no differences in post-transplant complications between the three different 2GTKI subgroups. Non-relapse mortality was 18% and 24% at 12 months and at 5 years, respectively. Relapse incidence was 36%, overall survival 56% and relapse-free survival 40% at 5 years. No differences in post-transplant outcomes were found between the three different 2GTKI subgroups. This prospective study demonstrates the feasibility of allo-HCT in patients previously treated with 2GTKI with a post-transplant complications rate comparable to that of TKI-naive or imatinib-treated patients.

Chronic granulomatous disease (CGD) is a primary immunodeficiency resulting in life-threatening infections and inflammatory complications. Allogeneic hematopoietic cell transplantation (allo-HCT) can cure the disease, but the indication to transplant remains controversial. We performed a retrospective multicenter study of 712 patients with CGD who underwent allo-HCT transplantation from March 1993 through December 2018. We studied 635 children (aged 1 antigen mismatch. Choice of conditioning regimen did not influence OS or EFS. In summary, we report an excellent outcome after allo-HCT in CGD, with low incidence of graft failure and mortality in all ages. Older patients and recipients of 1-antigen-mismatched grafts had a less favorable outcome. Transplantation should be strongly considered at a younger age and particularly in the presence of a well-matched donor.

The prognosis of patients with blast crisis (BC) chronic myeloid leukemia (CML) is still dismal. Allogeneic stem cell transplantation represents the only curative treatment option, but data on transplant outcomes are scarce. We therefore conducted a retrospective, registry-based study of adult patients allografted for BC CML, focusing on patients with active disease at transplant and pretransplant prognostic factors. One hundred seventy patients allografted for BC CML after tyrosine kinase inhibitor pretreatment between 2004 and 2016 were analyzed. Before transplant, 95 patients were in remission, whereas 75 patients had active BC. In multivariable analysis of the entire cohort, active BC at transplant was the strongest factor associated with decreased overall survival (hazrd ratio, 1.87; P = .010) and shorter leukemia-free survival (LFS; hazard ratio, 1.69; P = .017). For patients with BC in remission at transplant, advanced age (≥45 years), lower performance status (≤80%), longer interval from diagnosis BC to transplant (>12 months), myeloablative conditioning, and unrelated donor (UD) transplant were risk factors for inferior survival. In patients with active BC, only UD transplant was significantly associated with prolonged LFS and trended toward improved overall survival. In summary, survival of patients allografted for BC CML was strongly dependent on pretransplant remission status. In patients with remission of BC, conventional prognostic factors remained the major determinants of outcome, whereas in those with active BC at transplant, UD transplant was associated with prolonged LFS in our study. ispartof: BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION vol:25 issue:10 pages:2008-2016 ispartof: location:United States status: published

Contains fulltext : 202803.pdf (Publisher’s version ) (Open Access) This analysis included 56 myelofibrosis (MF) patients transplanted from family mismatched donor between 2009 and 2015 enrolled in the European Society for Blood and Marrow Transplantation database. The median age was 57years (range, 38 to 72); 75% had primary MF and 25% had secondary MF. JAK2 V617F was mutated in 61%. Donors were HLA mismatched at 2 or more loci. Stem cells were sourced from bone marrow in 66% and peripheral blood in 34%. The median CD34(+) cell dose was 4.8x10(6)/kg (range, 1.7 to 22.9; n=43). Conditioning was predominantly myeloablative in 70% and reduced intensity in the remainder. Regimens were heterogeneous with thiotepa, busulfan, fludarabine, and post-transplant cyclophosphamide used in 59%. The incidence of neutrophil engraftment by 28days was 82% (range, 70% to 93%), at a median of 21days (range, 19 to 23). At 2years the cumulative incidence of primary graft failure was 9% (95% CI 1% to 16%) and secondary graft failure was 13% (95% CI 4% to 22%). The cumulative incidence of acute graft-versus-host disease (GVHD) grades II to IV and III to IV was 28% (95% CI 16% to 40%) and 9% (95% CI 2% to 17%) at 100days. The cumulative incidence of chronic GVHD at 1 year was 45% (95% CI 32% to 58%), but the cumulative incidence of death without chronic GVHD by 1 year was 20% (95% CI 10% to 31%). With a median follow-up of 32 months, the 1- and 2-year overall survival was 61% (95% CI 48% to 74%) and 56% (95% CI 41% to 70%), respectively. The 1- and 2- year progression-free survival was 58% (95% CI 45% to 71%) and 43% (95% CI 28% to 58%), respectively, with a 2-year cumulative incidence of relapse of 19% (95% CI 7% to 31%). The 2-year nonrelapse mortality was 38% (95% CI 24% to 51%). This retrospective study of MF allo-SCT using family mismatched donors demonstrated feasibility of the approach, timely neutrophil engraftment in over 80% of cases, and acceptable overall and progression-free survival rates with relapse rates not dissimilar to the unrelated donor setting. However, strategies to minimize the risk of graft failure and the relatively high nonrelapse mortality need to be used, ideally in a multicenter prospective fashion.

Introduction: The prognosis of patients diagnosed with blast crisis (BC) chronic myeloid leukemia (CML) is dismal. Allogeneic stem cell transplantation (alloSCT) represents the only curative treatment option. In the current tyrosine kinase inhibitor (TKI) era, however, data on transplant outcomes in patients with BC CML, particularly those with active BC at transplant, are scarce. We hereby report on a multicentre, EBMT-registry based retrospective study of adult patients allografted for BC CML focusing on patients with active disease at transplant and pre-transplant prognostic factors. Patients and methods: Patients with BC CML at transplant (i.e. prior to the start of the conditioning) who underwent alloSCT after the year 2004 within the EBMT database were identified. Next, transplant centers were asked to report the exact disease status at transplant (including blood count, blast count in peripheral blood and bone marrow, achievement and type of remission with corresponding assessment dates, and the reason to proceed with alloSCT in BC CML). A total of 170 patients allografted for BC CML between 2004 and 2016 had complete data for analysis. Overall survival (OS) and leukemia-free survival (LFS) were calculated from date of alloSCT to the appropriate endpoint. For multivariable analysis of predictors of OS and LFS, Cox proportional hazard regression models were performed. Confounding prognostic factors (full models) were: age, disease status prior to alloSCT, Karnofsky performance status (KPS) prior to transplant, interval from diagnosis to transplant, year of transplant, stem cell source, conditioning intensity, donor type, and donor/recipient sex match. All patients provided informed consent for data collection and analysis. Results: Median age at alloSCT was 45 years (range [r], 18-75). Median time from diagnosis to alloSCT was 13.9 months (r, 1.6-367.4). Median follow-up time was 54.7 months (r, 0.1-135.2). Stem cell source was peripheral blood, bone marrow and cord blood in 145 (85%), 18 (11%) and 7 (4%) patients, respectively. Donor types were: unrelated (UD), matched related, and mismatched related in 91 (54%), 64 (38%), and 15 (9%) patients, respectively. Conditioning was myeloablative in 108 (64%) of patients. KPS at alloSCT was ≤80% in 31% of patients. Information on BCR-ABL mutations was available for 41 patients; T315I was present in 28 patients. After thorough analysis of disease parameters, a total of 95 patients had any kind of remission of BC CML (including secondary chronic phase) prior to transplant (termed BC in remission); 75 patients had active BC CML prior to transplant (termed BC active). Main reason for proceeding with alloSCT despite active disease was resistance/refractoriness towards TKI in combination with polychemotherapy. Extramedullary disease was documented in 4 patients. In uni- and multivariable analyses of the entire cohort, besides low KPS, only disease status prior to transplant was significantly associated with shorter OS and LFS (for BC active: HR 2.00, 95%CI 1.35-2.96, p=0.001 and HR 1.80 95%CI 1.27-2.57, p=0.001, respectively). Accordingly, for patients allografted for active BC estimated 3-year OS and LFS was rather short (23.8% 95%CI 13.6-34.0 and 11.6% 95%CI 3.0-20.2, respectively) and significantly lower as compared to patients allografted for BC in remission (3-year OS and LFS: 51.1% 95%CI 40.5-61.7 and 33.8% 95% CI 23.6-44.0, respectively) (Figure 1A and B). Consequently, prognostic factors for survival were analyzed separately according to disease status at alloSCT (slim models, Table 1). For patients with BC in remission at transplant advanced age, lower KPS, shorter interval from diagnosis to transplant, myeloablative conditioning, and UD transplant were risk factors for inferior survival, whereas in patients allografted for active BC, only UD transplant was associated with prolonged LFS and with a trend towards improved OS (Table 1). Conclusion: Survival of BC CML patients after alloSCT in the TKI era remains poor unless disease remission could be achieved. In patients who achieve remission prior to alloSCT, conventional prognostic indicators remain the determinants of transplant outcomes. In patients with active BC CML, UD transplantation appears to be associated with a survival advantage in our study. Disclosures Finke: Neovii: Consultancy, Honoraria, Other: travel grants, Research Funding; Medac: Consultancy, Honoraria, Other: travel grants, Research Funding; Riemser: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Other: travel grants, Research Funding. Tischer:Jazz Pharmaceuticals: Other: Jazz Advisory Board. Mayer:Eisai: Research Funding; Roche: Research Funding; Affimed: Research Funding; Novartis: Research Funding; Johnson & Johnson: Research Funding. Byrne:Novartis: Consultancy, Speakers Bureau; BMS: Consultancy, Speakers Bureau. Ganser:Novartis: Membership on an entity's Board of Directors or advisory committees. Chalandon:Roche: Membership on an entity's Board of Directors or advisory committees, Other: Travel costs.

Introduction: Chronic granulomatous disease (CGD) is a rare primary immunodeficiency disease characterized by impairment of the phagocyte NADPH-oxidase complex, resulting in deficient microbial killing and life-threatening bacterial and fungal infections. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curative approach, but it can be complicated by graft failure, graft versus-host disease (GvHD) and transplant-related mortality (TRM). In order to define prognostic risk factors in this setting, the IEWP of the EBMT performed a large retrospective registry study on 600 pediatric and adult patients with CGD undergoing allo-HSCT. Patients and Methods: We analyzed the outcome of patients with CGD who received allo-HSCT in EBMT centers between 1993 and 2017. The main end-points of the study were overall survival (OS) and event-free survival (EFS; events were death and primary or secondary engraftment failure) according to patient's age, donor type, stem cell source and conditioning regimen. One patient died before allo-HSCT and was excluded from analysis. Results: We studied 536 children (aged < 18 years) and 63 adults (aged ≥ 18 years) affected by CGD. The median follow-up was 45.37 months (IQR 15.8-81.8). Genetic results were available for 307 patients: inheritance was X-linked (75%) or autosomal recessive (25%). Median age at transplant was 7.2 years (range: 0.12-48.56). Conditioning regimen was Busulfan/Fludarabine (n=244; 41%), Busulfan/Cyclophosphamide (n=104; 17%), Treosulfan/Fludarabine (n=76; 13%), Treosulfan/Fludarabine/Thiotepa (n=52; 9%) or other drug combinations (n=123; 20%). Donors were human leukocyte antigen (HLA) matched related (MFD, 10/10; n=211, 40%), matched unrelated (MUD, 10/10 or 6/6 in UCB; n=201; 38%), mismatched related (MMFD, ≥ 9/10; n= 27; 5%) or mismatched unrelated (MMUD, ≥ 9/10 or 5/6 in UCB; n= 83; 16%). Stem cell source was bone marrow (BM; n=408; 69%), peripheral blood (PB; n=153; 26%) or umbilical cord blood (UCB; n=27; 5%). Donor engraftment occurred in 516 evaluable patients (88%), while primary or secondary engraftment failure occurred in 68 patients (12%). Seventy-nine patients (13%) died after allo-HSCT. The 2 year Kaplan-Meier estimate of OS and EFS were 87.1% (95% CI, 84.2-89.9) and 77.8% (95% CI, 74.2-81.4), respectively (Fig A). The 2-year cumulative incidence of grade II-IV acute GvHD, chronic GvHD and extensive chronic GvHD was 18.6% (95%, 15.1-22.2), 16.2 % (95%, 18.8-19.7) and 5.5% (95%, 3.4-7.7), respectively. A univariate cox model with spline term demonstrated that older age at transplant was associated with an increased risk of death (p=0.002). Children undergoing allo-HSCT had a superior 2y OS (88.1%; 95% CI 85.2-91.0), compared to adults (78.2%; 95% CI, 67.7-88.7), p=0.03 (Fig B). Patients undergoing allo-HSCT from a MFD had a superior EFS (86.5%; 95% CI 81.5-91.4) compared to MUD (73.3%; 95% CI 66.7-79.9), MMUD (78.2%; 95% CI 69-87.5) and MMFD (59.7; 95% CI 40.4-79.1), p< 0.001 (Fig C). Patients receiving BM grafts had superior 2y EFS (81.0%; 95% CI 76.9-85.1) compared to PB (72.5%; 95% CI 64.7-80.4) and UCB (66.7%; 95% CI 48.9-84.4), p=0.04. The pattern of disease inheritance and the choice of conditioning regimen didn't have an impact on outcome (Fig D). Fifty-three patients with graft failure underwent a second allo-HSCT and the 2y OS in this group was 82.1% (95% CI, 71.5-92.7). Year of transplantation didn't have an influence on outcome. Conclusion: This is the largest study describing the outcome of allo-HSCT in children and adults affected by CGD. We demonstrate an excellent outcome, with a low incidence of graft failure, TRM and GvHD. Older patients with CGD have reduced survival after allo-HSCT, indicating that transplant should be considered at a younger age. The use of a MMFD is associated with poorer outcome; indication to transplant in this setting should be carefully evaluated by the treating physicians. Disclosures Chiesa: Bluebird Bio: Consultancy; Gilead: Consultancy. Kalwak:medac: Other: travel grants; Sanofi: Other: travel grants. Sykora:Aventis-Behring: Research Funding; medac: Research Funding. Locatelli:Bellicum: Consultancy, Membership on an entity's Board of Directors or advisory committees; Miltenyi: Honoraria; bluebird bio: Consultancy; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees. Wynn:Orchard SAB: Membership on an entity's Board of Directors or advisory committees; Orchard Therapeutics: Equity Ownership; Chimerix: Research Funding; Genzyme: Honoraria; Bluebird Bio: Consultancy; Orchard Therapeutics: Consultancy; Chimerix: Consultancy. Zecca:Chimerix: Honoraria. Veys:Pfizer: Honoraria; Servier: Research Funding; Novartis: Honoraria. Slatter:Medac: Other: Travel assistance.

Allogeneic hematopoietic stem cell transplantation (HCT) may result in long-term disease control in high-risk chronic lymphocytic leukemia (CLL). Recently, haploidentical HCT is gaining interest because of better outcomes with post-transplantation cyclophosphamide (PTCY). We analyzed patients with CLL who received an allogeneic HCT with a haploidentical donor and whose data were available in the EBMT registry. In total 117 patients (74% males) were included; 38% received PTCY as GVHD prophylaxis. For the whole study cohort OS at 2 and 5 yrs was 48 and 38%, respectively. PFS at 2 and 5 yrs was 38 and 31%, respectively. Cumulative incidence (CI) of NRM in the whole group at 2 and 5 years were 40 and 44%, respectively. CI of relapse at 2 and 5 yrs were 22 and 26%, respectively. All outcomes were not statistically different in patients who received PTCY compared to other types of GVHD prophylaxis. In conclusion, results of haploidentical HCT in CLL seem almost identical to those with HLA-matched donors. Thereby, haploidentical HCT is an appropriate alternative in high risk CLL patients with a transplant indication but no available HLA-matched donor. Despite the use of PTCY, the CI of relapse seems not higher than observed after HLA-matched HCT.

PV and AL contributed equally Multiple studies from the EBMT registry and others have shown excellent survival rates after allogeneic haematopoietic stem cell transplantation (HSCT)for Wiskott-Aldrich syndrome (WAS) patients (Ozsahin et al, Blood 2008). The importance of myeloid engraftment for full disease correction has also been demonstrated (Moratto et al, Blood 2011). However, the vast majority of HSCTs in these studies were performed with (oral) busulfan/cyclophosphamide-based conditioning and in the early 2000 years or before. In 2005, the inborn errors working party (IEWP) of EBMT and ESID first recommended busulfan/fludarabine (BuFlu) or treosulfan/fludarabine (TreoFlu) based conditioning for primary immunodeficiencies such as WAS, with some centers deciding to add thiotepa (TT) to the conditioning. We performed a retrospective analysis via the EBMT and SCETIDE registries of WAS patients transplanted between 01/01/20006 and 12/31/2016 with these two regimens. The primary objective was to compare the overall (OS) and event-free survival (EFS) after HSCT with either BuFlu±TT or TreoFlu±TT conditioning. Secondary objectives included the influence of either conditioning regimen on acute and chronic GVHD, the degree of donor chimerism, incidence of secondary procedures after HSCT (2nd HSCT, stem cell boost, DLI, gene therapy or splenectomy) and rates of disease-specific complications after HSCT. At the time of this interim analysis, 174 patients were included, 92 (53%) with BuFlu±TT and 82 (47%) with TreoFlu±TT conditioning with a median age of 1.57 years (range 0.21-29.96) at HSCT and a median follow-up of 32.9 months (range 1.5-128.9). The donor was an HLA-matched sibling (MSD) in 30, a matched related donor (MRD) in 5, a matched unrelated donor (MUD, 9/10 or 10/10) in 105, a mismatched unrelated donor (MMUD, 5 years had a worse OS as compared to those 5 years or younger at HSCT (74.9% vs. 90.8%; log-rank test p=0.005). The type of donor had no influence on OS: 96.4% for MSD/MFD, 86.8% for MUD/MMUD and 87.7% for MMFD (log-rank test p=0.4). Whole blood chimerism was complete (>90% donor) in 60/75 evaluable patients (80%) at last follow-up or before secondary procedure (if a patient had one), 39/40 (98%) in the BuFlu±TT group and 21/35 (60%) in the TreoFlu±TT group. Twenty-six patients required a secondary procedure: stem cell boost in 4 patients, donor lymphocyte infusion in 9, 2nd HSCT in 15 and splenectomy in 1. Twenty-two of these 26 (84.6%) are alive and 14 of 16 with available chimerism data have a complete donor chimerism (>90%donor) at last follow-up. The 2-year cumulative incidence (CI) of secondary procedures was higher at 33.9% in the TreoFlu±TT versus 12.8% in the BuFlu±TT group (Gray's test p=0.017), and 2-year EFS (secondary procedure or death as event) was 61.4% in the TreoFlu±TT and 75.0% in the BuFlu±TT group (log-rank test p=0.2). Grade II-IV acute GVHD had the same incidence in both groups (100 day CI 24.4% vs. 26.3%; Gray's test p=0.849) and chronic GVHD of any grade was borderline more frequent in the TreoFlu±TT group (2 year CI 17.2% vs 6.7%; Gray's test p=0.054). The cumulative incidence of disease-specific complications occurring more than 6 months post HSCT (severe infections, bleeding, autoimmunity) was not different between the two groups (6.5% vs. 6.4%; Gray's test p=0.92). There was no malignancy reported after HSCT except for one EBV-post-transplant lymphoproliferative disorder (PTLD) 2.7 months after HSCT. In summary, HSCT with either BuFlu±TT or TreoFlu±TT conditioning reliably cures almost 90% of patients with WAS regardless of donor type. WAS-related complications are very rare events more than 6 months post HSCT. More patients required secondary procedures after treosulfan-based than busulfan-based conditioning. These data confirm the feasibility and efficacy of the regimens currently recommended by the IEWP. Disclosures Slatter: Medac: Other: Travel assistance. Chiesa:Gilead: Consultancy; Bluebird Bio: Consultancy. Kalwak:Sanofi: Other: travel grants; medac: Other: travel grants. Locatelli:Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; bluebird bio: Consultancy; Bellicum: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Miltenyi: Honoraria. Sykora:Aventis-Behring: Research Funding; medac: Research Funding. Zecca:Chimerix: Honoraria. Veys:Pfizer: Honoraria; Servier: Research Funding; Novartis: Honoraria.

Allogeneic Hematopoietic Stem Cell Transplantation Provides Cure for Adult Patients with Hemophagocytic Lymphohistiocytosis (HLH) : A Retrospective Study of The Chronic Malignancies and Inborn ErrorsWorking Parties (CMWP and IEWP) of The EBMT

Introduction: Allogeneic hematopoietic stem cell transplantation (HCT) is a treatment for CLL that can give long disease control. Even with the availability of kinase and BCL2 inhibitors, HCT is still performed in fit patients (pts) with high-risk CLL. Almost exclusively, outcomes on matched related and unrelated donor transplantations in CLL have been published. Recently, mismatched related donors are gaining interest because of the better outcome of haploidentical HCT with post-transplantation cyclophosphamide (PTCY). Methods: All pts with CLL who received a first allogeneic HCT with a mismatched related donor and whose data were available in the EBMT registry were analyzed. Median values and ranges are reported for continuous variables and percentages for categorical variables. The probabilities of overall survival (OS) and progression-free survival (PFS) were calculated using the Kaplan-Meier method and the log-rank test for univariate comparisons. Relapse/progression and nonrelapse mortality (NRM) were analyzed together in a competing risk framework. Statistical analyses were performed using SPSS and R. Results: One-hundred-seventeen pts with CLL (74% males) underwent a mismatched related donor transplantation between 1984 and 2015 (1984-1999: 10, 2000-2004: 18, 2005-2009: 23, 2010-2016: 66). Median follow-up after HCT was 8 months (range 0-187 months). Median age at transplantation was 54 years (yrs) (range 27-71 yrs). Median time from diagnosis to HCT was 67 months (range 4-207 months). Eighteen pts (17%) had previously undergone autologous stem cell transplantation (ASCT). Disease status at HCT was CR in 16% of pts, PR in 39% and SD/PD in 45%. The Karnofsky score was known for 98 pts; 96% had a score of 70% or more at the time of HCT. Fifty-eight percent of pts received reduced-intensity conditioning, 42% myeloablative conditioning. Peripheral blood stem cells were used in 68% of pts, bone marrow in 32%. The HCT was sex matched in 41% of recipient-donor pairs. The relationship of the donor to the patient was known for 34 pts; in 53% the donor was a child, in 38% a sibling and in 6% a parent. Forty pts (38%) received PTCY as GVHD prophylaxis. In the other 77 pts various methods of T-cell depletion (TCD) were used, but not all methods were specified. At least 56% of those pts had in vivo TCD. For the whole cohort of pts OS at 2 and 5 yrs was 46% and 37%, respectively. PFS at 2 and 5 yrs was 38% and 30%, respectively. The use of PTCY did not have a significant impact on OS (49% vs. 42% at 2 yrs, 44% vs. 33% at 5 yrs, p=0.35) and PFS (45% vs. 31% at 2 yrs, 40% vs. 22% at 5 yrs, p=0.15). CI of NRM in the whole group at 2 and 5 yrs were 41% and 45%, respectively. CI of relapse at 2 and 5 yrs were 21% and 25%, respectively. The CI of NRM and relapse at 2 and 5 yrs were not statistically different in pts who received PTCY compared to other types of TCD (NRM: 38% vs. 45% at 2 yrs, 43% vs. 49% at 5 yrs, p=0.45; relapse: 17% vs. 25% at 2 yrs, 17% vs. 29% at 5 yrs, p=0.33). For the whole cohort, the incidence of acute graft-versus-host disease (aGVHD) at 100 days was 34% for grade II-IV and 16% for grade III-IV with a median time of onset of 23 days (range 4-57 days). Conclusions: Mismatched related donor HCT resulted in a 5-year PFS in 30% of the pts. This result seems only slightly inferior to matched donor transplant (5 yrs PFS 37%1). NRM was higher than expected in this cohort, but comparable to other studies on haploSCT with in vivo T-cell depleted grafts. In conclusion, a mismatched related donor HCT may be considered for high-risk chemoimmunotherapy-refractory or 17p deleted/TP53 mutated CLL pts without options for kinase and BCL2 inhibitor therapy. More data are needed to assess the value of PTCY for GVHD prophylaxis in this specific context. References: 1. Schetelig J, de Wreede L, Moreno C, et al. Risk factors for adverse outcome in patients with Chronic Lymphocytic Leukemia (CLL) undergoing Allogeneic Hematopoietic Cell transplantation (alloSCT): a Retrospective EBMT Analysis. Abstract WP024, EBMT meeting 2015. Figure 1 Figure 1. Disclosures Ciceri: MolMed SpA: Consultancy. Foà:Ariad: Speakers Bureau; Pfizer: Speakers Bureau; BMS: Consultancy; Celgene: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Gilead: Consultancy, Speakers Bureau; Janssen-Cilag: Consultancy, Speakers Bureau; Genetech: Consultancy; Roche: Consultancy, Speakers Bureau. Hallek:Mundipharma: Consultancy, Honoraria, Other: travel support, Research Funding, Speakers Bureau; F. Hoffmann-LaRoche: Consultancy, Honoraria, Other: travel support, Research Funding, Speakers Bureau; AbbVie: Consultancy, Honoraria, Other: travel support, Research Funding, Speakers Bureau; Janssen-Cilag: Consultancy, Honoraria, Other: travel support, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Other: travel support, Research Funding, Speakers Bureau; Gilead: Consultancy, Honoraria, Other: travel support, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Other: travel support, Research Funding, Speakers Bureau. Schetelig:Sanofi: Honoraria. Kröger:Sanofi: Honoraria, Research Funding; Neovii: Honoraria, Research Funding; Riemser: Honoraria, Research Funding; Novartis: Honoraria, Research Funding.

Introduction: Allogeneic stem cell transplantation (SCT) remains a treatment option for patients with chronic myeloid leukemia (CML) that fail to respond to tyrosine kinase inhibitors (TKI). While the use of Imatinib seems to have no adverse impact on outcomes after transplant, little is known on the effects of prior use of second generation TKI (2GTKI). We present the results of a prospective non-interventional study (NIS) performed by the European Group for Blood and Marrow Transplantation (EBMT) of all consecutive allogeneic SCT for patients diagnosed with CML from 2009 to 2013. Methods: A prospective follow up of pre and post-transplant data was carried out by the EBMT Leiden office, including TKI therapy data, MED-B and a specific MED-C post transplant data. A total of 94 EBMT centers from 32 countries included 437 patients. Results: We present the results of the 383 patients that fulfilled all the inclusion criteria and had median follow-up of 37 months (1-77). The median age was 45 years (18-68) and 251 (65%) were males. Disease status at the start of 2GTKI was: First chronic phase - CP1 (123, 46%), Accelerated phase or >CP1 (67, 25%) and blast crisis (75, 28%). The choice of 2GTKI was: Dasatinib (155, 40%), Nilotinib (64, 17%) and a sequential combination of Dasatinib/Nilotinib with or without Bosutinib/Ponatinib (164, 43%). In addition, 29% of patients that received Dasatinib were in CP1 at the start of 2GTKI and at the time of SCT compared with 45% at the start and 40% at SCT for patients treated with Nilotinib. For patients that received both TKI in sequential combination, 63% were in CP1 at the start of 2GTKI but only 46% reached the SCT in CP1. Overall disease status at SCT was CP1 in 139 patients (38%), AP in 163 (45%) and BC in 59 (16%). The median interval from diagnosis to SCT was 22 months (2 - 267) and the median interval between starting 2GTKI and SCT was 10 months (1 - 191). The donor was an HLA identical sibling in 130 cases (35%) and unrelated in 244 (65%). The majority of SCT were performed using PBSC (295, 77%), while 272 (71%) were myeloablative and 111 (29%) reduced intensity conditioning. The EBMT score was low (0-2) in 26 (7%), intermediate (3-4) in 216 (62%) and high (5-7) in 107 (31%). Primary graft failure (PGF) occurred in 10 (3%) cases, while the incidence of acute GVHD was 34% (95% CI 29-39) and chronic GVHD (CGVHD) was 60% at 5 years (95% CI 54-66). CGVHD occurred at a median of 5.7 months (3-61) post SCT. Other post SCT complications included veno-occusive disease of the liver (VOD) in 6 cases (2%) and severe infection in 195 (65%). There were no differences in post-transplant complications amongst the 3 different 2GTKI subgroups. Overall non-relapse mortality was 18% (95% CI 14-22) at 12 months and 24% (95% CI 19-29) at 5 years. Relapse incidence was 36% (95% CI 29-42), overall survival was 56% (95% CI 50-62) and relapse-free survival was 40% (95% CI 33-47) at 5 years. Overall survival was 67% (95% CI 59-75) at 5 years for patients in CP1. No differences in post-transplant outcomes were found amongst the 3 different 2GTKI subgroups. However, the EBMT score, performance status and disease stage at 2GTKI and at SCT were predictive of overall and progression-free survival. Discussion: This prospective study demonstrates the feasibility of performing allogeneic SCT in CML patients previously treated with 2GTKI. The rate of post-transplant complications including graft failure, VOD, infections, GVHD and non-relapse mortality seems comparable to that of patients treated with Imatinib or TKI-naïve. We observed no differences between outcomes for patients receiving Dasatinib, Nilotinib or any other combination of 2GTKI (including Bosutinib and Ponatinib) pre-SCT. However, patients receiving Dasatinib were more likely to proceed to SCT in advanced phase than in CP1. Patients in CP1 have a very good overall survival despite prior treatment with 2GTKI. Of note, even after 2GTKI, the EBMT score remains a strong predictor of overall and disease-free survival for CML patients undergoing allogeneic SCT. Disclosures Schouten: Sanofi: Consultancy; Novartis: Consultancy. de Witte:Novartis: Honoraria, Research Funding; Celgene: Consultancy; Incyte: Consultancy. Kröger:Neovii: Honoraria, Research Funding; Sanofi: Honoraria, Research Funding; Riemser: Honoraria, Research Funding; Novartis: Honoraria, Research Funding.

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.