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Background Chronic graft-versus-host disease (cGvHD) is one of the most common life-threatening complications following allogeneic haematopoietic stem cell transplantation (alloHSCT). Understanding outcome after alloHSCT requires a full evaluation of the patient’s health status, including cGvHD and patient reported outcomes (PROs). In an effort to better understand practice patterns across European countries, a survey was initiated by the Integrated European Network on cGvHD (an EU-funded COST Action CA17138 EUROGRAFT, www.gvhd.eu) and the Transplant Complications Working Party of the European Society for Blood and Marrow Transplantation (EBMT). This report shares results of the survey, offering a snapshot view of current practice patterns in the context of long-term care of cGvHD patients. Methods Our self-designed 38-item online survey (Supplementary Material) was intended to collect data regarding transplant center characteristics, data registration practices, the use of NIH criteria in clinical routine, biopsies/biomarkers for clinical assessment, cGvHD cell-based therapies, and PROs. The survey used computer adapted testing methods and took ~10 min to complete. All centers participating in the COST Action EUROGRAFT and all EBMT centers performing alloHSCT were invited by email for participation in the survey. Data were collected between July 2019 and July 2020. Appropriate descriptive statistics were used. In case of multiple entries for a single center (n = 4), only the entry from the most senior staff member was included for the analysis. Missing data was reported as such. Findings Center characteristics Survey results are summarized in Table 1. A total of 72 centers out of 424 invited centers from 24 countries responded to the survey, representing ~17% of all alloHSCT centers and 19.6% of all transplanted patients within the EBMT network [1]. The majority of participating alloHSCT centers were from Europe with exception of three centers based in Asia and one in Latin America. Survey responses were mainly submitted by physicians and data managers. Of note, the size of the transplant programs differed between responding (mean ± SD, n = 47 ± 40 transplants/year) vs. non-responding (mean ± SD, n = 39 ± 31 transplants/year) centers (Supplementary Material).

We performed a study to find out how advances in modern medicine have improved the mortality risk of allogeneic stem cell transplantation. We analyzed major transplantation outcome parameters in adult patients on the European Society for Blood and Marrow Transplantation (EBMT) registry who had hematologic malignancies and had received transplants from matched sibling donors. We performed multivariate analyses using the Cox proportional-hazards model including known risk factors for nonrelapse mortality and a matched-pairs analysis. We identified 38 800 patients who fulfilled the inclusion criteria. Considerable changes in patient characteristics have occurred in the past decades, such as older age, different underlying diseases, and a higher proportion of patients with advanced disease. Major reasons for transplantation-related death in the 1980s were infectious complications and graft-versus-host disease. Nonrelapse mortality, measured at 1 year after transplantation, has decreased over time: 29.7% from 1980 through 1989, 24.4% from 1990 through 1999, 14.8% from 2000 through 2009, and 12.2% from 2010 through 2016. On multivariate analysis, the year of transplantation was associated with reduced nonrelapse mortality (P < .0001; hazard ratio [HR] [95% confidence interval (CI)], 0.8 [0.79-0.82], for 5-year intervals) and decreased overall mortality (P < .0001; HR [95% CI], 0.87 [0.86-0.88]. In the matched-pairs analysis of 3718 patients in each group, nonrelapse mortality at 1 year was 24.4% in the 1990s and 9.5% from 2013 through 2016 (P < .0001; HR [95% CI], 0.39 [0.34-0.43]). Transplantation-related mortality has decreased significantly in the past 40 years. These favorable data facilitate evidence-based treatment decisions on transplantation indications in the context of the availability of novel immunotherapies. ispartof: BLOOD ADVANCES vol:4 issue:24 pages:6283-6290 ispartof: location:United States status: published

The optimal reduced-intensity conditioning (RIC) for patients with acute lymphoblastic leukemia (ALL) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains unclear. We retrospectively analyzed 417 patients > 45 years with ALL in first complete remission who underwent a matched sibling or unrelated allo-HSCT and compared outcomes between fludarabine/busulfan (FLUBU, n = 127), fludarabine/melphalan (FLUMEL, n = 190), and fludarabine-TBI (FLUTBI, n = 100) conditioning. At 2 years, there were no differences between the groups in terms of cumulative incidence (CI) of relapse (40% for FLUBU vs 36% for FLUMEL vs 41% for FLUTBI, p = 0.21); transplant-related mortality (TRM) (18% for FLUBU, 22% for FLUMEL, 14% for FLUTBI, p = 0.09); overall survival (55% for FLUBU, 50% for FLUMEL, 60% for FLUTBI, p = 0.62) or leukemia-free survival (43% for FLUBU, 42% for FLUMEL, 45% for FLUTBI, p = 0.99), but GVHD-relapse-free survival was significantly lower in the FLUTBI group than FLUBU and FLUMEL group (18% vs 35% vs 28%, p = 0.02). However, this difference was lost in the multivariate analysis when adjusted for the in vivo T-cell depletion. Finally, the FLUMEL regimen was shown to be an independent risk factor for a higher TRM (HR 1.97, 95% CI 1.05-3.72, p = 0.04). We conclude that the three most popular RIC regimens yield similar transplant outcomes.

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Limited data is available on factors impacting the outcomes of second hematopoietic cell transplantation (HCT2) in patients with secondary acute myeloid leukemia (sAML). This study aimed to assess HCT2 outcome for sAML comparing reduced-intensity (RIC) to myeloablative (MAC) conditioning. Two hundred and fifteen patients were included: RIC (n = 134), MAC (n = 81). The median follow-up was 41.1 (95% CI: 26.7-69.3) and 28.5 (95% CI: 23.9-75.4) months, respectively. At two years, the relapse incidence (RI) was 58.3% versus 51.1% in RIC and MAC, respectively. The 2-year leukemia free survival (LFS) was 26.6% versus 26%, and the graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS) was 16.4% versus 12.1%, while OS was 31.4% and 39.7%, for RIC and MAC respectively. MVA showed a significantly lower RI [hazard ratio (HR) = 0.46 (95% CI, 0.26-0.8, p = 0.006)] and improved LFS [HR = 0.62 (95% CI, 0.39-0.98, p = 0.042)] with MAC versus RIC. The choice of conditioning regimen did not impact non-relapse mortality [HR = 1.14 (95% CI, 0.52-2.5, p = 0.74)], overall survival (OS) [HR = 0.72 (95% CI, 0.44-1.17, p = 0.18)] or GRFS [HR = 0.89 (95% CI, 0.59-1.36, p = 0.6)]. In conclusion, MAC was associated with a lower RI and superior LFS. These results support the use of MAC for eligible patients with sAML who are being considered for HCT2.

Risk assessment of allogeneic hematopoietic cell transplantation (allo-HCT) is hindered by the lack of current data on comorbidities and outcome. The EBMT identified 38,760 allo-HCT recipients with hematologic malignancies transplanted between 2010 and 2018 from matched sibling and unrelated donors with a full data set of pre-existing comorbidities. Multivariate analyses using the Cox proportional-hazards model including known risk factors for non-relapse mortality (NRM) were performed. We found that pre-existing renal comorbidity had the strongest association with NRM (hazard ratio [HR] 1.85 [95% CI 1.55-2.19]). In addition, the association of multiple pre-existing comorbidities with NRM was significant, including diabetes, infections, cardiac comorbidity, and pulmonary comorbidity. However, the HR of the association of these comorbidities with NRM was relatively low and did not exceed 1.24. Consequently, the risk of NRM was only moderately increased in patients with a high hematopoietic cell transplantation comorbidity index (HCT-CI) ≥ 3 (HR 1.34 [1.26-1.42]). In the current EBMT population, pre-existing non-renal comorbidities determined NRM after allo-HCT to a much lesser extent as compared with the underlying HCT-CI data. Improvements in management and supportive care as well as higher awareness based on the use of HCT-CI may have contributed to this favorable development. ispartof: BONE MARROW TRANSPLANTATION vol:57 issue:2 pages:183-190 ispartof: location:England status: published

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Metabolic syndrome (MetS) is associated with cardiovascular disease in the general population and is also a potential cardiovascular risk factor in survivors of haematopoietic cell transplantation (HCT). We report an EBMT cross-sectional, multi-centre, non-interventional study of 453 adult HCT patients surviving a minimum of 2 years post-transplant attending routine follow-up HCT and/or late effects clinics in 9 centres. The overall prevalence of MetS was 37.5% rising to 53% in patients >50 years of age at follow-up. There were no differences in rates of MetS between autologous and allogeneic HCT survivors, nor any association with graft-versus-host disease (GvHD) or current immunosuppressant therapy. Notably, there was a significantly higher occurrence of cardiovascular events (CVE, defined as cerebrovascular accident, coronary heart disease or peripheral vascular disease) in those with MetS than in those without MetS (26.7% versus 9%, p

Objectives Malnutrition in patients undergoing hematopoietic stem cell transplant (HSCT) can develop rapidly without appropriate nutritional support and affect morbidity and mortality. Guidance to monitor and manage nutrition status is described within the literature; however, whether this is applied in clinical practice is unclear. Methods This paper describes a cross-sectional survey to explore current practice approaches in nutrition support management and adherence to international guidelines. Results A total of 108 nurses from 108 centers across 16 countries replied to the questionnaire. A significant variation was observed regarding the availability of documents supporting the monitoring and management of nutrition status, application of recommendations, and nutritional practices. Discussion The findings revealed that country was the most important factor influencing the differences in practice; however, significant differences were also observed based on patient age group (pediatrics vs. adults), department composition (hematology + HSCT unit vs. HSCT unit alone), and availability of nutrition health care professionals. Behavioral differences regarding nutritional practice approaches could be indicative of differences in knowledge or subject awareness, as well as a reflection of diversity across health care system policies. Conclusions Guideline dissemination and raising awareness through educational campaigns are suggested approaches to improve health care professionals’ knowledge and sensitivity to this important topic.

Acute graft-vs.-host disease (aGvHD) is one of the most frequent causes of transplant-related mortality (TRM) after allogeneic hematopoietic cell transplantation (alloHCT). Its treatment is complex and costly. The aim of this study was to retrospectively analyze the impact of country-specific socioeconomic factors on outcome of patients who experience severe aGvHD. Adults with hematological malignancies receiving alloHCT from either HLA-matched siblings (n = 1,328) or unrelated donors (n = 2,824) developing grade 3 or 4 aGvHD were included. In univariate analysis, the probability of TRM at 2 years was increased for countries with lower current Health Care Expenditure (HCE, p = 0.04), lower HCE as % of Gross Domestic Product per capita (p = 0.003) and lower values of the Human Development Index (p = 0.02). In a multivariate model, the risk of TRM was most strongly predicted by current HCE (HR = 0.76, p = 0.006). HCE >median was also associated with reduced risk of the overall mortality (HR 0.73, p = 0.0006) and reduced risk of treatment failure (either relapse or TRM; HR 0.77, p = 0.004). We conclude that country-specific socioeconomic factors, in particular current HCE, are strongly associated with survival of patients who experience severe aGvHD. CA extern

Despite significantly improved preventive measures, acute graft-versus-host disease (aGVHD) remains as one of the most frequent complications after allogeneic hematopoietic stem cell transplantation (HCT). Its clinical grading is determined by the evaluation of its primarily affected organs, namely skin, liver and the gastro-intestinal tract. A number of existing grading systems, of which the 'Keystone Consensus' (Przepiorka D et al. BMT 1994) and MAGIC grading systems (Harris AC et al. BBMT 2016) are the most customary, have been proposed over the years to evaluate aGVHD severity based on the extent of aGVHD organ involvement. However, limitations remain regarding its association with clinical outcome. In the current era, particularly consensus grades I and II aGVHD are hardly distinguishable with respect to overall survival (OS). Given the discrepancies in aGVHD grading, we hypothesized that a data-driven approach would support the understanding and classification of aGVHD with respect to organ involvement, clinical outcome and risk cohorts. Here, we validated on a large, multi-national EBMT cohort a novel data-driven grading system for aGVHD that was previously developed by unsupervised learning applying principal component analysis on aGVHD organ stages (Turki AT et al. EHA 2020). The resulting Machine Learning (ML) aGVHD grading had 12 stages that were divided into 4 balanced ML-aGVHD grades to assess the severity of aGVHD, different from conventional grading. Our study included 19,617 adult patients with first HCT for hematologic malignancies between 2009 and 2018 and evidence of aGVHD. All donors except cord blood HCT were included. Detailed aGVHD organ involvement were required for the calculation of the ML-aGVHD score. Exclusion criteria were missing information on aGVHD organ involvement or follow up and very late onset aGVHD (> d+180). The baseline characteristics of this cohort reflect current HCT practice, with acute myeloid leukemia (55.3%) as predominant disease and a majority of unrelated donor HCT recipients (63.7%). Myeloablative conditioning was used in 46.7% of patients. In addition to baseline calcineurin inhibitors, 60.6% of patients received in-vivo T cell depletion with ATG or Campath. The ML-aGVHD grading distinguished 12 ML stages with significantly different clinical outcomes for OS (Figure 1a), non-relapse mortality (NRM) and relapse. The 4 ML-aGVHD grades (ML-I, stages 1-3; ML-II stages 4-6; ML-III, stages 7-9; ML-IV stages 10-12) revealed highly significant and clinically relevant differences for OS and NRM (p Figure 1 Figure 1. Disclosures Turki: CSL Behring: Consultancy; Jazz Pharma: Consultancy, Speakers Bureau; MSD: Consultancy, Speakers Bureau. Penack: Omeros: Consultancy; Shionogi: Consultancy; Priothera: Consultancy; Incyte: Research Funding; Takeda: Research Funding; Therakos: Honoraria; Pfizer: Honoraria; Neovii: Honoraria; Novartis: Honoraria; MSD: Honoraria; Jazz: Honoraria; Gilead: Honoraria; Astellas: Honoraria. Schoemans: Janssen: Membership on an entity's Board of Directors or advisory committees; CIBMTR: Consultancy, Other: travel grants; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: personal fees , Research Funding; Incyte: Membership on an entity's Board of Directors or advisory committees, Other: Travel grants and personal fees; Gilead: Other: travel grants; BHS: Membership on an entity's Board of Directors or advisory committees, Other: travel grants and personal fees , Research Funding; Jazz Pharmaceuticals: Other: personal fees; Takeda: Other: personal fees. Socie: Alexion: Research Funding. Reinhardt: Abbvie: Consultancy; AstraZeneca: Consultancy; Vertex: Consultancy; Merck: Consultancy; Gilead: Research Funding; CDL Therapeutics: Current holder of individual stocks in a privately-held company. Blaise: Jazz Pharmaceuticals: Honoraria. Kröger: Novartis: Research Funding; Riemser: Honoraria, Research Funding; Sanofi: Honoraria; Neovii: Honoraria, Research Funding; Jazz: Honoraria, Research Funding; Gilead/Kite: Honoraria; Celgene: Honoraria, Research Funding; AOP Pharma: Honoraria. Mielke: DNA Prime SA: Speakers Bureau; Gilead/KITE: Other: Travel support, Expert panel ; Miltenyi: Other: Data safety monitoring board; Novartis: Speakers Bureau; Celgene/BMS: Speakers Bureau; Immunicum: Other: Data safety monitoring board. Yakoub-Agha: Jazz Pharmaceuticals: Honoraria. Forcade: MSD: Other: Travel Support; Jazz: Other: Travel Support, Speakers Bureau; Gilead: Other: Travel Support, Speakers Bureau; Novartis: Consultancy, Other: Travel Support, Speakers Bureau. Basak: Saventic Health: Current holder of individual stocks in a privately-held company. Perić: therakos: Honoraria; servier: Honoraria; MSD: Honoraria; Astellas: Honoraria; NOVARTIS: Honoraria; Abbvie: Honoraria; Pfizer: Honoraria.

Introduction: As there is limited evidence to guide management of patients with steroid-refractory graft-versus-host disease (SR-GVHD) there is a broad variability of clinical practices. To document the current practice and assess the impact of emerging new drugs in SR-GVHD, Transplant Complications Working Party (TCWP) of the EBMT performed a survey among EBMT centers that covered specific treatment decisions on first- and second-line treatment of acute and chronic GVHD (aGVHD and cGVHD). Methods: The survey was conducted from December 2020 to March 2021 among EBMT centers. A questionnaire was developed by the study authors and used for data collection. It consisted of 40 questions focused on general approach in the first-line treatment, preferred second-line treatment in SR-GVHD and ancillary care in aGVHD and cGVHD. Results: 145 centers from 33 countries agreed to participate and responded to the questionnaire. First-line treatment of aGVHD was reported as rather homogenous; with most centers (68%) starting with lower doses of corticosteroids (CS) (2b. On the other hand, the evaluation of response to CS was more heterogeneous: at 3 days in 33%, at 5 days in 30%, at 7 days in 15% of centers and depending on severity of aGVHD in most other centers. In the presence of SR-aGVHD, 50% of centers consider inclusion of patients in clinical trials. Although as much as 85% of centers reported to have a standard operating procedure (SOP) for SR-aGVHD management, only 45% (n=66) have an established one or 2-agent second-line treatment; most frequently ruxolitinib (n=46) and/or extracorporeal photopheresis (ECP) (n=29). All other centers reported a very heterogeneous practice and listed multiple agents (range, 3-10) as second-line treatment options. In total, the most used agents for SR-aGVHD as shown in Figure 1A are ruxolitinib in 68%, ECP in 59%, mycophenolate-mofetil (MMF) in 27%, calcineurin inhibitors (CNI) in 25%, high-dose CS (>2mg/kg) in 15%, mesenchymal stem cells (MSC) in 14%, etanercept in 13%, infliximab in 11% and anti-thymocyte globulin (ATG) in 10% of centers. Clinical practice in first-line treatment of cGVHD again appeared relatively homogeneous; 58% of centers reported to treat mild forms with topical treatment only, unless affected organs could not be reached topically. In moderate/severe cGVHD, the majority (71%) of centers start with 0.5-1mg/kg of CS, in 45% with addition of CNI, while others use higher doses of CS +/- other agents. The evaluation of response was done before 4 weeks in 41% of centers, between 5-8 weeks in 41%, while a minority performed later response assessment or based the latter on organ affection/severity. In case of SR-cGVHD, 56% of centers would consider the inclusion in clinical trials, while only 65% have a SOP on management of these patients. One third of centers (35%) has an established multidisciplinary cGVHD team. Practices for SR-cGVHD again varied significantly, with most centers reporting on the use of more than 2 agents (range, 3-13) as second-line and with most applied agents as depicted in Figure 1B; ruxolitinib and ECP in 68% of centers, CNI in 40%, MMF in 37%, rituximab in 27%, imatinib in 25%, mTOR inhibitors in 23%, ibrutinib and methotrexate (MTX) in 19%, pulse of CS in 17%, MSC in 12% and PUVA therapy in 10% of centers. Conclusions:In summary, this survey revealed a rather homogenous first-line management of aGVHD and cGVHD based on steroids in the majority of centers. However, when first-line fails, the definition of SR-GVHD remains highly variable and SR-GVHD is still treated with a seemingly "trial and error" approach as demonstrated by significant variability of clinical practices among EBMT centers for second-line treatment. However, in line with recently published prospective trials, ruxolitinib comes forth as one of the most used therapeutic modalities in both SR-aGVHD and cGVHD, together with already widely administered ECP. On the contrary, ibrutinib has not emerged as standard of care in this setting. Future efforts should be invested in finding a standardized approach in SR-GVHD by directly comparing most applied second-line agents in prospective trials as well as evidence-based personalized treatment approaches. Figure 1 Figure 1. Disclosures Peric: Therakos, Servier, MSD, Astellas, Novartis, Abbvie, Pfizer: Honoraria. Schoemans: Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: personal fees , Research Funding; Incyte: Membership on an entity's Board of Directors or advisory committees, Other: Travel grants and personal fees; Gilead: Other: travel grants; CIBMTR: Consultancy, Other: travel grants; Janssen: Membership on an entity's Board of Directors or advisory committees; BHS: Membership on an entity's Board of Directors or advisory committees, Other: travel grants and personal fees , Research Funding; Jazz Pharmaceuticals: Other: personal fees; Takeda: Other: personal fees. Koenecke: Novartis: Consultancy; Janssen: Consultancy; BMS/Celgene: Consultancy; Kite/Gilead: Consultancy; EUSA Pharm: Consultancy. Basak: Saventic Health: Current holder of individual stocks in a privately-held company. Greinix: Celgene: Consultancy; Novartis: Consultancy; Sanofi: Consultancy; Takeda: Consultancy; Therakos: Consultancy. Penack: Omeros: Consultancy; Shionogi: Consultancy; Priothera: Consultancy; Incyte: Research Funding; Takeda: Research Funding; Therakos: Honoraria; Pfizer: Honoraria; Neovii: Honoraria; Novartis: Honoraria; MSD: Honoraria; Jazz: Honoraria; Gilead: Honoraria; Astellas: Honoraria.

The optimal reduced-intensity conditioning (RIC) for patients with acute lymphoblastic leukemia (ALL) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains unclear. We retrospectively analyzed 417 patients 45 years with ALL in first complete remission who underwent a matched sibling or unrelated allo-HSCT and compared outcomes between fludarabine/busulfan (FLUBU, n = 127), fludarabine/melphalan (FLUMEL, n = 190), and fludarabine-TBI (FLUTBI, n = 100) conditioning. At 2 years, there were no differences between the groups in terms of cumulative incidence (CI) of relapse (40% for FLUBU vs 36% for FLUMEL vs 41% for FLUTBI, p = 0.21); transplant-related mortality (TRM) (18% for FLUBU, 22% for FLUMEL, 14% for FLUTBI, p = 0.09); overall survival (55% for FLUBU, 50% for FLUMEL, 60% for FLUTBI, p = 0.62) or leukemia-free survival (43% for FLUBU, 42% for FLUMEL, 45% for FLUTBI, p = 0.99), but GVHD-relapse-free survival was significantly lower in the FLUTBI group than FLUBU and FLUMEL group (18% vs 35% vs 28%, p = 0.02). However, this difference was lost in the multivariate analysis when adjusted for the in vivo T-cell depletion. Finally, the FLUMEL regimen was shown to be an independent risk factor for a higher TRM (HR 1.97, 95% CI 1.05-3.72, p = 0.04). We conclude that the three most popular RIC regimens yield similar transplant outcomes.

Unmanipulated haploidentical allogeneic stem cell transplantation (Allo-SCT) has become an attractive alternative for patients lacking HLA-matched sibling or unrelated donors. However, data of outcome in ALL is still scarce. The outcomes of 1234 adult patients with ALL in first complete remission (CR1) who underwent Allo-SCT between 2007 and 2016 were analyzed. Comparison was done between haploidentical donor (Haplo) (136 patients), matched unrelated donor (MUD 10/10) (809 patients), and mismatched unrelated donor (MMUD 9/10) (289 patients). Univariate analysis showed similar outcomes in Haplo, MUD, and MMUD, including OS, LFS, RI, NRM, AGVHD, and CGVHD. In multivariate analysis, Haplo was not associated with worse outcomes compared to MUD 10/10 and MMUD 9/10. Indeed, compared to Haplo, the hazard ratio (HR) for LFS, OS, RI, NRM, AGVHD, and CGVHD were 1.1 (p = 0.7), 0.9 (p = 0.4), 1.35 (p = 0.2), 0.7 (p = 0.2), 1.1 (p = 0.8), and 0.8 (p = 0.2) for MUD, respectively, and 1.1 (p = 0.8), 1.0 (p = 1.0), 1.2 (p = 0.3), 0.8 (p = 0.4), 1.2 (p = 0.3), and 0.9 (p = 0.6) for MMUD, respectively. In conclusion, outcomes of adult patients with ALL in CR1 receiving Haplo Allo-SCT are comparable to MUD or MMUD transplants. Haplo should be considered as a clinically relevant option for patients lacking a matched sibling donor.

Few therapeutic options are available for patients with acute myeloid or lymphoblastic leukemia (AML/ALL) relapsing after a second allogeneic stem cell transplantation (alloSCT2). In selected patients a third allogeneic stem cell transplantation (alloSCT3) has been used, but no detailed analysis is available so far. The European Society for Blood and Marrow Transplantation (EBMT) registry was screened for patients with acute leukemia (AL) receiving alloSCT3 from an identical or alternative donor to treat AL in either haematological relapse or disease persistence after alloSCT2 between 2001 and 2018. Feasibility, efficacy, outcome, and risk factors of this approach were analyzed retrospectively. Forty-five patients (median age, 37 years, range 12-71) with AML (n=34) or ALL (n=11) were identified. Eleven patients received alloSCT3 in complete remission (CR), 34 had active disease. Fifteen patients were transplanted from the same donor at all three transplants, 30 patients had at least 2 different donors. Between alloSCT2 and alloSCT3, the donor was changed in 25 patients. After alloSCT3, 38 patients engrafted, and 26 achieved CR or CR with incomplete hematological reconstitution (CRi). Acute graft-versus-host disease (GvHD) grade II-IV was observed in 19%, chronic GvHD occurred in 13%. After 1-year, cumulative incidences of leukemia relapse and non-relapse mortality were 47% and 42%, respectively. Median progression free and overall survival (PFS/OS) from alloSCT3 were 2.5 and 4 months, respectively, 1-year PFS and OS were 11% and 20%,. Outcome was improved in patients with at least one donor change (1-year PFS/OS: 17%/30%), further factors for better outcome included an unrelated donor for alloSCT3, Karnofsky performance score >80, and more recent year of alloSCT3. Only patients with AML achieved >1 year OS. In conclusion, results after a third alloSCT are poor, limiting this procedure to few, highly selected patients. Recurrent relapses of acute leukemia after alloSCT remain an unmet therapeutic need.

Background: Haploidentical stem cell transplantation (Haplo HSCT) has emerged in the past three decades as an alternative curative option when an HLA match donor is not available. Over time, the use of Haplo has increased dramatically, reaching superimposable results when compared to unrelated and related HSCT strategies, confirming its validity. The widespread use of Haplo mainly relies upon technical advances, control of alloreactivity through graft-versus-host disease (GvHD) prophylaxis combined with a rapid and almost universal probability to find an Haplo donor for any candidate patient. The aim of our study was to provide a picture of acute (aGvHD) and chronic GvHD (cGvHD) incidence in Haplo HSCT across different platform in the past 15 years, where Haplo moved from ex-vivo T-cell depleted (TCD) platform to in-vivo TCD platform to the post-transplantation cyclophosphamide (PTCy). Methods: We compared the outcomes of adult patients receiving a 1st Haplo HSCT for any hematological malignancy according to GvHD prophylaxis - ex-vivo + in-vivo TCD (n=160), in-vivo only TCD (n=507) or PTCy (n=2593) - and reported to the EBMT registry in 2004-2016. Patients with missing data on disease status at last follow-up and GvHD information were excluded. Primary endpoint was GvHD-free & Relapse-free survival (GRFS) with events defined by death or relapse or grade ≥3 aGvHD or extensive (ext) cGvHD. Secondary endpoints were progression-free survival (PFS), overall survival (OS), aGvHD and cGvHD, incidence of relapse (IR) and non-relapse-mortality (NRM). Due to sample size in the first cohort of ex-vivo TCD, multivariate analysis compared only in-vivo TCD vs PTCy cohorts. Table 1 illustrates patients' characteristics. Results: Univariate analysis for 3-year outcomes are reported on table 2. PTCy provides better GRFS, OS, PFS, NRM versus ex-vivo or in-vivo. IR was not significantly different. Likewise, the 3-year CI of cGvHD and ext cGvHD were similar between PTCy, in vivo TCD and ex-vivo TCD (cGvHD 27% [25-29%], 25% [21-29%], 18% [12-25%], p 0.03; ext cGvHD 11% [10-12%], 10% [8-13%], 8% [4-13%], p 0.45). On the contrary the 100-day CI of grade ≥2 aGvHD were lower in the ex-vivo TCD vs PTCy and in-vivo TCD (19% [14-26%], 28% [26-30%], 32% [28-36%], p 0.002) while grade ≥3 aGvHD were lower in the PTCy group vs ex-vivo and in-vivo TCD (9% [8-10%], 11% [7-17%], 14% [11-18%], p After adjustment for diagnosis, patient age, disease status, Karnofsky PS, donor/patient gender and CMV, cell source, conditioning intensity, previous auto and year of transplant, the multivariable model comparing in-vivo TCD and PTCy showed better outcome for PTCy. Compared to in-vivo TCD, the hazards for GRFS was 0.76 for PTCy (p 0.004), the HR for PFS was 0.71 (p 0.001) and the HR for OS was 0.7 (p 0.0008), the HR for NRM was 0.63 (p 0.001). Moreover, compared to in-vivo TCD, PTCy yielded similar hazards for grade≥2 aGvHD (HR: 1.02, p 0.89), grade≥3 aGvHD (HR 0.79, p 0.27), cGvHD (HR 1.17, p 0.37), ext cGvHD (HR 1.18, p 0.52) and relapse (HR 0.8, p 0.1). Variables associated with GRFS were active disease, Karnofsky PS ≥90%, diagnosis, donor/patient gender and CMV. An ancillary analysis evaluating the stem cell source effect in the PTCy cohort only, demonstrates comparable outcome endpoints (OS, PFS, NRM, IR) at 2-year between bone marrow (BM) and peripheral blood (PB) PTCy. In univariate analysis GRFS and the 2-year CI of cGvHD were not different between BM and PB (GRFS 47% [45-50%], 46% [44-49%], p 0.085; 2-year CI of cGvHD 25% [23-28%], 27% [25-30%], p 0.2) while ext cGvHD, 100-day CI of grade ≥2 aGvHD and grade ≥3 aGvHD were lower in BM PTCy vs PB PTCy (ext cGvHD 8% [7-10%], 12% [10-14%], p Compared to BM PTCy, the HR for cGvHD was 1.55 for PB PTCy (p 0.001), the HR for ext cGvHD was 2.04 (p 0.0003), the HR for grade ≥2 aGvHD was 1,94 (p Conclusions: In the present EBMT registry study on more than 3000 patients transplanted from an Haplo donor, we report improved outcome (better GRFS - in spite of comparable chronic GvHD - OS and PFS, lower NRM) and widespread use in different diagnosis setting other than acute leukemia in PTCy platform. PTCy strategy provides a concrete progress into the field: even if cGvHD still represent a major issue, exploitation of BM PTCy seems to protect against most severe GvHD manifestation. Disclosures Mohty: Jazz Pharmaceuticals: Honoraria, Research Funding. Kröger:Sanofi-Aventis: Honoraria; Riemser: Research Funding; Novartis: Honoraria, Research Funding; Neovii: Honoraria, Research Funding; Medac: Honoraria; JAZZ: Honoraria; DKMS: Research Funding; Celgene: Honoraria, Research Funding. Basak:Celgene: Honoraria; Teva: Honoraria.

Background: Unmanipulated T-cell replete haploidentical allogeneic stem cell transplantation has become an attractive alternative choice for patients with no HLA matched sibling or unrelated donors. However data of outcome in patients with Acute Lymphoblastic Leukemia (ALL) is still scarce. The Acute Leukemia Working Party (ALWP) of the European Society for Blood and Marrow Transplantation (EBMT) conducted this study to compare the outcome of allogeneic transplantation (Allo-SCT) from haploidentical donor (Haplo) versus matched (MUD 10/10) or mismatched (MMUD 9/10) unrelated donor for patients with ALL in first Complete Remission (CR1). Methods: The outcomes of 1,234 adult patients with Philadelphia positive or negative (Ph+ / Ph-) B ALL or T ALL in CR1 who underwent Allo-SCT between 2007 and 2016 were analyzed. Comparison was made between Haplo (136 patients), MUD 10/10 (809 patients) and MMUD 9/10 (289 patients). Multivariate analyses were performed using the Cox proportional-hazard model. To control potential confounding factors between treatments that could influence outcome, propensity score matching was also performed between Haplo and the 2 other groups. Results: Main population characteristics are depicted in Table 1. Recipients of Haplo, MUD 10/10 and MMUD 9/10 were comparable concerning median age, time from diagnosis to Allo-SCT and myeloablative versus reduced intensity conditioning (MAC/RIC). However, Haplo transplants cohort differed in several characteristics from the MUD and MMUD patients groups. The percentage of female donors was higher in Haplo transplants and female to male mismatch was higher accordingly, CMV matched negative status was lower in Haplo. The source of stem cells was bone marrow (BM) versus peripheral blood (PB) stem cells in significantly higher percentage of Haplo transplants (53.7% vs 15.1% and 16.6% for MUD and MMUD respectively, p Univariate analysis showed similar results in Haplo, MUD and MMUD. Disease free survival (DFS) at 3 years was 49±11%, 53±4% and 55±7%, respectively (p=0.67) (Figure 1). Overall survival (OS) was 54±11%, 62±4% and 62±6%, respectively (p=0.11) (Figure 2). Relapse incidence (RI) and non-relapse mortality (NRM) at 3 years were not different either, RI was 28±9%, 28±4% and 25±6%, respectively (p=0.7) and NRM was 23±8%, 19±3% and 20±6%, respectively (p=0.6). Acute GVHD (AGVHD), either grade II-IV or grade III-IV and chronic GVHD (CGVHD) did not differ between the 3 groups (p=0.1, p=1.0 and p=0.6 respectively). The GVHD-relapse free survival (GRFS) was also not statistically different between the groups, 43±10%, 43±4% and 46±7%, respectively (p=0.7). After adjustment for center effect, patient age, donor/patient gender, donor and patient CMV serostatus, ALL type (B Ph- vs B Ph+ vs T), time from diagnosis to SCT, type of conditioning and cell source (PB vs BM), the multivariate Cox model showed that Haplo recipients did not experience worse outcomes compared to MUD 10/10 and MMUD 9/10. Indeed, compared to Haplo, the Hazard Ratio (HR) for DFS was 1.1 for MUD (p=0.7) and 1.1 for MMUD (p=0.8). The HR for OS in MUD and MMUD did not differ from Haplo either (HR=0.9, p=0.4 and HR=1.0, p=1.0 respectively). Moreover, compared to Haplo, SCT from MUD and MMUD were not associated with lower hazards for RI (HR=0.9, p=0.8 and HR=0.7, p=0.2 respectively), NRM (HR=0.7, p=0.2 and HR=0.8, p=0.4 respectively), AGVHD II-IV (HR=1.1, p=0.8 and HR=1.2, p=0.3 respectively) and CGVHD (HR=0.8, p=0.2 and HR=0.9, p=0.6 respectively). Propensity matching confirmed the results of the multivariate Cox analysis with no difference in outcome between Haplo, MUD and MMUD. Compared to Haplo the HR for DFS and OS were 1.04 (p=0.84) and 0.85 (p=0.50) for MUD and 0.9 (p=0.66) and 0.82 (p=0.48) for MMUD. Conclusions: Outcomes of adult patients with ALL in CR1 receiving Haplo Allo-SCT are comparable to MUD or MMUD transplants. Haplo should be considered as an additional option for patients lacking a matched sibling donor. Disclosures Tischer: Jazz Pharmaceuticals: Other: Jazz Advisory Board. Mohty:MaaT Pharma: Consultancy, Honoraria.

Metabolic syndrome (MetS) is defined as a clustering of five factors including (1) fasting hyperglycaemia (2) hypertriglyceridaemia (3) low HDL cholesterol (4) hypertension (5) obesity (high waist circumference). According to the International Diabetes Federation harmonised definition, a large waist circumference plus any other two features meet criteria for diagnosis of MetS. It is associated with raised risk of cardiovascular disease (CVD) by 3-fold and is increasingly recognised in patients after HCT. Recent guidelines for long-term HCT survivors recommend screening for MetS. We performed a large cross-sectional service evaluation of HCT survivors in centres working in accordance with international screening guidelines. We have previously presented interim results regarding the prevalence of MetS and associated risk factors and now present the final results. This was an EBMT approved cross-sectional, non-interventional study of consecutive HCT patients (allo and auto) aged 18+ years and a minimum of 2 year post-transplant attending routine follow-up HCT and/or late effects clinics in 9 centres. Centres completed proformas incorporating routine recording of the MetS parameters (given above) as well as performance status (ECOG); evidence of cardiovascular events; family history of premature CVD; and relevant drug history. Univariate comparison of patients and HCT characteristics between the 2 groups (MetS vs no MetS) was performed using non-parametric Mann-Witney U test for continuous variables and Chi-square test or Fisher test for categorical variables. All tests were two-sided. Multivariate logistic regression analyses were performed to predict MetS and cardiovascular events. Variables with a p-value Table 1 gives the population demographic, age, primary disease and transplant details. The prevalence of MetS was 30.4% (allo 29%, auto 35.6% ns). There was a significant difference in prevalence by age at follow-up (p This large study in HCT survivors confirms high prevalence of metabolic syndrome following both allogeneic and autologous HCT of 30.4% overall rising to 39% in those aged over 50 years at follow-up. The data support MetS being an age-related late effect of HCT that is strongly associated with not only cardiovascular events but also the occurrence of second cancers. Further analysis examining the relationship between intensity of treatment and prevalence of MetS and CVE is needed. The data supports routine screening for MetS of both allo and auto HCT patients. Early intervention of reversible features of MetS with lifestyle and medical management may reduce the risk of cardiovascular events, but this needs be tested in a randomised controlled trial setting. Meanwhile, screening and management should be robustly integrated within routine HCT long-term follow-up care. Table 1. Table 1. Disclosures Cortelezzi: janssen: Consultancy; novartis: Consultancy; roche: Consultancy; abbvie: Consultancy. Mohty:Jazz Pharmaceuticals: Honoraria, Research Funding, Speakers Bureau; Servier: Consultancy; Sanofi: Consultancy, Honoraria, Research Funding, Speakers Bureau; MaaT Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Speakers Bureau; Bristol Myers: Consultancy, Research Funding; Celgene: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Molmed: Consultancy; Janssen: Honoraria, Research Funding, Speakers Bureau. Kroeger:Novartis: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Riemser: Honoraria, Research Funding; JAZZ: Honoraria; Sanofi: Honoraria; Neovii: Honoraria, Research Funding. Snowden:Jazz & Sanofi: Other: Speaker fees at ASH; Jannssen/J&J: Other: Speaker fees.

Introduction Le Multiple Sclerosis Functionnal Composite (MSFC), evaluation clinique des patients suivis pour sclerose en plaques (SEP), comporte des limites : peu realisable en consultation, il n’apprecie pas le handicap en vie reelle. Objectifs Le DAM (Digital Assessement of Multiple Sclerosis) est une application mobile developpee afin de reproduire chacun des 3 tests de la MSFC en vie reelle. L’objectif est d’etablir une correlation entre le DAM et le MSFC. Patients et methodes Lors de cette etude monocentrique, 30 patients SEP ont ete recrutes dans le departement de neurologie de la Pitie-Salpetriere (Paris). Une evaluation de la MSFC et du DAM etait realisee lors de la visite d’inclusion (V0) et a M3. Grâce a une notification sur le telephone, deux evaluations DAM devaient etre faites au domicile a M1 et a M2. Une comparaison entre chacun des tests de DAM et de la MSFC a ete effectuee afin d’evaluer la reproductibilite et la robustesse des tests DAM a l’aide de tests de correlation. Resultats Le coefficient de correlation entre MSFC V0 et le DAM V0 (resultats aux tests exprimes en z-score) est de 0,71 (p Discussion Une meilleure auto-evaluation des patients SEP semble primordiale, pour mieux apprecier le retentissement de la SEP et son evolution. Le test de dexterite des membres superieurs du DAM etait le test le moins reproductible par rapport au test des 9 trous de la MSFC. Le test de marche des 25 pieds est le moins robuste (difficulte de mesurer la distance au domicile de maniere fiable). Ceci sera pris en compte dans la nouvelle version du DAM. Conclusion Le DAM est bien correle a la MSFC, meme au domicile du patient. Une etude multicentrique francaise est en cours d’elaboration pour evaluer les patients SEP dans leur milieu ecologique grâce a une nouvelle version du DAM. Informations complementaires Developpement de l’application DAM par Ad Scientiam. Subvention par le laboratoire Roche.