Acquired chromosomal abnormalities are important prognostic factors in patients with myelodysplastic syndromes treated with supportive care and with disease-modifying therapeutic interventions, ...including allogeneic hematopoietic stem cell transplantation. To assess the prognostic impact of cytogenetic characteristics after hematopoietic stem cell transplantation accurately, we investigated a homogeneous group of 523 patients with primary myelodysplastic syndromes who have received stem cells from human leukocyte antigen-identical siblings. Overall survival at five years from transplantation in good, intermediate, and poor cytogenetic risk groups according to the International Prognostic Scoring System was 48%, 45% and 30%, respectively (P<0.01). Both the disease status (complete remission vs. not in complete remission) and the morphological classification at transplant in the untreated patients were significantly associated with probability of overall survival and relapse-free survival (P<0.01). The cytogenetic risk groups have no prognostic impact in untreated patients with refractory anemia ± ringed sideroblasts (P=0.90). However, combining the good and intermediate cytogenetic risk groups and comparing them to the poor-risk group showed within the other three disease-status-at-transplant groups a hazard ratio of 1.86 (95%CI: 1.41-2.45). In conclusion, this study shows that, in a large series of patients with primary myelodysplastic syndromes, poor-risk cytogenetics as defined by the standard International Prognostic Scoring System is associated with a relatively poor survival after allogeneic stem cell transplantation from human leukocyte antigen-identical siblings except in patients who are transplanted in refractory anemia/refractory anemia with ringed sideroblasts stage before progression to higher myelodysplastic syndrome stages.
The aim of this retrospective study was to investigate the safety and efficacy of allogeneic hematopoietic cell transplantation (alloHCT) in patients pre-treated with ibrutinib. Eligible were ...patients aged >18 years allotransplanted for chronic lymphocytic leukemia (CLL) or mantle cell lymphoma (MCL) after prior exposure to ibrutinib who were registered with the EBMT registry. Seventy patients (CLL 48, MCL 22) were included. At the time of alloHCT, 73% of the patients were ibrutinib responsive. All patients except one engrafted, and acute GVHD grade 2-4 (3-4) was observed in 49% (12%) of 68 evaluable patients. The cumulative incidence of chronic GVHD was 54% 1 year after transplant. In the CLL group, 12-month non-relapse mortality, relapse incidence (RI), progression-free survival (PFS), and overall survival (OS) were 10, 30, 60, and 72%, respectively, and in the MCL group 5, 19, 76, and 86%, respectively. Pre-transplant ibrutinib failure and poor performance status predicted inferior RI, PFS and OS in the CLL group. In conclusion, ibrutinib does not affect the safety of a subsequent alloHCT. While the relatively high post-transplant relapse risk in ibrutinib-exposed patients with CLL deserves further study, in patients with MCL consolidating disease responses to ibrutinib with alloHCT seems to be a promising option.
Abstract One hundred and forty patients who had undergone hematopoietic stem cell transplantation (HSCT) for myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML) transformation after ...treatment of severe aplastic anemia (SAA) were identified in the European Group for Blood and Marrow Transplantation (EBMT) database. The median age at HSCT was 29 years (range, 1 to 66 years). The transplant donor was related in 49% cases and unrelated in 51% cases. The 5-year probability of relapse was 17%, and that of nonrelapse mortality was 41%. The 5-year overall survival was 45% ± 9%, better for patients untreated and patients in remission compared with patients with refractory disease. Our data indicate that allogeneic HSCT leads to prolonged survival in close to one-half of the patients transforming to MDS or AML from SAA.
Background
Autologous stem cell transplantation (ASCT) is a potential consolidation therapy for acute myeloid leukemia (AML). This study was designed to develop a prediction model for leukemia‐free ...survival (LFS) in a cohort of patients with de novo AML treated with ASCT during their first complete remission.
Methods
This was a registry study of 956 patients reported to the European Society for Blood and Marrow Transplantation. The primary outcome was LFS. Multivariate Cox regression modeling with backward selection was used to select variables for the construction of the nomogram. The nomogram's performance was evaluated with discrimination (the area under the receiver operating characteristic curve AUC) and calibration.
Results
Age and cytogenetic risk (with or without FMS‐like tyrosine kinase 3 internal tandem duplication) were predictive of LFS and were used for the construction of the nomogram. Each factor in the nomogram was ascribed points according to its predictive weight. Through the calculation of the total score, the probability of LFS at 1, 3, and 5 years for each patient could be estimated. The discrimination of the nomogram, measured as the AUC, was 0.632 (95% confidence interval CI, 0.595‐0.669), 0.670 (95% CI, 0.635‐0.705), and 0.687 (95% CI, 0.650‐0.724), respectively. Further validation with bootstrapping showed similar AUCs (0.629 95% CI, 0.597‐0.657, 0.667 95% CI, 0.633‐0.699, and 0.679 95% CI, 0.647‐0.712, respectively), and this suggested that the model was not overfitted. Calibration was excellent. Patients were stratified into 4 incremental 5‐year prognostic groups, with the probabilities of LFS and overall survival ranging from 25% to 64% and from 33% to 79%, respectively.
Conclusions
The Auto‐AML nomogram score is a tool integrating individual prognostic factors to provide a probabilistic estimation of LFS after ASCT for patients with AML.
An acute myeloid leukemia (AML)–autologous stem cell transplantation nomogram has been developed for the prediction of leukemia‐free survival after autologous stem cell transplantation in patients with AML undergoing transplantation during their first complete remission. The nomogram is based on age and cytogenetic risk (with or without FMS‐like tyrosine kinase 3 internal tandem duplication) and provides an individualized estimation of leukemia‐free survival.
Summary
Allogeneic Haematopoietic Stem Cell Transplant (allo‐HSCT) remains the only curative approach for Myelofibrosis (MF). Scarce information exists in the literature on the outcome and, indeed, ...management of those MF patients who relapse following transplant. We hereby report on the management and outcome of 202 patients who relapsed post allo‐HSCT for MF.
Even with the availability of targeted drugs, allogeneic hematopoietic cell transplantation (allo-HCT) is the only therapy with curative potential for patients with CLL. Cure can be assessed by ...comparing long-term survival of patients to the matched general population. Using data from 2589 patients who received allo-HCT between 2000 and 2010, we used landmark analyses and methods from relative survival analysis to calculate excess mortality compared with an age-, sex- and calendar year-matched general population. Estimated event-free survival, overall survival and non-relapse mortality (NRM) 10 years after allo-HCT were 28% (95% confidence interval (CI), 25-31), 35% (95% CI, 32-38) and 40% (95% CI, 37-42), respectively. Patients who passed the 5-year landmark event-free survival (N=394) had a 79% probability (95% CI, 73-85) of surviving the subsequent 5 years without an event. Relapse and NRM contributed equally to treatment failure. Five-year mortality for 45- and 65-year-old reference patients who were event-free at the 5-year landmark was 8% and 47% compared with 3% and 14% in the matched general population, respectively. The prospect of long-term disease-free survival remains an argument to consider allo-HCT for young patients with high-risk CLL, and programs to understand and prevent late causes of failure for long-term survivors are warranted, especially for older patients.
Introduction
The development of mixed donor recipient (MDR) chimerism is a frequent occurrence following allogeneic transplantation (alloSCT) for lymphoid malignancies. There is evidence that ...achievement of full donor (FD) lympho-haematopoietic chimerism (LHC) is associated with a lower chance of disease recurrence and consequently donor lymphocyte infusions (DLI) are commonly employed in this setting. There is however a paucity of data describing both the efficacy of DLI in achieving FD LHC and their toxicity in terms of inducing graft versus host disease (GVHD). We therefore undertook a large survey within the EBMT to determine the efficacy and toxicity of DLI when used for MDR LHC.
Methods and Patients
All centres within the EBMT database that had administered DLI for MDR LHC in patients undergoing an alloSCT for lymphoid malignancies were invited to submit additional data for this study. Data was provided for 135 patients from 36 centres. The median age at diagnosis was 44.6 years (15-64) and the median age at SCT was 47 years (range 19-68). Patients were diagnosed with DLBCL (n=17), follicular NHL (n=45), Hodgkin lymphoma (n=21), mantle cell lymphoma (n=32), T cell lymphoma (n=14) and other lymphoid malignancies (n=6). Prior autologous transplantation had been performed in 45 patients. 122 patients underwent reduced intensity conditioning prior to transplantation from a matched sibling donor (n=90), unrelated donor (n=42) or mismatched family donor (n=3). T cell depletion (TCD) of the graft was performed in 33 cases.
Results
MDR LHC was demonstrated by analysis of whole blood (WB) in 34 patients and in T cell and myeloid lineages in 101 patients. The median time from alloSCT to the demonstration of MDR LHC was 4.9 months (range 4.6-63) and the median time to the 1st DLI was 7.8 months (range 1-63). Patients received a median of 2 DLI (range 1-20) at a median starting dose of 1x106 CD3/kg recipient (range 0.1-380 x 106/kg). Of the 135 patients receiving DLI 121 were assessable for response with 94 (78%) achieving full donor LHC, 24 (20%) remaining MDR, 2 patients became fully recipient and one patient had a mixed response (FD in T cells but MDR in myeloid lineage). For the patients that received DLI for T cell MDR chimerism (N=71, with 64 assessable for response) 55 (86%) became FD, 8 (12.5%) remained MDR and 1 became fully recipient. For patients that received DLI for myeloid MDR chimerism (with or without MDR chimerism in the T lineage) (N=30, with 29 assessable for response) 17 (59%) converted to full donor in the myeloid lineage, 10 (34%) remained MDR, 1 had a mixed response and 1 became full recipient. If patients required 3 or more DLIs the chance of conversion to FD fell significantly to 55% compared to 89% for those that only received 1 DLI (p<0.001). There was a trend to a higher rate of conversion to FD in patients that had received a T replete graft (81%) compared to those that had received a T depleted graft (52%)(p=0.063). The dose of the first DLI and donor type had no impact on conversion to DLI.
Acute GVHD developed in 45 of 134 (34%) evaluable patients after the 1st DLI (grade I in 12, grade II in 12, grade III in 6, grade IV in 8 and grade unknown in 7). Chronic GVHD developed in 36 of 130 (28%) evaluable patients which was extensive in 13 (10%). Acute GVHD (grades II-IV) was seen more commonly after the 1st DLI than after 2 or more DLIs (68% post 1st DLI vs 14% after 2 or more DLIs at 100 days p=0.002) and in patients undergoing unrelated donor transplantation (62% vs 23% at 100 days, p=0.02). Chronic GVHD was more common after DLIs given to patients that had received a TCD graft (39% vs 17% p=0.007). The median follow-up after the 1st DLI was 70 months (range 11-149). Relapse following DLI occurred in 36 (27%) patients which was more common in patients receiving DLI for myeloid MDR chimerism compared to T cell MDR (40% vs 22.5%). Disease relapse occurred in 36 (27%) patients after receiving the first DLI, 11 of whom had achieved full donor FD LHC prior to relapse. In a time-dependent Cox model conversion to FD LHC was not protective against relapse.
Conclusions. In this large series of patients with lymphoid malignancies the administration of DLI is an effective strategy for achieving FD chimerism particularly when the MDR chimerism is restricted to the T cell lineage. Development of GVHD is a significant complicating factor particularly in the unrelated donor setting and when the original graft was T cell depleted.
Robinson:Roche: Consultancy, Honoraria, Speakers Bureau; Gilead: Honoraria, Speakers Bureau; Takeda: Consultancy, Honoraria, Speakers Bureau; Sandoz: Speakers Bureau. Chalandon:Roche: Membership on an entity's Board of Directors or advisory committees, Other: Travel costs. Finke:Novartis: Consultancy, Honoraria, Other: travel grants, Research Funding; Medac: Consultancy, Honoraria, Other: travel grants, Research Funding; Neovii: Consultancy, Honoraria, Other: travel grants, Research Funding; Riemser: Consultancy, Honoraria, Research Funding. Beelen:Medac: Consultancy, Other: Travel Support.
Introduction
Relapse of non-Hodgkin lymphoma (NHL) following allogeneic stem cell transplantation (alloSCT) is a common occurrence associated with a poor outcome with limited treatment options. Donor ...lymphocyte infusions (DLI) are commonly employed in this setting in an attempt to exploit the allogeneic graft versus lymphoma (GVL) effect to induce remissions. There is however a paucity of data describing the efficacy of DLIs in inducing remissions in NHL subtypes and the risk of subsequently developing graft versus host disease (GVHD). We report here the largest series of patients with NHL receiving DLI for relapse after alloSCT.
Methods
Patients relapsing after an alloSCT for NHL and receiving DLI were identified on the EBMT database. Centres were invited to contribute additional data. 118 patients follicular lymphoma (FL) n=28, diffuse large B cell lymphoma (DLBCL) n=28, T cell lymphoma (TCL) n=52 and mantle cell lymphoma (MCL) n=10 from 39 centres who received DLI as the only treatment for relapse were identified. Patients receiving DLI in combination with other therapy were excluded from this analysis. The median age at alloSCT was 50 (range 18-73) years. There were 81 male and 37 female patients who underwent an alloSCT with reduced intensity (RIC) (n=90) or myeloablative conditioning (MAC) (n=28) at a median of 2.4 (range 0.3-26.3) years from diagnosis. Allogeneic cells were provided from matched sibling (n=63), unrelated (n=47) or mismatched family (n=8) donors and 85 patients received either ATG/ALG or CAMPATH as part of GVHD prophylaxis. The median time from alloSCT to relapse was 3.8 months (range 18 days-67 months).
Results
Patients received a median of 1 (range 1-19) DLI at a median starting dose of 1.5 x106 CD3/kg (range 0.01-120x106 CD3/kg) at a median of 152 days (range 18-2136) post alloSCT. The median last dose of DLI was 10x106/kg (range 0.1-180x106/kg) given at a median of 353 days (range 41-2725) post alloSCT. The median time from relapse to the first DLI was 35 days (range 0-168). Acute GVHD and chronic GVHD prior to DLI was reported in 29% and 14% of patients, respectively. Of 93 evaluable patients 47 (51%) patients achieved a complete remission, 10 (11%) a partial remission, 13 (14%) stable disease and 23 (25%) had progressive disease following DLI. The median duration of response was 36 months (range 1-168). When analysed according to histology the overall response rate (ORR) (CR+PR) for FL was 84% (CR 68%), DLBCL 41% (32% CR), TCL 54% (46% CR) and MCL 86% (CR 71%). The median duration of responses for FL, DLBCL, TCL and MCL were 30 (range 2-150), 38 (4-76), 37 (range 1-168) and 50 months (13-116) respectively. With a median follow up of 77 months after the 1st DLI 36 (31%) patients remain in complete remission, 29 (25%) without any further therapy. 37 (35%) went on to receive additional antilymphoma therapy after the DLI. Of 17 patients with FL achieving a CR post DLI 12 (71%) remain in remission without further therapy at a median of 78 (9-158) months after DLI. Of 18 patients with TCL that achieved a CR with DLI, 15 (83%) remain in remission without further therapy at a median of 95 (range 42-161) months after DLI. Following the DLI 43 (36%) patients developed aGVHD (6 grade I, 13 grade II, 11 grade III, 9 grade IV, 4 grade unknown) and 33 (28%) developed cGVHD (11 limited, 20 extensive, 2 unknown). Following the first DLI the cumulative incidence of relapse was 31% (CI 22-41) at 4 years and of NRM 28% (CI 20-37). The 4-year PFS after 1st DLI was 39% (CI 30-50) and the OS, 44% (CI 35-54).
Conclusions
DLI induce significant rates of disease response in patients with NHL relapsing after alloSCT providing clear proof of principle of the allogeneic GVL effect. The rates of response are most impressive in FL and MCL. The majority of patients with TCL and FL that achieve a CR post DLI remain in remission with long term follow up. Acute and chronic GVHD is a significant complication of DLI.
Robinson:Sandoz: Speakers Bureau; Gilead: Honoraria, Speakers Bureau; Takeda: Consultancy, Honoraria, Speakers Bureau; Roche: Consultancy, Honoraria, Speakers Bureau. Chalandon:Roche: Membership on an entity's Board of Directors or advisory committees, Other: Travel costs. Beelen:Medac: Consultancy, Other: Travel Support. 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. Corradini:Amgen: Honoraria, Other: Advisory Board & Lecturer; Novartis: Honoraria, Other: Advisory Board & Lecturer; Abbvie: Honoraria, Other: Advisory Board & Lecturer; Sandoz: Other: Advisory Board; Sanofi: Honoraria, Other: Advisory Board & Lecturer; Gilead: Honoraria, Other: Advisory Board & Lecturer; Takeda: Honoraria, Other: Advisory Board & Lecturer; Roche: Honoraria, Other: Advisory Board & Lecturer; Janssen: Honoraria, Other: Lecturer; Celgene: Honoraria, Other: Advisory Board & Lecturer.
BACKGROUND: In patients with acute leukemia (AL), donor EBV (Epstein-Barr Virus) seropositive status significantly increases the risk of development of acute and chronic GVHD after allo-HSCT, while ...it has no influence on other transplant outcomes (OS, RFS, RI, NRM) (Styczynski et al , J Clin Oncol, 2016). No data are available on the impact of EBV serostatus on transplant outcomes in patients with other hematological malignancies.
OBJECTIVE: We analyzed the influence of the recipient's (R) and donor's (D) EBV serostatus on transplant outcomes (overall survival, OS; relapse-free survival, RFS; relapse incidence, RI; non-relapse mortality, NRM; acute graft-versus-host disease, aGVHD; chronic graft-versus-host disease, cGVHD) in patients with myeloid and lymphoid malignancies other than AL undergoing allo-HSCT.
PATIENTS AND METHODS: 12,931 allo-HSCTs performed between 1997 and 2016 for myeloid (58.1%) or lymphoid malignancies (41.9%), other than AL, with PB (76%) or BM±PB (24%) as a stem cell source were included in this retrospective Registry megafile IDWP EBMT study.
RESULTS:DEMOGRAPHICS : 48% had HSCT from a matched family donor, 4.2% from a mismatched family donor, and 47.8 from an unrelated donor. T-cell depletion was performed in vivo in 58.4%, and ex vivo in 7.9% patients. Conditioning regimen was myeloablative in 41.3%, RIC in 58.7%. Median follow-up was 4.7 years. TRANSPLANT OUTCOMES : EBV-seropositive patients receiving grafts from EBV-seropositive donors (EBV R+/D+ transplants) had worse transplant outcomes in comparison to EBV-seronegative patients receiving grafts from EBV-seronegative donors (EBV R-/D-): lower OS (59.6% vs 65.9%), lower RFS (51.1% vs 57.5%), higher incidence of chronic GVHD (49.5% vs 41.8%), and higher incidence of de novo chronic GVHD (30.5% vs 24.0%). No significant differences were found for: RI, NRM, and acute GVHD (Table 1). MULTIVARIATE ANALYSIS : Allo-HSCT from EBV-seropositive donors had higher risk of development of cGVHD (HR=1.13; p=0.0096). When 4 subgroups (R-/D-, R-/D+, R+/D-, R+/D+ EBV serology) were analyzed, the risk of cGVHD was higher for EBV R-/D+ (HR=1.22; p=0.0395), R+/D- (HR=1.21; p=0.0375), and for R+/D+ (HR=1.28; p=0.0013) when compared to R-/D- transplants. On the other hand, R/D EBV serostatus had no significant impact on OS, RFS, RI, NRM and development of acute GVHD. Finally, since the R-/D- combination patients were more likely to be children than R+/D+, this could explain the effect in univariate analysis on OS and RFS while the chronic GVHD effect was independent of age.
CONCLUSIONS: Allo-HSCT from EBV-seropositive donors are at 13% higher risk of chronic GVHD in patients with myeloid and lymphoid malignancies other than AL.
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Petersen:Sanofi: Membership on an entity's Board of Directors or advisory committees. Leblond:SERVIER: Honoraria, Membership on an entity's Board of Directors or advisory committees; GILEAD: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; JANSSEN: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ABBVIE: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ROCHE: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Honoraria; NOVARTIS: Honoraria, Membership on an entity's Board of Directors or advisory committees. Michallet:medac GmbH, Wedel, Germany: Honoraria, Other: Travel grants. Kröger:Janssen Global Services, LLC: Speakers Bureau; Amgen Inc.: Speakers Bureau; Novartis AG: Research Funding; RIEMSER Pharma: Research Funding; Neovii Pharmaceuticals AG: Speakers Bureau; Novartis AG: Speakers Bureau; Sanofi: Speakers Bureau.
Introduction
Haploidentical stem cells are becoming an alternative stem cell source for patients lacking an HLA-identical sibling or 10/10 HLA-matched donor. While an increasing number of studies for ...patients with acute leukemia, malignant lymphoma, and MDS are reported there are only very few results of haploidentical stem cell transplants in myeloma patients.
Method and patients
In EBMT registry 50 MMpatients with a median age of 55 y (r: 37 - 73) with relapse after autograft who received a mismatched related stem cell graft after myeloablative (n = 12, 25%) or reduced intensity conditioning (n = 37, 75%) between 2004 and 2014 were reported. The median time to relapse after single (n = 28, 56%) or tandem (n = 18, 36%) autologous stem cell transplantation was 6.2 months (r: 0.1 - 30.5) and the median time between last autograft and allograft was 17.4 months (r: 2 = 74 months).
At time of allograft 4 (8%) of the patients were in CR, 21 (42%) in PR, 9 (18%) had stable disease or minor response, and 15 (30%) had progressive disease. The majority (84%) received peripheral blood stem cells as graft source and GvHD prophylaxis with ex- or in-vivo T-cell depletion (CD34 selection or ATG) (Cyclophosphamide post transplant) was performed in 37% of the patients while 63% did not receive any in-vivo or ex-vivo T-cell depletion.
Results
After a median follow-up of 52 months (95% CI: 12-112) the cumulative incidence of non-relapse mortality at 1 year was 20% (95% CI: 9 - 31%) and the cumulative incidence of relapse at 3 years was 56% (95% CI: 42 - 70%) resulting in an estimated 3-year PFS and OS of 15% (95% CI: 5 - 26%) 31% (95% CI: 7 - 45%), respectively. Significant factor for improved OS in a univariate analysis was only the use of BM (3 y OS: 71% (95% CI: 38 -100%) vs. 24% (95% CI: 11 - 38%), p = 0.02) and for relapse a higher but not significant incidence for ex-vivo T-cell depletion was observed (p = 0.07). The use of cyclophosphamide post transplantation as GvHD prophylaxis did not influence NRM, relapse incidence, PFS, OS, or chronic GvHD.
Conclusion
Haploidentical stem cell transplantation after relapse to an autograft is feasible for MMpatients. Major treatment failure is the high incidence of relapse. Post-transplant cyclophosphamide had no major impact on outcome in this limited number of patients.
Dreger:medac: Other: Travel grants; AbbVie: Consultancy, Other: Travel grants, Speakers Bureau; Riemser: Consultancy, Research Funding; Jansen: Consultancy; Jansen: Consultancy; medac: Other; medac: Other: Travel grants; medac: Other: Travel grants; medac: Other; Gilead: Consultancy, Speakers Bureau; medac: Other; medac: Other; Riemser: Consultancy, Research Funding; Riemser: Consultancy, Research Funding; Riemser: Consultancy, Research Funding; AbbVie: Consultancy, Other: Travel grants, Speakers Bureau; AbbVie: Consultancy, Other: Travel grants, Speakers Bureau; AbbVie: Consultancy, Other: Travel grants, Speakers Bureau; Jansen: Consultancy; Jansen: Consultancy; Jansen: Consultancy; Gilead: Consultancy, Speakers Bureau; Riemser: Consultancy, Research Funding; Riemser: Consultancy, Research Funding; Gilead: Consultancy, Speakers Bureau; Riemser: Consultancy, Research Funding; Riemser: Consultancy, Research Funding; Riemser: Consultancy, Research Funding; AbbVie: Consultancy, Other: Travel grants, Speakers Bureau; Riemser: Consultancy, Research Funding; AbbVie: Consultancy, Other: Travel grants, Speakers Bureau; AbbVie: Consultancy, Other: Travel grants, Speakers Bureau; AbbVie: Consultancy, Other: Travel grants, Speakers Bureau; Riemser: Consultancy, Research Funding; Jansen: Consultancy; Riemser: Consultancy, Research Funding; Jansen: Consultancy; Gilead: Consultancy, Speakers Bureau; AbbVie: Consultancy, Other: Travel grants, Speakers Bureau; Jansen: Consultancy; AbbVie: Consultancy, Other: Travel grants, Speakers Bureau; Jansen: Consultancy; Gilead: Consultancy, Speakers Bureau; AbbVie: Consultancy, Other: Travel grants, Speakers Bureau; Gilead: Consultancy, Speakers Bureau; Jansen: Consultancy; Gilead: Consultancy, Speakers Bureau; Jansen: Consultancy; Gilead: Consultancy, Speakers Bureau; medac: Other: Travel grants; Jansen: Consultancy; Gilead: Consultancy, Speakers Bureau; Gilead: Consultancy, Speakers Bureau; Gilead: Consultancy, Speakers Bureau; Gilead: Consultancy, Speakers Bureau; medac: Other: Travel grants; medac: Other: Travel grants; AbbVie: Consultancy, Other: Travel grants, Speakers Bureau. Corradini:Amgen: Honoraria; Novartis: Honoraria; Roche: Honoraria; Sanofi: Honoraria; Takeda: Honoraria; Celgene: Honoraria; Janssen: Honoraria; Gilead: Honoraria. Zuckerman:BioSight Ltd.: Consultancy. Ciceri:GSK: Other: B-thalassemia gene therapy was developed by Fondazione Telethon and Ospedale San Raffaele and has been inlicenced by GSK that provides funding for the clinical trial, Research Funding. Petersen:Sanofi: Membership on an entity's Board of Directors or advisory committees. Schönland:Sanofi: Research Funding; prothena: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Speakers Bureau. Garderet:Amgen: Honoraria; Takeda: Honoraria.