ALBERT

Description: Sixty thalassemia patients (median age, 7 years; range, 1-37) underwent allogeneic hematopoietic stem cell transplantation (HSCT) after a preparation combining thiotepa, treosulfan, and fludarabine. Before HSCT, 27 children were assigned to risk class 1 of the Pesaro classification, 17 to class 2, and 4 to class 3; 12 patients were adults. Twenty patients were transplanted from an HLA-identical sibling and 40 from an unrelated donor. The cumulative incidence of graft failure and transplantation-related mortality was 9% and 7%, respectively. Eight patients experienced grade II-IV acute GVHD, the cumulative incidence being 14%. Among 56 patients at risk, 1 developed limited chronic GVHD. With a median follow-up of 36 months (range, 4-72), the 5-year probability of survival and thalassemia-free survival are 93% and 84%, respectively. Neither the class of risk nor the donor used influenced outcome. This treosulfan-based preparation proved to be safe and effective for thalassemia patients given allogeneic HSCT.

Description: This study investigated Thiotepa (TT) and Fludarabine (Fluda) as a preparative regimen for allogeneic peripheral stem cell transplantation in patients with myelodysplastic syndrome (MDS) or acute leukemia from MDS (MDS-AML) older than 50 or with comorbidities contraindicating standard conditioning. Patients were prepared with TT, given over 3 hours as an i.v. infusion at a dose of 10 mg/kg over two days (day -8 and day -7) and Fluda at the dose of 125 mg/m2 i.v. over five days ( from day -7 to day -3). Fresh or cryopreserved allogeneic peripheral stem cells were infused on day 0 or +1. Graft-versus-Host Disease (GvHD) prophylaxis consisted of cyclosporine A (CyA) at the dose of 1.5 mg/kg day as a continuous iv infusion from day -5 until engraftment. The CyA was then administered orally at the dose of 3 mg/kg twice a day. Doses were adjusted to maintain plasma level concentrations between 150–350 mg/dL. From day +60, in the absence of acute GvHD, the CyA was tapered down by 20% every 2 weeks until withdrawal. In addition, patients received methotrexate 10 mg/m2 on day +1, and 8 mg/m2 on days + 3, +6 and +11 after transplantation. At the time of transplantation, patients were classified in two risk groups (low vs high risk) according to IPSS score (low/intermediate-1 vs. intermediate-2/high) for MDS patients, and disease status (CR vs. not CR) for MDS-AML. Kaplan-Meier survival analysis was carried out to compare Overall Survival (OS), Transplant-Related Mortality (TRM) and probability of relapse. Fifty patients (29 males, 21 females) entered the study; the median age was 54 years (range 38–71). Sixteen MDS patients had a low/intermediate 1 score according to the International Prognostic Score System (IPSS), 16 had an intermediate 2/high IPSS score, 18 had MDS-AML. Thirty patients underwent transplantation as front-line therapy, 20 received one or more cycles of chemotherapy before transplant. Among the latter, nine with MDS-AML were in complete remission at the time of their transplant, while four were in a partial remission. The interval from diagnosis to transplantation ranged from 1 to 52 months (median value 11 months). Contraindications to a standard conditioning regimen were liver disease, hypertrophic cardiomyopathy secondary to hypertension or valvular stenosis, cardiac arrhythmia, diabetes mellitus, hypothyroidism, previous CNS bleeding, and a history of sepsis. All but one patient achieved engraftment, with full donor chimerism by day +30. Patients were followed up for a median time of 21 months (range 0.2–87). TRM at 1 and 2 years after transplantation was 25% and 33%; the 5-year probability of relapse was 27%. Twenty-six patients are alive in complete remission, and the 5-year OS is 50%. The 5-year OS was 73% and 28% in low- and high-risk patients respectively (p=0.002). TRM at 1 and 2 years after transplantation was 13% and 21% in the low-risk group and 39% and 45% in the high-risk group (p=0.046); the 5-year probability of relapse was 10% and 50% in the low- and high-risk group respectively (p=0.015). In a multivariate Cox regression, risk group retained a borderline significance (HR=2.6, p=0.07) when adjusted by age at transplantation (p=0.03) and interval from diagnosis to transplant (n.s.). The combination of Thiotepa and Fludarabine is an effective and well-tolerated conditioning regimen in patients with MDS or MDS-AML who are poor candidates for standard myeloablative transplantation, particularly in MDS patients with low/intermediate-1 IPSS score and MDS-AML patients in CR.

Description: Abstract 1221 Poster Board I-243 Introduction A subset of Multiple Sclerosis (MS) patients shows a clinical trend to a fast deterioration of disability despite the use of approved drugs. New immunosuppressive agents are currently employed only in the early phase of the disease but in almost 10% of patients they either do not show any clinical/ radiological improvement or have to be halted for different reasons. Autologous HSCT has been reported as a promising approach for MS patients unresponsive to the available therapies but long term clinical and laboratory follow-up with a stringent MRI monitoring are not yet available. We report here the long term follow-up of a prospective phase II multicenter trial of the Italian GITMO-Neuro cooperative network. Method 21 MS patients (4 Relapsing Remitting and 17 Secondary Progressive) were enrolled between 1999 and 2004 in a prospective trial, aimed to monitor both clinical outcome and MRI imaging. Patients were shown to be refractory to conventional treatments, had a EDSS between 5.0 and 6.5 and at least 1 Gadolinium (Gd) enhancing area in brain MRI. PBSC were mobilized with Cyclophosphamide (4g/m2 ) and Filgrastim; patients were conditioned with BEAM plus rabbit ATG (Thymoglobulin®, Genzyme) and infused with unmanipulated graft. The effect of HSCT was evaluated with serial monthly Gd-enhanced brain MRI for a pretreatment period of 3 months and compared with serial monthly Gd-enhanced MRI imaging for the following 6 months. Subsequently, MRI scans were carried out at, +9, +12, +18 + 24 and at the last follow-up. Clinical outcome was evaluated by both EDSS assessment and number of clinical relapses after the transplant. The same MRI scanning protocol was used at each neuroradiological examination: T1 and T2 total lesion load, new T2 lesions, new hypointense lesions, Gd enhancing activity and progression of brain atrophy were evaluated. Results All patients showed a sustained engraftment with modest early side effects, as previously reported (Saccardi R. et al. Blood 2005 105:2601-07). At a median follow up of 7 years (range 4-10 years) no late effects were reported. Two patients had a clinical relapse 5 years after the HSCT, spontaneously recovered. Nine patients showed a clinical progression at a median of 30 months (16 – 66) after transplant, while the others are either stable (7) or improved (5), as compared with baseline. No patients received any immunosuppressive treatment after HSCT. At MRI examination total lesion load assessed by T2 and T1 sequences remained stable through the follow-up, and only 5 new T2 lesions appeared after HSCT. No Gd enhancing activity was ever observed after transplantation in the examined cases. Brain atrophy progression was higher in the first 2 years after transplantation and then decreased significantly in the following years Conclusions The clinical and MRI results of this prospective study are extremely positive, considering that the majority of cases remained stable at a median of 7 years after transplantation. MRI activity, as evaluated with Gd enhancing areas and the appearance of new lesions, was absent or negligible. Also brain atrophy, rapidly progressing early after the transplant probably due to the suppression of the inflammation, was thereafter shown to be in the range of MS patients. The duration of the follow-up and the stringent MRI methodology provide an evidence of the efficacy of this procedure in this subset of aggressive MS patients. Disclosures No relevant conflicts of interest to declare.

Description: PNH is a rare acquired clonal disorder of the hematopoietic stem cell, characterized by a somatic mutation that inactivates the X-linked PIGA gene: this in turn results in deficiency on the cell surface of all proteins anchored by the glycosylphosphatidylinositol (GPI) molecule. Two of these proteins,CD55 andCD59, are complement regulators and their deficiency is responsible for the susceptibility of red cells (RBCs) from the mutant clone to lysis by activated complement. Since oxidative damage is another well-known mechanism of hemolysis (as in G6PD deficient red cells), we have investigated whether this plays a role also in PNH. To this end, we have carried out experiments on RBCs from healthy donors and on PNH-like RBCs (obtained in vitro from the same donors through the use of anti-CD55 and anti-CD59 blocking moAb). After exposure to AB0-compatible serum (in which thecomplement alternative pathway was activated by mild acidification) all PNH-like (but not normal) RBCs were lysed. In parallel experiments in which complement was blocked by eculizumab (ECU) - a moAb that binds to the complement component C5 and controls intravascular hemolysis in PNH patients - we measured the levels of reactive oxygen species (ROS) by the dichlorofluorescin diacetate assay. We found no significant difference of ROS levels between normal RBCs and PNH-like RBCs. We next tested in a similar way G6PD-deficient RBCs, because these are known to be exquisitely sensitive to oxidative damage. We found that ROS levels were significantly higher in the G6PD deficient RBCs that have been made PNH-like (Fig. 1). Thus, complement activation on the surface of PNH-like RBCs results in the production of ROS that can be demonstrated when C5-blockade prevents complement-mediated lysis of RBCs. The notion that G6PD deficiency can interact with PNH was strongly corroborated by the clinical observation of a 40yo woman from Sardinia (Italy) with a 2 years history of pancytopenia, who then developed florid hemolytic PNH: she had anemia with normal granulocyte and platelet counts, dark urine, high reticulocytosis, LDH up to 5x upper normal level, 95% GPI-negative granulocytes. When the patient was started on ECU. LDH levels promptly returned to normal, PNH RBCs rose from 20% (before ECU) to 42%, but reticulocyte count (~250x109/L) and blood transfusion requirement remained high (10 units in the last year). 39% of the GPI-negative RBCs had bound C3 fragments The peripheral blood smear revealed marked macro-anisocytosis, poikilocytosis, spherocytes, and hemighosts: a picture consistent with oxidative damage as seen in G6PD deficient patients during a hemolytic attack. The RBC G6PD activity was about one-half of normal (5 IU/g Hb), and DNA analysis revealed heterozygosity for the G6PD Mediterranean (Med) mutation. By mRNA sequence analysis we found that the GPI-negative clone expressed only the G6PD Med allele, suggesting that the PIG-A mutation took place in a stem cell in which the normal G6PD gene was on the inactive X-chromosome (G6PD, like PIG-A, is on the X chromosome); therefore, all the patients' PNH RBCs were also all G6PD deficient. We have previously shown that the clinical expression of PNH can be influenced by inherited factors: specifically, a polymorphism of the complement receptor 1 (CR1) gene correlates with the blood transfusion requirement of patients on ECU (Rondelli et al, Haematologica 2014). However, the patient here reported was homozygous for the more favorable allele ofCR1. Instead, in keeping with our experimental data, the poor response to ECU seen in this patient results probably from a unique interaction, within the same population of RBCs, between the acquired PNH abnormality and her inherited G6PD deficiency This type of interaction is novel and it seems to have pharmacogenetic implications. Indeed, on its own G6PD deficiency affects mildly the clinical expression of PNH, because complement activation causes RBC lysis regardless; however, paradoxically, when the lysis of PNH RBCs is prevented by C5 blockade, complement activation results in oxidative damage, with which PNH G6PD deficient RBCs are unable to cope. Except for one case previously reported by Oni et al (Blood 1970), this is the first detailed study of PNH associated with G6PD deficiency. Since in some parts of the world the frequency of G6PD deficiency can be as high as 30% or more, we expect that more cases of this association will be discovered in the future. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Description: Background. Transfusion-associated iron overload may increase the risk of infections both increasing bacterial or fungal growth and leading to the production of free iron that impairs immune system response. Anemia and transfusion dependency (TD) represent well known prognostic factors of survival in patients with myelofibrosis (MF). Compared to myelodysplastic syndrome (MDS), the role of iron overload on infection in MF has been scarcely explored. Methods. We identified consecutive adult patients diagnosed at our Centre with primary or secondary MF, between 1998 and 2018. Patients were stratified in 2 groups according to transfusion dependence defined as having received 〉2 unit of red blood cells (RBC) over 3 months. The total number of RBC units infused was also collected. All infections were recorded and graded according to Common Terminology Criteria for Adverse Events (CTCAE). Results. A total of 106 patients, median age 72 years (range 44-89) were retrospectively evaluated. A diagnosis of primary MF was performed in 75 of cases (71%), post Essential Thrombocythemia myelofibrosis (PET-MF) in 27 (25%) and post Polycythemia Vera myelofibrosis (PPV-MF) in 4 (4%). Splenomegaly was present in 83 patients (78%) and 30 (28%) reported constitutional symptoms.According to the IPSS, 43 patients (40 %) were classified at low or intermediate-1 risk, and 63 (60 %) at intermediate-2 or high risk. Molecular analysis was performed in 76 patients (72%): 54 of 76 patients (71%) were positive for the JAK2V617F mutation, 10 (13%) for CALR mutation, 4 (5%) for MPL, and 8 (11%) were negative for all tested mutations. Over time, 56 patients (53%) received hydroxyurea or other cytoreductive treatment, and 23 (22%) ruxolitinib. Overall, 39 patients (37%) were transfusion dependent with a median of 14 RBC units received during follow-up (range 4-199). The median serum ferritin level in the TD cohort was 840 ng/mL (range 130-12.129). Median observation time was 36 months (range 3-203). At last follow-up, 48 patients (45%) presented one or more infectious episodes. Total infectious events were 69 and 13 of them (19%) were defined as severe (grade 3-4 CTCAE). Anatomical site of infections was the respiratory tract in 28 (41%) of cases, gastro-intestinal in 22 (32%), gynecological-urological in 8 (11%), sepsis in 2 (3%), unspecified in the remaining cases. When detected, the etiological agents were bacterial in 8 (12%), viral in 5 (7%) and fungal in 4 (6%). The 60-month cumulative incidence of infection from diagnosis of MF was 64.1±6.5%. TD patients showed a higher incidence of infection (99±8.8% vs 53.3±8%, p=0.007) (Figure 1). In multivariate analysis no association was found between infection incidence and primary vs secondary MF, splenomegaly, age 〉65 years, ruxolitinib treatment; only transfusion dependencemaintained a significant association (p=0.019; HR=2.13; 95% C.I.=1.13-4.01). Among the 39 TD patients, the transfusion burden was significantly higher in those with infectious complication (median 24 RBC units vs 15 RBC units; p=0.012). The 60-month overall survival was 40±5.9%. Lower IPSS-risk (p

Description: 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. Disclosures 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.

Description: Background: The use of mismatched unrelated (MMUD) donor grafts in leukemic patients who are in need of allogeneic hematopoietic cell transplantation (HCT) and do not have a fully matched donor, represents an alternative therapeutic option. Data on HCT outcome after ≤6/8 MMUD are limited. Methods: We used the data set of the acute leukemia working party (ALWP) of the European society of blood and marrow transplantation (EBMT) in order to assess the transplantation outcome in patients (pts) with acute myelogenous or lymphoblastic leukemia (AML/ALL) transplanted from ≤6/8 MMUD (2-4 HLA mismatches at the allelic level at loci A, B, C and DR) in remission (CR), with no ex vivo T cell depletion (TCD). HCT were performed between 2000 and 2017. Multivariate analyses (MVA) were performed using the Cox proportional hazard model. Results: The study population consisted of 465 patients who met the inclusion criteria (AML 320, ALL 145). The median age at transplantation was 50.2 years (range, 18-71.8) and 34.8 years (range, 18.2-62.9); 54% and 64% were males in AML and ALL groups, respectively. Median follow up was 63 and 75 months, respectively. 69% and 66% were in CR1, while 31% and 34% were in CR2. 40% of AML pts had intermediate risk cytogenetics, 10% poor risk and 5% good risk (missing -45%), respectively. 37% of ALL pts were Ph positive, 22% Ph negative and 18% T ALL (17% B ALL with no Ph data, 6% missing immunophenotyping data). The number of HLA mismatches (HLAMM), it was 6/8 HLA MM - in 82% and 85%, 5/8- in 11.5% and 12% and 4/8- in 6% and 3% of AML and ALL pts, respectively. 85% of AML pts and 77% of ALL pts received PBSC graft. The conditioning regimen was myeloablative in the majority of patients (89% of AML and 61% of ALL pts). 82% and 77% underwent in vivo TCD, respectively. Graft versus host disease (GVHD) prophylaxis was CSA/MTX in 51% and 67% and CSA/MMF in 21% and 10% of AML and ALL pts, respectively. Engraftment was achieved in 97% and 95% of pts, respectively. The incidence of acute (a) GVHD grade (Gr) II-IV and Gr III-IV was 34% and 41% and 14% and 21% for AML and ALL pts, respectively. Total and extensive chronic(c) GVHD rates at 2y were 38% and 38% and 23% and 14%, respectively. The main causes of death were disease recurrence (37% in both), GVHD (29% and 22%) and infections (22% and 26%). In the entire population, 2 and 5y outcomes were: relapse incidence (RI) -28% (95% CI: 24 - 32) and 33% (95% CI: 28 - 37), non-relapse mortality (NRM)- 28% (95% CI: 24 - 32) and 30% (95% CI: 26 - 35); leukemia free survival (LFS) -44 % (95% CI: 39 - 48) and 37 % (95% CI: 32 - 41 ), overall survival -50% (95% CI: 45 - 55 ) and 41% (95% CI: 36 - 46) and GVHD free relapse free survival (GRFS)- 33% (95% CI: 29 - 38) and 27% (95% CI: 22 - 31), respectively. More than 2 HLA mismatches were associated with a higher incidence of aGVHD Gr II-IV (29% vs 15%, respectively). In MVA, RI was lower for ALL vs AML HR (95% CI) 0.60 (0.39-0.93), p=0.02. Disease status (CR2 vs CR1) was poor prognostic factor for RI, LFS and OS. Age was prognostic factor for NRM, LFS and OS. HLA- mismatch at locus DR was poor prognostic factor, giving increased NRM: HR (95% CI) 1.68 (1.1-2.5), p=0.02, and lower LFS: HR (95% CI), 1.42 (1.03-1.95), p= 0.03 and OS HR (95% CI) 1.46 (1.04-2.03), p=0.03 and higher GVHD Gr II-IV HR (95% CI) 1.48 (1-2.17), p= 0.048. Results of MVA in AML pts in CR1 were similar. GVHD prophylaxis with CSA/MMF in comparison to CSA/MTX resulted in higher NRM HR (95% CI) 2.2 (1.27-3.82), p=0.005 and lower GRFS HR (95% CI) 1.58 (1.06-2.35), p= 0.02. Notably, in 154 pts with AML in CR1 transplanted from 6/8 UD with in vivo TCD, C mismatches was associated with higher incidence of cGVHD, HR (95% CI) 2.52 (1.40-4.53), p= 0.002. Conclusions: HCT from ≤6/8 MMUD is an alternative transplantation option for acute leukemia pts in CR that can provide 40% 5y OS, 37% LFS and GRFS of 27%. DR mismatch is a poor prognostic factor. cGVHD incidence at 5y was 41% with 21% being severe and is associated in AML pts with HLA C mismatches. CSA and MTX is the preferred GVHD prophylaxis. Emerging novel agents will hopefully reduce the incidence of cGVHD in the near future and thus improve HCT from ≤6/8 MMUD outcome. Disclosures Rambaldi: Italfarmaco: Membership on an entity's Board of Directors or advisory committees, Other: travel support, Research Funding, Speakers Bureau; Omeros: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Membership on an entity's Board of Directors or advisory committees, Other: travel support, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Other: travel support, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Other: travel support, Research Funding, Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees, Other: travel support, Research Funding, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Other: travel support, Speakers Bureau; Jazz: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Socie:Alexion: Consultancy. Mielke:Celgene: Honoraria, Other: Travel support (via institution), Speakers Bureau; EBMT/EHA: Other: Travel support; Bellicum: Consultancy, Honoraria, Other: Travel (via institution); IACH: Other: Travel support; Jazz Pharma: Honoraria, Other: Travel support, Speakers Bureau; DGHO: Other: Travel support; Kiadis Pharma: Consultancy, Honoraria, Other: Travel support (via institution), Speakers Bureau; GILEAD: Consultancy, Honoraria, Other: travel (via institution), Speakers Bureau; ISCT: Other: Travel support; Miltenyi: Consultancy, Honoraria, Other: Travel and speakers fee (via institution), Speakers Bureau. Platzbecker:Celgene: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Novartis: Consultancy, Honoraria. Finke:Riemser: Honoraria, Other: research support, Speakers Bureau; Neovii: Honoraria, Other: research support, Speakers Bureau; Medac: Honoraria, Other: research support, Speakers Bureau. Mohty:Jazz Pharmaceuticals: Honoraria, Research Funding.

Description: Abstract 6 Background Simultaneous ATRA and chemotherapy (CHT) is the current gold standard for newly diagnosed APL resulting in ∼80% cure rates, while arsenic trioxide (ATO) is the treatment of choice for relapsed patients. ATO in variable combinations including ± ATRA ± CHT has also been tested as front-line therapy yielding encouraging results in several pilot studies as well as in two phase III studies conducted in China and the US. So far, no randomised studies have compared front-line CHT-free ATO+ATRA combination against the standard ATRA+CHT approach. Patients and Methods The phase III, randomised, prospective APL0406 trial was started in October 2007 by the Italian GIMEMA group and joined in November 2008 by the German SAL and AMLSG multicenter groups. Eligible patients were adults aged 18-15 d) grade ≥ 3 neutropenia and thrombocytopenia were significantly more frequent in patients in arm B as compared to those in arm A (P

Description: Background Anemia is a common symptom in patients with Myelodysplastic Syndromes (MDS) and although erythropoietic agents are often active, it is frequently treated with red blood cell (RBC) transfusions. A substantial proportion of patients might also eventually become transfusion-dependent and, Iron-chelating therapies might be important to minimize complications of iron overload. Objectives To investigate the impact of deferasirox therapy on health-related quality of life (HRQOL) of lower risk transfusion-dependent MDS patients over a one year period. Secondary objectives were to investigate relationships between HRQOL and ferritin levels and to explore the prognostic value of baseline HRQOL on the probability of achieving transfusion independence. Patients and Methods This was a prospective study whose clinical findings (i.e., primary endpoint was safety and tolerability) were previously reported. HRQOL was a secondary endpoint of the study and we herein report, for the first time, HRQOL prospective findings. Eligible patients included: MDS patients 18 years or older, International Prognostic Scoring System (IPSS) low or intermediate-1 risk and diagnosed with transfusional siderosis following a minimum of 20 blood transfusions. Patients received daily oral deferasirox at a dose between 10 and 30 mg/kg of body weight for a period of 1 year. HRQOL was assessed with the EORTC QLQ-C30. HRQOL at baseline and at 3, 6, 9 and 12 months after treatment start. The EORTC QLQ-C30 consists of 30 items and includes five functional scales (physical, role, emotional, social, and cognitive), three symptom (fatigue, nausea and vomiting and pain) and a global health status/QOL scale and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial difficulties). The mean trend of HRQOL over time was estimated via a linear mixed model with a one-step autoregressive covariance structure. Such covariance structure provided the best model fit among those investigated. Results Overall, 159 patients were screened at 37 centers. The median duration of disease at enrollment was 32 months and median number of units of packed RBC received was 37. Seven patients did not start treatment at all and thus there were 152 expected HRQOL forms at baseline assessment. Out of these, 146 patients returned the questionnaire yielding a baseline compliance of 96%. No statistically significant differences over time were found for any scale of the EORTC QLQ-C30. Figure 1 depicts mean scores over time for selected scales of: fatigue, physical functioning, pain and global HRQOL. No HRQOL differences were found between patients with serum ferritin levels lower or higher than 2000 μg/L (pretreatment median value) at baseline. Also, the possible impact of ferritin level on HRQoL over time was estimated via a linear mixed model with a one-step autoregressive covariance structure. Coefficients and p values are reported in table 1. The prognostic impact of baseline HRQOL on the probability of achieving transfusion independence (i.e., defined as freedom from transfusion for 3 consecutive months) was investigated. Higher severity of pain (P=0.007) was associated with a greater likelihood of achieving transfusion independence. Multivariate analysis, controlling for age, IPSS risk score, time from diagnosis, number of previous blood transfusions and baseline ferritin level confirmed the independent value of pain (P=0.003). Conclusion Current findings suggest that Deferasirox therapy does not decrease HRQOL in lower risk transfusion-dependent MDS patients. Patients with higher baseline pain severity seems more likely to achieve transfusion independence and further analysis is needed to understand underlying reasons. Disclosures: No relevant conflicts of interest to declare.

Description: Background: Hodgkin Lymphoma (HL) is characterized by an inflammatory background and it has been demonstratedthat the reactive myeloid cells may exert an immune suppressive effect that favors progression of disease. The easily measurable NLR, the ratio between absolute neutrophils counts (ANC) and absolute lymphocyte count (ALC) and LMR, the ratio between ALC and absolute monocyte count (AMC) have been reported to reflect both the systemic inflammation and the myeloid associated immune suppression. We previously identified NLR, and to a lesser extend LMR, at baseline, as predictor of progression free survival (PFS) in HL patients. Objectives: To validate NLR〉6 and LMR≤2 as predictor of clinical outcome at diagnosis in the context of a prospective clinical trial of newly diagnosed advanced stage (aa) HL patients treated upfront with a PET-2 risk-adapted strategy. Methods: According to HD 0607 trial (Gallamini, JCO 2018), 782 advanced-stage HL patients were treated with 2 ABVD courses and a PET-2 performed afterwards. PET-2 positive (PET-2+) patients (N=149) were randomized to either BEACOPP escalated (Be) plus BEACOPP baseline (Bb) (4+4 courses) or Be+Bb (4+4) and Rituximab. PET-2 negative (PET-2-) patients were treated with 4 additional ABVD and, upon CR achievement, randomized to either consolidation radiotherapy on the sites of initial bulky disease or no further treatment. PET scans were centrally reviewed by an expert panel by Blinded Independent Central Review. Results: Median NLR at baseline was 5.7 (IQ range 3.8-8.3). NLR was higher in younger patients (