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Multiple myeloma (MM) is characterized by recurrent relapses. Consequently, patients receive multiple therapy lines, including alkylating agents and immune modulators, which have been associated with secondary malignancies such as myelodysplastic syndrome (MDS). Anti-B-cell maturation antigen (BCMA) chimeric antigen receptor T cell (CART) therapy is efficacious in patients with relapsed/refractory (R/R) MM. However, the long-term complications, particularly MDS, are not well understood. Whether CART therapy causes or promotes MDS has not been thoroughly investigated. In this study, we explored the causal relationship between MDS and CART therapy. We retrospectively examined the prevalence of MDS-related morphological and mutational changes before and after administration of CART therapy in five patients. Among them, four developed MDS after CART therapy, while one had pre-existing MDS prior to CART. None of the four patients who developed post-CART MDS showed morphological MDS changes prior to CART therapy. However, all four patients exhibited molecular alterations associated with MDS in their pre-CART as well as post-CART therapy bone marrow. No new mutations were observed. Our findings provide initial evidence suggesting that anti-BCMA CART therapy in MM may promote expansion of pre-existing MDS clones rather than causing development of new clones.

Polatuzumab (Pola)-based regimens and chimeric antigen receptor T (CAR T) cells provide superior outcome compared to conventional chemoimmunotherapy in patients with relapsed/refractory diffuse large B cell lymphoma (R/R DLBCL). Choosing between these strategies remains controversial. The efficacy of CAR T versus Pola-rituximab(R) /Pola-bendamustine(B)-R in R/R DLBCL patients after failing ≥2 lines of treatment was compared in a retrospective, 'real-world' study. Propensity score matching, for age, lymphoma category (de-novo/transformed), number of prior lines, Eastern Cooperative Oncology Group performance status and lactate dehydrogenase level, was applied to control for differences in patients' characteristics. Response rate, progression-free survival (PFS) and overall survival (OS) were analyzed. A total of 82 patients, treated with CAR T (n=41) or Pola-based regimens (n=41), were included. No treatment-related deaths occurred with CAR T vs. 3 (7.3%) with Pola. The overall and complete response rates were 83% and 58% with CAR T vs. 66% and 44% with Pola-based-regimens (p=0.077 and p=0.18, respectively). At a median follow-up of 9 months (range 1-19.2) and 16 months (range 0.7-25.3) for the CAR T and Pola arm respectively, the median PFS has not been reached for CAR T vs. 5.6 months for Pola (95% CI 3.6-7.6, p=0.014). Median OS has not been reached for CAR T vs. 10.8 months (95% CI 2.2-19.4) for Pola (p=0.026). To conclude, in a real-world setting, treatment with CAR T achieved superior PFS and OS compared to Pola-based regimens in patients with R/R DLBCL.

The efficacy of polatuzumab vedotin in relapsed/refractory diffuse large B-cell lymphoma outside clinical study are undetermined. This retrospective study examined the efficacy and safety of polatuzumab vedotin administered in real life settings. Forty-seven patients, 31 with

We reviewed pre-diagnosis clinical data of 420 patients with pathologically confirmed myelodysplastic syndromes (MDSs) presenting with anemia. In 232 patients with yearly pre-diagnosis complete blood counts (CBCs), we also analyzed CBC kinetics in respects to a standardized timepoint in which all patients had similar levels of hemoglobin (Hgb). At the standardized timepoint (last documented 12 > Hgb ≥ 11 g/dL), occurring months-years before diagnosis, median CBC values were Hgb 11.4 g/dL, absolute neutrophil count (ANC) 2.7 × 103 (k)/mcl, and platelets (PLTs) 181 k/mcl. Gradual changes in CBC could be observed years prior to this timepoint, for the most part while within normal/near-normal limits. During this time, most patients had a coexisting alternative etiology for anemia. Patients with high-risk cytogenetic/blast features had a rapid and steeper decrease in counts in the last year before developing a concerning anemia (decrease in: Hgb 0.75 g/dL vs 0.55 g/dL; PLT 29.5 vs 4.5 k/mcl; ANC 0.86 vs 0.4 k/mcl, P = .03). Low-risk patients had a high rate of longstanding mild anemia (31% vs 16%, P = .05). Rate of development of cytopenia and number of involved hematopoietic lines were prognostic. In 65% of patients, with near normal CBC at the standardized timepoint, but in whom there was a decrease in multiple hematopoietic lines over the preceding year, the 5-year overall survival (5yOS) was 53% compared to 71% in patients with isolated slowly progressing anemia (20% of patients). In 15% of patients with mild cytopenia developing after both a rapid decrease and multiple involved lines, prognosis was dismal (5yOS 34%). In conclusion, kinetics of pre-MDS CBC values correlate with disease risk and survival.

Objectives To ascertain the relevance of bone marrow cellularity (BMC) to the interpretation of blast percentage (blast%) in MDS prognostication. Methods We compared survival prediction based on blast% adjusted to different levels of cellularity, compared to the survival based on the original IPSS-R blast% grouping. Results We analyzed 355 consecutive MDS patients. Cellularity, in and of itself or its interaction with blast%, was not associated with overall survival (OS). In a small subset of patients with a hypercellular marrow (15%; n = 26), dismal prognosis was observed at lower levels of blast%. For these cases OS was similar to higher IPSS-R blast groups. For example, within the Intermediate group (blast% 5%-10%), those with a hypercellular marrow and >6% blasts had an OS of 10 m similar to 16 m in the High (blast% 10%-19%) blast group. These changes did not translate into a significant improvement in overall prognostic power of a cellularity-adjusted IPSS-R (C index 0.71 vs. 0.70). Conclusion Adjusting blast% to cellularity did not improve prognostication. However, within IPSS-R-defined blast groups, a small subset of patients with relatively higher blast% and hypercellularity may have a worse prognosis than expected.

Background The assessment of health-related quality of life (HRQoL) in patients with myelodysplastic syndromes (MDS) is critical to organize more robustly patient-centered care. Therefore, availability of well-validated disease-specific HRQoL measures in this area is important. Objectives We investigate the validity of the Quality of Life in Myelodysplasia Scale (QUALMS), to assess HRQoL in MDS patients reported to the European MDS (EUMDS) Registry. A prior validation effort has been reported (Abel G, et al. Haematologica, 2016 June; 781-88), but this was largely a North American cohort and subscales suggested by the original principal components analysis had not been validated. Patients and Methods The QUALMS questionnaire was included in the EUMDS Registry (de Swart L, et al. Br J Haematol. 2015 Aug;170:372-83), a large international initiative including several European countries and Israel. We used proportions, median and interquartile range (IQR) to summarize patients' characteristics at baseline. We also assessed internal consistency and test-retest reliability by Cronbach's alpha (threshold for acceptability Cronbach's alpha ≥0.70). Confirmatory factor analysis (CFA) was used to examine the model fit for the underlying scale structure. The model performance was evaluated by Comparative Fit Index (CFI), the Tucker-Lewis Index (TLI), and the Root Mean Squared Error of Approximation (RMSEA), where acceptable values were >0.90 for CFI and TLI and RMSEA Results Overall, 270 MDS patients completed the QUALMS questionnaire, from 17 centers across four countries: Austria (N = 61), Israel (N = 67), The Netherlands (N = 37) and United Kingdom (N = 105). The majority of patients were male (67.4%) with a median age at diagnosis of 74 years (IQR =68.0-80.0) and a low MDS-CI score (n=158). CFA indicated acceptable model fit, respectively CFI=0.93, TLI=0.93 and RMSEA=0.07. For all analyses, the scales QUALMS-physical burden (P), QUALMS-emotional burden (E) and the total score showed satisfactory results, while the scale QUALMS-benefit finding (BF) showed worse results. Internal consistency and test-retest reliability were acceptable for the total score (TS) and all scales but BF (see figure). Pairwise correlations between QUALMS-P, QUALMS-E, TS and all the scales from EQ-5D-3L (including VAS) showed satisfactory concurrent validity (range from -0.67 to 0.60). Only the QUALMS-BF did not correlate with any of the EQ-5D-3L scales (range from -0.07 with EQ-VAS to 0.14 with EQ-5D Anxiety/ Depression). As per discriminant validity, all known-group comparisons were statistically significant and consistent with the underlying clinical construct for all scales apart for the QUALMS-BF. For example, the QUALMS-P mean scores were 75.8 vs 54.6 (p< 0.001) for patients with a higher vs lower KPS, while the corresponding QUALMS-BF mean scores were 49.4 vs 50.9 (p=0.829). The same profile resulted for responsiveness to change, where all scales reflected significant changes in Hb levels and in EQ-VAS score in the expected direction, while QUALMS-BF did not. For example, those patients who experienced a clinically meaningful deterioration in the VAS score also had also a worsening in QUALMS-P (Δ=-6, p=0.003), QUALMS-E (Δ=-1.8, p=0.075) and TS (Δ=-3, p=0.003). Conclusions Current findings provide novel evidence-based data that support the validity of the QUALMS for its use in European and Israeli patients with MDS. Implementation of the QUALMS in MDS research may further raise PRO standards in this area. Figure 1 Figure 1. Disclosures Efficace: Takeda: Consultancy; Janssen: Consultancy; Abbvie: Consultancy, Other: Grants (to Institution); Amgen: Consultancy, Other: Grants (to Institution). Mittelman: Janssen · Roche · Novartis · Takeda · Medison / Amgen · Neopharm / Celgene / BMS · Abbvie · Gilead: Research Funding; Novartis · Takeda · Fibrogen · Celgene / BMS · Onconova · Geron: Other: Clinical Trial Support; Onconova · Novartis · Takeda · Silence: Membership on an entity's Board of Directors or advisory committees; MDS HUB: Consultancy; Celgene / BMS · Novartis: Speakers Bureau. Van Marrewijk: Novartis Pharmacy B.V. Oncology Europe: Other: project manager of the EUMDS Registry, is funded from the EUMDS (educational grants from Novartis Pharmacy B.V. Oncology Europe); Amgen Limited: Other: project manager of the EUMDS Registry, is funded from the EUMDS (educational grants from Amgen Limited); Celgene International: Other: project manager of the EUMDS Registry, is funded from the EUMDS (educational grants from Celgene International); Janssen Pharmaceutical: Other: project manager of the EUMDS Registry, is funded from the EUMDS (educational grants from Janssen Pharmaceutical); Takeda Pharmaceuticals International: Other: project manager of the EUMDS Registry, is funded from the EUMDS (educational grants from Takeda Pharmaceuticals International); EU's Horizon 2020 program: Other: MDS-RIGHT (grant from EU's Horizon 2020 program) project budgets. de Witte: Takeda: Research Funding; Novartis: Research Funding; Janssen: Research Funding; Celgene: Research Funding; Amgen: Research Funding. Stauder: Celgene/BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Summary This multicentre study evaluated 5-year progression-free (PFS) and overall survival (OS) in early and advanced Hodgkin lymphoma (HL), where therapy was individualized based on initial prognostic factors and positron emission tomography-computed tomography performed after two cycles (PET-2). Between September 2006 and August 2013, 359 patients aged 18–60 years, were recruited in nine Israeli centres. Early-HL patients initially received ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) ×2. Depending on initial unfavourable prognostic features, PET-2-positive patients received additional ABVD followed by involved-site radiotherapy (ISRT). Patients with negative PET-2 and favourable disease received ISRT or ABVD ×2; those with unfavourable disease received ABVD ×2 with ISRT or, alternatively, ABVD ×4. Advanced-HL patients initially received ABVD ×2 or escalated BEACOPP (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, prednisone; EB) ×2 based on their international prognostic score (≤2 or ≥3). PET-2-negative patients further received ABVD ×4; PET-2-positive patients received EB ×4 and ISRT to residual masses. With a median follow-up of 55 (13–119) months, 5-year PFS was 91% and 69% for PET-2-negative and positive early-HL, respectively; 5-year OS was 100% and 95%, respectively. For advanced-HL, the PFS was 81% and 68%, respectively (P = 0·08); 5-year OS was 98% and 91%, respectively. PET-2 positivity is associated with inferior prognosis in early-HL, even with additional ABVD and ISRT. Advanced-HL patients benefit from therapy escalation following positive PET-2. EB can be safely de-escalated to ABVD in PET-2-negative patients.

Bone marrow (BM) metastases are known to worsen the outcome in patients with malignancies and alter the choice of the treatment regimen. In an attempt to identify routine parameters for the prediction of BM metastasis we evaluated the clinical and laboratory data of 103 patients with metastatic solid tumors. We also assessed which of these factors appeared to influence survival. Three laboratory abnormalities were found to be predictive of metastasis on BM biopsy: thrombocytopenia < 50 × 109/L OR 14.4; p = 0.02; hypocellular or dry tap aspirate OR 7.0; p = 0.02 and high serum alkaline phosphatase OR 6.5; p = 0.03. Three additional factors were found to be associated with deceased survival. Thrombocytopenia was associated with decreased survival from a median of 0.8 months to 4.1 months, p < 0.0001. Serum LDH levels more than twice the upper limit of normal were also reduced survival from 1.8 months versus 4.7 months, p = 0.03. Finally, the initial diagnosis of malignancy by bone marrow examination was associated with reduced survival from 1.8 months vs. 4.0 months, p = 0.03 in individuals where BM metastases were not the presenting feature of malignancies. Use of these simple clinical parameters may help in the early diagnosis of bone marrow metastases and improve clinical approach.

Azacitidine treatment is effective in higher risk MDS (HR-MDS), with less than 50 % response, lasting 2 years. Aza and lenalidomide (Len) have a potential synergistic effect. ViLen-01 phase IIa trial includes 6-month induction (Aza 75 mg/m(2)/day, days 1-5, Len 10 mg/day, days 6-21, every 28 days), 6-month consolidation (Aza 75 mg/m(2)/day, days 1-5, every 28 days), and 12-month maintenance (Len 10 mg/day, days 1-21, every 28 days). Response was evaluated according to IWG criteria. Totally, 25 patients enrolled, with an average of 76.3 years old (60-87), and 88 % with major comorbidities. Thirteen patients completed induction, 7 proceeded for consolidation, and 2 for maintenance. The overall response rate (ORR) was 72 % (18/25), with 6 (24 %) for CR, 3 (12 %) for marrow CR, and 9 (36 %) for hematologic improvement (HI). The 7 non-responding patients were on the study 3 days to 4.1 months. At 6 months, 4 of 6 evaluable patients achieved complete cytogenetic response and 2 with del (5q) at diagnosis. Adverse events (AEs) were as expected in these patients: grades III-IV, mainly hematologic-thrombocytopenia (20 patients) and neutropenia (13 patients). The common non-hematologic AEs were infections (14 patients), nausea (7), vomiting (7), diarrhea (7), and skin reactions (5). The median progression-free survival (PFS) was 12 ± 1.36 months, with median overall survival (OS) of 12 ± 1.7 months. Quality of life (FACT questionnaire) data were available for 12 patients with a tendency towards improved QoL. This trial with elderly HR-MDS patients with an expected poor prognosis demonstrates a high (72 %) response rate and a reasonable expected safety profile but a relatively short PFS and OS.

Background The Anti-CD20 monoclonal antibody Rituximab suppresses B-lymphocytes and may induce hypogammaglobulinemia in treated patients. The incidence and clinical significance of rituximab induced hypogammaglobulinemia in lymphoma patients is underestimated. Methods We retrospectively analyzed the rates of hypogammaglobulinemia, infection and infection-related mortality in 136 lymphoma patients who were treated with a combination of chemotherapy and rituximab. Results Rituximab given in more than 8 doses (OR 6.05, 95% CI: 1.24-29.5), relative hypogammaglobulinemia at time of lymphoma diagnosis (OR 4.2, 95% CI: 1.26-14.1) and the combination of fludarabine with rituximab (OR 3.4, 95% CI: 1.24-9.47) were factors significantly associated with prolonged (more than 6 months) hypogammaglobulinemia. The combination of fludarabine and rituximab (OR 6.4, 95% CI: 1.49-27.0) and secondarily prolonged hypogammaglobulinemia (OR 4.5, 95% CI: 1.19-18.5) were found to be predictive factors for severe infections and infection-related mortality. Conclusion These data suggest the importance of following serum immunoglobulin levels before and after combination immuno-chemotherapy, particularly in patients with recurrent infections or relapsed/refractory disease.

Structural mitochondrial abnormalities as well as genetic aberrations in mitochondrial proteins have been known in Myelodysplastic syndrome (MDS) , yet there is currently little data regarding the metabolic properties and energy production of MDS cells. In the current study we used state-of-the-art methods to assess OXPHOS in peripheral blood cells obtained from MDS patients and healthy controls We then assessed the effect of food supplements- Coenzyme Q10 and carnitine on mitochondrial function and hematological response .We show here for the first time that in low risk MDS there is a significant impairment of mitochondrial respiration in peripheral blood cells and this can be improved with food supplements. We also show that such myelodysplastic syndrome, mitochondria, oxidative phosphorylation, coenzyme Q10, seahorse XF analyzer. supplements lead to improvement in cytopenia's and quality of life.

Introduction Azacitidine (AZA) dose reduction is a common practice in cytopenic patients. However, a correlation between AZA dose and infection complications has never been studied. Patients and Methods Higher-risk patients with myelodysplastic syndrome or acute myeloid leukemia treated with AZA in 18 Israeli hospitals between the years 2008 and 2011 were included in a former national survey. To reveal the effect of AZA dosage on infection risk we limited our analysis to the infection rate after the first AZA dose alone. We excluded subsequent cycles of AZA from the analysis, because infectious events during these cycles might be related to other cofactors such as disease response to AZA therapy. Results After the first AZA cycle, infectious events were more frequent after doses of 75 mg/m 2 for 7 days than 75 mg/m 2 for 5 days (36/106 [34%] and 10/67 [14.9%], respectively; P = .008), regardless of the patient's age. Of the 46 recorded infectious events, the causative pathogen was identified as bacterial in 25 (54.3%) and as viral or fungal in 2 (4.3%) and 2 (4.3%) cases, respectively. No pathogen was identified in 17 (37%) cases. Infections were significantly more prevalent among patients who presented with platelet counts P = .012) and poor risk cytogenetics (40.7% vs. 19.8%; P = .008). Conclusion Reduction of AZA dose might decrease infection rate and therefore should be considered in patients with high infection risk.

Introduction The therapeutic options for diffuse large cell B cell lymphoma (DLBCL) patients (pts) that fail to respond/relapse after≥2 treatment regimens are limited. The SCHOLAR-1 study reported an overall response/ complete remission (ORR/CR) rates of 26%/ 7% with a median overall survival (OS) of 6.3 months in chemorefractory and early relapsing DLBCL pts. Polatuzumab vedotin (Pola) is a conjugated antibody that delivers the microtubule inhibitor MMAE to CD79b-expressing cells. Polatuzumab administered in combination with Bendamustine-Rituximab (P-BR) has been recently approved by the FDA for pts with relapsed/refractory (R/R) DLBCL that failed to respond≥2 prior therapies. The current study investigated the tolerability and efficacy of Pola mainly with BR, in DLBCL pts, treated through a compassionate program after failing ≥2 prior regimens. Methods Data of all pts with consecutive R/R DLBCL, treated with Pola-BR or Pola-R (2-8 cycles) in 11 Israeli centers between 6/2018 and -5/2019 were analyzed. Inclusion criteria for this study were: R/R DLBCL (denovo and transformed follicular lymphoma [t-FL]), age ≥ 18 years, ≥ 2 prior treatments. We evaluated pt characteristics, treatment details and toxicities, overall response and CR rates, progression free survival (PFS) and OS. Cox regression model was used to define factors affecting outcomes. Results 34 patients- (denovo DLBCL, n=24 and t-FL, n=10 ⌈50% -non CGB and 50% - GCB type⌉) were included. Median age at Pola administration was 65.5 (range 60-72) years. Stage ≥3 disease was recorded in 88% and IPI ≥3 in 73.5%. Median prior lines was 3 (range 3-5); including anthracyclines and rituximab in 100% and cisplatin-based regimens in 91%. 32% relapsed after ASCT and 9% after CART infusion. 53% had primary refractory disease, 29% had refractory relapse and 18% had prior sensitive relapse. 22 pts received Pola-B, mostly with Rituximab (n=19), and 12 received Pola-R. In 5 pts, Pola-based regimen was used as a bridge for Allo SCT (all responded CR, n=4 and PR, n=1) and in 6 as a bridge to CARTs (all responded CR n=1, PR n=2, SD n=3). Median number of Pola B cycles was 3 (3-5) and median Pola-R cycles was 4 (3-6). Median B dose per cycle was 90 mg/m2 (45-90). GCSF was used in 47%. Early treatment discontinuation due to progressive disease (PD) occurred in 8 (23%) of the entire cohort: 23% of Pola-B pts and 25% of Pola-R pts. Safety: Hematological AEs grade 3-4, reported with Pola- B vs Pola-R were: neutropenia (45.5.% vs 33%), thrombocytopenia (25% vs 8%) and anemia (23% vs 17%). Infections were recorded in 41% and 36% of Pola-B pts and Pola-R respectively. Neutropenic fever was reported in 36% in Pola-B pts and none in Pola-R. Pulmonary infections were recorded in 33.3% and 27.3% of Pola-B and Pola-R pts respectively, resulting in death in one pt. Peripheral neuropathy occurred in 18% of Pola- B pts (grade ≤2) vs 8% with Pola -R. Hospitalization due to AEs was recorded in 41% of Pola-B vs 25% of Pola-R. Pola dose reduction due to AE was reported in 1 pt (8%) in the Pola-R. Efficacy: ORR for the entire cohort was 65%, including 38% CRs and 27% PRs. 12% pts attained SD and 23% experienced PD. ORR was higher in non-GCB than in GCB pts 80% vs 43% (p=0.036). Median follow up of the entire cohort from Pola administration was 4.4 months (range 0.6-11.4). 6 months projected OS and PFS were 83% and 63%, respectively. Post Pola treatment in pts that failed to respond/Relapsed post pola: 8 patients had PD; 3 died from progression, 1-CART, 1-Allo SCT, 2-paliative care and 1-unknown. Additional 5 pts progressed during follow up; 4-CART and 1-palliative care. 1 patient continues Pola treatment after achieving SD. Univariate analysis for factors predicting PFS and OS GCB type (HR-1.816, P=0.055), Primary refractory vs relapsed disease (HR-1.507, p=0.049) and a higher number of prior lines since diagnosis (HR-1.35, p=0.079) tended to be associated with shorter time to progression. T-FL vs denovo DLBCL was associated with decreased OS (p=0.008). Data of 60 patients, including pts treated recently, therefore, not evaluable at the time of abstract submission, would be presented at ASH. Conclusions The toxicity of Pola-based regimen was relatively low. Pola based treatment provided an encouraging PFS and OS in pts with R/R DLBCL that failed to respond ≥2 prior therapies, treated in a real-life setting. Primary refractory disease, higher number prior lines and t-FL vs denovo DLBCL were associated with inferior outcome. Figure Disclosures Herishanu: Roche: Honoraria; AbbVie: Honoraria; Janssen: Honoraria.

Background: The majority of the patients with low risk myelodysplastic syndrome (MDS) become RBC-transfusion-dependent and thus symptoms resulting from iron overload and oxidative stress may develop. Yet, iron-chelation has not been part of the standard treatment for these patients. The purpose of this study was to assess the effect of deferiprone (L1), an iron chelator, on oxidative stress parameters in iron overloaded and blood dependent patients with low risk MDS. Methods: This work was supported by a grant from Apopharma. Nineteen low risk MDS patients were enrolled. Patients were classified as very low-, low- and intermediate-risk disease, according to the Revised International Prognostic Scoring System (IPSS-R). Inclusion criteria were a cumulative transfusion burden of >20 red blood cells (RBC) units and evidence of iron overload (serum ferritin >1,000 ng/mL). Deferiprone at a dose of up to a maximum dose of 100 mg/kg was administrated for 4 months. Blood samples were taken at baseline, at each monthly visit, and at the end of the study. The samples were tested for oxidative stress parameters: reactive oxygen species (ROS), phosphatidylserine (PS), glutathione (GSH) and membrane lipid peroxidation (LP); iron parameters: serum ferritin and cellular labile iron pool (LIP), and CBC. The primary efficacy variable as a measurement of oxidative stress was ROS. Student's t-test was applied for statistical analyses. Results: Patients (n=19) were treated with deferiprone in a daily dose of 25-100 mg/kg, median of 50 mg/kg/day. Eight patients received treatment for 120 days and completed the study. One of them had mild neutropenia that resolved after short discontinuation of the study drug and finished the study with no more complications. Eleven patients did not finish the study: eight patients due to gastrointestinal (GI) adverse effects, two patients withdrew their consent (one of them after mild neutropenia that resolved) and one patient was killed in a car accident. We thus had measurements of at least two time points for 16 of the patients. The median number of RBC transfusions during study period was 11 (2-20). The primary efficacy variable ROS, as a measurement of oxidative stress, was significantly decreased, in all three lineages: platelet, RBC and neutrophils (decrease of 32%, 33% and 32% respectively, each at P=0.001). Deferiprone administration was also associated with a reduction in other cellular markers of oxidative stress in RBC: PS, GSH, LP and LIP (decrease of 54%, 98%, 300%, and 42% respectively, each at P=0.001). No significant changes were observed in serum ferritin levels, likely due to the short treatment period in patients on repeated transfusion requirements. Conclusions: This is the first prospective study on chelation with Deferiprone in MDS patients. Our data provide preliminary evidence that administration of Deferiprone in a median daily dose of at 50 mg/kg can decrease iron-induced oxidative stress in iron-overloaded MDS patients. Of note, no events of agranulocytosis were observed. The future remains challenge is to prove that reduction in iron toxicity will eventually translate into a clinically meaningful improvement. Prof. Rachmilewitz who unfortunately passed away last year, had a significant contribution to the conception and design of this study. Disclosures No relevant conflicts of interest to declare.

Introduction: The treatment of advanced Hodgkin lymphoma (HL) has undergone many changes in recent years. The original International Prognostic Score (IPS) introduced by Hasenclever et al (1998) was based on a cohort of 1618 patients (pts) mainly treated with MOPP-ABV or ABVD between the years 1983 and 1992. One third (33%) of those pts also underwent involved field radiation therapy (IFRT). Staging was based on CT. The 5-y freedom from progression (FFP) results ranged between 84% and 42%, depending on the presence of 0-≥5 risk factors. The IPS has been validated in a number of studies and settings. Currently, staging is based on baseline PET/CT, which upgrades the disease stage in 15% and downgrades it in 5% of pts compared to CT scan. Positive interim PET/CT (PET-2) is predictive of an inferior prognosis in pts with early and advanced HL. Based on these findings, several studies have used a positive PET-2 as an indication for therapy escalation. However, the majority of relapses still occur in pts with negative PET-2, highlighting the need for additional prognostic markers. We evaluated baseline factors and lab results in a prospectively collected database of pts enrolled in a multicenter clinical trial (NCT00392314) where treatment was modified based on PET-2 results. The current study aimed to develop a model for refined prediction of HL progression risk in advance-disease pts with negative PET-2, using baseline risk factors. Methods: Pts with advanced classic Hodgkin lymphoma (HL) were stratified according to their baseline IPS; treatment was modified according to PET-2 results. Pts with IPS 0-2 initially received 2 ABVD cycles and those with IPS ≥ 3 received 2 cycles of escalated BEACOPP (EB). In the former group, if PET-2 was positive without evidence of disease progression, therapy was escalated to EB with involved site radiation therapy (ISRT) given to residual masses. If PET-2 was negative in both IPS strata, 4 additional ABVD cycles were administered. We evaluated whether traditional IPS parameters continued to predict relapse when treatment was modified based on PET-2 results, and assessed the need for new cutoffs based on ROC curves using univariate and multivariate Cox proportional hazard models. Results: Of 185 enrolled pts, 33 (18%) experienced disease progression and 27 (15%) had a positive PET-2. The 5-y PFS for the whole group, PET-2 negative and PET-2 positive subgroups was 80%, 82% and 68%, respectively (p=0.07). Eight of 33 (28%) relapsed pts had a positive Deauville score (≥3). On univariate analysis of traditional IPS parameters, male gender, age >45, stage IV disease were not found to be associated with a significantly increased hazard ratio (HR) for progression. New cutoffs for lymphocyte count and albumin level predictive of relapse were determined. The following parameters were significantly (P Conclusions: The current analysis, using data prospectively collected during a phase II study but analyzed retrospectively after pts had been stratified by IPS, suggests a scoring model that could refine the IPS-based identification of pts at a higher risk for disease progression, even if their PET-2 is negative. The findings imply that pts with 2 new risk factors (19% of pts) may need to initiate more intensive therapy than ABVD. However, given the retrospective nature of the analysis, its results should be interpreted with caution. The model needs to be verified in an independent cohort of pts with advanced HL using uniform treatment protocols. Table 1 Table 1. Disclosures Bairey: Janssen: Consultancy.