Abstract: Introduction. Blast phase (BP) is the terminal and most incurable phase of myelofibrosis (MF) and occurs in a not negligible fraction of patients (pts). In the pre-ruxolitinib (RUX) era, peripheral blasts, thrombocytopenia, unfavorable cytogenetics, and high risk category were identified as predictors of BP. RUX is the standard of care for symptomatic MF; however, information on clinical/laboratory correlates of BP in RUX-treated pts is not available. Aims. The primary objective of the study is to assess real-world data on incidence, risk factors and outcome of BP in RUX-treated MF pts. Methods. A multicentre observational retrospective study on RUX-treated MF pts was conducted in 20 European Hematology Centers. Data were extracted from an electronic database that included consecutive pts treated with RUX from June 2011. Data cut-off was June 2019. Risk category was assessed at RUX start according to the Dynamic International Prognostic Score System (DIPSS) or the Myelofibrosis Secondary to PV and ET Collaboration Prognostic Model (MYSEC-PM) in pts with post-Polycythemia Vera (PV)/post-Essential Thrombocythemia (ET) MF (secondary MF, SMF). A time-to-event (BP) analysis was conducted with Fine & Gray model with death/time of stem cell transplant as competing risks. Variables tested for association with BP were: age≥65yr, sex, transfusion-dependency, PLT 〈 150x109/l, peripheral blasts ≥3%, marrow fibrosis grade, CALR-unmutated genotype, unfavorable karyotype, spleen length (≥10 cm), total symptoms score (≥20), previous hydroxyurea (HU), alkylating agents, and interferon (IFN) use, time from MF diagnosis to RUX start, and PV/ET duration. Cumulative Incidence Function among risk categories for DIPSS and MYSEC-PM was calculated applying the Gray's model. Results . Overall, 589 MF pts were included and observed for 1833 pt-yrs from RUX start (median, 35.4 mos). Diagnosis was PMF in 304 pts (51.6%), PPV-MF in 164 pts (27.8%) or PET-MF in 121 (20.6%); 58.4% males. Molecular status was: JAK2V617F (82.5%), CALR (11.3%) and MPLW515K/L (1.1%); 5.1% were triple negatives. Overall, 368 (62.5%) pts received ≥1 cytoreductive therapy before RUX, specifically: HU, n. 357; alkylating agents, n. 47; anagrelide, n. 33; and IFN, n. 29. Median time from MF diagnosis to RUX start was 1.3 yrs. DIPSS for the whole cohort was: INT-1 (52.9%), INT-2 (40.1%), and HIGH (7%). DIPSS distribution in PMF pts was: INT-1 (47.8%), INT-2 (45.7%), and HIGH (6.5%), while SMF pts were categorized at LOW (11.1%), INT-1 (43.1%), INT-2 (31.2%) and HIGH (14.6%) risk according to the MYSEC-PM. Overall, 65 (11%) developed BP. In 61 pts, BP caused RUX withdrawal after a median time of 1.2 yrs (0.7-6.2); in 4 pts BP occurred after RUX stop (median time: 2.4 yrs). BP incidence rate was 3.6 x100 pt-yrs and was comparable in PMF and SMF (p=0.1). In univariate analysis, the probability of BP evolution for the PMF cohort was significantly reduced by previous IFN use (p=0.001). In SMF, predictors for BP in univariate analysis were PLT 〈 150 x109/l (p=0.001), blasts ≥3% (p=0.002), grade 3 marrow fibrosis (p=0.03) and PV/ET duration ≥ 10 yrs (p=0.02); previous IFN significantly reduced the risk of BP (p=0.02). In multivariable analysis, PLT 〈 150 x109/l (HR 2.4, 95% CI 1.1-5.4, p=0.03), blasts ≥3% (HR 3.3, 95% CI 1.4-7.5, p=0.004) and previous IFN (HR 0.1, 95% CI 0.02-0.8, p=0.04) remained significant. High DIPSS risk significantly predicted BP in PMF (p=0.04, HR [95% CI]: 2.6 [1.1-6.5] ) but not in SMF (p=0.40). In this latter cohort, only the MYSEC-PM was associated with BP (p=0.02, HR 1.7 [95% CI]: [1.1-2.8] ) (Fig.1). Estimated HRs, in reference to the lower score category, were: 1.10 for INT-1, 1.82 for INT-2, and 4.04 for HIGH risk. HR for HIGH risk, comparing to all lower risk groups, was 3.53 (95% CI: 1.53-8.11). Overall, 54 (81.8%) BP pts died and median survival was 2.8 mos. Survival after BP was not influenced by type of MF, previous response to RUX, and type of salvage treatment. Conclusions. Thrombocytopenia and peripheral blasts at RUX start identified pts at higher risk of BP in SMF, while previous IFN use was associated with reduced BP evolution in both PMF and SMF, suggesting a possible disease-modifying action of this agent. Also, this analysis supports the ability of MYSEC-PM in predicting BP in pts with SMF. Despite RUX use, outcome after BP remained dismal, confirming the need for newer treatment strategies. Disclosures Palandri: Novartis: Consultancy, Honoraria. Breccia:Incyte: Honoraria; Celgene: Honoraria; Novartis: Honoraria; Pfizer: Honoraria; BMS: Honoraria. Tiribelli:Incyte: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees. Benevolo:Novartis Pharmaceuticals: Consultancy. Bonifacio:Novartis: Honoraria; Amgen: Honoraria; Pfizer: Honoraria; Incyte: Honoraria; BMS: Honoraria. Iurlo:Pfizer: Honoraria; BMS: Honoraria; Incyte: Honoraria; Novartis: Honoraria. Elli:Novartis: Membership on an entity's Board of Directors or advisory committees. Abruzzese:BMS: Consultancy; Incyte: Consultancy; Novartis: Consultancy; Pfizer: Consultancy. Sgherza:Novartis: Honoraria; BMS: Honoraria; Pfizer: Honoraria; Incyte: Honoraria. Cavazzini:Pfize: Honoraria; Incyte: Honoraria; Novartis: Honoraria. Crugnola:Novartis: Honoraria; Incyte: Honoraria. Isidori:Janssen: Honoraria; Novartis: Honoraria; Gilead: Honoraria. Heidel:Novartis: Consultancy, Research Funding; Celgene: Consultancy; CTI: Consultancy. Latagliata:Janssen: Honoraria; Novartis: Honoraria; Pfizer: Honoraria; Celgene: Honoraria. Trawinska:Novartis: Consultancy, Honoraria. Krampera:Janssen: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Cuneo:Roche: 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; Gilead: Honoraria, Speakers Bureau; Abbvie: Honoraria, Speakers Bureau; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Cavo:takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel accommodations, Speakers Bureau; janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel accommodations, Speakers Bureau; bms: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; novartis: Honoraria. Palumbo:Novartis: Honoraria; Janssen: Honoraria; Celgene: Honoraria; Amgen: Honoraria; Hospira: Honoraria; Teva: Honoraria.

Abstract: Abstract 4545 The use of Peripherally-Inserted Central Catheters (PICC) as an alternative to Central Venous Catethers (CVC) is becoming very frequent in different setting of patients. To highlight the role of PICC also in patients with haematological malignancies, we revised our single Institute experience from 11/2008 to 7/2009. On the whole, 33 PICCs (BARD Groshong 4 Fr) were inserted in 32 patients [M/F 11/21, median age 59.9 years, Interquartile Range (IR) 47.1 – 74.7] for a total number of 1979 days. Twelve patients had Acute Myelogenous Leukemia (AML), 3 Acute Lymphoblastic Leukemia (ALL), 6 Non-Hodgkin Lymphoma (NHL), 5 Hodgkin Lymphoma (HD), 6 Myelodysplastic/Myeloproliferative Disorders (MDS/MPD); as to disease phase, 6 patients were at onset, 10 in complete response (3 before consolidation therapy and 7 before autologous peripheral stem-cell transplantation), 5 at disease relapse, 7 in chronic phase with transfusional requirement and 4 in advanced phase. PICC was successfully inserted in all cases with US-guide (in 21 cases via basilica vein, in 11 via brachial vein and in 1 via cephalic vein). At insertion, platelets count was 〈 50 × 109/l in 17/33 cases (51.5%) while WBC count was 〈 1.0 × 109/l in 6/33 cases (18.1%). An accidental PICC extraction occurred after 13 days; in addition, there were 2/33 (6.0%) (0,03/1000 gg) thrombophlebitic complications after 15 and 21 days respectively and 6/33 (18.1%)(0.10/1000 gg) infective complications [4 sepsis catheter-related from Staphylococci (3) or Acromobacter (1) and 2 local flogistic infiltration]. On the whole, 17/33 PICCs (51.5%) were removed after a median period of 39 days (IR 17 – 64); the reasons for removal were completion of treatment in 4 patients, death unrelated to the PICC in 6 and catheter-related complications in 7 (5 for infection, 1 for thrombosis and 1 for accidental extraction). The remaining 16/33 PICCs (48.5%) are still in use after a median period of 73 days (IR 30 – 93). In conclusion, PICC seems to be a useful, safe and promising alternative to conventional CVC for many haematological malignancies in a wide spectrum of clinical settings, ranging from intensive chemotherapy (including autotransplant procedure) to chronic management and very advanced phases requiring palliative approach. Disclosures: No relevant conflicts of interest to declare.

Abstract: Introduction: Hydroxyurea (HU) is the recommended treatment in patients (pts) with polycythemia vera (PV) at high thrombotic risk. In 2013, European LeukemiaNet (ELN) guidelines defined criteria for response to HU including hematology and clinical parameters (Barosi G, Blood 2013). Yet, estimates of ELN response rates and of their influence on clinical outcomes are lacking. Methods: The "PV-NET" is a European multicentre observational clinical study including now 530 cases of PV followed in 16 European Hematology Centers. Inclusion criteria are: 2016 WHO diagnosis of PV; availability of clinical/laboratory data at diagnosis and during follow-up; age≥18 yrs. Data cut-off was June 2019. A time-to-event (thrombosis, hemorrhage, evolution into blast phase [BP] or myelofibrosis [MF] ) analysis was calculated from HU start with Fine & Gray model with death as competing risk. Overall survival (OS) was calculated from HU start to last contact/death (log-rank p). Response to HU was defined per ELN criteria: Complete (CR): Hematocrit (Hct) 〈 45% without phlebotomies (PHL) & PLT ≤400×109/L & WBC ≤10×109/L & normal spleen size & no PV-related symptoms; Partial (PR): Hct 〈 45% without PHL or response in 3/4 criteria. Results: Overall, 438 required HU and were observed for 3069 pt-yrs. Characteristics at diagnosis were: median age: 62.3 yrs (22.3-89.5); males: 52.5%; median (range) WBC/PLT count, x109/l: 10.8 (1.1-33)/490 (143-1070); median hemoglobin (g/dl)/Hct (%): 18.6/56 (males); 17.6/54.7 (females); 56 (12.8%) and 30 (6.9%) pts had a thrombosis prior to or at diagnosis, respectively. Overall, 327 (74.7%) pts reported at least one PV-related symptom and 166 pts (37.9%) had a palpable spleen (≥10 cm: 8.4%). Median time from diagnosis to HU start was 2.9 (0.07-238) mos. At HU start, 350 (79.9%) pts were at high thrombotic risk. HU was used first-line in 426 (97.3%) pts and second-line in 12 pts (10 pts after interferon). Median HU dose was 0.5 g/d (0.25-2); 21.7% of pts received ≥ 1 g/d. After HU start, 36 pts presented 50 all-grades thromboses (arterial: 50%; grade ≥3: 51.1%), for an incidence rate of 1.6 per 100 pt-yrs (grade ≥3: 0.7). Thromboses were: deep/superficial vein thrombosis (32%/10%), acute myocardial infarction (12%), stroke (10%), transient ischemic attack (12%), spleen infarction (12%), retinal artery occlusion (4%), pulmonary embolisms (6%), and one splanchnic vein thrombosis. Thirteen bleedings (gastrointestinal: 61.5%; mucocutaneous: 30.8%; one hemothorax) occurred in 11 pts, for an incidence rate of 0.5 (grade ≥3: 69.2%). Overall, 12 progressions to BP and 29 MF evolutions were recorded (incidence rates: 0.5 and 1.3 X 100 pt-yr); 31 pts died. At the time of best response to HU, 62.3% of pts had at least one elevated hematology value; 231 (52.7%) pts continued PHL during HU (median PHL per yr: 2.5 [1-4]) (Fig.1). Per ELN criteria, 125 pts (28.6%) and 228 (52%) achieved a CR and PR, respectively, while 85 (19.4%) had no response (NR). The type of ELN response to HU (CR vs PR vs NR) did not affect the probability of thrombosis (p=0.56), hemorrhages (p=0.70), evolution to BP (p=0.60) or MF (p=0.14), and OS (p=0.37). After a median follow-up from HU start of 4.2 yrs, 95 (21.7%) patients discontinued HU. The percentage of pts who discontinued HU was 8.4%, 16.2% and 19.4% at 5, 10 and 15 yrs and was significantly lower in CR pts compared to pts with PR and NR (p=0.02). The overall HU discontinuation rate was 4.1 per 100 pt-yr. Reasons for HU discontinuations were: failure to control hct and/or leucocytosis and/or thrombocytosis (16.9%), failure to reduce splenomegaly and/or symptoms (7.4%), MF (12.6%) or BP (4.2%) evolution, second neoplasia (4.2%). A total of 52 pts (54.7%) discontinued due to HU-related toxicity, specifically: skin lesions (46.3%), oral aftosis (14.6%), gastrointestinal disorders (12.2%), fever (9.8%), thrombocytopenia (9.8%), and anemia (7.3%). Survival was not influenced by HU discontinuation (p=0.50). Conclusions: ELN-defined CR was rarely achieved by HU-treated pts, mainly due to low HU doses and PHL requirement, and did not influence outcome parameters. These data outline the relatively low utility in the current clinical practice of ELN criteria for the evaluation of HU treatment; their implementation would be relevant to base therapy changes on prognostic considerations. Finally, around 20% of pts discontinued HU, confirming that there is room for improvement in PV treatment strategy. Disclosures Palandri: Novartis: Consultancy, Honoraria. Elli:Novartis: Membership on an entity's Board of Directors or advisory committees. Benevolo:Novartis Pharmaceuticals: Consultancy. Tiribelli:Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees. Bonifacio:Novartis: Honoraria; Amgen: Honoraria; Pfizer: Honoraria; Incyte: Honoraria; BMS: Honoraria. Cavazzini:Pfize: Honoraria; Incyte: Honoraria; Novartis: Honoraria. Palumbo:Novartis: Honoraria; Teva: Honoraria; Celgene: Honoraria; Janssen: Honoraria; Amgen: Honoraria; Hospira: Honoraria. Heidel:Novartis: Consultancy, Research Funding; Celgene: Consultancy; CTI: Consultancy. Crugnola:Incyte: Honoraria; Novartis: Honoraria. Cuneo:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Honoraria, Speakers Bureau; Abbvie: Honoraria, Speakers Bureau; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Krampera:Novartis: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees. Breccia:Novartis: Honoraria; Celgene: Honoraria; BMS: Honoraria; Pfizer: Honoraria; Incyte: Honoraria. Cavo:sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel accommodations, Speakers Bureau; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel accommodations, Speakers Bureau; novartis: Honoraria; takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; bms: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Latagliata:Celgene: Honoraria; Pfizer: Honoraria; Janssen: Honoraria; Novartis: Honoraria.

Abstract: Introduction . The 2016 WHO criteria identified early primary myelofibrosis (early-PMF) as an individual entity with different clinical/laboratory presentations and a significantly better outcome compared to overt PMF. No information is available on the therapeutic effects of ruxolitinib (RUX) in the context of each disease separately. Aims . To report the differences between early and overt PMF patients (pts) treated with RUX in terms of baseline clinical/laboratory characteristics, response to treatment and toxicity. Methods . A clinical database was created in 23 European Hematology Centers including retrospective data of 537 MF pts treated with RUX from Jan 2011 to July 2018. Spleen and symptoms response (SR & SyR) to RUX were evaluated according to the 2013 IWG-MRT criteria. Hematologic toxicity and infections were graded according to the WHO scale. Overall survival (OS) and progression-free survival (PFS) were estimated from diagnosis using the Cox proportional hazards regression model, with adjustment for the dynamic international prognostic score system (DIPSS) and left-truncation. Results . A total of 199 pts had a diagnosis of early (n. 59, 29.7%) or overt (n. 140, 70.3%) PMF confirmed by bone marrow biopsy at RUX start and were included in this analysis. At RUX start, median age was 68.4 yrs (26.5-88.9) and 66.3% of pts had a spleen palpable at ≥10 cm below the left costal margin (LCM) (median spleen length: 12 cm). Median hemoglobin value and total symptoms score (TSS) were 10.5 g/dL and 20 (0-80), respectively. DIPSS distribution was: intermediate-1 (50.5%), intermediate-2 (42.1%), high (7.4%). Molecular status was: JAK2V617F 72.3%, CALR 13.7%, MPLW515K/L 3.1%, triple-negative 5%. Median time from diagnosis to RUX start was 22.4 mos (0.1-394). Compared to overt PMF pts, pts with early PMF started RUX with higher hemoglobin levels (median, 11.6 vs 10.4 g/dl, p=0.01) and lower circulating blast counts (p 〈 0.001), and were more frequently at intermediate-1 DIPSS risk (69.6% vs 42.5%, p 〈 0.001). RUX starting and 12-weeks titrated doses were comparable in the two groups. At 3 and 6 months, 43.1% and 48.9% of early-PMF pts achieved a SR, compared to 27.9% and 31.3% of overt-MF pts (p=0.04 and p=0.04, respectively). The rate of SyR was also higher in early-PMF pts at 3 months (82.5% vs 68.8%, p=0.05) and at 6 months (90.0 vs 73.7, p=0.02). In the first 12 months from RUX start, anemia/thrombocytopenia of all grades occurred in 75.6%/43.1% and 86.3%/60.0% of early and overt PMF pts, respectively (p=0.11 and p=0.03). At 3 months, anemia was more frequent in overt PMF pts (94.7% vs 80.0%, p=0.01), with 32.6% of pts having a grade 3-4 anemia compared to 17.8% in early PMF (p=0.02). The incidence of thrombocytopenia was also higher in overt PMF at 3 (51.5% vs 36.2%, p=0.05) and 6 (52.9% vs 35.8%, p=0.04) months, with only 2.2% and 2.5% of pts having a grade 3-4 thrombocytopenia, respectively. Seventy-five pts had at least one grade ≥2 infectious episode during RUX therapy. Considering death as competing risk, the cumulative risk of infections grade ≥2 was comparable in the two cohorts (p=0.4). Overall, 108 pts discontinued RUX (52.5% and 55.0% of early and overt PMF pts, p=0.7). Evolution into acute leukemia (AL) occurred in 21 pts. After a median follow-up of 23 months, 69 pts died (19 early), specifically because of progression of myelofibrosis (38%), AL (16.9%), infections (11.3%), hemorrhage/thrombosis (12.6%), second neoplasias (8.5%) or transplant-associated toxicity (2.8%), other causes (9.9%). OS (p=0.88) and PFS (p=0.86) were comparable in early and overt PMF pts. Conclusions . This study indicates for the first time that early PMF represents a category of pts that is projected to have better responses and lower toxicities from RUX treatmemt. In the setting of RUX therapy, a WHO-defined diagnosis may contribute to better identify pts who may deserve a strict monitoring during treatment. Disclosures Palandri: Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Palumbo:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Abruzzese:BMS: Consultancy; Pfizer: Consultancy; Novartis: Consultancy; Ariad: Consultancy. Foà:INCYTE: Other: ADVISORY BOARD; GILEAD: Speakers Bureau; JANSSEN: Other: ADVISORY BOARD, Speakers Bureau; ROCHE: Other: ADVISORY BOARD, Speakers Bureau; CELTRION: Other: ADVISORY BOARD; ABBVIE: Other: ADVISORY BOARD, Speakers Bureau; AMGEN: Other: ADVISORY BOARD; NOVARTIS: Speakers Bureau; CELGENE: Other: ADVISORY BOARD, Speakers Bureau. Vitolo:Takeda: Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Gilead: Speakers Bureau; Sandoz: Speakers Bureau. Aversa:Basilea: Honoraria, Membership on an entity's Board of Directors or advisory committees; Astellas: Honoraria; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Merck: Honoraria; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees. Cuneo:Roche: Other: advisory board, Speakers Bureau; Abbvie: Other: advisory board, Speakers Bureau; Gilead: Other: advisory board, Speakers Bureau; janssen: Other: advisory board, Speakers Bureau. Di Raimondo:Celgene: Honoraria; Takeda: Honoraria, Research Funding. Cavo:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: Honoraria, Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Breccia:Incyte: Honoraria; Pfizer: Honoraria; Novartis: Honoraria; BMS: Honoraria.

Abstract: The main objective of this study was to compare the long-term health-related quality of life of patients with acute promyelocytic leukemia (APL) treated with all-trans retinoic acid (ATRA) plus arsenic trioxide (ATO) vs ATRA plus standard chemotherapy. Patients previously enrolled in the randomized controlled trial APL0406 were considered eligible for this follow-up study. The following patient-reported outcome measures were used: the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core30 (EORTC QLQ-C30), the EORTC Quality of Life Questionnaire Chemotherapy-Induced Peripheral Neuropathy 20 (QLQ-CIPN20), and the Short Form Health Survey 36 (SF-36). The prevalence of late comorbidities and health problems was also assessed. The clinical significance of differences was evaluated based on predefined thresholds. A total of 161 of 232 potentially eligible patients were analyzed, of whom 83 were treated with ATRA-ATO and 78 were treated with ATRA chemotherapy. The median time since diagnosis of the study sample was 8 years. The 2 largest clinically meaningful differences in the EORTC QLQ-C30 were observed for role functioning (Δ = 8.4; 95% confidence interval [CI], 0.5 to 16.3) and dyspnea (Δ = −8.5; 95% CI, −16.4 to −0.7), favoring patients treated with ATRA-ATO. With regard to the SF-36 results, a clinically relevant better physical component score (Δ = 4.6; 95% CI, 1.3 to 7.8) was observed in patients treated with ATRA-ATO, but this was not the case for the mental component score. The 2 groups showed similar profiles in the scores of the EORTC QLQ-CIPN20 scales and in the prevalence of late comorbidities. Overall, our findings suggest that the greater and more sustained antileukemic efficacy of ATRA-ATO is also associated with better long-term patient-reported outcomes than ATRA chemotherapy. This study was registered at www.clinicaltrials.gov as #NCT03096496.

Abstract: The development of different generations of BCR-ABL1 tyrosine kinase inhibitors (TKIs) has led to the high overall survival of chronic myeloid leukemia (CML) patients. However, there are CML patients who show resistance to TKI therapy and are prone to progress to more advanced phases of the disease. So, implementing an alternative approach for targeting TKIs insensitive cells would be of the essence. Dihydroorotate dehydrogenase (DHODH) is an enzyme in the de novo pyrimidine biosynthesis pathway that is located in the inner membrane of mitochondria. Here, we found that CML cells are vulnerable to DHODH inhibition mediated by Meds433, a new and potent DHODH inhibitor recently developed by our group. Meds433 significantly activates the apoptotic pathway and leads to the reduction of amino acids and induction of huge metabolic stress in CML CD34+ cells. Altogether, our study shows that DHODH inhibition is a promising approach for targeting CML stem/progenitor cells and may help more patients discontinue the therapy.

Abstract: Health-related quality of life (HRQoL) is an important goal of therapy for patients with myelodysplastic syndromes (MDS); however, little is known about HRQoL of these patients at clinical presentation. We report HRQoL profile of newly diagnosed patients with MDS across both the the International Prognostic Scoring System (IPSS) and IPSS-Revised (IPSS-R) classifications, stratified by sex and age group categories, aiming to also establish European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core30 (EORTC QLQ-C30) reference values for these patients. Analysis was based on 927 patients with a median age of 73.3 years (interquartile range, 66.0–79.2), of whom 506 and 421 with lower- and higher-risk disease respectively, according to the IPSS classification. HRQoL was assessed with the EORTC QLQ-C30 and substantial differences by age groups and sex, between and within lower- and higher-risk disease categories were observed. For example, within higher-risk disease patients, the youngest group (ie, 30–59 years) tended to report clinically meaningful worse outcomes across various functional and symptom domains compared with older age groups. We also developed 2 regression models allowing for the prediction of EORTC QLQ-C30 reference scores for patients classified according to either the IPSS or the IPSS-R. Investigation of prevalence rates for clinically important problems and symptoms at diagnosis revealed a substantial burden of the disease with 〉 50% of patients reporting clinically important problems with physical functioning and dyspnea in both lower- and higher-risk disease. Our findings may help to enhance the interpretation of HRQoL outcomes in future MDS studies and to better contextualize HRQoL data from routine practice settings.

Abstract: Abstract 1019 Poster Board I-41 INTRODUCTION: Erythroleukemia is characterized by a peculiar marrow feature: a proliferation of erythroblasts greater than 50% and of myeloblasts greater than 30%, according to the FAB classification. Treatment strategies are usually indistinct from other forms of acute myeloid leukemia (AML), with the exception of acute promyelocytic leukemia. Although generally considered as a very aggressive subtype of AML, very few data are available concerning epidemiologic features and specific outcome of erythroleukemia among AMLs. MATERIALS AND METHODs: Adult patients with AML consecutively enrolled in the GIMEMA trials AML10 and LAM99p were retrospectively analyzed with the aim of evaluating the epidemiologic features and outcome of acute erythroid leukemia (FAB M6) characterized by morphological/cytochemical criteria after central revision, in comparison with non-M6 AML. RESULTs: Among 1675 AML patients, 59 (3.6%) were identified as M6; 39 were males and 20 females, the median age was 49 years (range 25.9-60.8), the median WBC count at diagnosis 2.7 × 109/l (range 0.7-41.8), the median Hb level 7.8 gr/dl (range 5.1-11.8) and the median platelet count 38 × 109/l (range 6-245). Univariate analysis showed a statistical difference between the M6 cases and the non-M6 series enrolled in these two clinical trials with regard to: incidence of male gender (p=0.03), prevalence of older age (p=0.001), leukopenia at diagnosis (p 〈 0.0001), decreased levels of Hb (p=0.0006), lower platelet count (p=0.05), peripheral blast count (p 〈 0.0001) and increased PMN count (p 〈 0.0001). A previous myelodisplastic phase was reported in 5.6% of M6 cases compared to 1.7% in the other AML subtypes (p=0.07). Analysis of response to intensive chemotherapy, evaluated as ITT, showed that 64.4% of M6 patients achieved a complete remission (CR) compared to 69.6% in the other FAB subtypes (p=0.39); a similar induction death rate (13.5%) was observed in both groups. Overall survival (OS) at 60 months was 29.5% in M6 patients and 34% in the other FAB types (p=0.75), as shown in the figure; no significant difference was recorded also with regard to disease-free survival (DFS): 44% in M6 vs 39.7% in the other FAB types after 60 months of follow-up (p=0.59). For patients who obtained a CR, the cumulative incidence of relapse (CIR) showed no statistical differences: 45% at 60 months in M6 vs 46.9% in the other types, p=089). Also the cumulative incidence of non-relapse mortality (CINRM) at 60 months was similar in both groups: 10.7% in M6 vs 13.4% in the other types, p=0.62. CONCLUSIONs: Despite the higher incidence of some risk factors - higher age, higher proportion of myelodisplastic pre-phase and cytopenias - in this rare form of AML the CR duration and the OS are similar to those observed in the other more frequent forms of AML. Based on this analysis, the prognosis of this form of acute leukemia does not differ from that of the other subtypes. Disclosures: No relevant conflicts of interest to declare.