ALBERT

Description: Background Venous thrombosis (VT) frequently complicates the clinical course of cancer. Reported incidence of VT in many hematological neoplasms is up to 10%, a value comparable to that of solid tumors. Available data on the incidence and management of VT in Acute Leukemia (AL) are scanty and quite discordant. We have performed a multicenter retrospective study with the primary objective to evaluate the incidence of venous thrombotic complications in a population of patients with AL. Secondary objective was to evaluate the management of these complications in patients with AL. Materials and Methods Available clinical records of out and in-patients diagnosed with AL from January 2008 to June 2013 in 4 Regional Reference Hospitals were analyzed. Cases of venous thrombosis (VT), including thrombosis in atypical sites [Retinal occlusion (RO) and Cerebral Sinus Thrombosis (CST)], were reported in the current study. All data were recorded in a dedicated database. Available laboratory tests at diagnosis of VT included complete blood cells count (CBC), basal coagulation tests (PT, aPTT, fibrinogen), Antithrombin, anticoagulant Protein S and C and D-dimer. Instrumental Diagnosis of deep vein thrombosis (DVT), pulmonary embolism (PE) and RO and CST was performed according to ACCP guidelines. In the statistical analysis, logistic regression model was applied. Fisher’s exact test was used to determine relationships between categorical variables. All P-values represented were two-sided, and statistical significance was declared when P〈 0.05. Results Over a population of 831 patients with AL, 37 cases of VT were recorded, mainly (34/37 cases) in hospitalized patients: 24 cases were associated with Acute Myeloid Leukemia (AML) and 13 with Acute Lymphoblastic Leukemia (ALL). In the cohort of patients with VT, 23 were males (14 with AML, 9 with ALL) and 14 females (4 with AML, 10 with ALL), with a mean age of 46 ± 13,1 years; mean age of patients with AML and VT was 49 ± 12,8 years; mean age of patients with ALL and VT was 40,2 ± 12,2 years. Twelve patients presented at least a concomitant chronic disease; no one was receiving anticoagulant prophylactic treatment with low molecular weight heparin (LMWH) during hospitalization. There were 23 cases of DVT of upper arms, 9 cases of proximal DVT of limbs (one complicated with PE), 2 cases of RO, 1 of CST and 1 case of intracardiac clot. In 28/37 (75,6%) cases of recorded VT, a central venous catheter (CVC) was placed (Figure 1); moreover, 21/23 events of DVT of upper arms were significantly associated with a CVC insertion (p〈 0.01). In the other 2 cases, one patient had a bulky mediastinal disease and 1 was diagnosed with promyelocytic AML. VT occurred during chemotherapy (CHT) in 32/37 (86.4%) cases, the remaining 5 cases were diagnosed in concomitance with leukemia: in 20 cases, VT occurred at induction, in 7 at consolidation and in 5 during salvage CHT. In both subgroups with VT, there was no statistical significant difference between time at diagnosis of VT and time at diagnosis of AL. At CBC, thrombocytopenia was the most frequently observed laboratory abnormality. Basal coagulation tests and anticoagulant levels were normal in all cases. Inherited prothrombotic mutations were available only for 9/37 cases, 1 case was heterozygous for Factor V Leiden and 1 for Factor II (G20210A) mutation. Most VT episodes (32/37) were treated with LMWH at therapeutic doses for the first month after diagnosis, a dose reduction was recorded in the following months, mainly related to severe thrombocytopenia after CHT ; 1 case was treated with unfractioned heparin; four cases did not receive any treatment due to severe thrombocytopenia. No cases of VT–related deaths nor fatal complications during treatment for VT were recorded. Treatments with LMWH lasted from 3 to 6 months. All patients clinically recovered from VT, only 2 late recurrences (PEs) were observed. Conclusions The incidence (4.5%) of VT in the analyzed cohort of patients with AL is almost similar to only one previous report, even if the involved sites distribution appears quite different. In particular, RO has never been reported. Atypical sites VT must be suspected to be correctly diagnosed and treated. Anticoagulant treatment schedules and duration in patients with AL is influenced by many factors, mainly related to CHT and severe thrombocytopenia. The optimal management of VT in patients with AL requires further, prospective studies. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 190 Type and duration of anticoagulation is still matter of debate in cancer patients with acute Deep Vein Thrombosis (DVT) of the lower limbs. Residual Vein Thrombosis (RVT) has been proven to be effective for assessing the optimal duration of oral anticoagulants in non cancer patients (Siragusa S et al Blood 2008:112:511-5). In the present study we evaluate the role of a RVT-based management of anticoagulation with Low-Molecular Weight Heparin in cancer patients with acute DVT. Materials and Methods. Patients with active cancer and a first episode of DVT were treated with LMWH for 6 months (the first month at full dosage followed by dose reduction of 25% in the next 5 months). At the end of treatment, they were managed according to RVT findings: those with RVT were randomized to continue anticoagulants for 6 additional months (Group A1) or to stop it (Group A2), while patients without RVT stopped LMWH (Group B). Outcomes were recurrent venous thromboembolism and/or major bleeding; patients were followed up for one year after LMWH discontinuation. Results. Over a period of 36 months, 409 patients were evaluated; 62 were excluded (refusal, need for continuing anticoagulation, etc). In total, 347 were included in the study (Table 1). RVT was detected in 242 (69.7%) patients; recurrent events occurred in 21.9% of those randomized to discontinue and 14.2% of those who continued LMWH. In patients without RVT (105, 30.3%), recurrent events occurred in 3 cases (2.8%) (Table 2 and Figure 1). The adjusted Hazard Ratio (HR) for age and sex between RVT groups (Group A2 vs A1) was 1.58 (95% confidence interval [CI], 0.85–2.93; P=.145). The adjusted HR between group A1 versus RVT-negative group (B) was 4.54 (CI 2.3–6.66; P =.028). Five major bleeding events occurred in Group A1 and two events both in Group A2 and B (Table 2). Overall, 89 (25.6%) patients died due to cancer progression after a median follow-up of 10.2 months after heparin withdrawn. Conclusions. The Cancer DACUS is the first ever study evaluating an individual marker for assessing duration of anticoagulation in active cancer population. Final results of the study show that absence of RVT identifies a group of patients at low risk for recurrent thrombosis who can safely stop LMWH after 6 months. Disclosures: No relevant conflicts of interest to declare.

Description: Background: The clinical consequences of Deep Vein Thrombosis (DVT) have the potential to be serious yet are frequently unrecognized in the Intensive Care Unit (ICU). We hypothesized that both undetected and clinically evident VTE would affect the prognosis of critically ill patients Purpose: To systematically review whether a diagnosis of DVT in critically ill patients affects clinically important outcomes including length of stay, duration of mechanical ventilation and mortality. Material and Methods: Data sources used were the MEDLINE, EMBASE and PUBMED databases. Studies selected evaluated one or more of the following outcomes: duration of patient stay in hospital and in ICU, hospital and ICU mortality, and duration of mechanical ventilation. Two investigators independently extracted and reviewed data from each study; including study and patient characteristics and outcomes. Statistical heterogeneity was evaluated using the I2 statistic; Cohen’s Kappa for inter-rater agreement was used to assess inter-rater reliability. Data was pooled using the Mantel-Haenszel method and a random effects model using Review Manager. Results: Five studies were included in the systematic review. Patients diagnosed with DVT compared to those without DVT had increased ICU and hospital stay (7.3 days (95% confidence interval [CI] 1.4 to 13.2; P= 0.02) and 16.5 days (95% CI 1.51 to 30.59; P= 0.03), respectively. Duration of mechanical ventilation was increased by 3.41 days (95 % CI −1.12 to 7.94; P=0.14). Patients diagnosed with DVT also had increased relative risk (RR) for ICU mortality of 9.19 (95% CI 1.07 to 78.65, P=0.04) and a trend towards increased hospital mortality (RR 14.32 [95% CI 0.59 to 347.96, P = 0.10]). Conclusions: A diagnosis of DVT upon ICU admission appears to affect clinically important outcomes including length of ICU and hospital stay and ICU mortality. Further research involving larger prospective study designs are warranted. Outcomes Study Duration of mechanical ventilation in days (DVT/NO DVT) Hospitalization length In days (DVT/NO DVT) ICU Stay In days (DVT/NO DVT) Hospital mortality rate (DVT/NO DVT) n (%) ICU mortality rate (DVT, n/NO DVT, n) Legend PEPP: positive end-expiratory pressur * IQR ** median “ [95%CI]) ^ Necessity for ventilation measured by PEEP ≥10: DVT/no DVT: 11 (42%)/37 (21%) Ibrahim
 2002 18.9±19.7/14.6±12.9M
 p=0.310 31.4±21.7/27.5± 18.2
 p=0.375 18.6±14.6/15.9±1.04
 p=0.388 8.9 (34.6%)/26.8(32.1)
 p=0.815 n/a Velmahos
 1998 Not given. ^ 49±32/31±24, p=〈 0.05 34±31/19±18, p=

Description: Abstract 3327 Background: Critically ill patients are at high risk of developing venous thromboembolism (VTE) during their stay in the intensive care unit (ICU) because of premorbid medical and surgical conditions. The clinical consequences of Deep Vein Thrombosis (DVT) have the potential to be serious yet are frequently unrecognized in the Intensive Care Unit (ICU). In contrast to the extensive documentation on the short and long–term outcomes of patients with DVT evaluated in other clinical settings, little is known about the clinical course of this disease in the ICU setting. We hypothesized that both undetected and clinically evident VTE would affect the prognosis of critically ill patients. Purpose: To systematically review whether a diagnosis of DVT in critically ill patients affects clinically important outcomes including length of stay, duration of mechanical ventilation and mortality. Material and Methods: MEDLINE and EMBASE databases were searched up to June 2010. Two reviewers performed study selection independently. Studies were selected if evaluate one or more of the following outcomes: hospital and ICU mortality, duration of patient stay in hospital and in ICU, and duration of mechanical ventilation. Two investigators independently extracted and reviewed data from each study; including study and patient characteristics and outcomes. Association between DVT and hospital and ICU mortality, and the mean difference of duration of patient stay in hospital and in ICU, and duration of mechanical ventilation in patients with and without DVT were calculated using a random-effects model (DerSimionan and Laird method). Pooled results are reported as relative risk (RR) and mean difference and are presented with 95% confidence interval (CI) and with 2-sided P values. A P value of .05 or less was considered statistically significant. Statistical heterogeneity was evaluated using the I2 statistic, which assesses the appropriateness of pooling the individual study results [22]. The I2 value provides an estimate of the amount of variance across studies due to heterogeneity rather than chance. Cohen's Kappa for inter-rater agreement was used to assess inter-rater reliability. Results: Six studies for a total of 1518 patients were included in the systematic review. Patients diagnosed with DVT compared to those without DVT had increased ICU and hospital stay (7.3 days (95% CI 1.4 to 13.2; P= 0.02) and 16.5 days (95% CI 1.51 to 30.59; P= 0.03), respectively. Duration of mechanical ventilation appeared to be increased in patients with DVT although this difference was not statistically significant (weighted mean difference: 3.41 days 95 % CI –1.12 to 7.94; P=0.14). Patients diagnosed with DVT also had a marginally significant increase in the RR of hospital mortality (RR 1.31 95%CI,0.99 to 1.74,P=0.06), and a non statistically significant increase in the RR of ICU mortality (RR 1.96; 95% CI 0.74 to 5.19; P = 0.17). Conclusions: A diagnosis of DVT upon ICU admission appears to affect clinically important outcomes including length of ICU and hospital stay and hospital mortality. Further research involving larger prospective study designs are warranted. Disclosures: No relevant conflicts of interest to declare.

Description: Objectives Relapsed/refractory AML patients  have a poor prognosis; allogeneic hematopoietic stem cell transplantation (HSCT) is the only chance in this setting to achieve long-term disease-free survival (1). It was previously established the activity of clofarabine plus cytarabine in AML relapse (clofarabine dosed once daily for 5 days with 40 mg/m2  followed 4 hours later by ara-C at 1 g/m2 per day)(2).However, modifications of this combination in AML therapy of relapsed/refractory patients warrant further evaluation. Therefore, our goal was to determine the efficacy and safety of clofarabine at lower dosage followed by  cytarabine (Ara-C) in adult patients with relapsed or refractory acute myeloid leukemia (AML) and to evaluate the capacity of this regimen as a bridge for HSCT. Methods Patients aged 18-65 years with refractory/relapsed AML were treated at the dose of clofarabine 30 mg/mq on days 1-5 and cytarabine 1000 mg/mq gg on days 1-5. We evaluated the complete remission rate (CRR), duration of remission (DOR) and overall survival (OS). Minimal residual disease (MRD) by molecular targeting was considered in all patients. Results Twenty-five (25) patients aged 29-64 years (median 47), who were fit for allogenetic HCT,  received one cycle of 30 minutes infusion of  clofarabine 30 mg/mq, followed 4 hours later by 3 hours infusion of  intermediate dose cytarabine 1000 mg/mq  days 1-5. Only in the first three patients this schedule was followed by gentuzumab. Nine (36%) patients had refractory disease (seven after one induction regimen, one after two previous regimes, one after a prior hematopoietic stem cell transplant (HSCT);  16 (64%) patients  were in their first (12 patients) or second relapse (4 patients); among the 12 patients in first relapse, 5 were from an allogeneic stem cell transplant.  Fourteen patients (56%)  achieved a complete remission (CR), seven (28%) was refractory and 4 (16%) died of treatment related mortality. Eleven (44%) patients  underwent (9 in CR) to allogeneic transplants or DLI infusion (3 patients refractory, and 8 patients relapsed), only one  patient underwent to autologous transplant. One patient, who was relapsed after prior HSCT, obtained a CR but he developed acute  graft vs host disease after therapy  and died in molecular CR*.  Among all patients underwent HSCT after Clofa/Ara-c salvage, six patients (50%) are still alive and in complete remission, six patients (50%) died because of  HSCT complications or AML relapse. The complete remission rate (CRR) was  (56,00 %), the median  Overall Survival  was 5 months for all patients (range 1-38 M), 11 Months for those underwent to tranplantation and 1,5 Months for non transplanted group. Treatment was complicated by neutropenic fever (n=17), grade III-IV mucositis (n=2) , skin rush  (n=4) grade II- III, hepatic transaminase elevations (n=2).  Two (n=5) patient died before their disease status could be evaluated. Conclusions These preliminary results suggest that combination treatment with clofarabine 30 mg/mq and ARA-C 1000 mg/mq is effective in this particularly poor prognosis category of patients, resulting in an ORR very favorably,  representing a potential “bridge” toward bone marrow transplant procedures (among the 14 patients who achieved a CR, twelve (85%) proceeded to HSCT, and six are still alive). The safety profile is acceptable in this relapsed/refractory population, and our results are very similar to previous regimes using higher clofarabine dosages.  More studies with this combination in adults are warranted. References 1 Estey E. Treatment of relapsed and refractory acute myeloid leukemia. Leukemia. 2000;14:476-479. 2. Faderl S et al, “Results of a pase 1-2 study of clofarabine in combination with cytarabine (ara-C)”Blood 2005 Disclosures: No relevant conflicts of interest to declare.

Description: Background. Clinical advantages of extensive screening for occult cancer in patients with idiopathic Deep Vein Thrombosis (DVT) is still debated since this approach improves early detection of cancer but not cancer-related mortality. Recently, we have demonstrated that patients with Residual Vein Thrombosis (RVT), 3 months after DVT, have a high risk for cancer in the subsequent 2 years (Siragusa S et al. Blood2005;106(11):OC262). At the present it is unknown whether RVT assessment may be used to select patients, with idiopathic DVT, who require screening for occult cancer. Objective of the study. We conducted a prospective study evaluating whether a RVT-based screening for cancer is sensitive and influences cancer-related mortality. Study design. Prospective with two cohorts of DVT patients: the first cohort was monitored for clinical overt cancer only (Group A), while the second (Group B) received complete screening for occult neoplasm and subsequent surveillance. Materials and methods. Consecutive patients with a first episode of DVT who presented RVT after 3 month of anticoagulation and without signs and/or symptoms for overt cancer. Screening for occult cancer was based on: ultrasound and/or CT scan of the abdomen and pelvis, gastroscopy, colonoscopy or sigmoidoscopy, hemoccult, sputum cytology and tumor markers. These tests were extended with mammography and Pap smear for women and ultrasound of the prostate and total specific prostatic antigen (PSA) for men. All investigations had to be completed within four-weeks from the assessment of RVT. All patients were followed-up for at least 2 years. Incidence and cancer-related mortality was compared between the two groups by survival curves (Kaplan-Mayer) and related Breslow test for statistics. Results. Over a period of 6 years, 345 patients were included in the analysis: first cohort included 213 patients (Group A), second cohort 132 (Group B). Clinical characteristics between groups were homogenous. During the follow-up, 8.4% of patients developed overt cancer in group A; in group B, 8.3% of patients had diagnosed cancer at the moment of extensive screening while one new case (0.7%) occurred during the follow-up (Table). The sensitivity of this approach was 91.6% (95% confidence intervals 74.7–108.5). Cancer-related mortality was 6.5% in group A and 3.0% in group B (p〈 0.001) (Figure). Conclusions. Our study demonstrates that RVT-based screening for occult cancer improves early detection as well as cancer-related mortality. Cancer events during surveillance Characteristic Group A (n= 213) Group B (N= 132) *4+0.5 months. **At least 24 months Cancer, No (%) at screening time* - - **10 (8.3) Cancer, No (%) during clinical surveillance** 18 (8.4) 1 (0.7) Density incidence (cases x 1000 p/y) 41.9 40.3 Mean time cancer diagnosis (months ±SD) 6.9 (1.3) 3.6 (0.7) Cancer-related mortality, No (%) 14 (6.5) 4 (3.0) Cancer-related mortality, mean time (months ±SD) 19 (3.4) 18 (2.8) Figure: Cancer - related mortality Figure: Cancer - related mortality

Description: Introduction ROMEI (CINC424AIT04 Ruxolitinib Observational study in Myelofibrosis treated patiEnts in Italy) is a prospective observational study that aims to bridge the knowledge gap between the clinical experience of registration trials and routine patient management by following roughly 200 myelofibrosis (MF) patients (pts) treated with ruxolitinib in everyday clinical practice. Enrollment began in April 2017 and ended in May 2018. Methods The primary endpoint is to evaluate changes in symptoms and quality of life during treatment with ruxolitinib through the Myeloproliferative Neoplasm 10 (MPN-10) disease-specific questionnaire and EuroQoL-5D-5L (EQ-5D-5L) general health questionnaire. Secondary endpoints: spleen length (change from baseline in palpable spleen length from left costal margin), effects on bone marrow fibrosis, changes in patient-reported outcome (Myelofibrosis 7-Items Symptom Scale), overall survival (OS), adherence to treatment, safety and tolerability, and changes in work and productivity impairment. This first interim analysis evaluated only the primary endpoint, spleen length, OS and safety of the first pts with at least 24 weeks of exposure to ruxolitinib. Results At data cut-off (April 30, 2018), 93 of the 216 enrolled pts were potentially evaluable, 91 for safety (2 were not treated) and 82 for primary and secondary endpoints. Median age at enrollment was 70 years (range 24 - 85) and 56% of pts are male. Forty-eight pts (48) (59%) had PMF, 20 (24%) had PPV-MF and 14 (17%) had PET-MF. IPSS score: Int-1 for 4 pts (5%), Int-2 for 48 pts (59%), high risk for 29 pts (35%) and missing for 1 patient (1%). Median time from diagnosis to enrollment was 4 months (range 0 - 247 months). Prior medications for MF were reported for only 35 of the 82 evaluable pts, 33 of whom received hydroxyurea. Mean MPN-10 total score improved from 34.48 ± 17.26 (range 0 - 77) at baseline to 21.87 ± 14.72 (range 0 - 70) at Week 24, with mean change equal to -12.61 (95% CI: -16.25; -8.97). Across the board improvements were observed for all symptoms except for fever (Fig.1a), the greatest being seen in unintentional weight loss (-2.57 ± 3.42 [min; max: -10; 10]), night sweats (-2.07 ± 3.47 [min; max: -10; 10]) and itching (-2.07 ± 3.47 [min; max: -10; 10]). Mean EQ-5D-5L index values were stable during the observation period: 0.79 ± 0.15 (range 0.23 - 1.00) at baseline and 0.82 ± 0.16 (range 0 - 1.00) at Week 24, with a mean change of 0.03 (95% CI: 0.00; 0.06). Mean EQ-VAS value was 60.79 ± 20.43 (range 0 - 100) at baseline and then improved slightly at each visit to reach a value of 67.24 ± 19.86 (range 10 - 100) at Week 24. Mean spleen length decreased from 9.78 ± 5.65 cm (range 0 - 24) at baseline to 4.97 ± 5.91 cm (range 0 - 24) at Visit 5, corresponding to a mean absolute change of -5.82 cm (95% CI: -7.23; -4.41 cm) and a percentage change of -58.56% (95% CI: -69.55; -47.57%). The proportion of patients with a ≥ 50% reduction in palpable spleen length increased at each visit: 0.36 (95% CI: 0.24; 0.48) at Visit 2, 0.52 (95% CI: 0.39; 0.65) at Visit 3, 0.62 (95% CI: 0.50; 0.75) at Visit 4 and 0.64 (95% CI: 0.51; 0.77) at Visit 5. Best changes from baseline in spleen volume % in evaluable pts is shown in Figure 1b. OS at Week 24 was 95%, with 4 of the 82 patients dying. Adverse events (AE) were reported for 63 of the 91 safety pts (69%) and 245 AEs were reported overall, 26 of which were grade 3 or 4. SAEs were reported for ten patients, 4 of whom experienced drug-related SAEs. Forty (40) drug-related AEs were reported. Detailed safety information will be available at the meeting venue. Conclusion Preliminary data of the ROMEI study confirm the efficacy of ruxolitinib in everyday clinical practice in terms of spleen response and symptom relief. The improvements from baseline observed in the MPN 10 and EQ-5D-5L scores at Week 24 were however not as considerable as those reported in pivotal and registration trials. This difference may be related to the shorter median time from diagnosis to start of treatment (only 4 months). Our patients had been living with myelofibrosis for a shorter time and treating them with an effective drug earlier, when disease burden is likely lower, may account for the less appreciable improvement in patient perceptions of symptoms and quality of life. Disclosures Breccia: Pfizer: Honoraria; Incyte: Honoraria; BMS: Honoraria; Novartis: Honoraria. Palumbo:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees. Cilloni:Janssen: Membership on an entity's Board of Directors or advisory committees; celgene: Membership on an entity's Board of Directors or advisory committees. Abruzzese:Pfizer: Consultancy; BMS: Consultancy; Novartis: Consultancy; Ariad: Consultancy. Morelli:Novartis: Employment. Palandri:Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Passamonti:Celgene: 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; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Description: Background. Ponatinib is a third-generation tyrosine kinase inhibitor indicated for adult patients with resistant or intolerant chronic phase (CP), accelerated phase (AP) or blast phase (BP) chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia, or for those carrying the T315I mutation. In the real-world setting, there is a paucity of data regarding the use of ponatinib. The goal of the Observational study of Iclusig® (ponatinib) Treatment in patients with CML in Italy (OITI) is to evaluate treatment patterns and outcomes, including the safety and efficacy of ponatinib, in patients with CML treated in hematology centers in Italy since January 2015, when ponatinib became commercially available. Methods. This ongoing, non-interventional study includes patients aged ≥18 years with CP, AP or BP CML who initiated ponatinib treatment in routine clinical practice across 40 centers (academic and hospital settings) as of October 2018. The study population consists of a prospective cohort, including patients who started treatment with ponatinib after site activation during the ongoing enrolment period; a retrospective cohort, including patients who started treatment with ponatinib but who died or were lost to follow-up prior to site activation; and a retrospective/prospective cohort, including patients who started treatment with ponatinib prior to site activation and are still on treatment. Demographic, efficacy and safety data are collected from patient medical charts at study entry and at routine care visits. The primary endpoint is complete cytogenetic response (CCyR) rate in patients with CP CML 6 months after starting ponatinib treatment. Here, the first interim analysis after ≥6 months' observation is presented for the retrospective and retrospective/prospective cohorts. Results. At time of data analysis (02 July 2019), 56 patients (53 CP, 1 AP and 2 BP CML) had been enrolled across 21 Italian centers. Twenty-eight (50.0%) patients had received ponatinib as second-line (2L) treatment and 33.9% received ponatinib in third-line (3L). Twenty (35.7%) patients had a history of cardiovascular events and 23 (41.1%) had a history of hypertension. Among patients with CP, AP and BP CML, median age at study entry was 59.1, 33.7 and 48.5 years, respectively; among 37 evaluable patients, 12 (32.4%), 1 (2.7%) and 1 (2.7%) patient(s) had a confirmed BCR-ABL1 mutation. Of evaluable patients, 4 (10.8%) had the T315I mutation. The starting dose of ponatinib for patients with CP CML was 45 mg once daily in 41.5% of patients, 30 mg in 39.6% of patients and 15 mg in 17.0% of patients; 1 (1.9%) patient started ponatinib at another dose. Median treatment duration was 23.9 months (range, 3.3-49.9 months) at the time of analysis. At Month 6, 88.6% of patients with CP CML achieved a CCyR. Additionally, 37.5% and 15.0% of evaluable patients with CP CML achieved a major molecular response (MMR; MR3.0) and a deep molecular response (MR4.5), respectively (Table 1). Estimated progression-free survival rates for patients with CP CML at Months 12 and 24 were 86.6% (95% CI, 77.8-96.4%) and 83.7% (95% CI, 73.8-94.9%), respectively. Corresponding overall survival rates were 96.2% (95% CI, 91.1-100.0%) and 93.1% (95% CI, 85.6-100.0%), respectively. Thirty (53.6%) patients had treatment-related adverse events (TRAE). The most frequent TRAEs were hypertension (n=6), skin lesion (n=2), increased lipase (n=2), rash (n=2) and pain in extremity (n=2). The only hematologic TRAE reported was thrombocytopenia (n=1). Dose interruptions occurred in 13 patients: for TRAEs (n=5, 38.5%), medical decision (n=4, 30.8%) or other causes (n=4, 30.8%; comprising death in 3 cases and 1 attempt at treatment-free remission). Conclusions. Data show that ponatinib has a favorable efficacy and safety profile in patients with CML treated in standard clinical practice in Italy. By Month 6, most patients had achieved CCyR and 44% of patients achieved MMR in 2/3L. Furthermore, the probability of survival at 2 years was more than 90%. No new safety signals emerged with ponatinib treatment than those previously reported. The early use of ponatinib (84% of patients received it as 2/3L treatment) as well as careful dose selection appear key to the safety and efficacy outcomes observed in this preliminary study evaluation. Disclosures Iurlo: Incyte: Other: Speaker Honoraria; Pfizer: Other: Speaker Honoraria; Novartis: Other: Speaker Honoraria. Annunziata:Pfizer: Consultancy; Incyte: Consultancy; Novartis: Consultancy. Albano:Incyte: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Spadano:Incyte: Speakers Bureau; Pfizer: Speakers Bureau. Bonifacio:BMS: Honoraria; Amgen: Honoraria; Pfizer: Honoraria; Incyte: Honoraria; Novartis: Honoraria. Abruzzese:BMS: Consultancy; Incyte: Consultancy; Novartis: Consultancy; Pfizer: Consultancy. Pellegrino:Inycte Biosciences Italy S.R.L: Employment. Galimberti:Inycte Biosciences Italy S.R.L: Employment. Foà:Celltrion: Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Speakers Bureau; Roche: Consultancy, Speakers Bureau; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Consultancy, Speakers Bureau; Shire: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Consultancy, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Shire: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celltrion: Membership on an entity's Board of Directors or advisory committees. Breccia:Celgene: Honoraria; BMS: Honoraria; Novartis: Honoraria; Pfizer: Honoraria; Incyte: Honoraria.

Description: Abstract 3161 Purpose: Patients with haematological disorders frequently require the insertion of medium or long-term central venous catheters (CVCs) for stem-cell transplantation, the administration of chemotherapy, or transfusions. Although peripherally inserted central catheters (PICCs) have been in use for many years, little data exist on their use in patients receiving intensive chemotherapy and blood progenitor cell transplantation. Methods: Evidence-based interventions were implemented in our department from November 2009 to July 2012, and include: 1.An high level nurse education program for correct practices and prevention of catheter-associated complications. was developed for PICC nursing team; 2) The use of ultrasound guide for the insertion of the tip of PICCs, thanks to a special operator training; 3) Bedside placement and confirmed PICC tip placement by chest radiography after removal of the guidewire and before the securing of the catheter; 4) Maintenance of maximum sterile barrier precautions during PICC insertion and aftercare; 5) chlorhexidine preparation, replace 10% povidone iodine for skin antisepsis; 6) adoption of PICC patient nurse archive, including the information of weekly PICC line review at our department for each patient. Aim: Here, we carried out a clinical prospective investigation to determine the efficacy of these interventions in reducing the rate of PICC-related complications (thrombotic events, exit site infection and other complications requiring early removal of PICCs); the studied population included hematology patients receiving intensive chemotherapy compared to allogeneic/autologous stem cell transplant recipients. Results: Three hundred sixty-four (364) PICCs were in place in 299 patients for a total of 41.111 PICC days ( range, 1–482 days; mean 112,94 days); 292 were inserted in patients receiving conventional chemotherapies, and 72 in patients undergoing allogeneic or autologous hematopoietic stem cell transplantation (SCT). Sixty-six (60) PICCs were inserted during severe thrombocytopenia (platelets 〈 50 × 10(9)/L), seventy (70) during severe neutropenia (neutrophils 〈 0.5 × 10(9)/L) and thirty-eight (38) during antithrombotic prophylaxis. Predominantly, patients had Lymphoma (50%). The rate of major complication was very low: 15 thrombotic complications PICC-related (4%; 0.36 per 1,000 CVC days), and 3 CRBSI (0,8%; 0.07 per 1,000 CVC days) during neutropenia. Mechanical complications occurred in 52 catheters, and were accidental dislodgement (30), catheter break (3), catheter inadequate (19); other reasons for catheter removal were completion of therapy (137), lumen occlusion (19) and death (58). Interesting, taking in account the underlying disease, lymphoma and leukemia patients have, respectively, an increased risk of developing a CRBSI and a thrombotic PICCs-complication when submitted to hematopoietic stem cell transplantation (SCT) (see table 1). However, compared with allogeneic/autologous stem cell transplant group, the intensive chemotherapy group was associated with a marginally lower incidence of CRBSI complication rate (0.6 % vs 1.0 %, 0.10 vs 0.60 per 1,000 CVC days) [odds ratio (OR) 2,042]; no relevant differences in terms of thrombotic complications between the two cohorts (4.11 % vs 4.17%), 0.29 vs 0.39 per 1,000 CVC days) [odds ratio (OR) 1.014]. Conclusions: Our findings suggest, therefore, PICC devices are a viable and safe option for management of the haematology patients receiving intensive chemotherapy and even in patients particularly prone to infective and thrombotic complications such as patients receiving blood stem cell transplantation. Disclosures: No relevant conflicts of interest to declare.

Description: Since myeloproliferative neoplasms (MPN) pose a significant risk for vascular and thrombotic complications, cytoreductive therapies, such as hydroxyurea (HU), interferon (IFN) inhibitors, and Janus kinase (JAK) inhibitors are recommended for patients at high risk. However, these agents also place patients at increased risk for drug-related cutaneous adverse events. Herein, we review the literature on skin toxicity related to the use of drugs for the treatment of MPN. Overall, the cytoreductive agents used for MPN are generally well tolerated and considered to be safe, except IFN, for which dropout rates as high as 25% have been reported. While IFN is known to give rise to flu syndrome, it rarely leads to hematological alterations. The most common hematological side effects of HU are mild and include granulocytopenia, anemia, and thrombocytopenia. The JAK inhibitor ruxolitinib has been associated with cytopenia and a higher incidence of viral infections, as well as increased risk for basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Based on the present analysis, it can be concluded that cutaneous toxicity is not a negligible complication of commonly used treatments for MPN. While further research is needed, patients on these agents, and especially those with a history of cutaneous malignancies, should undergo thorough skin examination before and during therapy. In addition, detailed history is critical since many patients who develop non-melanoma skin cancer have multiple preexisting risk factors for cutaneous carcinogenesis.