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The role of Ann Arbor staging in determining treatment intensity after achieving a negative positron emission tomography (PET) has not been established in classical Hodgkin lymphoma (cHL). Patients with stage I–IV cHL, received three cycles of ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) and an interim PET scan (PET3). PET3-negative patients received no further therapy. PET3-positive patients received three additional cycles of ABVD plus involved-field radiation therapy or salvage chemotherapy, if refractory to ABVD, and were re-evaluated by PET scan (PET6). Study endpoints were 3-year progression-free survival (PFS) and overall survival (OS) rates. Two hundred and thirty-nine patients with early-stage and 138 with advanced-stage were evaluable. Overall, 260 patients (70%) were PET3-negative and had higher 3-year PFS (90% vs. 65%; P < 0 0001) and OS (98% vs. 92%; P = 0 007) rates than PET3-positive patients. All PET3-negative patients, regardless of disease stage at diagnosis, achieved similarly good PFS (90–91%; P = 0 76) and OS (97–99%). The only independent prognostic factor for PFS was PET3-negativity (Hazard ratio 3 8; 95% confidence interval 2 4–6 3; P < 0 0001). This study suggests that cHL patients who achieve a negative PET3 following ABVD have an excellent outcome, regardless of stage at diagnosis. An appropriately powered, phase III trial will be necessary to confirm these findings. Fil: Pavlovsky, Astrid. Fundación Para Combatir la Leucemia; Argentina. Centro de Hematología Pavlovsky; Argentina Fil: Fernández, Isolda. Fundación Para Combatir la Leucemia; Argentina. Centro de Hematología Pavlovsky; Argentina Fil: Kurgansky, Nicolas. Doctus; Argentina Fil: Prates, Virginia. Hospital Italiano de La Plata; Argentina Fil: Zoppegno, Lucia. Hospital General San Martín; Argentina Fil: Negri, Pedro. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto Privado de Hematología y Hemoterapia; Argentina Fil: Milone, Gustavo. Fundación Para Combatir la Leucemia; Argentina Fil: Cerutti, Ider. Idhea Clinica Hematologica Dr Cerutti Ider; Argentina Fil: Zabaljauregui, Soledad. Academia Nacional de Medicina de Buenos Aires; Argentina Fil: Mariano, Romina. Provincia de Entre Rios. Hospital San Martin; Argentina Fil: Grecco, Horacio F.. Sanatorio Dr. Julio Méndez; Argentina Fil: Basquiera, Ana Lisa. Hospital Privado Universitario de Cordoba.; Argentina Fil: Saba, Silvia. Hospital Rodolfo Rossi; Argentina Fil: Rudoy, Silvia. Clínica Modelo de Morón; Argentina Fil: Sackmann, Federico. Fundación Para Combatir la Leucemia; Argentina Fil: Castano, Vanesa. Idhea Clinica Hematologica Dr Cerutti Ider; Argentina Fil: Remaggi, Guillermina. Fundación Para Combatir la Leucemia; Argentina Fil: Cabrejo, María del Rosario. Sanatorio Dr. Julio Méndez; Argentina Fil: Roveri, Eriberto. Idhea Clinica Hematologica Dr Cerutti Ider; Argentina Fil: Casale, María Florencia. Instituto Privado de Hematología y Hemoterapia; Argentina. Hospital General Centeno; Argentina Fil: Cabane, Vanina. Clínica Dr. Roberto Raña; Argentina Fil: Taus, Rossana. Hospital Rodolfo Rossi; Argentina Fil: Venturini, Claudia. Instituto Privado de Hematología y Hemoterapia; Argentina Fil: Sakamoto, Francisco. Instituto Privado de Hematología y Hemoterapia; Argentina Fil: Varela, Ana I.. Sanatorio Las Lomas Sociedad Anonima.; Argentina Fil: Riddick, Maximiliano Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Matemáticas; Argentina Fil: Pavlovsky, Santiago. Fundación Para Combatir la Leucemia; Argentina

Background: ALL in adults is considered a heterogeneous disease with poor prognosis. However, adolescents and young adults (AYA) display intermediate characteristics as compared with children. Risk groups and response predictors are essential to guide the treatment. Aims: The aim of this report was to evaluate the experience of Ph-negative ALL in AYA patients (pts) treated with the pediatric Argentine type-BFM protocol, assessing predictors of response in terms of overall survival (OS) and event-free survival (EFS). Methods: We performed a retrospective multicenter analysis of AYA pts diagnosed between 2013 to 2021, from 16 Argentine institutions who were treated following the pediatric Argentine type-BFM protocol. Response to prednisone (PR) at day(d) 8 ( Results: One hundred and seventy-three patients similarly distributed among private and public institutions were analyzed. The median (Md) age was 22 years (15-40) with a male predominance (66%). At diagnosis, 23% presented central nervous system (CNS) involvement, 79.5% B and 20.5% T immunophenotype, 29% CD20 positive, 16% adverse cytogenetic/molecular findings and 29% no data. Ph-like screening was not routinely performed assessed only in 13% revealing two CRLF2 and one PDGFRB rearrangements. Twenty-one (12%) of pts underwent allogeneic bone marrow transplantation (Allo-HSCT) at 1 st line, 20 with MRD negative and 1 MRD positive at the time of the procedure.Of 171 pts, 155 (91%) achieved MCR, 12 (7%) were refractory, 3 (2%) died prior/during induction and 1 (0.6%) patient dropped out of treatment; 144 (84%) achieved negative MRD, 22 (13%) positive MRD and 5 (3%) were not evaluated. The Md to reach CR and MRD (-) was 33d (IQR 31-42) and 35d (IQR 32-73), respectively. With a Md follow-up of 16 months (1-79), 52 pts (30%) relapsed and 68 pts (39%) died. Early deaths at 3 months occurred in 8 (5%) pts, 5 related to treatment and 3 to disease. The Md OS and EFS were 58 and 34 months, respectively. Prognostic predictors analyzed were sex, white blood counts (WBC) at diagnosis (limit of 30 x10 -9/L), age (limit of 30 years), CNS involvement, cytogenetic/molecular findings, PR at d8, MRD in bone marrow (BM) at d15, 33 and 78. In the univariate analysis, response at d8, MRD at d15, 33 and 78 were useful to predict both OS and EFS, adding age and WBC in terms of OS. Similar results were obtained when patients who underwent Allo-HSCT were censored at the time of the procedure. (Table). In the multivariate analysis, positive MRD at d33 and d78 (and WBC in OS) maintained their independent adverse prognostic impact in relation to OS and EFS. Allo-HSCT showed benefits in pts with MRD >0.1% at d33 and >0.01% at d78 in terms of OS (d33: NR vs. 11 m, p =0.048, HR 0.3, 95%CI [0.1-0.9]; d78: NR vs. 8 m, p =0.009, HR 0.4, 95%CI [0.2-0.8]) and EFS (d33: NR vs. 6 m, p =0.022, HR 0.2, 95%CI [0.1-0.8]; d78: NR vs. 5 m, p =0.003, 0.1 HR, 95%CI [0.02-0.5]). The adverse risk of positive MRD at day 33 and 78 in terms of OS and EFS was overcome when pts were transplanted. Summary/Conclusion: The results show that positive MRD at d33 and 78 independently impacted on OS and EFS in our series and that Allo-HSCT overcame their adverse risk. Our data confirms the relevance of using pediatric protocols in AYA. On the other hand, the importance of prognostic tools in order to improve the outcome of AYA patients, reinforcing their inclusion in current guidelines. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Context: Clinical data from controlled trials report an improvement in QoL in patients with CLL in ibrutinib monotherapy. Reallife evidence is necessary to confirm this data. Objective: The disease control when treatment is initiated could lead to decreasedfatigue. It is likely that treatment with ibrutinib could result in animprovement in QoL in our real-world population. Primaryobjective: evaluate impact of ibrutinib treatment in QoL. Wedefined a clinically meaningful improvement 3 points in FACITfatigue score. Secondary Endpoints: Detect a 10% improvement byEQ5D VAS. Correlate baseline and follow-up hemoglobin levels(meaningful improvement 1g/dL). Design: This is a prospective,longitudinal, single arm study enrolling consecutive CLL patientsunder ibrutinib monotherapy either as first or further line oftreatment. Median follow-up was 7 months (range 1-28). Setting:Patients are recruited in an academic referral center in BuenosAires. Interventions: QoL was explored with FACIT-fatigue andEQ5D visual-analogue-scale (VAS) questionnaires (with copyrightpermission). Assessment by results reported by patient questionnaires are completed on months 0-1-3-6 and 12 since the beginningof treatment. Main Outcomes Measures: We are reporting preliminary results after 3 months of treatment compared to baseline.Statistical Analysis: data was analyzed with the Sign Test (BinomialTest). Results: A total of 21 CLL patients who started ibrutinibbetween 2016 and 2018 were included. Median age was 75 years(range 57-84); 12 patients (57%) were males. Ibrutinib was first-linetherapy in 7 patients (33%), second-line in 7 patients (33%) and 7patients (33%) received 3 previous lines. After 3 months oftreatment, the median change in FACIT-fatigue score 3 pointswas reached in 13 patients (62%) as compared to baseline(p=0.024). After 3 months of treatment there was no evidence of amedian change >10% on the EQ5D VAS (p=0.593) nor a significant improvement on hemoglobin level (p=0.105).Conclusions: These results suggest an early improvement of fatiguewithin the first 3 months of treatment with ibrutinib. Longerfollow-up and larger number of patient are necessary to confirm thisdata and determine the further improvements of QoL withcontinuous treatment and correlation with hemoglobin changes. Fil: Mela Osorio, Maria Jose. Fundación Para Combatir la Leucemia; Argentina Fil: Pavlovsky, Carolina. Fundación Para Combatir la Leucemia; Argentina Fil: Pavlovsky, Astrid. Fundación Para Combatir la Leucemia; Argentina Fil: Fernandez, Isolda. Fundación Para Combatir la Leucemia; Argentina Fil: Massa, Federico Sackmann. Fundación Para Combatir la Leucemia; Argentina Fil: Ferrari, Luciana. Fundación Para Combatir la Leucemia; Argentina Fil: Juni, Mariana. Fundación Para Combatir la Leucemia; Argentina Fil: Riddick, Maximiliano Luis. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Matemáticas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Cálculo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Pavlovsky, Miguel A.. Fundación Para Combatir la Leucemia; Argentina

Myelofibrosis is a myeloproliferative neoplasm associated with progressive cytopenias and high symptom burden. MF patients with thrombocytopenia have poor prognosis but the presence of thrombocytopenia frequently precludes the use of JAK2 inhibitors. In this study, we assessed quality of life and symptom burden in 418 MF patients with (n = 89) and without (n = 329) thrombocytopenia using prospective data from the MPN-QOL study group database, including the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) and Total Symptom Score (MPN10). Thrombocytopenia, defined as platelet count 9/L (moderate 51–100 × 109/L; severe ≤50 × 109/L), was associated with anemia (76% vs. 45%, p < 0.001), leukopenia (29% vs. 11%, p < 0.001), and need for red blood cell transfusion (35% vs. 19%, p = 0.002). Thrombocytopenic patients had more fatigue, early satiety, inactivity, dizziness, sad mood, cough, night sweats, itching, fever, and weight loss; total symptom scores were also higher (33 vs. 24, p < 0.001). Patients with severe thrombocytopenia were more likely to have anemia (86% vs. 67%, p = 0.04), leukopenia (40% vs. 20%, p = 0.04), and transfusion requirements (51% vs. 20%, p = 0.002) but few differences in symptoms when compared to patients with moderate thrombocytopenia. These results suggest that MF patients with thrombocytopenia experience greater symptomatic burden than MF patients without thrombocytopenia and may benefit from additional therapies.

The myeloproliferative neoplasms, including polycythemia vera, essential thrombocythemia and myelofibrosis, are distinguished by their debilitating symptom profiles, life-threatening complications and profound impact on quality of life. The role gender plays in the symptomatology of myeloproliferative neoplasms remains under-investigated. In this study we evaluated how gender relates to patients' characteristics, disease complications and overall symptom expression. A total of 2,006 patients (polycythemia vera=711, essential thrombocythemia=830, myelofibrosis=460, unknown=5) were prospectively evaluated, with patients completing the Myeloproliferative Neoplasm-Symptom Assessment Form and Brief Fatigue Inventory Patient Reported Outcome tools. Information on the individual patients' characteristics, disease complications and laboratory data was collected. Consistent with known literature, most female patients were more likely to have essential thrombocythemia (48.6% versus 33.0%; P

Purpose Polycythemia vera (PV) is a myeloproliferative neoplasm (MPN) associated with disabling symptoms and a heightened risk of life-threatening complications. Recent studies have demonstrated the effectiveness of JAK inhibitor therapy in patients with PV patients who have a history of prior hydroxyurea (HU) use (including resistance or intolerance), phlebotomy requirements, and palpable splenomegaly. We aimed to determine how these features contribute alone and in aggregate to the PV symptom burden. Patients and Methods Through prospective evaluation of 1,334 patients with PV who had characterized symptom burden, we assessed patient demographics, laboratory data, and the presence of splenomegaly by disease feature (ie, known HU use, known phlebotomy requirements, splenomegaly). Results The presence of each feature in itself is associated with a moderately high symptom burden (MPN symptom assessment form [SAF] total symptom score [TSS] range, 27.7 to 29.2) that persists independent of PV risk category. In addition, symptoms incrementally increase in severity with the addition of other features. Patients with PV who had all three features (PV-HUPS) faced the highest total score (MPN-SAF TSS, 32.5) but had similar individual symptom scores to patients with known HU use (PV-HU), known phlebotomy (PV-P), and splenomegaly (PV-S). Conclusion The results of this study suggest that patients with PV who have any one of the features in question (known HU use, known phlebotomy, or splenomegaly) have significant PV-associated symptoms. Furthermore, it demonstrates that many PV symptoms remain severe independent of the number of features present.

This multicenter, open-label study evaluated the efficacy and safety of decitabine in patients from Argentina and South Korea with myelodysplastic syndromes or chronic myelomonocytic leukemia. Of 106 patients who received decitabine 20 mg/m(2) intravenously over 1 h once daily for 5 days in 4-week cycles, 99 patients were evaluable after receiving at least two cycles. The overall improvement rate was 35% (19% complete response +4% marrow complete response +4% partial response +8% hematologic improvement). Overall survival at 2 years was 71%. Treatment-related adverse events included febrile neutropenia, thrombocytopenia and bleeding, asthenia, fatigue, and eosinophilia. After complete response (CR), three patients received an allogeneic stem cell transplant. Four patients who relapsed after CR responded to decitabine retreatment. Acute myelogenous leukemia developed during follow-up in 21% of patients. Decitabine in a 5-day outpatient administration schedule was effective and well tolerated in typical clinical practice settings in South America and Asia.

Objective: To determine the prevalence of JAK2 V617F mutation and its clinical correlation in patients with chronic myeloproliferative disorders (CMD): polycythemia vera (PV), essential thrombocythemia (ET) and idiopathic myelofibrosis (IMF). Materials and methods: Detection of JAK2 V617F mutation by allele specific-PCR. Results: One hundred and three patients with CMD were included in the study. JAK2 V617F distribution was PV 40/45 (89%), ET 30/43 (69%), and IMF 7/15 (47%). In PV and ET patients only, 18 had thrombosis at diagnosis and 12 during follow-up (these were microvascular: 11, venous: 7 and arterial: 12); of these 28/70 (40%) were JAK2pos versus 2/18 (11%) JAK2neg; P=0·02. In a median of 4 years, two patients with PV JAK2pos evolved to myelofibrosis and one patient with PV presented in leukemic transformation (JAK2pos before and after transformation); six patients died: four patients with IMF and two patients with PV. Conclusions: We found an association between JAK2 V617F and thromboti...

Symptom burden in myeloproliferative neoplasms (MPNs) is heterogeneous even among patients within the same MPN diagnosis. Using cluster analysis from prospectively gathered symptom burden data in 1470 international patients with essential thrombocythemia (ET), polycythemia vera (PV), or myelofibrosis (MF), we assessed for the presence of clusters and relationship to disease features and prognosis. In MF (4 clusters identified), clusters significantly differed by Dynamic International Prognostic Scoring System (DIPSS) risk (P < .001), leukopenia (P = .009), thrombocytopenia (P < .001), and spleen size (P = .02). Although an association existed between clusters and DIPSS risk, high symptom burden was noted in some low and intermediate-1-risk MF patients. In PV (5 clusters identified), total symptom score increased across clusters (P < .001), but clusters did not significantly differ by PV risk or the risk assessment variable of age. Among ET patients (5 clusters identified), clusters differed by gender (P = .04), anemia (P = .01), and prior hemorrhage (P = .047). Total symptom score increased across clusters (P < .001), but clusters did not significantly differ by International Prognostic Score for ET risk including the risk assessment variables. Significant symptom heterogeneity exists within each MPN subtype, sometimes independent of disease features or prognosis.

Background: Myeloproliferative neoplasms (MPN) including polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF) are clonal hemopathies characterized by burdensome symptom profiles and impaired quality of life. Few studies have evaluated patient-reported outcomes during treatment with non-experimental pharmacological regimens. Aims: The Myeloproliferative Neoplasm Quality of Life (MPN-QOL) Study Group aims to objectively quantify MPN symptom severity, frequency and quality of life at baseline and throughout treatment with non-experimental therapies utilizing the Myeloproliferative Neoplasm Symptom Assessment Form - Total Symptom Score (MPN-SAF TSS; JCO 2012). In this abstract, we provide updated results for the prospective international cohort trial currently in active enrollment: the MPN Experimental Assessment of Symptoms by Utilizing Repetitive Evaluation (MEASURE) trial. Methods: This study aims to recruit 180 international ET, PV, and MF (including primary MF and post-ET or post-PV MF) patients receiving non-experimental medical therapy and/or phlebotomy. Patients complete the MPN-SAF for seven consecutive days at enrollment and repeat the survey for an additional seven consecutive days between 90 days and six months. Patients also complete the European Organisation for Research and Treatment of Cancer (EORTC) and M.D. Anderson Symptom Inventory (MDASI) instruments at enrollment and on the first day of the second assessment. At visits, physicians acquired demographic, laboratory, physical examination, and radiographic data. Descriptive statistics were used to summarize data. Results: Clinical Data The MEASURE trial opened for enrollment in 2012 and remains in recruitment phase with 15 participating international sites. To date, 39 patients have been enrolled and 25 have completed both study visits. Participants include ET (28%), PV (24%), and MF (48%; 50% primary MF, 8% post-ET, 42% post-PV) patients. The majority of patients are male (64%) and of expected age (mean 69.3, range 39-89) for the disorders. Seventeen percent had prior thrombosis, 9% required red blood cell transfusion, and none reported prior splenectomy or hemorrhage. Mean hematologic measures included hemoglobin 13.2 g/dL, WBC count 11.4 x109/L, ANC 8.5 x109/L, and platelets 514 x109/L. Therapies received prior to enrollment included aspirin (n=16), hydroxyurea (n=11), phlebotomy (n=8), warfarin/clopidogrel/anticoagulation (n=8), erythropoietin (n=2), and interferon (n=1). The most common current MPN therapies were hydroxyurea (n=9), aspirin (n=9), interferon (n=4), and phlebotomy (n=2). Symptom Assessment In comparing MPN-SAF TSS mean symptom scores, all symptoms except bony pain improved between the first and second visits, including fatigue, early satiety, abdominal discomfort, inactivity, concentration, night sweats, itching, fever, weight loss, and overall quality of life (Figure1). Total MPN-SAF TSS scores improved from a mean of 32.3 to 25.9. On the EORTC, mean scores for physical, role, emotional, and social functioning improved from the first to the second visit (Figure 2). Cognitive functioning showed a slight decline. Global health status measure improved from 60.2 to 72.9. On the MDASI, symptom severity scores decreased from 3.6 to 2.8 from the first to second visit (Figure 3). Symptom distress measure decreased from 4.1 to 3.0. Discussion: Interim results from the MEASURE trial demonstrate that standard, non-experimental treatment regimens offer improvement in quality of life-related symptoms on multiple patient-reported survey instruments including the MPN-SAF TSS, EORTC QLQ-C30, and MDASI. Updated data including symptom correlations and mutational analysis to be presented at the 2016 ASH conference. Disclosures Ross: Novartis Pharmaceuticals: Honoraria, Research Funding; BMS: Honoraria. Radia:Novartis: Honoraria; Pfizer: Honoraria. McMullin:Novartis: Honoraria, Speakers Bureau. Cargo:Novartis: Honoraria; Celgene: Honoraria, Research Funding. Sekhar:Novartis: Research Funding. Mesa:Gilead: Research Funding; CTI Biopharma: Research Funding; Galena: Consultancy; Ariad: Consultancy; Incyte: Research Funding; Novartis: Consultancy; Celgene: Research Funding; Promedior: Research Funding.

Introduction: Early reduction of BCR-ABL transcript level has been associated with improved outcomes in CML treatment. Inability to achieve early molecular response(MR) at 3 months (M3>10%) is considered a predictor factor for unfavourable outcome. However, the kinetics of BCR-ABL transcript level reduction measured at early time points have shown to be an independent predictor of response.The aim of this analysis was to determine whether the "M3-M6" status is critical to categorize CML patients (pts) focusing in high-risk group. Method: Molecular monitoring was performed in all pts prior treatment (M0), at months 3 (M3), 6 (M6), 12 (M12) and every 6 months thereafter, applying Q-PCR method according international recommendations. Results of BCR-ABL1 transcript level were reported on the international scale as IS-BCR-ABL %. Optimal responses: M3≤10%, M6≤1%, M12≤0,1%. Deep responses (MR4.0): ≤0,01% or undetectable/10.000 ABL copies. Results: A total of 70 CML pts were included, median age 49 (19-82), female 39%. First line treatment: sustained branded 81% and generic 19% TKIs. Imatinib 59%, Dasatinib and Nilotinib 41%. Sokal risk score: low (L) 51%, intermediate (In) and high (H) 49%. Optimal responses at molecular milestones: 75% at M3, 72% at M6, 61% at M12 and 53% pts achieved MR4.0. Event-free survival (EFS) was evaluated according to time point M3: M3≤10% group had significantly better EFS compared with the M3>10% (96% vs 70%; P=0.028). M3-M6 status defined 4 groups of pts: M3≤10%-M6≤1%, M3≤10%-M6>1%, M3>10%-M6≤1%, M3>10%-M6>1%. Molecular response evolution by M3-M6 status is described in Table 1. EFS stratified by groups according to combined M3-M6 responses showed significant differences: 92% for group 1, 87% for group 2, 68% for group 3, 54% for group 4. (P=0.002). M6 time point was shown to be critical in 32 high-risk pts (H+In): 17 pts with M6 ≤1% showed significant differences in MR4.0 achievement compared to 15 pts with M6 >1% (82% vs 27% P=0.02). Better EFS was observed in this high-risk group under branded vs generic TKIs treatment (97% vs 54% P=0.04). Statistical differences in deep responses and MMR at M12 were observed between branded and generic TKIs independently of Sokal risk (P=0.06, P=0.02). Conclusions: M3≤10% pts showed a favourable evolution with better EFS than M3>10% group. However not all patients with M31%. In pts with M3 >10% and optimal response at M6 also showed higher MR4.0 rate. Our study supports that M6 is a crucial endpoint to predict MMR at M12 and deep responses in CML pts.Pts with M3≤10% without optimal response at M6 (>1%) had a worse evolution than those slow responders who showed M3>10% and M6≤1%.High-risk pts are still a challenge, observing better outcomes in those under branded TKIs treatment. The M3-M6 status would be a prognostic marker of responses and EFS in chronic phase CML pts treated with TKIs. Our data support the critical role of M6 response in non-optimal M3>10% pts and intermediate and high risk Sokal score. Treatment adherence is mandatory for achieving and sustaining optimal responses. This multicentric Argentine study, reinforces the importance of clinical follow-up and molecular monitoring under IS standardization at early time points. Education on early molecular monitoring with adequate resources must continue to be an objective in our region. Table 1 Table 1. Disclosures Pavlovsky: Roche: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Speakers Bureau. Moiraghi:Novartis: Speakers Bureau; Bristol: Speakers Bureau. Varela:Novartis: Speakers Bureau; Bristol: Speakers Bureau. Enrico:Novartis: Honoraria, Patents & Royalties; Bristol Myers squib: Speakers Bureau. Brodsky:International PNH Registry: Other: -; Alexion Pharma Argentina: Speakers Bureau. Pavlovsky:Novartis: Speakers Bureau; Janssen: Speakers Bureau; Bristol Myers Squib: Speakers Bureau.

BACKGROUND: Symptom burden in essential thrombocythemia (ET) and polycythemia vera (PV) is severe even among individuals with low risk disease (Blood 2012. 12;123(24):3803-10). New therapies exist which alleviate the severe symptom burden and reduce splenomegaly in ET and PV patients (N Engl J Med 2015; 372:426-435). This analysis is the first to date to evaluate thresholds at which symptom-based treatment can be considered for ET and PV patients who are intolerant or resistant to hydroxyurea (HU). METHODS: Patient demographics, symptom burden, and disease traits were collected from ET and PV patients at a single time point during therapy. The MPN-10 total symptom score (TSS, JCO 2012;30(33)4098-103) was utilized to assess symptom burden. Symptom criteria models were determined as previously described among a population of MF patients (Scherber et. al. EHA 2016: a2250). Cutoffs were then evaluated in a cohort of ET and PV patients to assess for utility as a symptom model among this population. RESULTS: Demographics and symptom burden: 838 PV and 867 ET patients with previous hydroxyurea therapy were included in this analysis. Patients were of mean age (54.9 years ET, 64.0 years PV) and gender (69.2% female ET, 55.7% female). Mean disease duration was 6.0 years for ET and 7.3 years for PV.Among ET and PV patients, 15.0% and 24.2% had prior thrombosis respectively. In evaluating prognostic risk, ET patients tended to be low (45.5%) or intermediate risk (42.9%) with only a minority of patient meeting criteria forhigh risk disease (11.6%). Laboratory findings: ET patients had a mean platelet value of 598.7x 109/L(SD=283.4). Among PV patients, mean hematocrit was 45.8% (SD=8.1) and 42.6% of patients had a hematocrit of greater than 45%. White blood cell count was normal between the two groups (ET mean 8.3 x 109/L, PV mean 9.0 x 109/L). Symptoms: Mean worst symptom severity was 6.4 out of 10 (SD=2.7). Among ET patients, worst symptom was most frequently fatigue (32.7%, mean 5.0/10, SD=3.1, overall prevalence 88%) followed by night sweats (13.6%, mean 2.0/10, SD=3.0, overall prevalence 53%) and concentration difficulties (8.6%, mean 3.1/10, SD=3.0, overall prevalence 68%). For PV, worst individual symptom items were most frequently fatigue (29.2%, mean 5.2/10, SD=3.0, overall prevalence 91%), pruritus (14.1%, mean 3.2/10, SD=3.2, overall prevalence 69%), and night sweats (12.8%, mean 2.5/10, SD=3.0, overall prevalence 57%). Cutoff Scoring: 47.0% of ET patients fit criteria for TSSgreater than to equal to 20; 59.0%% had a single itemgreater than 5; and 45.7% had both a TSS greater than or equal to 20 and a single item greater than 5. Among PV participants, 54.5% had aTSS greater than to equal to 20; 66.1% had a single itemgreater than 5; and 51.5% had both a TSS greater than or equal to 20 and a single item greater than 5. Each scoring method was significantly associated with individual item scores (Table 1). Prognostic scoring was not significantly associated with any of the symptom cutoffs evaluated. Correlations: Among ET patients, a prior history of thrombosis was significantly associated with having a worst symptom item greater than 5 (p=0.043). ET patients with lower hemoglobin were significantly more likely to meet criteria for a MPN-10 score greater than or equal to 20 or to meet combined criteria for a MPN-10 greater than or equal to 20 and single worst item greater than 5 (for both p=0.01 or less). For PV, lower hematocrit levels were significantly associated with having an individual worst symptom score of greater than 5 (44.9% versus 46.7%, p=0.0376). CONCLUSION: Assessment of ET and PV symptoms, now measurable through standardized and practical instruments such as the MPN-10, is an integral part of determining therapeutic impact of newer therapies in both clinical practice and trial settings. In our modeling, patients with severe symptom burden profiles are well represented by utilizing cutoff criteria including aworst individual symptom item of greater than 5 out of 10, an MPN-10 score of greater than or equal to 20, or combined criteria of both cutoffs. These cutoffs can be considered when determiningwhich HU intolerant or resistant patients would most benefit fromsymptom orientedtreatment. Disclosures Kiladjian: AOP Orphan: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Honoraria, Research Funding. Schouten:Novartis: Consultancy; Sanofi: Consultancy. Etienne:BMS: Speakers Bureau; ARIAD: Speakers Bureau; Pfizer: Speakers Bureau; novartis: Consultancy, Speakers Bureau. Harrison:Incyte Corporation: Honoraria, Speakers Bureau; Shire: Honoraria, Speakers Bureau; Gilead: Honoraria, Speakers Bureau; Baxaltra: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Other: travel, accommodations, expenses, Research Funding, Speakers Bureau. Radia:Pfizer: Honoraria; Novartis: Honoraria. Cervantes:AOP Orphan: Membership on an entity's Board of Directors or advisory committees; Baxalta: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Vannucchi:Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Mesa:Promedior: Research Funding; Celgene: Research Funding; CTI: Research Funding; Gilead: Research Funding; Incyte: Research Funding; Galena: Consultancy; Ariad: Consultancy; Novartis: Consultancy.

BACKGROUND: The presence of constitutional symptoms has been associated with increased mortality risk in myelofibrosis (MF) (Blood 2010;115(9):1703-8). New therapies exist which alleviate the severe symptom burden profile observed in MF patients but are only approved for use in those with intermediate-2 or high risk disease (N Engl J Med 2012;366:787-798). However, it has been proposed that there are patients who may benefit from symptom based treatment regardless of prognostic score (Am Soc Hematol Educ Program 2014;2014:277-286). We have recently characterized symptom score cutoffs at which patients would statistically benefit from treatment based on symptom scores alone (Scherber et. al. EHA 2016: a2250). These treatment thresholds included aMyeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS or MPN-10) total score of greater than or equal to 20, a worst individual item score of greater than 5, or a combined criteria of those with both an MPN-10 total score of greater than or equal to 20 and a worst individual item score greater than 5. This abstract represents an additional analysis of our MF cohort to better characterize the profile of patients who meet criteria for symptom-based therapy. METHODS: Patient demographics, symptom burden via the MPN-10 score (JCO 2012;30(33)4098-103), and disease traits were collected from MF patients and their physicians at a single time point during therapy. Previously we identified MPN-10 cutoffs via AkaikeÕs Information Criterion (AIC) analysis (Ecology 2014;95: 631-6), which represented the optimal model among all models specified for the data at hand to determine which patients would most benefit from symptom-directed therapy. RESULTS: Demographics. 695 MF patients without previousruxolitinib therapy were included in this analysis. Overall, of 455 patients (65.4%) fit a cutoff of having a single worst symptom item of greater than 5/10. 401 patients (57.7%) had a MPN-10 score of equal to or greater than 20. A total of 381 (54.8%) patients fit both of these criteria. A distribution of worse MPN-10 individual scores is shown in Table 1. Mean TSS score was 26.4 (SD=17.7). Symptom Criteria Associations. Demographics and disease traits: Neither mean age or age greater than 60 was significantly associated with meeting any of the symptom score cutoff criteria. Females were significantly more likely to meet any of the symptom score cutoffs (for all criteria, p=0.0003 or less). Patients with splenomegaly, particularly spleen size of greater than 15cm below the LCM, were significantly more likely than those with a normal sized spleen to meet any of the three criteria (spleen enlargement of any size p=0.014 or less; spleen greater than 15cm p=0.0114 or less). Patients who met any of the three symptom criteria tended to have a longer MPN duration, although this trend did not meet significance. A prior history of thrombosis was not associated with achieving any cutoff criterions. Symptom burden: Individuals who met the any symptom criteria were significantly more likely to have higher DIPSS prognostic risk score (for all p=0.0002 or less). Laboratory values: For those meeting criteria for a worst symptom greater than 5, mean WBC was 11.7 vs 9.1 x 109/L (p=0.025) and platelet count was 238.7 versus 329.1 (p=0.023). For those meeting criteria for a TSS greater than or equal to 20, mean WBC was 11.8 vs 9.5 x 109/L (p=0.04). For individuals meeting both criteria, mean WBC was 11.9 vs 9.5 x 109/L (p=0.034). The presence of peripheral blasts were significantly more common in patients with an individual worst symptom score greater than 5 (p=0.0364). Hemoglobin level was not significantly associated with symptom criteria for any cutoffs. CONCLUSION: Our analysis indicates that patients who would be treated based on symptom criteria are similar to patients who would be treated based on high risk features such as high DIPSS prognostic score, concerning blood count abnormalities (i.e., leukocytosis, thrombocytopenia, presence of peripheral blasts), and splenomegaly (particularly massive splenomegaly). Thrombosis history and age were not associated with criterion cutoff assignment, and it is notable that elderly age nor history of thrombosis alone would likely alter treatment choice other than anticoagulation. This data supports that JAK2 inhibitor treatment be strongly considered in patients meeting symptom based criteria. Disclosures Dueck: Bayer: Honoraria. Kiladjian:Novartis: Honoraria, Research Funding; AOP Orphan: Membership on an entity's Board of Directors or advisory committees, Research Funding. Zweegman:Celgene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Takeda: Honoraria, Research Funding. Schouten:Sanofi: Consultancy; Novartis: Consultancy. Etienne:ARIAD: Speakers Bureau; Pfizer: Speakers Bureau; novartis: Consultancy, Speakers Bureau; BMS: Speakers Bureau. Harrison:Shire: Honoraria, Speakers Bureau; Gilead: Honoraria, Speakers Bureau; Baxaltra: Consultancy, Honoraria, Speakers Bureau; Incyte Corporation: Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Other: travel, accommodations, expenses, Research Funding, Speakers Bureau. Radia:Novartis: Honoraria; Pfizer: Honoraria. Cervantes:Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Baxalta: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AOP Orphan: Membership on an entity's Board of Directors or advisory committees. Vannucchi:Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Mesa:Promedior: Research Funding; Celgene: Research Funding; CTI: Research Funding; Gilead: Research Funding; Incyte: Research Funding; Galena: Consultancy; Ariad: Consultancy; Novartis: Consultancy.

BACKGROUND A high cure rate may be attained for locally advanced, undifferentiated nasopharyngeal carcinoma (NPC) in children, provided that a combined modality of treatment is employed. Both local and systemic therapies are necessary. Results at a single pediatric institution were analyzed. METHODS From November 1988 to December 1997, 16 consecutive patients were treated with NPC at the Hospital Garrahan in Buenos Aires, Argentina. The authors were able to evaluate 11 patients (9 boys and 2 girls); their median age was 12 (range, 8–14) years. Chemotherapy consisted of 3 courses, every 3 weeks, of 5-fluorouracil (500 mg/m2) plus bleomycin (15 mg/m2) daily for 4 days, with cisplatin (100 mg/m2) added the last day. External beam radiotherapy was delivered over a median of 52 (range, 45–63) days, to a median cumulative dose to the primary site of 55 (range, 50–61.2) grays (Gy). The median dose for the lower neck area was 45 (range, 45–55.8) Gy. All patients received radiotherapy to the primary site and to the initially involved lymphoid areas, with daily single doses of 1.8 Gy (5 of 7 days per week). RESULTS The main symptoms at onset were cervical mass (100%), epistaxis (54%), cephalalgia (36%), and trismus (36%). All cases were Stage IV (American Joint Committee on Cancer and International Union Against Cancer TNM system). Complete response was achieved in 45% of patients after initial chemotherapy. With a median follow-up of 63 (range, 23–119) months, disease free survival (with standard error [SE]) and overall survival estimates were 61% (16%) and 91% (9%), respectively, at 75 months. Acute toxicity due to therapy was tolerable. Chronic sinusitis (73%), hypothyroidism (73%), and mild (64%) or moderate (9%) neck fibrosis were detected at follow-up. CONCLUSIONS Although this series is small, the authors concluded that NPC patients have a good chance of survival in the setting described, in spite of locally advanced disease. Chemotherapy might be useful in preventing the development of systemic metastases. Cancer 2000;89:690–5. © 2000 American Cancer Society.

BACKGROUND The association between t(8;21) and granulocytic sarcoma (GS) is well known, but to the authors' knowledge the prognostic significance of GS in these patients has not been defined clearly. METHODS Between January 1990 and July 1999 174 children with acute myeloid leukemia were admitted to the study institution. Translocation (8;21) was identified in 20 patients (11.5%). Eighteen patients were evaluable for the current study and 8 presented with GS at the time of diagnosis (GS+). RESULTS The authors defined two groups of patients: those who were GS+ and those who were GS−. One patient in the GS+ group and two patients in the GS− group died during the induction phase of the study. Complete remission was achieved in seven patients in the GS+ group and eight patients in the GS− group. Two patients developed a recurrence in the GS+ group as did one patient in the GS− group. The event free-survival probability (the standard error) was 58% (18%) in the GS+ group and 70% (14%) in the GS− group. Localization of GS was in only one site in seven patients and at multiple sites in one patient. Patients with an epidural mass received local radiotherapy (one patient) or surgery (two patients). Two of these patients developed paraplegia as sequelae: one patient after surgery and one patient after radiotherapy. One patient with orbital GS received local radiotherapy because of progressive proptosis. The remaining four patients had a complete resolution of the GS with chemotherapy only. CONCLUSIONS In the current study of patients with t(8;21)(q22;q22), the presence of granulocytic sarcoma was not found to be an adverse prognostic factor. However, careful attention should be paid, especially to patients with an epidural site, to avoid sequelae. Chemotherapy appears to be the optimum treatment for these children. Cancer 2000;88:1939–44. © 2000 American Cancer Society.

We describe an 8 year old boy who had received chemotherapy for an acute promyelocytic leukemia and developed a secondary leukemia 27 months after the diagnosis of this first malignancy. Blasts cells were positive for cytoplasmic markers CD22, CD3 and myeloperox-idase. Cell surface T and myeioid-associated markers were also detected. Cytogenetic study disclosed monosomy 7. The patient achieved complete remission, but relapsed 15 months later with identical immunophenotypic and cytogenetic findings. Three-lineage commitment is proved by the expression of specific criteria for myeloid, and lymphoid T and B typing. A multipotent immature progenitor must be the target of leukemogenic agents. The prognosis is obviously ominous.

Background Acute myeloid leukemia (AML) is well-recognized as one of the most important second malignancies. We report the occurrence of secondary AML (sAML) in our institution. Procedure From September 1987 to August 1996 we have observed sAML in 9 patients (median age 4 years), 5 of them previously treated for hematologic malignancies (group I): acute lymphoblastic leukemia (n = 2), AML (n = 1), non-Hodgkin lymphoma (n = 1). Hodgkin disease (n = 1), and 4 of these 9 patients treated for solid tumors (group II): neuroblastoma (n = 1), retinoblastoma (n = 1), Wilms tumor (n = 1), and central nervous system germinoma (n = 1). Results All the patients had topoisomerase II inhibitors as part of treatment of their first malignancy, but only 5 patients received epipodophyllotoxins. Alkylating agents were part of primary therapy in 8 of 9 patients. The latency period for the development sAML was 26.5 (range = 2-55) months. The morphologic FAB features of sAML were M5 (n = 5), M4 (n = 3), and M2 (n = 1). Cytogenetic studies showed r11q23 in 3 patients, all of them with prior hematological malignancies. Initial therapy for sAML in all cases was chemotherapy (including cytarabine in combination with idarubicin and etoposide or doxorubicin or mitoxantrone). Three patients died during induction and 6 achieved complete hematologic response. Three of these patients remain disease free at +15, +51, and +99 months post-remission (including one post allogeneic BMT). The remaining 3 patients died, 1 in complete remission one month after diagnosis and 2 relapsed and died with progressive disease (one post allogeneic BMT). Conclusions Secondary AML is a sequela of oncologic treatments with specific cytogenetic abnormalities and poor outcome. A few patients can achieve long-term survival even with standard chemotherapy.

Purpose. To report the feasibility and results of a study based on the BFM-ALL-NHL/86 protocol for B-non-Hodgin's Lymphoma (NHL) and β-Acute Lymphoblastic Leukemia (B-ALL) in Argentina. Design. Prospective, single arm, non-randomized trial. Patients and Methods. From August 1988 to December 1993, 87 consecutive patients with B-NHL/B-ALL were admitted and 82 were eligible. The therapy was stratified according to stage. All patients received a cytoreductive prephase with cyclophosphamide and prednisone. Those with stage I-II were treated with three 5-day blocks of combined intense chemotherapy including dexamethasone, cyclophosphamide, ifosfamide, cytarabine, teniposide, doxorubicin, and 500 mg/m 2 of methotrexate as a 24 hour continuous infusion. Stage III received 6 blocks and those with stage IV/B-ALL received 6 intensified blocks in which 2 g/m 2 of 24 hour continuous infusion methotrexate and vincristine were added. Triple intrathecal therapy was given for CNS prevention. After the first two blocks the response was assessed and those; with a partial response were offered optionallya second look surgery or local radiotherapy. Results. With a median follow-up of 38 (range 16-71) months, the event-free survival (pEFS: for the whole group was 0.69 (Stage I-II n = 16 pEFS = 0.94, stage III n = 50 pEFS = 0.66, Stage IV n = 7 pEFS = 0.43, B-ALL n = 9 pEFS = 0.66). Patients with stage III abdominal tumors who achieved a partial response by imaging studies - after induction had a significantly higher risk of relapse than those with a complete response (p = 0.02). Relapse was the most frequent event Toxicity was mainly hematological. Conclusions. The application of this protocol was feasible in our setting and its results comparable to the German study. Patients with stage I-II had an excellent outcome. Those with stage III and B-ALL achieved an encouraging event-free survival, however those with abdominal tumors and partial response to induction chemotherapy fared less favourably. This strategy was less effective for patients with initial CNS disease.

Background We have previously reported on the high prevalence and severity of challenges with intimacy and sexuality amongst a large international cohort of MPN patients (Emanuel JCO 2012). We sought to further analyze the relationships between issues of intimacy (sexual desire and function), their relationships to MPN disease features, individual MPN symptom prevalence and severity, language, and overall quality of life. Methods Data was collected among an international cohort of patients with MPNs. Subjects completed the BFI, MPN-SAF, and EORTC QLQ-C30 instruments. Surveyed symptoms on the MPN-SAF included the patient’s perceptions of common MPN-related symptoms and overall quality of life (QOL) on a 0 (absent) to 10 (worst imaginable) scale. Specifically, the MPN-SAF sexuality item asked about “problems with sexual desire or function”. Total symptom score (TSS) was computed based on 10 symptom items using the published scoring algorithm on a 0 (all reported symptoms absent) to 100 (all reported symptoms worst imaginable) scale. Pairwise associations between the MPN-SAF sexuality item and continuous and categorical covariates were investigated using Pearson correlations and analysis of variance/t-tests, respectively. Multivariate regression models were used to investigate impact of groups of covariates on the sexuality item with the final multivariate model selected using forward regression. Results Demographics A total of 1908 MPN patients (essential thrombocythemia=799, polycythemia vera=671, myelofibrosis=432, missing=6) completed the sexuality item. Participants were of typical age (median=60, range 15-94) and gender (female=53%). Overall, 1218 subjects described sexuality related complaints (score >0) with an overall mean symptom score of 3.5 (median=2.0, SD=3.7, range 0-10); 725/1908 (38%) patients had severe sexuality related complaints (score >4). Univariate Analysis Among the QLQ-C30 functioning scales, all domains had similar statistically significant correlations (r=-.26 to -.32, all p Multivariate Analysis In a multivariate model of MPN-SAF sexuality containing all QLQ-C30 functioning scales, physical (p=0.001), emotional (p=0.01), cognitive (p=0.005) and social (p=0.002) functioning were all statistically significant. Numerous symptoms were also significant in a multivariate model of MPN-SAF sexuality containing all other MPN-SAF symptoms (all p Conclusions Sexuality related complaints have been linked to both physiologic and psychologic origins and are highly prevalent within the MPN population. The results of this study congruently identified close associations between sexuality and function within emotional, cognitive and social domains. Additionally, the correlations of sexuality issues with MPN symptoms and disease features further suggest this item is a key correlate of overall functionality and quality of life. Future investigations into the causative factors and biological correlates of this complaint may assist in addressing this ongoing challenge. Disclosures: Etienne: novartis: Consultancy, Membership on an entity’s Board of Directors or advisory committees; Bristol Myers Squibb: Consultancy, Membership on an entity’s Board of Directors or advisory committees; Pfizer: Membership on an entity’s Board of Directors or advisory committees; Ariad: Membership on an entity’s Board of Directors or advisory committees. Roy:Novartis, BMS: Honoraria. Harrison:Novartis: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Sanofi: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; YM Bioscience: Honoraria, Membership on an entity’s Board of Directors or advisory committees; Celgene: Honoraria; Shire: Speakers Bureau; S Bio: Honoraria, Membership on an entity’s Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity’s Board of Directors or advisory committees. Birgegard:Vifor Pharma: Honoraria. Mesa:Eli Lilly and Co: Research Funding; Genetech: Research Funding; Gilead: Research Funding; Incyte: Research Funding; Sanofi: Research Funding; NS pharma: Research Funding; Celgene: Research Funding.

Abstract 1726 Background: We previously reported that symptom burden among persons with ET and PV can be severe and adversely affect QOL. The presence of severe symptoms is linked to poor prognosis. There is considerable inter-subject heterogeneity regarding which symptoms are present in which subjects. No studies have empirically evaluated whether disease characteristics can be grouped in related symptom clusters. Using our previously validated 18 item Myeloproliferative Neoplasm Assessment Form (MPN-SAF) (Blood 2011;118:401–408) given in conjunction with the 9 item Brief Fatigue Inventory (BFI) (Cancer 1999;85:1186–1196), we sought to evaluate symptom burden by means of cluster analysis. Methods: Data was collected from an international cohort of subjects with MPNs including demographics, disease features and the completed BFI and MPN-SAF instruments. Surveyed symptoms included fatigue, early satiety, abdominal pain and discomfort, inactivity, headaches, concentration, dizziness, extremity tingling, insomnia, sexual difficulties, mood changes, cough, night sweats, pruritus, bone pain and fever on a 0 (absent) to 10 (worst-imaginable) scale. Development of symptom clusters was based on consideration of r-squared in hierarchical clustering using Ward linkage. Final cluster assignment was based on the nonhierarchical k-means method. Comparisons between symptom clusters were based on ANOVA and chi-squared tests. Results: Subject Demographic and Disease Characteristics: Data from 1,141 subjects with PV (N=519) and ET (N=622) was prospectively collected (Chinese 236, French 305, German 45, Italian 114, Dutch 191, English 56, Spanish 109, Swedish 85. Age (mean 59, range, 26–87) and gender (54% F) were typical. Five clusters were selected (Figure 1). Frequencies of prior bleeding, spleen size, anemia, presence of any lab abnormality, language, gender, and MPN type varied significantly between clusters (P Cluster 1: The “Reduced Symptom” Profile (n=421 (37%; 60% ET, 40% PV) The largest cluster, subjects had increased complaints of sexual difficulties and fatigue. There was a slightly higher proportion of subjects with ET (60%) versus PV. There were fewer lab abnormalities (28% prevalence) and less prior bleeding (3%) compared to other clusters. Spleen size was smallest of the cluster (1 cm below costal margin). Cluster 2: The “Fatigue-dominant” Group (n=286 (25%; 56% ET, 44% PV)). Subjects in this cluster were predominantly female and had relatively few laboratory abnormalities (19%) than other cohorts. They are characterized by high severity of fatigue compared to end-organ symptoms. Symptom profiles emphasize fatigue, QOL and insomnia with some end-organ complaints. The cohor 63% of the cohort. Cluster 3: The “End-Organ Complaints” Group (n=210 (18%; 49% ET, 51% PV)). Male predominant (56%), subjects had mainly macro-vascular symptom complaints including sexual difficulties, insomnia, and overall QOL, with few microvascular related symptoms (low itching/night sweats). Cluster 4: “Cognitive Complaints” Cluster (n=110 (10%; 53% ET, 47% PV)). The smallest cluster and female predominant (64%), main complaints include fatigue, insomnia, loss of concentration, numbness, and sad mood. Cluster 5: The “Highly Symptomatic” Cluster (n=114 (10%; 44% ET, 56% PV)). Subjects had many cognitive complaints and symptoms correlated with severe micro-vascular abnormalities (pruritus) and or splenomegaly. This cluster had the largest spleen sizes (mean 3 cm), the highest prevalence of prior thrombosis (29%), and highest frequency of lab abnormalities (43%). Cognitive and end-organ complaints were rated as most severe. Conclusion: This analysis offers new means of evaluating persons with PV and ET utilizing symptom clusters. Laboratory and physical abnormalities differed significantly between symptom clusters indicating that our groupings likely result from biological alterations present in specific disease phenotypes. Future studies should investigate correlations between clusters and prognosis and genotype. Disclosures: Kiladjian: Celgene: Research Funding; Novartis: Honoraria, Research Funding; Shire: Honoraria. Roy:Novartis, BMS: Speakers Bureau. Harrison:Novartis: Honoraria, Research Funding, Speakers Bureau; YM Bioscience: Consultancy, Honoraria; Sanofi Aventis: Honoraria; Shire: Honoraria, Research Funding. Vannucchi:Novartis: Membership on an entity's Board of Directors or advisory committees. Passamonti: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; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees. Mesa:Incyte: Research Funding; Lilly: Research Funding; Sanofi: Research Funding; NS Pharma: Research Funding; YM Bioscience: Research Funding.

Abstract 1731 Background: Symptom burden in primary, post-ET and post-PV myelofibrosis (MF) is frequently severe and correlates with a poor prognosis. However, symptom manifestations are heterogeneous with variable presence of specific symptoms, splenomegaly and cytopenias. We sought to identify the spectrum and features of MF symptomatic phenotypes by cluster analysis of prospectively gathered information on MF symptoms and disease features. Methods: Data was collected among an international cohort of subjects with MF. Data included demographics, disease features and completion of the Brief Fatigue Inventory (BFI) and Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) (Blood 2011; 118:401–408). Surveyed symptoms addressed key disease features on a 0 (absent) to 10 (worst-imaginable) scale. Cluster development was based on consideration of r-squared in hierarchical clustering using Ward's linkage. Final cluster assignment was based on the nonhierarchical k-means method. Comparisons between symptom clusters were based on ANOVA and chi-squared tests. Results: Subject Demographic and Disease Characteristics: Data from 329 prospectively enrolled persons with MF was collected (Chinese 102, French 54, German 19, Italian 22, Dutch 45, English 51, Spanish 29, Swedish 7) including 223 PMF, 67 post-ET MF and 39 post-PV MF patients. Participants were of typical age (mean 59) and gender (47% F). Among all participants, four natural symptom clusters were identified (Figure 1). Among clusters, disease features including leukopenia, thrombocytopenia, and enlarged spleen varied significantly between clusters (P Cluster 1: The “Fatigue Dominant with Few Lab Abnormalities” Profile (n=150 (46%; 69% PMF, 20% post-ET MF, 11% post-PV MF)). Cluster 1, the largest, is characterized by fatigue-dominant complaints in the setting of the lowest overall MPN-SAF TSS and highest proportion of males (59%). Individuals among this group have the lowest prevalence of laboratory abnormalities (65% total; anemia, 67%; thrombocytopenia, 20%) or clinical deficiencies including enlarged spleen (average 6.0 cm below costal margin), prior thrombosis (9%), prior hemorrhage (5%) or prior RBC-transfusions (20.4%). Interestingly, individuals in this group are most likely to have had prior splenectomy (5.8%). Cluster 2: The “Cognitive Complaints with Enlarged Spleen” Cluster (n=105 (32%; 65% PMF, 20% post-ET MF, 15% post-PV MF)). Cluster 2 is the 2nd largest cluster. Subjects have relatively few abnormal lab values (67% vs 65%–77%) but have high severity of fatigue, sexual difficulties, insomnia, inactivity and reduced QOL. These individuals have the largest spleen size (8.7cm below costal margin). Cluster 3: The “Nighttime and Cognitive Complaints” Group (n=53 (16%; 64% PMF, 25% post-ET MF, 11% post-PV MF)). Cluster 3 is the smallest cluster. Subjects have many cognitive and nighttime-related complaints including sexual difficulties, night sweats, insomnia, and concentration problems. Subjects with post-ET MF are predominant. This cluster also has the 2ndsmallest spleen size (7 cm) or history of prior thrombosis (9.6%), hemorrhage (7.8%) or requirement for transfusions (21.2%). Cluster 4: The “Severe Fatigue with Few End-organ Complaints” Cluster (n=21 (6%; 81% PMF, 14% post-ET MF, 5% post-PV MF)). Cluster 4 is the most symptomatic cohort with the highest proportion of subjects with PM. There is a lower frequency of end-organ complaints including abdominal pain, cough, and headaches. Symptoms including sexual difficulties, sad mood and insomnia are predominant. No subjects had prior splenectomy. Subjects also have the highest prevalence of prior thrombosis (29%), hemorrhage (14%), and transfusions (43%). Additionally, this cohort has the largest prevalence of lab abnormalities (77%) with thrombocytopenia (71%), leukopenia (41%) and anemia (41%). Conclusion: This analysis will allow us to examine a new framework for evaluating persons with MF using symptom profiles and is the 1st cluster evaluation of MF. Lab and physical findings contrast significantly between symptom clusters indicating these phenotypic symptoms likely result from etiological factors present in specific disease phenotypes. Future studies should evaluate whether there is a correlation between cluster profiles, prognosis and genotype. Disclosures: Kiladjian: Celgene: Research Funding; Novartis: Honoraria, Research Funding; Shire: Honoraria. Roy:Novartis, BMS: Speakers Bureau. Harrison:Novartis: Honoraria, Research Funding, Speakers Bureau; YM Bioscience: Consultancy, Honoraria; Sanofi Aventis: Honoraria; Shire: Honoraria, Research Funding. Vannucchi:Novartis: Membership on an entity's Board of Directors or advisory committees. Passamonti: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; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees. Mesa:Incyte: Research Funding; Lilly: Research Funding; Sanofi: Research Funding; NS Pharma: Research Funding; YM Bioscience: Research Funding.

Background: The Philadelphia chromosome negative myeloproliferative neoplasms (MPNs), including essential thrombocythemia (ET), polycythemia vera (PV) and myelofibrosis (MF) all have a time dependent risk of progression to either an advanced myelofibrotic state (post ET/PV MF) and/or to acute myeloid leukemia. The impact of disease duration upon the MPN symptom burden is not well understood, nor are the precise mechanisms of disease progression. We sought to better understand the impact of disease duration on MPN symptom burden. Methods: Symptom burden data was collected utilizing the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) amongst MPN patients, collected at the time of an office visit in an international cohort of MPN patients as previously described (Scherber et. al.). Symptom burden assessment was a previously validated 27-item symptom burden questionnaire scored on a 0-10 scale (0= as good as it can be, 10 = as bad as it could be). The patient or provider was asked to report the time since MPN diagnosis. MPN duration was determined to be early if the diagnosis was established between 0 to 5 years ago, intermediate if the diagnosis was established between 6 to 10 years ago, and late if the diagnosis was established 11 years ago or more. Anemia was defined as a red blood cell count less than 10 g/dL, leukopenia was defined as a white blood cell count was below 4 x 109, and thrombocytopenia if the platelet count was below 150 x109. Statistical significance was calculated using ANOVA f-test and chi squared. Results: Patient demographics and disease burden: A total of 1443 patients responded to the survey, including 592 (41%) ET, 549 (38%) PV, and 302 (21%) MF patients, including 181 (60%) primary MF, 67 (22%) post-ET MF, and 54 (18%) post-PV MF. Among MF patients, mean duration of MPN diagnosis was 9 years, and mean duration MF diagnosis was 4.7 years. Among respondents, 757 fit criteria for early disease duration, 353 fit criteria for intermediate disease duration, and 333 fit criteria for late disease duration. Respondent mean age was 62 years and approximately half of respondents were female (55%). Patients with longer diagnosis duration tended to be older (p=0.009) and were most likely to have anemia (0.02), leukopenia (p=0.01), or thrombocytopenia (p=0.03). These individuals were also most likely to have a history of hemorrhage (p=0.007) or require red blood cell transfusions (p Combined cohort symptom burden: On average among the combined cohort of ET, PV and MF patients, symptoms tended to worsen with time with this effect being significant for symptom items of fatigue (BFI, p Symptom burden in MPN subtypes. When evaluating specific MPN types, patients with essential thrombocythemia experienced significantly greater sexual difficulties over time (p=0.03). The severity (p=0.01) and incidence (p=0.03) of pruritus and incidence of night sweats (p Discussion Overall, significant worsening in symptom burden can be recognized over time for individuals diagnosed with MPNs. Diagnosis may not necessarily correlate with disease duration as the timing of diagnosis may be delayed from onset of disease. Given the intent of this abstract to evaluate changes with disease duration, we did not investigate correlations between symptom burden and cytopenias. We do know that risk factors for survival in the MPNs include older age and thrombosis, however, disease duration should be investigated as an alternative marker of burden in future survival studies. Disclosures Harrison: CTI Biopharma: Consultancy, Honoraria, Speakers Bureau; Shire: Speakers Bureau; Gilead: Honoraria; Novartis: Honoraria, Research Funding, Speakers Bureau; Sanofi: Honoraria, Speakers Bureau. Kiladjian:Incyte Corporation: Consultancy; Novartis: Other: Travel grant; Research Funding paid to institution (Hôpital Saint-Louis et Université Paris Diderot); Novartis: Consultancy. Zweegman:Celgene: Research Funding; Janssen: Research Funding; Takeda: Research Funding. Barbui:Novartis: Speakers Bureau. Etienne:Novartis: Consultancy, Honoraria, Other: Congress Travel/Accomodations, Research Funding, Speakers Bureau; BMS: Consultancy, Honoraria, Speakers Bureau; ARIAD: Consultancy, Honoraria, Speakers Bureau. te Boekhorst:CTI Biopharma: Consultancy; Novartis: Consultancy. Vannucchi:Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Other: Research Funding paid to institution (University of Florence), Research Funding; Shire: Speakers Bureau; Baxalta: Membership on an entity's Board of Directors or advisory committees. Mesa:Novartis. Research- incyte, Gilead, cti, Genentech, promedior, NS Pharma: Consultancy.

Background Response to TKI is the most important predictor of survival in CML and its early acquisition predicts the achievement of deep molecular responses (MR) (Baccarani et al. Blood 2013). In current ELN recommendations, the optimal time point to achieve Major Molecular Response (MMR) is defined at 12 months (mo) after diagnosis of CML however, not achieving MMR is not a failure criterion at any time point (Saussele et al, Blood 2014). There are controversies about when CML therapy must be changed in pts who do not achieve MMR after 12 mo of treatment. We wonder if pts achieving late MMR are less likely to achieve deep MR or are at risk of progression to accelerated phase (AP) or blast crisis (BC). Objectives We aim to identify predictive factors for achievement of deep MR and improvement of failure-free survival (FFS). Other objective was to determine if delay in MMR acquisition predicts outcomes in order to justify an optimal landmark for changing TKI reducing the risk of failure. Methods Between 2000 and 2015, 122 consecutive adult pts with CP CML were treated with various TKI modalities. Adherence (ADH) monitoring occurred in every visit and was reported in medical records, optimal ADH defined as >90% of dose completed. Cytogenetic and MR were defined according to ELN definitions and followed the procedures as described elsewhere (Cross et al. Leukemia 2012). In particular, BCR-ABL Results From 122 pts diagnosed with CP CML, 110 pts received 1st line imatinib (IM) 400mg daily and constitute the basis of the analysis. Median age was 48 years (14-82), 65% were males, 82% low Sokal score. With a median follow-up of 107 mo (IQR 69.5-141) 82% pts are still on initial IM, 4.5% died and 1.8% were lost to follow-up. A total of 20 pts (18%) discontinued Imatinib, 9% due to intolerance and 9% due to failure. At 15 years, FFS was 88% and OS 95%.The proportion of pts treated with IM who achieved CCyR at 6mo and MMR at 12mo was 84% and 38% respectively. Median-time to achieve MMR and MR4.0 was 2.6 and 3.6 years respectively. By logistic regression analysis CCyR at 6mo OR 5,6 (95% CI 1,6-19,00), MMR at 12mo OR 5,3 (95% CI 1,4-21,0), ADH OR 7,0 (95% CI 1,3-37,0) and not MMR at 24mo OR 2,5 (95% CI 0,9-7,2) resulted independent predictors for achieving MR4.0 and confirm earlier observations. In Cox model of proportional hazards for risk of failure, time to achieve MMR HR 1,02 (95% CI 1,01-1,04), ADH HR 6.1 (95% CI 1,38-26,8), and Sokal HR 4,7 (95% CI 1,12-19,3) were independent predictors of failure. Time to achieve MMR is a continuous variable, so the HR associated with it, is equivalent to a 2% monthly increase in the risk of failure. To calculate HR in other time intervals, the product of the coefficient model (B) and time of interest (in mo) were used as an exponent of the base of the natural logarithm (e). Not reaching MMR at 12 mo correlates with higher risk of failure: hazard-risk (HR) 1.30, (95% CI 1.28-1.30) and the risk increases with every passing year not achieving MMR (Table 1). Table 1.Time to MMR as predictor of progressionNo MMR achievement in different time intervalsHRCI 95%After 12 mo of TKI1,30(1,3-1,3)After 24 mo of TKI1,70(1,7-1,7)After 30 mo of TKI2,21(2,2-2,2)After 60 mo of TKI3,74(3,7-3,8) Conclusions The prognostic value of CCyR at 6mo and MMR at 12mo was confirmed. The association between early MMR and deep MR was confirmed. In this long-term follow-up Latin American real-world cohort of patients ADH was also an early predictor for achievement of deep MR. Although good responses are obtained with IM, some patients still progress, this is the reason why it is necessary to identify those who will relapse so as to consider a change in treatment to another TKI at a convenient time point. Time to achieve MMR, ADH, and Sokal Risk score were independent predictors of failure. Not achievement of MMR at 12mo correlates with increased risk of failure. The risk increases annually in proportion to the time delay. Patients who are delayed in reaching MMR should be controlled closely. Disclosures Pavlovsky: Novartis: Honoraria, Speakers Bureau; Janssen: Honoraria, Speakers Bureau. Pavlovsky:Novartis - Bristol: Speakers Bureau.

Background: Thrombotic and hemorrhagic complications are commonly encountered in uncontrolled essential thrombocythemia (ET). Both anagrelide and hydroxyurea (HU) have proven efficacious in cytoreduction as well as reducing these events and remain first line therapy for most high-risk ET patients. Independent of their role in risk-reduction, little is known about how these therapies impact patient symptomatology or quality of life. In this study, we compared the clinical and symptomatic profiles of ET patients receiving HU or anagrelide against patients with no previous experience with these agents. Methods: Data was assessed from a prospectively collected international database of ET patients in which demographics, disease features, and ET symptoms utilizing the myeloproliferative neoplasm symptom assessment form (MPN-SAF; Scherber et al, 2011). The MPN-SAF includes the patient's perceptions of common MPN-related symptoms and overall quality of life (QOL) on a 0 (absent) to 10 (worst imaginable) scale. Total symptom score (TSS) was computed based on symptom items using the published scoring algorithm on a 0 (all reported symptoms absent) to 100 (all reported symptoms worst imaginable) scale. ET risk scores were calculated using the IPSET scoring algorithm (Passamonti 2012). Thrombocytopenia was defined as a platelet count Results Hydroxyurea vs. HU Naive A total of 402 ET patients with active HU use were compared to 392 ET patients with no history of HU use. Patients using HU were older (63.5 years vs. 52.3 years, p Anagrelide vs. Anagrelide Naive A total of 49 ET patients with active anagrelide use were compared to 794 ET patients with no history of anagrelide use. Patients using anagrelide had a longer mean disease duration (8.1 years vs. 5.8 years) and were more anemic (9.1% vs. 1.2%, p HU vs. Anagrelide A total of 402 patients currently using HU were compared to 39 patients currently using anagrelide. Overall, HU users were slightly older (63.5 years vs. 55.1 years, p Discussion In this retrospective analysis, it does not appear cytoreduction with either HU and/or anagrelide has a significant impact on ET symptom burden despite reducing vascular events. Importantly, the higher risk scores in HU patients did not translate directly into greater patient symptomatology supporting previous studies demonstrating a poor association between these two items. Prospective trials measuring ET symptom change, in the setting of randomized trials will better quantify impact of cytoreduction on symptom burden as well as quantify impact of newer agents such as interferon or jak inhibition. Figure 1. Symptom Comparisons Between HU, Anagrelide and Other Therapy Figure 1. Symptom Comparisons Between HU, Anagrelide and Other Therapy Disclosures Kiladjian: Incyte Corporation: Consultancy; Novartis: Other: Travel grant; Research Funding paid to institution (Hôpital Saint-Louis et Université Paris Diderot); Novartis: Consultancy. Zweegman:Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding. Harrison:Sanofi: Honoraria, Speakers Bureau; Shire: Speakers Bureau; Gilead: Honoraria; CTI Biopharma: Consultancy, Honoraria, Speakers Bureau; Novartis: Honoraria, Research Funding, Speakers Bureau. Cervantes:Sanofi-Aventis: Consultancy; Novartis: Consultancy, Speakers Bureau; CTI-Baxter: Consultancy, Speakers Bureau. Barbui:Novartis: Speakers Bureau. Etienne:ARIAD: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Other: Congress Travel/Accomodations, Research Funding, Speakers Bureau; BMS: Consultancy, Honoraria, Speakers Bureau. Roy:Novartis: Consultancy, Research Funding; BMS: Consultancy, Research Funding. te Boekhorst:Novartis: Consultancy; CTI Biopharma: Consultancy. Vannucchi:Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Shire: Speakers Bureau; Novartis: Other: Research Funding paid to institution (University of Florence), Research Funding; Baxalta: Membership on an entity's Board of Directors or advisory committees. Mesa:Novartis. Research- incyte, Gilead, cti, Genentech, promedior, NS Pharma: Consultancy.

Introduction: Chemoimmunotherapy with 6 cycles of fludarabine, cyclophosphamide and rituximab (FCR) is considered standard therapy for physically fit patients with chronic lymphocytic leukemia (CLL). Due to treatment toxicity, some patients are unable to undergo standard 6 cycles of FCR. We evaluated safety and efficacy of abbreviating FCR treatment to 4 cycles in a cohort of 35 untreated physically fit CLL patients who achieved CR with negative minimal residual disease (MRD). Patients and methods: Within 150 physically fit CLL patients treated with FCR on 1st line at our Center, from April 2003 to November 2014, a subgroup of 35 patients interrupted treatment after achieving negative MRD at the end of the 4th cycle. Median age at start of treatment was 62.8 years (34-81). Binet A/B: 24pts and C: 11. CD38 expression was positive (>7% off cells) in 57.1% and negative in 9% of the pts. A bone marrow biopsy was performed at start of treatment and 1 month post 4th cycle. Response was assessed in peripheral blood (PB) or bone marrow (BM). Negative MRD was defined as < 10-4. We used NCI criteria for response modified for the evaluation of MRD by flow cytometry. Progression was defined according to the NCI recommendations. Overall survival (OS) was defined as the time of initiation of therapy until death or last follow-up and progression free survival (PFS) as the time to progression. Data analysis included frequency and contingency tables, survival curves were plotted by the Kaplan Meier method. Treatment schedule: Fludarabine 25 mg/m2 IV day 1-3, cyclophosphamide 250 mg/m2 IV day 1-3, rituximab 375 mg/m2 IV day 3 cycle 1 and day 1 cycles 2-4, in all cycles every 28 days. Results: All 35 patients had negative MRD in PB after one month post 4th cycle. In addition, 28 had bone marrow evaluation showing CR with negative MRD in all of them. No splenomegaly nor hepatomegaly, enlarged lymphadenopathies nor lymphocytosis was observed in all the patients with negative MRD. After a median follow-up of 57 months (7 -141), median PFS was 65.8 months, not being yet reached the median of OS. PFS and OS at 72 months was 46% and 68% respectively. A total of 10 pts ( 3.5%) died: 7 on progressive disease, 3 on secondary neoplasms. Patients who progressed before 24 months had a median of survival of 22 months; median not reached on the group who progressed after 24 months (p=0.0001). Neutropenia grade 3-4 and infectious events were observed in 25.7% and 9.1% during all cycles respectively. Grade 3-4 neutropenia showed to increase over time (Cycle 1: 24%, Cycle 4: 39%). There was no treatment related death. Conclusion: With a long median follow-up, abbreviating treatment to 4 courses of FCR in patients who obtained negative MRD showed durable remissions with high PFS and OS at 72 months, minimizing treatment related toxicity. Sixty five percent of the patients who progressed after 24 months are still alive. Large randomized trials will be necessary to confirm our data. Disclosures Pavlovsky: Bristol Myers Squibb: Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Speakers Bureau. Pavlovsky:Novartis: Honoraria, Speakers Bureau; Janssen: Honoraria, Speakers Bureau.

Background Myelofibrosis (MF) is a clonal myeloproliferative neoplasm (MPN) associated with a high degree of symptomatology, progressive cytopenias and potential to transform into acute myelogenous leukemia (AML). Thrombocytopenia amongst MF patients is a proven negative prognostic indicator and predictor of transformation to AML. Ruxolitinib is an effective JAK inhibitor for MF symptoms and splenomegaly, but is not indicated in patients with severe thrombocytopenia. Phase III trials of pacritinib have shown alleviation of the MF symptom burden amongst patients with thrombocytopenia (ASCO 2015 Mesa et. al.). In this study, we assessed the symptom burden of MF patients with significant thrombocytopenia who were naïve to pacritinib. Methods Data was assessed from a prospectively collected international database of MF patients in which demographics, disease features, and MF symptoms utilizing the myeloproliferative neoplasm symptom assessment form (MPN-SAF; Scherber et al, 2011). The MPN-SAF includes the patient's perceptions of common MPN-related symptoms and overall quality of life (QOL) on a 0 (absent) to 10 (worst imaginable) scale. Total symptom score (TSS) was computed based on symptom items using the published scoring algorithm on a 0 (all reported symptoms absent) to 100 (all reported symptoms worst imaginable) scale. MF risk scores were calculated using the DIPSS criteria (Gangat, 2011). Thrombocytopenia was defined as a platelet count Results Demographic and Disease Features: A total of 418 patients with (n=89) and without (n=329) thrombocytopenia completed the MPN-SAF. Patients with thrombocytopenia were slightly younger (57.4 vs. 61.0, p=0.01) with longer disease durations (11.9 years vs. 8.8 years, p=0.0489) and had a higher prevalence of primary myelofibrosis (PMF; 82% vs. 66%, p=0.01). The presence of thrombocytopenia was associated with other laboratory abnormalities including anemia (60.7% vs. 25.3%, p Symptoms Scores for individual MPN-SAF items were assessed for each subgroup. Patients with thrombocytopenia had markedly higher total symptom scores than patients without thrombocytopenia (32.8 vs. 24.1, p Discussion MF patients with thrombocytopenia have distinctive clinical characteristics and face a significantly more severe symptom burden. Importantly, despite thrombocytopenia being a recognized risk factor for disease advancement, no correlations are noted between patient symptomatology and risk category. In addition, patients with severe thrombocytopenia do not differ symptomatically from patients with moderate thrombocytopenia despite having more severe anemia, leukopenia and transfusion requirements. This implies that the degree of symptomatology expressed by thrombocytopenic MF patients occurs independent from the exact platelet value. Conclusion The results of this study suggest that patients with thrombocytopenia will benefit from aggressive symptomatic control, potentially from targeted agents. Figure 1. MF Symptoms in Patients With and Without Thrombocytopenia Figure 1. MF Symptoms in Patients With and Without Thrombocytopenia Disclosures Kiladjian: Novartis: Consultancy; Novartis: Other: Travel grant; Research Funding paid to institution (Hôpital Saint-Louis et Université Paris Diderot); Incyte Corporation: Consultancy. Zweegman:Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding. Harrison:Shire: Speakers Bureau; CTI Biopharma: Consultancy, Honoraria, Speakers Bureau; Sanofi: Honoraria, Speakers Bureau; Gilead: Honoraria; Novartis: Honoraria, Research Funding, Speakers Bureau. Cervantes:Novartis: Consultancy, Speakers Bureau; Sanofi-Aventis: Consultancy; CTI-Baxter: Consultancy, Speakers Bureau. Barbui:Novartis: Speakers Bureau. Etienne:ARIAD: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Other: Congress Travel/Accomodations, Research Funding, Speakers Bureau; BMS: Consultancy, Honoraria, Speakers Bureau. Roy:BMS: Consultancy, Research Funding; Novartis: Consultancy, Research Funding. Vannucchi:Shire: Speakers Bureau; Novartis Pharmaceuticals Corporation: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Baxalta: Membership on an entity's Board of Directors or advisory committees. Mesa:Novartis. Research- incyte, Gilead, cti, Genentech, promedior, NS Pharma: Consultancy.

Abstract 3839 BACKGROUND: We have previously reported on the validation of the 18 item Myeloproliferative Neoplasm Assessment Form (MPN-SAF) (Blood 2011;118:401–408) given in conjunction with the 9 item Brief Fatigue Inventory (BFI) (Cancer 1999;85:1186–1196) to assess symptomatic burden in an international sample of MPN patients (pts), including validation in English, Italian, Swedish, German, French, Spanish, and Dutch. We desired to assess the utility of an average total symptom score (TSS) from the most pertinent and representative MPN symptoms for purposes of assessing the burden of symptoms in MPN pts, and subsequent tracking in response to therapy. METHODS: Data was collected among an international cohort of MPN pts and their physicians, including patient demographics and disease features and completion the BFI, MPN-SAF and the EORTC-QLQ-C30. Among pts who completed at least 5 of 10 specific items on the BFI and MPN-SAF, an average score was calculated as the TSS. TSS items included “worst” fatigue from the BFI and 9 items from the MPN-SAF including concentration, early satiety, inactivity, night sweats, itching, bone pain, abdominal discomfort, weight loss and fever. The TSS thus had a possible range of 0–10 with 10 representing the highest level of symptom severity. Data was then analyzed for internal consistency, and divergent, convergent validity, and construct validity. RESULTS: Patient Demographic and Disease Characteristics:1433 MPN pts were prospectively enrolled (Argentina 22, France 482, Germany 59, Italy 186, Netherlands 236, Puerto Rico 10, United Kingdom 57, United States 102, Spain 157, Sweden 114, Uruguay 8) including 594 ET, 538 PV and 293 MF pts (8 missing; MF: 61% Primary MF, 23% post-ET MF, 15% post-PV MF). 1408 pts completed at least 5 of the 10 items necessary to calculate a TSS. Pts were of characteristic age (mean 62, range 20–94) and gender (54% female) common to disease. TSS Burden of MPN Symptoms: Consistent with prior studies, the majority of pts (>50%) were symptomatic in each TSS item except for items associated with high disease severity, namely bone pain (48.6%), weight loss (30.6%) and fever (18.4%). Fatigue carried the highest symptom intensity (4.4, SD=2.8), followed by problems with concentration (2.5, SD=2.8) and early satiety (2.5, SD=2.7). Overall mean TSS was 2.1 (SD=1.6). Divergent Validity: TSS significantly differed among MPN disease subtypes (p4, n=480) versus non-clinically deficient QOL (2 of 6 common MPN-related symptoms as clinically significant (2.8, n=400) versus 0.50 except social functioning [r=0.48]). Additionally, excellent correlations were observed between the TSS and EORTC-QLQ-C30 fatigue and pain symptom scales (r>0.5, p1). Factor loadings ranged from 0.43 for fever and weight loss to 0.71 for inactivity. The single factor suggests that the arithmetic mean of the 10 items is an appropriate global TSS score. CONCLUSION: The TSS demonstrated excellent psychometric properties. Overall, results of validity and internal consistency indicate that the TSS is a concise, valid, and accurate assessment of symptom burden among MPN pts. This new scoring will facilitate ease of implementation of the MPN-SAF into larger clinical trials and reduce ambiguity associated with interpreting response outcomes. Future analyses to investigate the impact of therapies on TSS are ongoing. Disclosures: No relevant conflicts of interest to declare.

PURPOSE: To assess the value of initial peripheral blast count in patients with acute lymphoblastic leukemia (ALL) and prednisone good response (PGR). PATIENTS AND METHODS: From January 1990 to December 1995, 403 consecutive patients with newly diagnosed ALL were enrolled in the authors' protocol 1-ALL90-BFM/HPG. Prednisone good response was defined as a blast count of less than 1,000/microL and a prednisone poor response (PPR) as a blast count of at least 1,000/microL, both in peripheral smears, after 7 days of oral prednisone (60 mg/m2 per day) and one intrathecal dose of methotrexate. In the PGR group, patients were divided into two subgroups: patients who had less than 1,000 blasts/microL at diagnosis and those with at least 1,000 blasts/microL at diagnosis. RESULTS: Three-hundred thirty-seven patients (90%) had PGR and 37 had (10%) PPR. At 5-year follow-up, event-free survival estimates were 67 +/- 3.8% and 38 +/- 8% for PGR and PPR, respectively (P = 0.0001). In the PGR group, 114 patients (34%) had an initial blast count of less than 1,000/microL and 223 (66%) had an initial blast count of at least 1,000/microL. The authors compared the clinical and laboratory characteristics of these subgroups at diagnosis and outcome and detected significant differences in white cell count, incidence of T immunophenotype, and presence of mediastinal or spleen enlargement. However, there were no differences in response to induction treatment, death in complete remission, relapses, or event-free survival probability. CONCLUSIONS: In the PGR group, regardless of the initial blast count, both subgroups had the same outcome. The PGR group with an initial blast count of at least 1,000/microL had significantly higher white cell counts. T markers, and mediastinal or spleen enlargement at diagnosis. Response to prednisone is a practical, inexpensive, and good prognostic factor in childhood ALL.

Introduction Myelofibrosis (MF) and Post PV/ET MF represents a group of debilitating hematological disorders in which quality of life (QOL) is severely compromised in most patients as a result of persistent constitutional symptoms, progressive cytopenias, and splenomegaly. Conventional therapeutic modalities have largely focused on symptoms palliation rather than cure. Allogeneic stem cell transplantion (ASCT) remains the only potential curative option for intermediate and high risk disease. Till now, outcome data for MF have historically focused on survival benefit. Until now, few studies have evaluated the QOL, financial burden, and symptom response in MF patients undergoing treatment including ASCT. The development of the Myeloproliferative Symptom Assessment Form Total Symptom (MPN-SAF TSS) score in 2012 allows us to objectively quantify with a standardized tool these crucial aspects of patients care. The Myeloproliferative Neoplasm Quality of Life (MPN-QOL) Study Group aims to objectively quantify symptomatic response to standard available treatments by utilizing the MPN-SAF TSS. We introduce two MPN-QOL prospective trials currently in active enrollment: The MPN Experimental Assessment of Symptoms by Utilizing Repetitive Evaluation (MEASURE) Trial and the Symptoms Yielded in Myelofibrosis Patients after Transplant as Objectified by MPN-SAF TSS (SYMPTOMS) Trial. Our intention with these studies is to quantify the QOL and symptom burden of PMF and post PV/ET MF patients undergoing treatment including ASCT. Methods The MEASURES trial is a prospective questionnaire based study evaluating the responsiveness of the MPN-SAF TSS in detecting symptomatic changes in target symptoms for an anticipated 180 ET, PV and MF (including primary MF, post-ET and post PV MF) patients receiving non-experimental medical therapy (aspirin, hydroxyurea, anagrelide, interferon, busulfan, melphalan, cladribine, thalidomide, lenalidomide, prednisone, danazol, ruxolitinib) and/or phlebotomy. Patients complete the MPN-SAF for seven consecutive days at the time of enrollment and repeat the survey for an additional seven consecutive days between 90 days and six months. Patients also complete the MDASI, EORTC and Global Impression of Change Items on the first day of the second assessment. Physicians acquire demographic, laboratory, physical examination and radiographic data, along with serial response assessments. In parallel, the SYMPTOMS trial is prospective questionnaire based study evaluating the QOL of patients undergoing ASCT utilizing MPN-SAF TSS, the FACT-BMT, Global Impression of Change, and a financial questionnaire. Patients will be evaluated at various time points pre-transplant, day 30, day 100 and 1 year post-transplant. Participants (N=110) will be prospectively enrolled from Mayo Clinic Arizona (MCA) with other centers to soon join. To date we have enrolled 5 patients from MCA on the SYMPTOMS trial and 32 patients on the MEASURES trial. Results Both trials began open enrollment in the summer of 2012 and remain in recruitment phase. Our updated preliminary data will be presented at the ASH 2013 meeting Conclusion Myeloproliferative Neoplasms have been associated with debilitating symptom profile that can significantly impair the QOL. We recognize the burden of this disease and treatment and have therefore initiated two ongoing parallel prospective trials with goals to quantify the QOL and symptom burden of MPN patients. By quantifying degree of burden and impairment in QOL in a standardized format in MPN patients undergoing a range of treatments, we will in the future be better able to inform our patients of the likely benefits and toxicities of the available treatment options. Disclosures: Birgegard: Vifor Pharma: Honoraria.

Background We have previously reported on the significant, but heterogeneous baseline MPN symptom burden among an international sample of MPN patients (including essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF)) utilizing the MPN Symptom Assessment Form (MPN-SAF) and the derivative Total Symptom Score (MPN-SAF TSS). Recent clinical trials have sought to determine optimal MPN symptom response criteria, such as absolute 10 point improvement in MPN SAF TSS for ET/PV (ELN Criteria, Barosi et. al. Blood 2013) and 50% reduction in MPN-SAF TSS for MF (IWG-MRT, Tefferi et. al. Blood 2013). We sought to determine the role of improvement in MPN-SAF TSS quartiles as potential thresholds to assess symptomatic response to therapy. Methods Utilizing prospectively gathered MPN-SAF TSS (Emanuel et. al. JCO 2012) in patients we assessed potential thresholds of response by evaluating quartile thresholds for severity of symptom burden. The MPN-SAF TSS was scored as the average of 10 symptoms (individual symptoms scores of 0-10, with a total score of 0 (best) to 100 (worst)). MPN-SAF TSS quartiles were identified by the percentage of scores between 0-24% (quartile 1 (Q1)), 25-49% (quartile 2 (Q2)), 50-74% (quartile 3 (Q3)), 75-100% (quartile 4 (Q4)). Results MPN-SAF TSS Quartiles: MPN-SAF TSS quartiles were identified among 1858 MPN patients (ET N=775, PV N=654, and MF N=423). Overall MPN-SAF TSS scores of 0 - 7 were designated as Q1, 8 - 17 as Q2, 18 - 31 as Q3, and ≥ 32 was as Q4. MPN-SAF TSS scores were significantly different between clusters (p Associations Between Quartiles and Demographic/ Disease Factors: As quartiles increased, the proportion of PV and ET patients diminished and MF increased (Table 1, p Associations Between Individual Symptoms and MPN-SAF TSS Quartiles: All individual symptoms measured in the MPN-SAF TSS were significantly worse in quartiles as they increased (p Evaluation of Prognostic Scoring and MPN-SAF TSS Quartiles: Comparison of each patients individual risk score (IPSET, PV, DIPSS for MF) and worsening symptom quartile showed the highest correlation with MF patients (DIPSS) (Table 1). However, ET and PV risk scores were not surrogates for symptom burden by quartile. Conclusions Distribution of MPN patient symptomatic burden by MPN-SAF TSS quartiles provides an easy-to-calculate method to cluster and analyze MPN patients of similar burden. Although MF patients are most prevalent in the most severe quartile of MPN symptomatology it is notable that Q4 has many patients with PV and ET. Future prospective efforts are ongoing to assess the potential of using changes in quartile (i.e. improving from Q3 to Q1) as potential symptomatic response thresholds. Disclosures: Etienne: novartis: Consultancy, Membership on an entity’s Board of Directors or advisory committees; Bristol Myers Squibb: Consultancy, Membership on an entity’s Board of Directors or advisory committees; Pfizer: Membership on an entity’s Board of Directors or advisory committees; Ariad: Membership on an entity’s Board of Directors or advisory committees. Roy:Novartis, BMS: Honoraria. Harrison:Gilead: Honoraria, Membership on an entity’s Board of Directors or advisory committees; S Bio: Honoraria, Membership on an entity’s Board of Directors or advisory committees; Shire: Speakers Bureau; Celgene: Honoraria; YM Bioscience: Honoraria, Membership on an entity’s Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; Novartis: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau. Vannucchi:Novartis: Honoraria, Membership on an entity’s Board of Directors or advisory committees. Birgegard:Vifor Pharma: Honoraria.

Introduction MF is a myeloproliferative neoplasm characterized by bone marrow fibrosis, splenomegaly, cytopenias and constitutional symptoms. Since the identification of JAK2V617F mutation and development of anti JAK molecules, the course of the disease has changed. Ruxolitinib is a JAK1 and JAK2 inhibitor recently approved for patients (pts) with primary and secondary MF. In Argentina, pts could access the ruxolitinib through CUP. Analysis of this multicenter protocol provides a preliminary data set, follow up and efficacy results. Objectives To assess the efficacy (reduction in spleen size/improvement in constitutional symptoms) and toxicity. To investigate risk groups modifications during follow-up. Methods In Argentina, 36 pts with myelofibrosis, including primary MF (PMF) and post polycythemia vera (PPV) received ruxolitinib through CUP regardless of JAK2 mutational status. Study period: September 2011 to June 2013. The participating physicians provided information of the disease characteristics by completing a data form. Splenomegaly was evaluated by physical exam, and constitutional symptoms were categorized as present or absent. Retrospective analysis was performed based on data at baseline (n 36), after 3 months (n 30), 6 months (n 24) and 12 months (n 14). Results Median follow-up is 10 months (1-20). The median age is 65 years (30-79), 64% were men and 36% women. There were 72% positive for the JAK2 V617F mutation, 69% had PMF and 31% Post-PV. At admission 89% of pts had received ≥1 lines of therapy for MF prior to ruxolitinib: hydroxyurea 77%, thalidomide 26%, erythropoietin 23%, others: corticosteroids, interferon, anagrelide, danazol, busulfan, splenic radiation, cytarabine, and 6-mercaptopurine. The distribution of risk category according to DIPSS was: 61% high, 19% Intermediate 2, 17% Intermediate 1, and 3% low. Median value for spleen size was 15 cm (4-33) below the costal margin. Constitutional symptoms were present in 71% of the patients and 33% were transfusion dependent. ECOG (Eastern Cooperative Oncology Group) was zero 28%, one 44%, two 22%, three 3%, and four 3%. The median hemoglobin, leucocytes and platelets was 10 g/dl (4.8-15.2); 13, 4 x 109/L (3.6-64) and 217 x 109/L (75-850), respectively. Peripheral blood blasts ≥ 1% in 44% of pts. Ruxolitinib therapy was initiated at 40 mg/d in 16 pts (50%), 30 mg/day in 9 pts (28%), and at a lower dose in the minority of pts. The median value for spleen size at 3, 6 and 12 months was 10, 8 and 6.5 cm, representing decrease of 20%, 41% and 42% from baseline, respectively (fig 1.). In 13 of 29 pts (45%) spleen size decreased ≥ 50% in 3 months. Constitutional symptoms not present at 3, 6 and 12 months in 79%, 100% and 87% of pts, respectively. Improvement in ECOG class was noted in 73%, 69 % and 73% at the above mentioned time points, respectively. Persistence of transfusion dependence at 3, 6 and 12 months was seen in 33, 24 and 27% of the patients. Hemoglobin median levels during treatment (g/dL): at baseline 10.1, at 3 months 8.5, at 6 months 9.7, and at 12 months 9.5. During follow-up, 27% pts shifted to a lower risk group, 2 pts (7%) to a higher group due to worsening anemia, and 67% did not change its category. Hematologic adverse events (AE) were anemia and thrombocytopenia in 8 pts (Grade 1 and Grade 3 according to CTCAE v4.0), 31% of pts required dose adjustment. There were no suspensions of medication because of cytopenia. Others AE > 10% were: headache, musculoskeletal pain, and diarrhea ( Conclusion Ruxolitinib is an effective therapy that reduced spleen size and improved constitutional symptoms with an acceptable toxicity profile in this group of pts. During follow up at 12 months, a quarter of pts shifted to a lower risk group. Our data is consistent with previous reports Disclosures: Barreyro: GSK: Employment. Enrico:Bristol Myers Squibb: Speakers Bureau; Pfizer: Membership on an entity’s Board of Directors or advisory committees; Novartis: Membership on an entity’s Board of Directors or advisory committees. Lanari Zubiaur:Novartis: Membership on an entity’s Board of Directors or advisory committees. Pavlovsky:Novartis: Consultancy. Sackmann:Novartis: Membership on an entity’s Board of Directors or advisory committees. Bengió:Novartis: Member advisory Board Myelofibrosis Other.

Background We have previously reported on the high prevalence and severity of insomnia amongst a large international cohort of MPN patients (Emanuel JCO 2012). We sought to further analyze the relationships between insomnia and the MPN disease features (in particular splenomegaly, status of blood counts), individual MPN symptom prevalence and severity, language, and overall quality of life. Methods Data was collected among an international cohort of patients with MPNs. Subjects completed the BFI, MPN-SAF, and EORTC QLQ-C30 instruments. Surveyed symptoms on the MPN-SAF included the patient’s perceptions of common MPN-related symptoms and overall quality of life (QOL) on a 0 (absent) to 10 (worst imaginable) scale. Specifically, the MPN-SAF insomnia item asked about “difficulty sleeping”. Total symptom score (TSS) was computed based on 10 symptom items using the published scoring algorithm on a 0 (all reported symptoms absent) to 100 (all reported symptoms worst imaginable) scale. Pairwise associations between the MPN-SAF insomnia item and continuous and categorical covariates were investigated using Pearson correlations and analysis of variance/t-tests, respectively. Multivariate regression models were used to investigate impact of groups of covariates on the insomnia item with the final multivariate model selected using forward regression. Results Demographics A total of 1992 MPN patients (essential thrombocythemia=834, polycythemia vera=703, myelofibrosis=449, unknown=6) completed the insomnia item. Participants were of typical age (median=61, range-15-94) and gender (female=54%). Overall, 1307 subjects endorsed the MPN insomnia item (score >0) with an overall mean symptom score of 3.0 (median=2.0, SD=3.1. range=0-10); 603/1992 (30%) of patients had severe insomnia related complaints (score >4). Univariate Analysis Among QLQ-C30 functioning scales, emotional functioning most highly correlated with the MPN-SAF insomnia item (r=-.47, p Multivariate Analysis In a multivariate model of MPN-SAF insomnia containing all QLQ-C30 functioning scales, physical, emotional, and cognitive functioning along with global health status/QOL were all significant (all p Conclusions Insomnia is highly prevalent and severe in MPN patients and closely correlates with most other MPN-related symptoms and functional domains bearing a multi-faceted impact on overall quality of life. Correlations between insomnia and emotional, cognitive, and physical complaints including depression/sad mood, concentration problems, night sweats, and numbness/tingling in the extremities suggest that the cause of MPN-related sleep complaints is likely complex. Future studies should evaluate the impact of interventions on MPN associated insomnia as well as its biological underpinnings. Disclosures: Etienne: novartis: Consultancy, Membership on an entity’s Board of Directors or advisory committees; Bristol Myers Squibb: Consultancy, Membership on an entity’s Board of Directors or advisory committees; Pfizer: Membership on an entity’s Board of Directors or advisory committees; Ariad: Membership on an entity’s Board of Directors or advisory committees. Roy:Novartis, BMS: Honoraria. Harrison:Novartis: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Sanofi: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; YM Bioscience: Honoraria, Membership on an entity’s Board of Directors or advisory committees; Celgene: Honoraria; Shire: Speakers Bureau; S Bio: Honoraria, Membership on an entity’s Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity’s Board of Directors or advisory committees. Birgegard:Vifor Pharma: Honoraria.

We report a 7-year old white girl who was admitted because of acute severe hepatic failure. Her complete blood count revealed pancytopenia and a bone marrow aspiration was consistent with acute lymphoblastic leukemia (ALL). Blasts cells were positive for cytoplasmic CD3 and cell surface T-associated markers. Viral, metabolic, immune and toxic causes for hepatic failure were ruled out. Treatment pre-phase with prednisone was started and liver function tests clearly improved after one-week therapy. However, due to her hepatic insufficiency, daily etoposide was administered orally during 15 days. On day 33 complete remission was achieved and hepatic function was normal, except for an increase in the bilirubin level which normalized on day 72. She received our current treatment for intermediate risk ALL and is still receiving continuation phase therapy, currently, with normal liver function and good tolerance to chemotherapy + 8 months after achieving complete remission.

We report results achieved in our institution with an acute lymphoblastic leukaemia risk-oriented treatment trial opened in January 1990 and closed on December 1995. The study was similar to the German ALL-BFM’90, except for using Protocol III for the standard-risk group, 2 g/m 2 of methotrexate in Protocol M, and preventive cranial irradiation for the high-risk group only. The high-risk group included mostly patients with prednisone poor initial response and/or adverse cytogenetic features. This analysis included 374 patients, whose mean age was 6 years (range: 1 month–17 years). The overall complete remission rate was 94.4% (353/374) and the 5-year event-free survival (standard error) probability is 64(5)%. The 5-year event-free survival estimates for each risk group were: (1) high-risk group 37(5)%; (2) intermediate-risk group 66(1)%; and (3) standard-risk group 74(4)% ( P =0.0001). There are significantly higher-rates of isolated bone marrow and testicular relapses in the high-risk subset of patients. Our dismal results and the published experience, lead us to conclude that the optimal treatment for these high-risk acute lymphoblastic leukaemia patients is not currently known.