Spleen Length Research Articles

Ultrasound assessment of normal liver, spleen, and kidney dimensions in southwest Nigerian children: a bedside formula for sonologists.

Knowledge of the normal sizes of the liver, spleen, and kidneys is important to radiologists when assessing for pathology using ultrasound scan. The need for a local determination of a easy-to-use formula for estimating the expected normal sonographic dimensions of these organs in children in order to serve as baseline when assessing them for pathology cannot be over emphasized. To determine ultrasonographic sizes of the liver, spleen, and kidneys among primary school children in southwestern Nigeria and correlate these with anthropometric measures to provide local reference data and an easy-to-use formula for assessing these organs for pathology in clinical practice. This is an observational, cross-sectional study using 1000 public primary school children in Ogbomoso. Sonographic dimensions of their liver, spleen, and both kidneys with anthropometric parameters were obtained and correlated. Data were analyzed using SPSS version 20. The liver span was higher in boys than in girls (P = 0.048) while the left lobe of the liver was higher in girls than in boys (P = 0.003). The spleen length was higher in boys than in girls (P = 0.011). There was no gender difference in kidney dimensions (P > 0.05). All anthropometric measures correlated significantly (P < 0.001) with organ dimensions. Body surface area is the strongest predictor of the liver and kidney sizes (P < 0.001) and height for spleen size (P < 0.001). Nomograms for the liver, spleen, and kidneys and regression equations for estimating the dimensions of these organs were formulated based on the best multivariate correlates.

Magnetic resonance elastography to quantify liver disease severity in autosomal recessive polycystic kidney disease.

To evaluate whether liver and spleen magnetic resonance elastography (MRE) can measure the severity of congenital hepatic fibrosis (CHF) and portal hypertension (pHTN) in individuals with autosomal recessive polycystic kidney disease (ARPKD), and to examine correlations between liver MRE and ultrasound (US) elastography. Cross-sectional study of nine individuals with ARPKD and 14 healthy controls. MRE was performed to measure mean liver and spleen stiffness (kPa); US elastography was performed to measure point shear wave speed (SWS) in both liver lobes. We compared: (1) MRE liver and spleen stiffness between controls vs. ARPKD; and (2) MRE liver stiffness between participants with ARPKD without vs. with pHTN, and examined correlations between MRE liver stiffness, spleen length, platelet counts, and US elastography SWS. Receiver operating characteristic (ROC) analysis was performed to examine diagnostic accuracy of liver MRE. Participants with ARPKD (median age 16.8 [IQR 13.3, 18.9] years) had higher median MRE liver stiffness than controls (median age 14.7 [IQR 9.7, 16.7years) (2.55 vs. 1.92kPa, p = 0.008), but MRE spleen stiffness did not differ. ARPKD participants with pHTN had higher median MRE liver stiffness than those without (3.60kPa vs 2.49kPa, p = 0.05). Liver MRE and US elastography measurements were strongly correlated. To distinguish ARPKD vs. control groups, liver MRE had 78% sensitivity and 93% specificity at a proposed cut-off of 2.48kPa [ROC area 0.83 (95% CI 0.63-1.00)]. Liver MRE may be a useful quantitative method to measure the severity of CHF and pHTN in individuals with ARPKD.

Growth, immunity, relative gene expression, carcass traits and economic efficiency of two rabbit breeds fed prebiotic supplemented diets

The current study designed to evaluate the effect of oligosaccharide supplemented diets on growth performance, histomorphometric changes, economic efficiency and genetic expression of some growth and immunity-relative genes. One hundred and twenty weaned male rabbits, six weeks of age of two breeds (NZW and APPRI) were randomly allocated into six equal groups; the first supplemented with 0.3% Mannan-oligosaccharide (MOS), the second supplemented with 0.05% Isomalto-oligosaccharide (IMO) and the third considered a control group. Each group contained ten equal replicates. The highest Final body weight and feed consumption were recorded in MOS and IMO groups compared with control. Fortified feed diet with IMO significantly increased duodenal villi area and length than MOS and control groups. At the same time, Spleen white bulb area and length were significantly higher in MOS and IMO than control. Supplementation of MOS and IMO significantly improved carcass traits, economic efficiency and induced certain modifications in some major key genes involved in the regulation of nutrients metabolism, immunity and growth in different tissues. In conclusion, dietary supplementation of MOS and IMO had a desirable positive impact on productive and economic efficiency in the rabbit.

Thalidomide for the Treatment of Thrombocytopenia and Hypersplenism in Patients With Cirrhosis or Thalassemia.

Hypersplenism and thrombocytopenia are common complications of liver cirrhosis or thalassemia, but current treatment strategies are limited. This study aimed to evaluate the efficacy and safety of thalidomide in the treatment of hypersplenism and thrombocytopenia in patients with liver cirrhosis or thalassemia. A total of 31 patients with hepatic cirrhosis (n=19) or thalassemia (n=12) diagnosed with hypersplenism and thrombocytopenia (platelet count [PLT] <100×109/L) were included in this prospective cohort study between January 2015 and May 2017. Patients were treated with thalidomide (150–200 mg/d) plus conventional therapy. Spleen length, PLT, leukocyte count (WBC), absolute neutrophil count (ANC), and hemoglobin level (Hb) were measured at baseline, 3, 6, and 12 months. Any adverse events were noted. All of the 31 patients were showed a progressive increase PLT during the 12-month follow-up, and similar results were obtained when subgroup analyses were performed based on the primary disease (cirrhosis or thalassemia). WBC, ANC, and Hb also increased progressively during the 12-month follow-up. Spleen length decreased progressively during the follow-up. No serious adverse events occurred. Thalidomide is a potential treatment for thrombocytopenia caused by hypersplenism in patients with cirrhosis or thalassemia.

Haematological Parameters and Spleen Rate of Asymptomatic and Malaria Negative Children in Edo South District, Nigeria.

Background:Malaria is commonly associated with alteration in haematologic cells of infected individuals in both the acute uncomplicated and severe phases. Whether this alteration occurs in the asymptomatic phase of the disease is still being investigated.Objectives:To examine the haematocrit, thrombocytes, and monocytes levels of children with asymptomatic malaria compared with age/sex-matched controls who are malaria parasite negative and living in a stable malaria endemic region. It also set out to identify spleen rate of the children and to compare it with that observed in malaria negative controls.Methods:One hundred well-nourished children 2–9 years old with asymptomatic malaria parasitaemia and 100 age- and sex-matched malaria negative controls were recruited by multi-stage sampling from schools in a malaria endemic region of Nigeria. Malaria diagnosis was by microscopy, and each haematologic parameter was analysed following standard protocols.Results:Mean (±) monocyte count of 2.25 ± 0.9 × 109 cells/L observed in asymptomatic malaria children was significantly higher than 1.34 ± 0.5 × 109 cells/L observed in those with no malaria (p = 0.00). Mean (±) thrombocyte count was significantly lower (asymptomatic 203.64 ± 45.90 × 109 cells/L Vs no malaria 230.91 ± 57.40 × 109 cells/L) (p = 0.00). Spleen rate in the children was 15.5%. Presence of splenomegaly was not statistically significantly fewer in children with asymptomatic malaria parasitaemia (ASMP) (14/31) when compared to those who were malaria parasite negative (17/31) (χ2 = 0.34, p = 0.57). Similarly, there was no significant difference in the mean [±] spleen length of children with ASMP (n = 14; 2.86 ± 0.9 cm) and those who were malaria negative (n = 17; 2.53 ± 0.6 cm) (t = 1.22, p = 0.23).Conclusion:Thrombocytopaenia and monocytosis could be pointers to malaria parasitaemia in asymptomatic phase in a stable malaria region.

A Study on Morphometric Dimensions of Human Fetal Spleen at Different Gestational Ages

Introduction:The spleen is the largest hemolymphatic organ of the human body that plays a significant role in Hematopoiesis and immune phagocytosis. Recent studies have emphasized the importance of spleen as hematopoietic organ in fetal period, role in synthesis of immunoglobulins &amp; defense of human body against infections. A thorough knowledge of splenic morphometry and dimensions is vital in comprehending the development of spleen in fetal period.Aim:The aim of the study is to study detailed morphometric analysis human fetal splenic specimens of various gestational ages and compare the findings with earlier studiesSubjects and Methods:The present study included 40 fetal cadaveric spleen and morphometric features i.e.,length, breadth, width and weight of spleen were measured.Results:The average weight of the fetal spleen was 1.98 gm and varied from 0.1 to 5.1 gm. The average length, breadth and width of spleen in prenatal group were 2.21 cm, 1.39 cm and 0.645 cm respectively. In the present study the average weight of the fetal spleen was 1.98 gm and varied from 0.1 to 5.1 gm. There was statistically significant increase in splenic weight till 33 weeks.Conclusion:Knowledge of spleen size at different gestational ages will help in early detection and diagnosis of splenic anomalies, identifying congenital malformations, early diagnosis and prompt treatment of intrauterine infections.

Quantitative analysis of morphometric variations of human spleen - A cadaveric study

The spleen is a largest collection of lymphoid tissue with diverse hemopoietic and phagocytic function. Recent experimental data have clearly defined immunological functions of spleen in innate and adaptive immunity, as a frontline of host defense against various infections. A comprehensive knowledge of splenic anatomical variations and morphometric dimensions is crucial in deciphering the role of spleen in health &amp; infirmity. The aim of the study is to perform detailed morphometric analysis human splenic specimens with relation to age &amp; gender differences and compare the findings with earlier studies. The present study included 40 cadaveric spleen and morphometric features i.e., length, breadth, width and weight of spleen were measured. The average splenic weight observed was 178.5 gm and range was 100 to 300 gm. The average length, breadth and width of spleen were 11.9 cm, 7.33 cm and 3.4 cm respectively. The average splenic volume in the present study was 167.27 cc. There was a significant increase in splenic volume till 40-49 years followed by steady decline. The awareness of the morphology and dimensions of the spleen is of fundamental importance to the hematologists, clinicians, radiologists, prosectors and surgeons while performing surgical procedures on spleen.

MR elastography, T1 and T2 relaxometry of liver: role in noninvasive assessment of liver function and portal hypertension.

To evaluate the correlation between liver stiffness as measured on MR elastography and T1 and T2 relaxation times from T1 and T2 mapping with clinical parameters of liver disease, including the MELD score, MELD-Na and ALBI grade, and endoscopically visible esophageal varices. 223 patients with known or suspected liver disease underwent MRI of the liver with T1 mapping (Look-Locker sequence) and 2D SE-EPI MR elastography (MRE) sequences. 139 of these patients also underwent T2 mapping with radial T2 FS sequence. Two readers measured liver stiffness, T1 relaxation times and T2 relaxation times, and assessed qualitative features such as presence or absence of cirrhosis, ascites, spleen length, and varices on conventional MRI images. A third reader collected the clinical data (MELD score, MELD-Na Score, ALBI grade, and results of endoscopy in 78 patients). Significant moderate correlation was found between MELD score and all three imaging techniques for both readers (MRE, r = 0.35 and 0.28; T1 relaxometry, r = 0.30 and 0.29; T2 relaxometry, r = 0.45, and 0.37 for reader 1 and reader 2 respectively). Correlation with MELD-Na score was even higher (MRE, r = 0.49 and 0.40; T1, r = 0.45 and 0.41; T2, r = 0.47 and 0.35 for reader 1 and reader 2 respectively). Correlations between MRE and ALBI grade was significant and moderate for both readers: r = 0.39 and 0.37, higher than T1 relaxometry (r = 0.22 and 0.20) and T2 relaxometry (r = 0.17, and r = 0.24). Significant moderate correlations were found for both readers between MRE and the presence of varices on endoscopy (r = 0.28 and 0.30). MRE and T1 relaxometry were significant predictors of varices at endoscopy for both readers (MRE AUC 0.923 and 0.873; T1 relaxometry AUC = 0.711 and 0.675 for reader 1 and reader 2 respectively). Cirrhotic morphology (AUC = 0.654), spleen length (AUC = 0.610) and presence of varices in the upper abdomen on MRI (AUC of 0.693 and 0.595) were all significant predictors of endoscopic varices. Multivariable logistic regression model identified that spleen length and liver MRE were significant independent predictors of endoscopic varices for both readers. MR elastography, T1 and T2 relaxometry demonstrated moderate positive correlation with the MELD score and MELD-Na Score. Correlation between MRE and ALBI grade was superior to T1 and T2 relaxometry methods. MRE performed better than T1 and T2 relaxometry to predict the presence of varices at endoscopy. On multivariate analyses, spleen length and MRE were the only two significant independent predictors of endoscopic varices.

From Maternal Grazing to Barn Feeding During Pre-weaning Period: Altered Gastrointestinal Microbiota Contributes to Change the Development and Function of the Rumen and Intestine of Yak Calves.

Understanding the altered gastrointestinal microbiota is important to illuminate effects of maternal grazing (MG: maternally nursed and grazed) and barn feeding (BF: supplied milk replacer, starter feed, and alfalfa hay) on the performance and immune function of yak calves. Compared with the MG group, the significantly increased body weight, body height, body length, chest girth, and organ development of liver, spleen, and thymus were identified in the BF group, which were resulted from the significantly increased dry matter intake, increased concentrations of propionate, butyrate, isobutyrate, and valerate, increased ruminal pectinase, duodenal α-amylase, jejunal α-amylase and trypsin, and ileal trypsin, and promoted gastrointestinal epithelial development. Furthermore, genera of Sharpea, Sphingomonas, Atopobium, Syntrophococcus, Clostridium_XIVb, Acinetobacter, Oscillibacter, Dialister, Desulfovibrio, Bacteroides, Lachnospiracea_incertae_sedis, and Clostridium_sensu_stricto, which were involved in utilization of non-fibrous carbohydrate and further beneficial to improve the gastrointestinal digestion, development, and immune functions, were significantly increased in the BF group. Meanwhile, the significantly enhanced ruminal epithelial immune functions and intestinal immune functions based on enhanced ruminal immune related pathway, duodenal IL-1β, jejunal IL-1β, IL-2, TNF-α, and IFN-γ, and ileal IL-1β were identified in the BF group, which also may induced by the increased abundance of gastrointestinal microbiota. Overall, barn feeding significantly increased the diversity of species and abundance of microbes which used different carbohydrates and further benefit to the growth and immune function of yak calves.

Clinical Benefit Derived from Decitabine Therapy for Advanced Phases of Myeloproliferative Neoplasms

Treatment options are limited for patients with advanced forms of myeloproliferative neoplasms (MPN) including blast-phase disease (MPN-BP). Decitabine has frequently been deployed but its efficacy and safety profile are not well described in this population. We retrospectively reviewed 42 patients treated with decitabine either alone or in combination with ruxolitinib at our institution: 16 with MPN-BP, 14 with MPN accelerated-phase (MPN-AP), and 12 with myelofibrosis with high-risk features (MF-HR). The median overall survival (OS) for the MPN-BP patients was 2.6 months, and for those who received ≥2 cycles of decitabine therapy, it was 6.7 months (3.8–29.8). MPN-BP patients with a poor performance status and who required hospitalization at the time of the initiation of decitabine had a dismal prognosis. After a median follow-up of 12.4 months for MPN-AP patients, and 38.7 months for MF-HR patients, the median OS was not reached for either cohort, with 1 and 2 patients alive at 60 months, respectively. The probability of spleen length reduction and transfusion independence within 12 months of initiating decitabine was 28.6 and 23.5%, respectively. The combination of decitabine and ruxolitinib appeared to improve overall survival versus single-agent decitabine (21 and 12.9 months, respectively). Decitabine, alone or in combination with ruxolitinib, appears to have clinical benefit for patients with advanced phases of MPN when initiated early in the disease course prior to the development of MPN-BP.

Splenic T1ρ as a noninvasive biomarker for portal hypertension.

There is a need for noninvasive methods for the diagnosis and monitoring of portal hypertension (PH). To 1) assess the correlation of liver and spleen T1 and T1ρ measurements with portal pressures in patients with chronic liver disease, and 2) to compare the diagnostic performance of the relaxation parameters with radiological assessment of PH. Prospective. Twenty-five patients (M/F 16/9, mean age 56 years, range 21-78 years) undergoing portal pressure (hepatic venous pressure gradient [HVPG]) measurements. 1.5T abdominal MRI scan, including T1ρ and T1 mapping. Liver and spleen T1ρ and T1 , radiological PH score, and (normalized) spleen length were evaluated. Spearman correlation of all MRI parameters with HVPG was assessed. The diagnostic performance of the assessed parameters for prediction of PH (HVPG ≥5 mmHg) and clinically significant PH (CSPH, HVPG ≥10 mmHg) was determined by receiver operating characteristic (ROC) analysis. The mean HVPG measurement was 7.8 ± 5.3 mmHg (PH, n = 18 [72%] including CSPH, n = 9 [36%]). PH score, (normalized) spleen length and spleen T1ρ significantly correlated with HVPG, with the strongest correlation found for spleen T1ρ (r = 0.613, P = 0.001). Spleen T1ρ was the only parameter that showed significant diagnostic performance for assessment of PH (area under the curve [AUC] 0.817, P = 0.015) and CSPH (AUC = 0.778, P = 0.024). Normalized spleen length also showed significant diagnostic performance for prediction of CSPH, with a slightly lower AUC (= 0.764, P = 0.031). The radiological PH score, T1ρ and T1 of the liver and T1 of the spleen, did not show significant diagnostic performance for assessment of CSPH (P > 0.075). Spleen T1ρ showed a significant correlation with portal pressure and showed improved diagnostic performance for prediction of CSPH compared to radiological assessment. These initial results need confirmation in a larger cohort. 1 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2020;52:787-794.

Impact of Disease Burden in Myelofibrosis Patients: A Sub Analysis from Italian Romei Observational Study

Impact of Disease Burden in Myelofibrosis Patients: A Sub Analysis from Italian Romei Observational Study

Baseline Mutational Status of Patients with Myelofibrosis and Anemia in the Realise Trial and Impact on Outcome

Baseline Mutational Status of Patients with Myelofibrosis and Anemia in the Realise Trial and Impact on Outcome

Results of PAC203: A Randomized Phase 2 Dose-Finding Study and Determination of the Recommended Dose of Pacritinib

Results of PAC203: A Randomized Phase 2 Dose-Finding Study and Determination of the Recommended Dose of Pacritinib

Risk Factors for Progression to Blast Phase and Outcome in 589 Patients with Myelofibrosis Treated with Ruxolitinib: Real-World Evidence

Risk Factors for Progression to Blast Phase and Outcome in 589 Patients with Myelofibrosis Treated with Ruxolitinib: Real-World Evidence

Analysis of Predictive Factors for Early Response to Ruxolitinib in 266 Patients with Myelofibrosis from the Polish Adult Leukemia Group (PALG) Registry

Background: Ruxolitinib (RUX), an inhibitor of JAK1/JAK2 kinases, is the only drug approved for the treatment of myelofibrosis (MF). The main clinical effects of RUX therapy include decrease of splenomegaly and reduction of burden of constitutional symptoms. Importantly, predictive factors influencing response and toxicity of RUX are largely unknown. Since 2017 therapy with RUX has been reimbursed in Poland for patients (pts) with MF, and large proportion of these pts has been followed for drug efficacy and tolerance within registry of the Polish Adult Leukemia Group (PALG). Objectives: The primary objective of the study was to identify baseline factors influencing probability of achievement of early response to RUX in MF. Patients and Methods: We retrospectively analyzed outcome of treatment with RUX after 6 months of therapy within the Polish Ministry of Health RUX reimbursement program in pts with primary MF (PMF) and MF secondary to polycythemia vera (post-PV MF) or essential thrombocythemia (post-ET MF). The inclusion criteria to the RUX reimbursement program were as follows: 1) diagnosis of MF confirmed by a recent bone marrow biopsy, 2) intermediate-2 or high risk IPSS, and 3) presence of splenomegaly and constitutional symptoms. Response to RUX was objectively categorized in regard to splenomegaly and MF symptoms. "Spleen Response" was defined as ≥ 50% reduction of the difference between baseline maximal length of spleen and upper limit of normal (120mm) measured by ultrasonography while "Symptoms Response" was defined as ≥50% reduction of the MF constitutional symptoms as assessed by MPN-SAF TSS score. Influence of potential prognostic factors (age, sex, time from MF diagnosis to RUX treatment, PMF vs post-ET MF and post-PV MF, leukocytosis, number of platelets, hemoglobin level, IPSS, DIPSS, grade of fibrosis in bone marrow, genetic status of MF) on probability of response was tested by univariate and multivariate logistic regression. Results: We enrolled 266 MF pts (56.8% PMF, 26.7% post-PV MF, 16.5% post-ET MF) undergoing treatment with RUX in 14 Polish hematology centers. Pts' median age was 67 years (range 21-86), while 59% of the group were females. Thirty-two% of pts were classified as high risk, 56% as intermediate-2 risk and 12% as intermediate-1 risk according to DIPSS score. JAK V617F mutation was found in 83%, CALR in 12%, MPL in 1.5%, and 3.5% of pts were triple negative. The median time from diagnosis of MF to start of RUX therapy was 30 months (range 0-321). At RUX therapy initiation median spleen length was 210 mm (range 100-300), and median symptoms score was 41 (range 4-93). During first six months the therapy has been continued in all but 26 (9.8%) pts in whom the treatment was withdrawn mainly because of lack of effectiveness. The most common hematologic adverse events included anemia (grade ≥3 in 27% of pts) and thrombocytopenia (grade ≥3 in 8% of pts). Major thrombotic events occurred in 3 pts. Among infectious complication 11 upper respiratory tract infections, 4 urinary tract infections, 3 herpes zoster infections, 3 pneumonias of unknown etiology and 1 case of tuberculosis were reported. Regarding the established categories of response to RUX, at 6th month of therapy "Spleen Response" was detected in 50% of patients. The only pre-treatment factor significantly associated with the probability of achievement of "Spleen Response" by multivariable analysis was leukocytosis ≥25 G/L (OR 3.57, 95%CI 1.40-9.06, p=.007). In contrast "Symptoms Response" after 6 months of RUX therapy was found in larger proportion of patients accounting for 77% of the studied population. Multivariable analysis revealed that time-interval between MF diagnosis and RUX start (p=.028) and platelets &gt;200 G/L (OR 2.09, 95%CI 1.16-3.77, p=.014) remained significant predictors of "Symptoms Response". Conclusions: In this study we found that in real life setting efficacy of RUX is more promising, especially in terms of symptoms reduction, and better tolerated, as compared to the results of randomized COMFORT studies. Furthermore, our analysis revealed that simple laboratory parameters such as leukocytosis and platelets number may constitute useful predictors of early response to RUX therapy. Finally, since shorter time interval between MF diagnosis and RUX therapy correlated with better "Symptoms Response", introducing RUX earlier during the course of the disease may be more beneficial for pts. Disclosures Gora Tybor: Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Golos:Novartis: Honoraria. Sacha:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Lewandowski:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Niesiobedzka-Krezel:Novartis: Honoraria. Bieniaszewska:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Grzybowska-Izydorczyk:Novartis: Honoraria. Seferynska:Novartis: Honoraria. Patkowska:Novartis: Honoraria. Świstek:Novartis: Honoraria. Jamroziak:Janssen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding.

Disease and Clinical Characteristics of Patients with Myelofibrosis Enrolled in the MOST Study

Introduction: Myelofibrosis (MF) is a chronic Philadelphia chromosome-negative myeloproliferative neoplasm characterized by progressive bone marrow (BM) fibrosis, extramedullary hematopoiesis, splenomegaly, constitutional symptoms, and shortened survival. Data pertaining to the clinical characteristics and treatment patterns of patients with low-risk MF are limited; most studies have focused on patients with intermediate- and high-risk MF. The ongoing Myelofibrosis and Essential Thrombocythemia Observational STudy (MOST) was designed to characterize the demographics, disease burden, patient-reported outcomes, and management of patients with MF or essential thrombocythemia (ET) in clinical practices throughout the United States (NCT02953704). This analysis describes demographic and clinical characteristics of patients with low-risk MF enrolled in MOST. Methods: MOST is an ongoing multicenter, non-interventional, longitudinal, prospective, observational study in patients with MF or ET. Eligible patients with MF were at least 18 years old and had low- or intermediate-1 (INT-1) risk by age alone according to the Dynamic International Prognostic Scoring System (DIPSS). Patients participating in blinded investigational drug trials, having life expectancy ≤6 months, or having other concurrent myeloid malignancies were excluded. Data from patient records were entered into an electronic case report form during usual-care visits over a planned 36-month observation period. Data were analyzed with descriptive statistics. Results: A total of 232 patients with MF were enrolled between November 29, 2016 and March 29, 2019 at 124 sites. Two-hundred patients with low-risk (n=77) or INT-1 risk by age alone (n=123) MF were included in this analysis (data cut-off date, June 17, 2019); 32 patients were excluded due to incorrect risk categorization (n=27) or unanswered prognostic factors at enrollment (n=5). At enrollment, the median age was 68 (range, 35-88) years, 58% were aged &gt;65 years, 49% were women, and 89% were white. Thirteen patients (7%) had a documented family history of MF, ET, or polycythemia vera. Of 157 patients with manual spleen assessment at enrollment, 55 (35%) had palpable splenomegaly; median spleen length was 7 (range, 1‒22) cm in 35 patients with available measurements. The median time from MF diagnosis to enrollment was 1.7 (range, 0.0-37.7) years; most patients (75%) were diagnosed within 5 years of enrollment. Of patients with available data, 93% (185/200) were reported to have undergone BM biopsy/aspiration and 82% (162/198) had mutation testing (MT) at the time of diagnosis; most patients had received both BM biopsy and MT (151/196 [77%]). Data from MT conducted prior to or within 30 days of diagnosis were available for 142 patients (71%); 134/142 patients (94%) were tested for a JAK2 mutation, of whom 95/134 (71%) were positive (Table 1). At enrollment, approximately half of patients with available data (97/190 [51%]) had hemoglobin below normal range, and approximately one-third had platelets (68/188 [36%]) or leukocytes (58/186 [31%]) above normal range (Table 2). The most common signs reported at the time of enrollment included lactate dehydrogenase greater than the upper limit of normal (41%), palpable spleen (31%), and leukocytosis (&gt;11 × 109/L; 24%). Across both risk groups, 111 patients (56%) were receiving MF-directed monotherapy at enrollment (low-risk, 43/77 [56%]; INT-1 by age alone, 68/123 [55%]). Low-risk patients received hydroxyurea (HU; 23/43 [54%]), ruxolitinib (15/43 [35%]), interferon (4/43 [9%]), or anagrelide (1/43 [2%]); INT-1 patients received ruxolitinib (30/68 [44%]), HU (28/68 [41%]), interferon (8/68 [12%]), or anagrelide (2/68 [3%]). Five patients (3%) were receiving &gt;1 MF-directed therapy. Less than half of low- (34/77 [44%]) and INT-1- (50/123 [41%]) risk patients were receiving no MF-directed therapy at enrollment. Conclusion: These real-world data provide insight into the clinical characteristics, diagnosis, and treatment patterns of patients with low- or INT-1 risk (by age alone) MF in the United States. Data from this trial will help characterize the rate at which patients transition from low- or INT-1-risk disease to higher risk categories of disease and how management is affected by disease progression. Disclosures Gerds: Sierra Oncology: Research Funding; Imago Biosciences: Research Funding; Incyte: Consultancy, Research Funding; Celgene Corporation: Consultancy, Research Funding; CTI Biopharma: Consultancy, Research Funding; Pfizer: Consultancy; Roche: Research Funding. Lyons:Texas Oncology: Equity Ownership; Amgen: Consultancy; McKesson: Other: Leadership. Colucci:Incyte: Employment, Equity Ownership. Kalafut:Incyte: Employment, Equity Ownership. Paranagama:Incyte: Employment, Equity Ownership. Verstovsek:Promedior: Research Funding; Blueprint Medicines Corp: Research Funding; CTI BioPharma Corp: Research Funding; Genetech: Research Funding; Pragmatist: Consultancy; Pharma Essentia: Research Funding; Astrazeneca: Research Funding; Ital Pharma: Research Funding; Protaganist Therapeutics: Research Funding; Constellation: Consultancy; Incyte: Research Funding; Roche: Research Funding; NS Pharma: Research Funding; Celgene: Consultancy, Research Funding; Gilead: Research Funding; Novartis: Consultancy, Research Funding; Sierra Oncology: Research Funding.

Final Analysis at 5 Years Follow up of Patients with MPN-Associated Splanchnic Vein Thrombosis Treated with Ruxolitinib in a Phase 2 Study

Background: A myeloproliferative neoplasm (MPN) is frequent underlying cause of splanchnic vein thrombosis (SVT). We reported that ruxolitinib, a JAK1/2 inhibitor, was safe in patients (pts) with MPN-associated SVT and effective in reducing spleen size at the planned primary analysis at 24 weeks (w) in an investigator-initiated phase II clinical trial (Pieri L, AJH 2016). Herein we present final long term follow up (FU) data. Methods. A total of 21 MPN-SVT entered the trial in 2012. Pts who completed the 24w core study and well tolerated the drug and had evidence of clinically-significant improvement were allowed to enter an extension phase up to w72, then entered a long term FU. The drug was provided by Novartis, that had no role in trial design nor in data analysis. Safety data were reported as cumulative incidence of adverse events (CTCAE v4.03). Clinical responses were defined according to ELN and IWG-MRT criteria. Results. Patients disposition. Eighteen patients were alive at last follow-up at a median of 5.5y, range 3.7-6.5y. Two pts died before w72 (hepatocarcinoma; unknown cause), 1 pt died at w252 (sepsis). Diagnosis of the 18 pts was: PMF 8 (44%), PV 5 (28%), ET 4 (22%), PET-MF 1 (6%). The DIPSS risk score of the 8 pts with PMF was low in 4 and intermediate-1 in 4. At last FU, 14 patients are still on ruxolitinib (78%), 10 pts still on clinical trial, 4 pts shifted to commercial drug. Four pts (22%) withdrawn treatment after w72 because of inefficacy, withdrawal of consent, unknown reasons, shift to observation only (1 each). Safety. Thirteen pts (72.2%) had adverse events; the median number of events per patient was 5 (range, 0-37). Five pts had G2 thrombocytopenia plus 1 pt G3 (28%), 9 had G2 anemia (50%), 1 had G2 neutropenia (6%). There were 4 non-hematologic G3 adverse events (22%), one drug-related (CPK increase) that resolved with dose reduction. Six pts developed G1-2 infections (33%), 4 had Herpes Zoster reactivation (22%), 1 developed second cancer (pheochromocytoma at w96; 6%). Efficacy. Spleen response (defined as percentage reduction of spleen length from left costal margin (LCM) from baseline value as by IWG-MRT criteria) was available in 16 of 18 pts on treatment. Of 8 pts who obtained spleen response at w72, 4 pts had a complete response, while the remaining 4 pts had a spleen reduction &gt;50%. At last FU, 6 of 8 pts (75%) adjudicated as spleen responders at w72 maintained the response. None of the 8 pts who had not obtained a spleen response at w72 acquired it at the last FU. According to ELN/IWG-MRT criteria of disease response, 7 pts had partial response, 11 had stable disease. At abdominal vessel eco scan, thrombosis improved in 3 of 12 evaluated pts (25%) and remained stable in the remaining 9. Of the 16 pts with endoscopic evaluation at last FU, complete resolution of oesophageal varices was documented in 3/12 with baseline varices (25%), worsening in 4 (33%), stable in 5 (42%), while no de-novo formation of F1 varices was documented in the remaining 4 (33%). No pt had gastrointestinal bleeding episodes. Exploratory endpoints. Included changes in the level of JAK2V617F variant allele burden (VAF) at last FU, available in 13 of 15 JAK2V617F mutated pts. VAF remained stable in 2 pts (13%), increased by 34% (range 25-40) in 3 pts, while 8 pts (62%) had a reduction &gt;10% (range 18-96), of whom 6 (46%) had a reduction &gt;50% (median 82%, range 70-96). By correlative analysis of JAK2 VAF changes and spleen response, 3 of 6 pts with VAF reduction of &gt;50% had complete spleen response, as compared to none of the 3 pts who had an increase of VAF. Conclusions. After a median follow-up of 5.5 years, ruxolitinib continues to be safe in pts with MPN-associated SVT and maintains efficacy against splenomegaly in 33% of the pts. Of note, the large majority of pts (67%) showed stabilization or improvement of oesophageal varices, supporting the hypothesis that sustained reduction of enlarged spleen might contribute to decrease the upstream venous system pressure. Significant reduction of JAK2V617F VAF&gt;50% was documented in 40% of the pts, although it was not clearly correlated with clinical improvement. Disclosures Rumi: novartis: Honoraria, Research Funding. Vannucchi:Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; Italfarmaco: Membership on an entity's Board of Directors or advisory committees; CTI BioPharma: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. OffLabel Disclosure: Ruxolitinib use in essential thrombocythemia

Phase 2 Study of Ruxolitinib (RUX) in Combination with 5-Azacitidine (AZA) in Patients (pts) with Myelofibrosis

Phase 2 Study of Ruxolitinib (RUX) in Combination with 5-Azacitidine (AZA) in Patients (pts) with Myelofibrosis

A Phase II Trial of Azacitidine (AZA) in Combination with Ruxolitinib (RUX) in Myelodysplastic Syndrome/Myeloproliferative Neoplasms (MDS/MPNs)

A Phase II Trial of Azacitidine (AZA) in Combination with Ruxolitinib (RUX) in Myelodysplastic Syndrome/Myeloproliferative Neoplasms (MDS/MPNs)