Spleen Length Research Articles

Risk Factors for Infections in Myelofibrosis: Role of Disease Status and Treatment. A Study on 507 Patients

Background: Infectious complications represent one of the main causes of morbidity and mortality in patients (pts) with Primary Myelofibrosis (PMF), Post-Essential Thrombocythemia and post-Polycythemia Vera MF (PET/PPV-MF). Up-to-date, very few data are available on incidence and outcome of infectious complications. Also, risk factors of this potentially fatal complication are still to be investigated and defined. This is particularly relevant in the era of targeted therapy in MF, since an increased infectious risk has been reported in pts treated with ruxolitinib (RUX), a JAK1/2 inhibitor.Aims: To evaluate risk factors for severe infections in a large cohort of MF patients.Methods: Clinical and laboratory data of pts with MF were retrospectively collected from the database of 5 Italian Hematology Centers. Severe infections were defined according to the CTCAE. The study was approved by the Ethic Committee of each participating Centers.Results: Between 1980 and Aug 2014, 507 pts with PMF (362 pts, 71%), or PET-MF (14%) or PPV-MF were diagnosed and followed for a median follow-up of 4.2 yr (0.5-30.1). Baseline characteristics were (median): age, 66 y (range, 26-87); ≥65 y, 54%; male, 59%; hemoglobin (Hb), 11.9 g/dL (4-17.9); Hb <10 g/dL, 25%; PLT, 376×109/L (4-2513); PLT <100×109/L, 8%; spleen enlargement, 71% (spleen length ≥10cm: 20.5%); constitutional symptoms, 20%. International Prognostic Score System (IPSS) was low (21%), intermediate-1 (intm-1, 37%), intermediate-2 (intm-2, 25%), high (17%). Molecular analysis was performed on 321 pts (63%) and was positive in 83% (JAK2V617F), 12% (CALR), 3% (MPLW515K/L); 6 pts (2%) were triple negative. Karyotype was abnormal in 46 (17%) out of 265 evaluable pts (unfavorable in 13 pts; 5%). Three hundred and sixty-five (72%) received cytoreductive therapy (mainly hydroxyurea, 88%) and 71 patients (14%) received corticosteroids (defined as ≥ one cycle of prednisone at the dose of 1mg/Kg/daily for at least a month). Smoking habit was present in 165 patients (37%) and diabetes mellitus in 66 (13%).Overall, 112 pts (22%) experienced 160 infectious events (grade 3-4, 45%), for an incidence rate of 3.9% pt-y. The cumulative incidence was 20%, 33% and 51% at 5, 10 and 20 y, respectively. Infections were: bacterial (143 events, 89%; pneumonia: 80 cases, 56%); VZV reactivations (11 events, 7%), nodal TBC (3 events, 2%), fungal infections (3 events, 2%). Infectious complications represented the causes of death in 10 (7%) out of 134 deceased pts. Among baseline features, age≥65 y (p=0.001), primary vs secondary MF (p=0.009), spleen length>10 cm below left costal margin (p=0.006), high/intm-2 IPSS (p<0.0001) significantly correlated with higher infectious risk; in multivariate analysis, an high/intm-2 IPSS category and massive splenomegaly confirmed their negative impact (p=0.02 and p=0.04, respectively).Overall, 128 pts at intm-2/high IPSS risk were treated with RUX for a median time of 23 mos (1-41). Infection-free survival at 5 years was comparable in RUX-treated pts compared to non RUX-treated intm-2/high risk pts (76% vs 67%, p=0.82). In the RUX-treated cohort, age ≥65 y (p=0.008), JAK2 allele burden ≥75% (p=0.03) and steroids exposure before RUX (0.007) correlated with an increased infectious risk. Multivariate analysis confirmed age and corticosteroids utilization as independent negative prognostic risk factors (p=0.003 and p=0.043, respectively). Also, patients who obtained a spleen reduction higher than 50% during RUX therapy were projected to a better infection-free survival compared to non-responders (89% vs 70% at 12 mos, p=0.001)Summary/Conclusion. This large study confirms severe infections as frequent and potentially fatal events in MF. Also, this study has led to the identification of the main baseline features associated with increased infectious risk, namely baseline IPSS category and massive splenomegaly. Surprisingly, RUX therapy did not seem to significantly increase the risk of infections, despite its immunosuppressant properties. Yet, the successful use of RUX in terms of spleen response was found to correlate with a significant reduction of the probability to develop an infectious complication. Conversely, a combined or sequential use of corticosteroids and RUX may further increase the risk of infectious complications and therefore require a careful evaluation. DisclosuresMartinelli:MSD: Consultancy; BMS: Speakers Bureau; Roche: Consultancy; ARIAD: Consultancy; Novartis: Speakers Bureau; Pfizer: Consultancy.

EXPAND: A Phase 1b, Open-Label, Dose-Finding Study of Ruxolitinib in Patients with Myelofibrosis (MF) and Low Platelet Counts (50 × 109/L to 99 × 109/L) at Baseline

EXPAND: A Phase 1b, Open-Label, Dose-Finding Study of Ruxolitinib in Patients with Myelofibrosis (MF) and Low Platelet Counts (50 × 109/L to 99 × 109/L) at Baseline

Phase 1b/2 Study of the Efficacy and Safety of Sonidegib (LDE225) in Combination with Ruxolitinib (INC424) in Patients with Myelofibrosis

Phase 1b/2 Study of the Efficacy and Safety of Sonidegib (LDE225) in Combination with Ruxolitinib (INC424) in Patients with Myelofibrosis

An Open-Label, Multicenter, 2-Arm, Dose-Finding, Phase 1b Study of the Combination of Ruxolitinib and Buparlisib (BKM120) in Patients with Myelofibrosis: Results from HARMONY Study

An Open-Label, Multicenter, 2-Arm, Dose-Finding, Phase 1b Study of the Combination of Ruxolitinib and Buparlisib (BKM120) in Patients with Myelofibrosis: Results from HARMONY Study

Long Term Follow up of a Phase 2 Study of Ruxolitinib in Patients with Splanchnic Vein Thrombosis Associated with Myeloproliferative Neoplasm

Long Term Follow up of a Phase 2 Study of Ruxolitinib in Patients with Splanchnic Vein Thrombosis Associated with Myeloproliferative Neoplasm

Four Weeks Administration Schedule of Ropeginterferon Alfa-2b (AOP2014/P1101) in Polycythemia Very Patients Allows Maintaining of Efficacy with Favorable Toxicity Profile in the Phase I/II Peginvera Stud

Four Weeks Administration Schedule of Ropeginterferon Alfa-2b (AOP2014/P1101) in Polycythemia Very Patients Allows Maintaining of Efficacy with Favorable Toxicity Profile in the Phase I/II Peginvera Stud

Relationship Between Patient-Reported Outcomes (PROs) and Health-Related Quality of Life (HRQoL) and Efficacy in Patients with Myelofibrosis in the Phase III Persist-1 Trial of Pacritinib Vs. Best Available Therapy (BAT)

Introduction: Myelofibrosis (MF) is a life-threatening hematologic malignancy characterized by splenomegaly and debilitating symptoms including fatigue, abdominal pain, night sweats, bone pain, pruritus, and unintentional weight loss. The myeloproliferative neoplasm symptom assessment form (MPN-SAF) is a PRO tool designed to measure MF-related symptom burden and was developed and validated at Mayo Clinic. It was modified (MPN-SAF total symptom score [TSS] and TSS 2.0) for use in the PERSIST-1 and PERSIST-2 phase 3 trials. For PERSIST-1, when examining the 6 common symptoms in both TSS versions (tiredness, night sweats, early satiety, itchiness, bone pain, and abdominal pain), pacritinib-treated patients (pts) had significant improvements in TSS overall and in individual symptoms vs BAT; Pt Global Impression of Change (PGIC) was also significantly improved for pts receiving pacritinib. Improvements in EORTC-QLQ-C30 scales were noted in the pacritinib arm (Mesa, EHA 2015). The proportion of pts achieving spleen volume reduction (SVR) ≥35% at Week 24 was significantly greater with pacritinib vs BAT (ITT: 19.1% vs 4.7%, p=0.0003; evaluable at baseline and Week 24: 25.0% vs 5.9%; p=0.0001). This analysis examines relationships between TSS improvement and changes in splenomegaly and HRQoL outcomes.Methods: Pts who received no prior JAK inhibitor therapy were randomized 2:1 to oral pacritinib 400 mg once daily or BAT. Pts were stratified by DIPSS risk (Int-1/Int-2 vs High) and platelet count (<50,000/μL vs 50,000/μL to <100,000/μL vs ≥100,000/μL). Pts must have had a baseline total TSS ≥13 using MPN-SAF TSS 2.0. Each symptom is rated on a scale from 0 (absent) to 10 (worst imaginable) using MPN-SAF TSS and TSS 2.0. Results for the 6 symptoms common to both TSS versions are reported. Additional PROs used for assessment of HRQoL included EORTC QLQ-C30 and EQ-5D-5L. In multivariate logistic regressions, odds of TSS reduction ≥50% at Week 24 were modeled as a function of Week 24 SVR ≥35%, spleen length reduction (SLR) ≥ 50%, PGIC, improvement in each EORTC scale, and improvement in EQ-5D-5L Overall Health State (OHS) and in each dimension individually while adjusting for treatment (pacritinib vs BAT). Correlations were examined in all pts and by baseline platelet counts (<50,000/μL, <100,000/μL, and ≥100,000/μL).Results: A total of 327 pts were enrolled (PAC: 220, BAT: 107). 62% of pts had primary MF, 32% had baseline platelets <100,000/μL, and 16% had baseline platelets <50,000/μL. TSS reduction ≥50% was found to be associated with SVR ≥35% and improvement in splenomegaly (SLR ≥50%). In the total pt population, there was a significant association between TSS reduction and SVR (odds ratio [OR]=2.60, p=0.016). In all pts, there was a significant association between TSS reduction and improvements in OHS as measured by EQ-5D-5L (OR=2.30, p=0.013). TSS reductions were also marginally associated with improvements in the QLQ-C30 Global Health Scale (GHS)/QoL Scale (OR=1.92, p=0.050) and, though not statistically significant, there was a trend of improvement in perceived overall health as measured by PGIC (OR=2.16, p=0.118). TSS reductions were further examined in pts grouped by baseline platelet count. Improvement in EQ-5D-5L OHS was marginally associated with TSS reductions in pts with platelets <50,000/μL (OR=6.03, p=0.057). For pts with platelets <100,000/μL, reductions in TSS were significantly associated with reductions in splenomegaly (SLR ≥50%; OR=9.53, p=0.004), and improvements in the QLQ-C30 GHS/QoL domain (OR=4.03, p=0.022) as well as the EQ-5D-5L OHS (OR=5.49, p=0.008). A significant association between TSS reductions and SVR ≥35% was observed in pts with platelets ≥100,000/μL (OR=3.99, p=0.005). In all pts, improvements in Fatigue as measured by QLQ-C30 were significantly associated with TSS reductions (OR=2.20, p=0.019) as well as in pts with baseline platelets <50,000/μL (OR=17.88, p=0.008) and <100,000/μL (OR=10.18, p<0.001).Conclusions: In the total pt population, TSS reduction was associated with improvements in spleen response and perceived overall health. This trend was also observed in pts with low baseline platelet counts. Additionally, TSS reduction was significantly associated with improvements in fatigue, a major contributor to poor HRQoL in pts with MF. This reinforces the clinical relevance of measuring TSS using a validated instrument as an endpoint in MF trials. DisclosuresMesa:NS Pharma: Research Funding; Pfizer: Research Funding; Gilead: Research Funding; Incyte Corporation: Research Funding; CTI Biopharma: Research Funding; Novartis Pharmaceuticals Corporation: Consultancy; Genentech: Research Funding; Promedior: Research Funding. Off Label Use: This abstract discusses off-label use of pacritinib. Harrison:Shire: Speakers Bureau; Novartis: Honoraria, Research Funding, Speakers Bureau; Gilead: Honoraria; CTI Biopharma: Consultancy, Honoraria, Speakers Bureau; Sanofi: Honoraria, Speakers Bureau. Cervantes:Novartis: Consultancy, Speakers Bureau; Sanofi-Aventis: Consultancy; CTI-Baxter: Consultancy, Speakers Bureau. Dean:CTI Biopharma: Employment, Equity Ownership. Wang:CTI Biopharma: Employment, Equity Ownership. Yang:Baxalta: Employment, Other: Stock. 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.

Assessing the Safety and Efficacy of Ruxolitinib in a Multicenter, Open-Label, Expanded-Access Study in Japanese Patients with Myelofibrosis (MF)

Assessing the Safety and Efficacy of Ruxolitinib in a Multicenter, Open-Label, Expanded-Access Study in Japanese Patients with Myelofibrosis (MF)

Safety and Efficacy of Ruxolitinib in an 1869-Patient Cohort of JUMP: An Open-Label, Multicenter, Single-Arm, Expanded-Access Study in Patients with Myelofibrosis

Safety and Efficacy of Ruxolitinib in an 1869-Patient Cohort of JUMP: An Open-Label, Multicenter, Single-Arm, Expanded-Access Study in Patients with Myelofibrosis

Spleen Size Is Significantly Influenced by Body Height and Sex: Establishment of Normal Values for Spleen Size at US with a Cohort of 1200 Healthy Individuals.

To define height- and sex-corrected normal values for spleen length and volume determined with ultrasonography (US). The authors performed a retrospective data review of stem cell donors who had provided written informed consent for stem cell donation and use of anonymized data and biologic materials for scientific and quality control purposes. Spleen length, spleen volume, and anthrophometric data were correlated in 1230 healthy volunteers to identify variables that affect spleen size. Multiple linear regression analysis was performed to weight effects of various variables on spleen size. Linear regression through the 95th percentile for men and women of different height cohorts generated the formula for the upper limit of normal for spleen length and volume. For validation, the upper limit of normal was calculated for each volunteer and compared with the observed value. Formulae to calculate the additional percentiles were similarly generated and validated. A cohort of 75 volunteers was analyzed twice to assess the stability of spleen length and volume over time. Spleen length and volume were significantly and independently associated with sex (length: P < .001; volume: P = .012), body height (P < .001 for both), and weight (P < .001 for both), with men and taller and heavier individuals having longer and larger spleens. The spleen length of 20 of 324 women (6%) and 234 of 906 men (26%) exceeded the previously reported upper limit of normal of 12 cm. Repeat measurements indicated that spleen length (median difference, 0.10 cm; range, -1.8 to 1.7 cm) and volume (median difference, 3 cm(3); range, -106 to 142 cm(3)) were quite stable. A mobile application that performs these calculations is available for download. The authors define height- and sex-corrected normal values for spleen length and volume for women with a body height of 155-179 cm and men with a body height of 165-199 cm and propose validated algorithms to gauge the percentile of an individual's spleen size.

Platelet count combined with right liver volume and spleen volume measured by magnetic resonance imaging for identifying cirrhosis and esophageal varices.

To determine whether the combination of platelet count (PLT) with spleen volume parameters and right liver volume (RV) measured by magnetic resonance imaging (MRI) could predict the Child-Pugh class of liver cirrhosis and esophageal varices (EV). Two hundred and five cirrhotic patients with hepatitis B and 40 healthy volunteers underwent abdominal triphasic-enhancement MRI and laboratory examination of PLT in 10(9)/L. Cirrhotic patients underwent endoscopy for detecting EV. Spleen maximal width (W), thickness (T) and length (L) in mm together with spleen volume (SV) and RV in mm(3) were measured by MRI, and spleen volume index (SI) in mm(3) was obtained by W × T × L. SV/PLT, SI/PLT and RV × PLT/SV (RVPS) were calculated and statistically analyzed to assess cirrhosis and EV. SV/PLT (r = 0.676) and SI/PLT (r = 0.707) increased, and PLT (r = -0.626) and RVPS (r = -0.802) decreased with the progress of Child-Pugh class (P < 0.001 for all). All parameters could determine the presence of cirrhosis, distinguish between each class of Child-Pugh class, and identify the presence of EV [the areas under the curve (AUCs) = 0.661-0.973]. Among parameters, RVPS could best determine presence and each class of cirrhosis with AUCs of 0.973 and 0.740-0.853, respectively; and SV/PLT could best identify EV with an AUC of 0.782. The combination of PLT with SV and RV could predict Child-Pugh class of liver cirrhosis and identify the presence of esophageal varices.

Eltrombopag dose predictors in thrombocytopenic subjects with hepatitis C virus infection.

This study aims to identify patient characteristics that predict effective eltrombopag dosage for the treatment of Hepatitis C virus (HCV)-related thrombocytopenia. Demographic, clinical and genetic data collected from thrombocytopenic patients (n = 1463, age ≥ 18 years) with chronic HCV infection who were able to achieve a target platelet count of > 90 × 10(9) /L following eltrombopag treatment. Patients were categorized into four groups (25, 50, 75, and 100 mg) based on the eltrombopag dose needed to achieve the target platelet count. Eltrombopag dose predictors were identified using a two stage approach. First, bivariate analysis, using anova for continuous variables and Chi-square test for categorical variables, was performed to identify possible predictors of eltrombopag dose (P < 0.05). Second, ordinal logistic regression with stepwise addition followed by backward deletion was then performed using predictors identified in bivariate analysis step to produce final model containing independent predictors at P < 0.05. Ordinal logistic model identified several predictors of eltrombopag dose. Predictors of higher eltrombopag dose include: having a HCV genotype 2 or 3, being Central/South Asian, being White (Caucasian or European heritage), increased weight, and increased spleen length. Predictors of lower eltrombopag dose include: female gender, increased age, having a higher ALP plasma concentration, increased creatinine clearance, increased baseline lymphocytes count, and increased baseline platelet count. In conclusion, this study identified patient characteristics that predict effective eltrombopag dose for the treatment of HCV-related thrombocytopenia. Early selection of the optimal eltrombopag dose expedites the initiation of antiviral therapy. This is expected to improve the antiviral therapy outcome before the patient progress into liver decompensation.

Ruxolitinib (RUX) in combination with 5-Azacytidine (AZA) as therapy for patients with myelofibrosis (MF)

Ruxolitinib (RUX) in combination with 5-Azacytidine (AZA) as therapy for patients with myelofibrosis (MF)

Ruxolitinib treatment for myelofibrosis: Efficacy and tolerability in routine practice

Ruxolitinib has been shown in two randomized clinical trials to be effective in alleviating systemic symptoms and reducing spleen size in patients with myelofibrosis (MF). We retrospectively evaluated efficacy and tolerability of ruxolitinib in a cohort of unselected MF patients treated in routine clinical practice. One hundred and two patients who began ruxolitinib therapy were identified in 13 participating centers. Ninety three of the patients receiving ruxolitinib for at least 3 months were evaluated for treatment efficacy and toxicity. Median age at ruxolitinib initiation was 67 years. Indications for treatment were constitutional symptoms (15%), symptomatic splenomegaly (6%) or both (76%). Two patients received ruxolitinib for other indications. The median initial ruxolitinib dose was 30mg/day. Median duration of therapy was 11 months. Eighty two patients (88.2%) responded to therapy, 76 (84.4%) patients had improvement in constitutional symptoms and 60 patients (70.6%) had reduction in spleen length. While on ruxolitinib, 30% of patients had grade 3–4 anemia and 12.9% of patients had grade 3–4 thrombocytopenia. Thirteen patients (14%) discontinued therapy. This analysis of a cohort of MF patients treated with ruxolitinib in routine clinical practice demonstrates the efficacy and tolerability of this drug outside of a highly monitored clinical trial setting.

The Role of Spleen Stiffness in Determining the Severity and Bleeding Risk of Esophageal Varices in Cirrhotic Patients.

Esophageal varix and its hemorrhage are serious complications of liver cirrhosis. Recent studies have focused on noninvasive prediction of esophageal varices. We attempted to evaluate the association of liver and spleen stiffness (LS and SS) as measured by acoustic radiation force impulse imaging, with the presence and severity of esophageal varices and variceal hemorrhage in cirrhotic patients.We measured LS and SS, along with endoscopic examination of esophageal varices for a total of 125 cirrhotic patients at a single referral hospital in this prospective observational study. The diagnostic utility of noninvasive methods for identifying varices and their bleeding risk was compared, including LS, SS, spleen length, Child-Pugh score, and various serum fibrosis indices.Esophageal varices were present in 77 patients (61.6%). SS was significantly higher in patients with varices than in those without varices (3.58 ± 0.47 vs 3.02 ± 0.49; P < 0.001). A tendency toward increasing SS levels was observed with increasing severity of varices (no varix, 3.02 ± 0.49; F1, 3.39 ± 0.51; F2, 3.60 ± 0.42; F3, 3.85 ± 0.37; P < 0.001). SS was significantly higher in patients who experienced variceal hemorrhage than in those who did not (3.80 ± 0.36 vs 3.20 ± 0.51; P = 0.002). An optimal cut-off value of SS for high-risk varices (≥F2) or variceal hemorrhage was 3.40 m/s.SS was significantly correlated with the presence, severity, and bleeding risk of esophageal varices. Prompt endoscopic evaluation of variceal status and prophylactic measures based on the SS may be warranted for cirrhotic patients.

Screening for significant chronic liver disease by using three simple ultrasound parameters

ObjectivesChronic liver diseases remain asymptomatic for many years. Consequently, patients are diagnosed belatedly, when cirrhosis is unmasked by lifethreatening complications. We aimed to identify simple ultrasound parameters for the screening of patients with unknown significant chronic liver disease. MethodsThree hundred and twenty seven patients with chronic liver disease, liver biopsy, and ultrasound examination were included in the derivation set. 283 consecutive patients referred for ultrasound examination were included in the validation set; those selected according to the ultrasound parameters identified in the derivation set were then referred for specialized consultation including non-invasive fibrosis tests and ultimately liver biopsy if liver fibrosis was suspected. ResultsIn the derivation set, three ultrasound parameters were independent predictors of severe fibrosis: liver surface irregularity, spleen length (>110mm), and demodulation of hepatic veins. The association of ≥2 of the three above parameters provided 49.1% sensitivity and 86.9% specificity. In the validation set, at ≥2 of the three parameters were present in 23 (8%) of the patients. Among these patients, 8 had liver fibrosis (F≥1), 5 had significant fibrosis (F≥2) and two cirrhosis. ConclusionThe generalized search of three simple ultrasound signs in patients referred for abdominal ultrasound examination may be an easy way to detect those with silent but significant chronic liver disease.

혼합모형을 이용한 반복 측정된 변수들 간의 상관분석

Repeated measurements on each variables of interest often arise in bioscience or medical research. We need to account for correlations among repeated measurements to assess the correlation between two variables in the presence of replication. This paper reviews methods to estimate a correlation coefficient between two variables in repeated measurements using the variance-covariance matrix of linear mixed effect models. We analyze acoustic radiation force impulse imaging (ARFI) data to assess correlation between three shear wave velocity (SWV) measurements in liver or spleen and spleen length by ultrasonography. We present how to obtain parameter estimates for the variance-covariance matrix and correlations in mixed effects models using PROC MIXED in SAS.

1,25-dihydroxyvitamin D3 regulates the development of chronic colitis by modulating both T helper (Th)1 and Th17 activation.

T helper (Th)1 and Th17 cells play a critical role in inflammatory bowel disease (IBD). 1,25-dihydroxyvitamin D3 (1,25(OH)2 D3 ) has emerged as a direct regulator of immune system function. Mice were grouped as follows: Control group (received PBS, n = 10), DSS group (received 2% DSS and PBS, n = 10), and DSS+VD group (received 2% DSS and 1,25(OH)2 D3 , n = 10). The disease activity index (DAI), colon length, and damage store of the mice were observed; the spleen length, weight, spleen index, and mononuclear cells of spleen were measured; mononuclear cells from mesenteric lymph nodes (MLN) were measured, and the levels of Th 1 and Th17 cytokines in the colon mucosa and spleen were measured. Mice in the DSS group developed severe diarrhea, rectal bleeding, and marked BW loss. Histological examination revealed extensive ulceration and inflammatory cell infiltration in the colon, and the structure of the spleen was disordered, infiltrated with inflammatory cytokines in red pulp. In the DSS group, mononuclear cell numbers from MLN and spleen were increased, and enhanced proteins and mRNA levels of Th 1 and Th17 cytokines were detected. In the DSS+VD group, 1,25(OH)2 D3 ameliorated the inflammation of the colon and spleen. In addition, 1,25(OH)2 D3 down-regulated the levels of Th 1 and Th17 cytokines. 1,25(OH)2 D3 represents a novel therapeutic drug for UC, which may correlate to inhibit the activation of Th1 and Th17 cells.

Response to ruxolitinib in patients with intermediate‐1–, intermediate‐2–, and high‐risk myelofibrosis: results of the UK ROBUST Trial

Myelofibrosis is characterized by splenomegaly and debilitating constitutional symptoms that negatively impact patients' quality of life. ROBUST, a UK, open-label, phase II study, evaluated the safety and efficacy of ruxolitinib in patients with myelofibrosis (N = 48), including intermediate-1 risk patients. The primary composite endpoint was the proportion of patients achieving treatment success [≥ 50% reduction in palpable spleen length and/or a ≥ 50% decrease in Myelofibrosis Symptom Assessment Form Total Symptom Score (MF-SAF TSS)] at 48 weeks. This was the first time that efficacy of ruxolitinib in myelofibrosis has been evaluated based on these criteria and the first time the MF-SAF was used in a population of patients solely from the United Kingdom. Overall, 50% of patients and 57% of intermediate-1 risk patients, achieved treatment success; reductions in spleen length and symptoms were observed in all risk groups. The majority of patients (66.7%) experienced ≥ 50% reductions from baseline in spleen length at any time. Improvements in MF-SAF TSS were seen in 80.0%, 72.7%, and 72.2% of intermediate-1, intermediate-2, and high-risk patients, respectively. Consistent with other studies of ruxolitinib, the most common haematological adverse events were anaemia and thrombocytopenia. Results indicate that most patients with myelofibrosis, including intermediate-1 risk patients, may benefit from ruxolitinib treatment.

Spleen size in cirrhosis of different etiologies.

The purpose of this study was to evaluate the impact of cirrhosis etiology on spleen size as measured by sonography and computed tomography (CT). The spleen images of 139 patients with cirrhosis secondary to alcohol abuse, hepatitis C, or nonalcoholic steatohepatitis were reviewed retrospectively. The maximum diagonal spleen length on a single sonogram and maximum spleen diameter on axial, coronal, or sagittal CT, whichever was largest, was compared among the etiologic groups. In 127 patients who underwent sonography, the mean spleen size ± SD on sonography in the alcohol group (13.1 ± 2.5 cm) was significantly smaller than in the hepatitis C (15.0 ± 3.4 cm) and nonalcoholic steatohepatitis (15.2 ± 3.0 cm) groups (95% confidence intervals of the mean difference, 0.6 to 3.3 and 0.8 to 3.4 cm, respectively). In 87 patients who underwent CT, the mean spleen size on CT in the alcohol group (14.0 ± 2.7 cm) was smaller than in the hepatitis C (15.9 ± 3.4 cm) and nonalcoholic steatohepatitis (15.5 ± 3.6 cm) groups, but the difference was not statistically significant. The spleen sizes on both sonography and CT in 79 patients were strongly correlated (r = 0.88; P < .0001). Spleen size in patients with cirrhosis varies by the etiology of the disease. Therefore, to apply spleen size as a diagnostic or prognostic criterion in this context, it is important to recognize that cutoff values derived from spleen size in one etiologic group may not produce the same results when extrapolated to another etiologic group.