Equivalent thrombotic risk with Warfarin, Dabigatran, or Enoxaparin after failure of initial direct oral anticoagulation (DOAC) therapy.

BACKGROUND: The direct oral anticoagulants (DOACs) are now commonly regarded as first line anticoagulants in most cases of venous thromboembolism (VTE). However, the optimal choice of subsequent anticoagulant in instances of first line DOAC failure is unclear. OBJECTIVES: To describe and compare outcomes with second line anticoagulants used after DOAC failure. METHODS: Patients seen at an urban hospital system for an episode of acute VTE initially treated with either apixaban or rivaroxaban who experienced a subsequent recurrent thrombosis while on anticoagulation (1st recurrent thrombosis) were included. RESULTS: In total, 166 patients after apixaban or rivaroxaban failure were included. Following DOAC failure (1st recurrent thrombosis), the subsequent anticoagulant was warfarin in 60 patients (36%), dabigatran in 42 patients (25%), and enoxaparin in 64 patients (39%). Enoxaparin was preferentially prescribed in patients with a malignancy-associated etiology for 1st recurrent thrombosis (p < 0.01). The median follow-up time in our cohort was 16 months. There was no difference in 2nd recurrent thrombosis-free survival (p = 0.72) or risk for major bleeding event (p = 0.30) among patients treated with dabigatran, warfarin, or enoxaparin. CONCLUSIONS: In this retrospective analysis of patients failing first line DOAC therapy, rates of 2nd recurrent thrombosis and bleeding did not differ among subsequently chosen anticoagulants. Our study provides evidence that the optimal 2nd anticoagulant is not clear, and the choice of 2nd anticoagulant should continue to balance patient preference, cost, and provider experience.

Conventional Cytogenetic Analysis and Array CGH + SNP Identify Essential Thrombocythemia and Prefibrotic Primary Myelofibrosis Patients Who Are at Risk for Disease Progression.

The Philadelphia chromosome-negative myeloproliferative neoplasms (Ph-MPNs) are a heterogeneous group of clonal hematopoietic malignancies that include polycythemia vera (PV), essential thrombocythemia (ET), and the prefibrotic form of primary myelofibrosis (prePMF). In this study, we retrospectively reviewed the karyotypes from conventional cytogenetics (CC) and array Comparative Genomic Hybridization + Single Nucleotide Polymorphism (aCGH + SNP) in patients with ET or prePMF to determine whether the combined analysis of both methodologies can identify patients who may be at a higher risk of disease progression. We performed a comprehensive genomic review on 169 patients with a clinical diagnosis of ET (154 patients) or prePMF (15 patients). Genomic alterations detected by CC or array-CGH + SNP were detected in 36% of patients. In patients who progressed, 68% had an abnormal genomic finding by either technology. There was a shorter progression-free survival (PFS) among patients who were cytogenetically abnormal or who were cytogenetically normal but had an abnormal aCGH + SNP result. Leveraging the ability to detect submicroscopic copy number alterations and regions of copy neutral-loss of heterozygosity, we identified a higher number of patients harboring genomic abnormalities than previously reported. These results underscore the importance of genomic analysis in prognostication and provide valuable information for clinical management and treatment decisions.

An overlooked mimic? Autoimmune myelofibrosis-A scoping review of the literature.

BACKGROUND AND OBJECTIVES: Autoimmune myelofibrosis (AIMF) is a rare cause of bone marrow fibrosis (BMF) occurring in the presence or absence of a defined autoimmune disease (secondary or primary AIMF, sAIMF/pAIMF, respectively). Unlike primary myelofibrosis (PMF), AIMF responds well to immunosuppressive therapy with a benign clinical course. Diagnostic criteria for AIMF in opposition to PMF have been lacking, though recent work has helped better characterise molecular and pathological features of AIMF, improving diagnostic precision. METHODS: Using a modern clinical and pathophysiological understanding of AIMF, we apply scoping review methodology and rigorous case-criteria to retrospectively analyse the case literature. We examine its patient-population, describing patient-associated factors, presentation, bone marrow pathology, genetics, treatment and outcomes. RESULTS: Fifty-five studies were identified, describing 139 AIMF patients. Patients were mostly young females (~4:1 ratio female:male, median age 40.8 years) and typically presented with cytopenias. Splenomegaly was rare. sAIMF was more common than pAIMF (~3:1 ratio), and most cases responded well to immunosuppressive therapy. CONCLUSIONS: Our results strengthen the emerging picture of AIMF's patient population, natural history and response to treatment. Further work should continue to use reproducible diagnostic criteria, and explore AIMF's pathophysiology, response to different therapies, and sequelae over larger timescales, as well as differences between pAIMF, sAIMF and PMF.

Exclusion of Acute Myeloid Leukemia Patients with Central Nervous System Involvement from Clinical Trials: An Analysis of the National Institutes of Health Clinical Trials Registry from 2012-2022.

INTRODUCTION: Central nervous system (CNS) involvement in acute myeloid leukemia (AML) can be successfully treated with intrathecal chemotherapy and carries debatable prognostic impact. However, patients with CNS involvement are commonly excluded from clinical trials at an unknown rate. We systematically evaluated exclusion criteria of AML clinical trials based on CNS involvement and determined associations with clinical trial characteristics. METHODS: The National Institutes of Health Clinical Trials Registry was searched for interventional adult AML trials between 2012-2022 that were phase I, II, or III and relevant trial characteristics were extracted. RESULTS: 1270 trials were included in the analysis with 790 trials (62.1%) explicitly excluding CNS involvement. There was no significant change in rates of CNS exclusion over the past decade. CNS exclusion was higher in trials that included the non-transplant population compared to trials exclusive to the transplant population (66.9% vs. 43.8%, p<0.01). Non-transplant trials were also more likely to exclude patients with a history of or ambiguous timing of CNS involvement (p<0.01). Phase III trials were associated with more liberal definitions of CNS exclusion (history or ambiguous timing) as compared to phase I and II trials that had higher rates of excluding patients with only active CNS involvement (P<0.01). CONCLUSION: A majority of AML clinical trials, particularly in the non-transplant setting, exclude patients with CNS involvement. Many of these trials, most notably phase 3 trials, exclude patients not only with active, but any history of CNS involvement. Further research is needed to determine optimal management of these patients in order to increase representation in large clinical trials.

New Treatments for Myelofibrosis.

OPINION STATEMENT: Currently approved therapies for myelofibrosis (MF) consist of JAK inhibitors, which produce meaningful improvements in spleen size and symptom burden but do not significantly impact leukemic progression. In addition, many patients develop resistance or intolerance to existing therapies and are left without meaningful therapeutic options. There has been recent rapid development of agents in MF that may be able to fill these unmet needs. Importantly, most treatments currently in clinical development have targets outside the JAK-STAT pathway, including BET, BCL-2/BCL-xL, PI3k, HDM2, PIM-1, SINE, telomerase, LSD1, and CD123. These therapies are being tested in combination with JAK inhibitors in the front-line setting and in patients with a suboptimal response, as well as a single agent after JAK inhibitor failure. This next generation of agents is likely to produce a paradigm shift in MF treatment with a focus on combination treatment targeting multiple areas of MF pathophysiology.

Persistent leukocytosis in polycythemia vera is associated with disease evolution but not thrombosis.

There are unresolved questions regarding the association between persistent leukocytosis and risk of thrombosis and disease evolution in polycythemia vera (PV), as much of the published literature on the topic does not appropriately use repeated-measures data or time-dependent modeling to answer these questions. To address this knowledge gap, we analyzed a retrospective database of 520 PV patients seen at 10 academic institutions across the United States. Taking hematologic laboratory data at ∼3-month intervals (or as available) for all patients for duration of follow-up, we used group-based trajectory modeling to identify latent clusters of patients who follow distinct trajectories with regard to their leukocyte, hematocrit, and platelet counts over time. We then tested the association between trajectory membership and hazard of 2 major outcomes: thrombosis and disease evolution to myelofibrosis, myelodysplastic syndrome, or acute myeloid leukemia. Controlling for relevant covariates, we found that persistently elevated leukocyte trajectories were not associated with the hazard of a thrombotic event (P = .4163), but were significantly associated with increased hazard of disease evolution in an ascending stepwise manner (overall P = .0002). In addition, we found that neither hematocrit nor platelet count was significantly associated with the hazard of thrombosis or disease evolution.

Low-risk polycythemia vera and essential thrombocythemia: management considerations and future directions.

Thrombotic events are a distinctive feature of the myeloproliferative neoplasms (MPNs) polycythemia vera (PV) and essential thrombocythemia (ET). Patients with these MPNs may also experience a poor quality of life secondary to symptom burden, as well as progression of disease to acute leukemia or myelofibrosis. Over the years, various risk stratification methods have evolved in order to attempt to predict thrombotic risk, which is the largest contributor of morbidity and mortality in these patients. More than half of PV and ET patients are low- or intermediate-risk disease status at the time of diagnosis. While therapeutic development is presently focused on high-risk patients, there is a paucity of therapies, outside of aspirin and therapeutic phlebotomy, which can reduce the thrombotic risk or delay disease progression in low-risk patients. In this review, we first describe the various complications that patients with PV and ET experience, and then detail our evolving understanding of risk stratification in these diseases. We then highlight the available evidence on the management of low-risk PV and ET and include a description of novel therapies currently under investigation in this space. We conclude with recommendations for future directions to advance our understanding and improve the treatment of low-risk PV and ET.

Momelotinib for the treatment of myelofibrosis with anemia.

Myelofibrosis is a myeloproliferative neoplasm characterized by splenomegaly, debilitating constitutional symptoms and bone marrow failure. Disease-related anemia is common and associated with an inferior quality of life and survival. Unfortunately, few therapies exist to improve hemoglobin in myelofibrosis patients. Momelotinib is a JAK1/JAK2 inhibitor that also antagonizes ACVR1, leading to downregulation of hepcidin expression and increased availability of iron for erythropoiesis. In clinical testing, momelotinib has demonstrated a unique ability to improve hemoglobin and reduce transfusion burden in myelofibrosis patients with baseline anemia, while producing reductions in spleen size and symptom burden. This review explores the preclinical rationale, clinical trial data and future role of momelotinib in the evolving therapeutic landscape of myelofibrosis.

Patients with myelofibrosis (MF), a blood cancer, experience many symptoms including tiredness, night sweats and an increased spleen size. They also may experience low red blood cell counts (anemia) and require blood transfusions. MF is normally treated with medications called JAK inhibitors, but they worsen anemia. Momelotinib is a new JAK inhibitor that may be able to improve anemia. This is a review article that covers the available information on momelotinib and describes how this new drug may be incorporated into the future treatment of MF.

Contemporary Risk Stratification and Treatment of Chronic Myelomonocytic Leukemia.

Chronic myelomonocytic leukemia (CMML) is a hematologic malignancy characterized by absolute monocytosis, one or more lineage dysplasia, and proliferative features including myeloid hyperplasia, splenomegaly, and constitutional symptoms. Because of vast clinical heterogeneity in presentation and course, risk stratification is used for a risk-adapted treatment strategy. Numerous prognostic scoring systems exist, some of which incorporate mutational information. Treatment ranges from observation to allogeneic hematopoietic stem cell transplantation. Therapies include hydroxyurea for cytoreduction, hypomethylating agents, and the JAK1/2 inhibitor ruxolitinib to address splenomegaly and constitutional symptoms. Recently, oral decitabine with cedazuridine was approved and represents a convenient treatment option for CMML patients. Although novel therapeutics are in development for CMML, further work is needed to elucidate possible targets unique to the CMML clone. In this review, we will detail the pathophysiology, risk stratification, available treatment modalities, and novel therapies for CMML, and propose a modern treatment algorithm. IMPLICATIONS FOR PRACTICE: Chronic myelomonocytic leukemia (CMML) is a clinically heterogenous disease, which poses significant management challenges. The diagnosis of CMML requires bone marrow biopsy and aspirate with thorough evaluation. Risk stratification and symptom assessment are essential to designing an effective treatment plan, which may include hypomethylating agents (HMAs) in intermediate or high-risk patients. The recently approved oral decitabine/cedazuridine provides a convenient alternative to parenteral HMAs. Ruxolitinib may be effective in ameliorating proliferative symptoms and splenomegaly. Allogeneic stem cell transplantation remains the only treatment with curative potential; however, novel therapies are in clinical development which may significantly alter the therapeutic landscape of CMML.

Risk factors and outcomes of COVID-19 in New York City; a retrospective cohort study.

Coronavirus disease 2019 (COVID-19) is a global pandemic and information on risk factors for worse prognosis is needed to accurately identify patients at risk and potentially provide insight into therapeutic options. In this retrospective cohort study, including 3703 patients with laboratory confirmed COVID-19, we identified risk factors associated with all-cause mortality, need for hospitalization and mechanical ventilation. Male gender was independently associated with increased risk of hospitalization (adjusted odds ratio [ORadj ]: 1.62; 95% confidence interval [95% CI]: 1.38-1.91)), mechanical ventilation (ORadj : 1.35; 95% CI: 1.08-1.69) and death (ORadj : 1.46; 95% CI: 1.17-1.82). Patients > 60 years had higher risk of hospitalization (ORadj : 5.47; 95% CI: 4.29-6.96), mechanical ventilation (ORadj : 3.26; 95% CI: 2.08-5.11) and death (ORadj : 13.04; 95% CI: 6.25-27.24). Congestive heart failure (ORadj: 1.47; 95% CI: 1.06-2.02) and dementia (ORadj : 2.03; 95% CI: 1.46-2.83) were associated with increased odds of death, as well as the presence of more than two comorbidities (ORadj : 1.90; 95% CI: 1.35-2.68). Patients with COVID-19 of older age, male gender, or having more than two comorbidities are at higher risk of hospitalization, mechanical ventilation and death, and should therefore be closely monitored.

Emerging drugs for the treatment of myelofibrosis: phase II & III clinical trials.

INTRODUCTION: Myelofibrosis is a clonal hematologic malignancy with clinical manifestations that include cytopenias, debilitating constitutional symptoms, splenomegaly, bone marrow fibrosis and a propensity toward leukemic progression. While allogeneic hematopoietic stem cell transplantation can be curative, this therapy is not available for the majority of patients. Ruxolitinib and fedratinib are approved JAK2 inhibitors that have produced meaningful benefits in terms of spleen reduction and symptom improvement, but there remain several unmet needs. AREAS COVERED: We discuss novel therapies based upon published data from phase II or III clinical trials. Specifically, we cover novel JAK inhibitors (momelotinib and pacritinib), and agents that target bromodomain and extra-terminal domain (pelabresib), the antiapoptotic proteins BCL-2/BCL-xL (navitoclax), MDM2 (navtemadlin), phosphatidylinositol 3-kinase (parsaclisib), or telomerase (imetelstat). EXPERT OPINION: Patients with disease related cytopenias are ineligible for currently approved JAK2 inhibitors. However, momelotinib and pacritinib may be able to fill this void. Novel therapies are being evaluated in the upfront setting to improve the depth and duration of responses with ruxolitinib. Future evaluation of agents must be judged on their potential to modify disease progression, which current JAK2 inhibitors lack. Combination therapy, possibly with an immunotherapeutic agent might serve as key components of future myelofibrosis treatment options.

The utility of thrombophilia and hematologic screening in live liver donation.

BACKGROUND: Most centers perform some degree of hematologic screening, including thrombophilia testing, on prospective live liver donors. The nature and extent of such screens are not standardized, and there is limited evidence regarding hematologic risk stratification. METHODS AND RESULTS: We present an experience of hematologic screening among prospective liver donors. Five-hundred-eightyfour patients were screened for liver donation between 1/2013 and 1/2020, of whom 156 (27%) proceeded to donor hepatectomy. Thirty-three of 428 (8%) declined patients were excluded for hematologic indications. Hematologic indications were the 2nd most frequent medical indications for exclusion (trailing only hepatologic indications). The most common reason for hematologic exclusion was concern regarding thrombophilia. Nevertheless, 21 patients with evidence of possible thrombophilia proceeded to donor hepatectomy, and none incurred hematologic complications. Similarly, seven patients with screening findings concerning for increased bleeding risk (most often thrombocytopenia) underwent donor hepatectomy without hematologic complication. Three of 156 (2%) of patients who underwent donor hepatectomy incurred a hematologic complication (all thrombotic, none fatal). None of these patients had any evident hematologic risk factor on screening. CONCLUSION: This study underscores the difficulty of hematologic risk stratification among prospective living donors, however, suggests that some patients with relatively mild risk factors may be safe for donation.

The Efficacy of Etoposide-Based Therapy in Adult Secondary Hemophagocytic Lymphohistiocytosis.

Data supporting the use of etoposide-based therapy in hemophagocytic lymphohistiocytosis (HLH) arise largely from pediatric studies. There is a lack of comparable data among adult patients with secondary HLH. We conducted a retrospective study to assess the impact of etoposide-based therapy on outcomes in adult secondary HLH. The primary outcome was overall survival. The log-rank test was used to compare Kaplan-Meier distributions of time-to-event outcomes. Multivariable Cox proportional hazards modeling was used to estimate adjusted hazard ratios (HRs) with 95% confidence intervals (CIs). Ninety adults with secondary HLH seen between January 1, 2009, and January 6, 2020, were included. Forty-two patients (47%) received etoposide-based therapy, while 48 (53%) received treatment only for their inciting proinflammatory condition. Thirty-three patients in the etoposide group (72%) and 32 in the no-etoposide group (67%) died during follow-up. Median survival in the etoposide and no-etoposide groups was 1.04 and 1.39 months, respectively. There was no significant difference in survival between the etoposide and no-etoposide groups (log-rank p = 0.4146). On multivariable analysis, there was no association between treatment with etoposide and survival (HR for death with etoposide = 1.067, 95% CI: 0.633-1.799, p = 0.8084). Use of etoposide-based therapy was not associated with improvement in outcomes in this large cohort of adult secondary HLH patients.

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.

Safety, Efficacy, and Long-Term Outcomes of Anticoagulation in Cirrhotic Portal Vein Thrombosis.

BACKGROUND: The role of anticoagulation (AC) in the management of cirrhotic patients with portal vein thrombosis (PVT) remains unclear. AIMS: We conducted a retrospective study of cirrhotic patients diagnosed with PVT from 1/1/2000 through 2/1/2019, comparing those who received AC to those who did not. METHODS: Outcomes included rate of complete radiographic resolution (CRR) of PVT, recanalization of occlusive PVT (RCO), PVT extension, major bleeding, and overall survival (OS). The log-rank test was used to compare Kaplan-Meier distributions of time-to-event outcomes. Multivariable Cox-proportional-hazards modeling was used to estimate adjusted hazard ratios (HRs) with 95% confidence intervals. RESULTS: A total of 214 patients were followed for a median 27 months (IQR 12-48). Eighty-six patients (39%) received AC. AC was associated with significantly greater CRR (48% vs. 27%, p = 0.0007), (multivariable HR for CRR with AC; 2.49 (1.54-4.04, p = 0.0002)). AC was also associated with significantly greater RCO (69% vs. 28%, p = 0.0013), (multivariable HR for RCO with AC; 4.86 (1.91-12.37, p = 0.0009)). Rates of major bleeding were similar with and without AC (20% vs. 17%, p = 0.5207), multivariable HR for major bleeding with AC; 1.29 (0.68-2.46, p = 0.4423)). OS rates in the AC and no-AC groups were 83% and 70%, respectively (p = 0.1362), (HR for death with AC; 0.69 (0.38-1.28, p = 0.2441)). Among 75 patients who had CRR, 10 (13%) experienced recurrent PVT during follow-up (none were receiving AC at the time of recurrence). CONCLUSIONS: AC appears safe and effective for the treatment of cirrhotic PVT; however, prospective studies to confirm these findings and evaluate additional outcomes are needed.

The Impact of Socioeconomic Status on the Clinical Outcomes of COVID-19; a Retrospective Cohort Study.

There have been limited data assessing the influence of disadvantaged socioeconomic status (SES) on the incidence and clinical outcomes of COVID-19 patients within the diverse communities of the United States. Here, we aim to investigate the association between poverty level, as an indicator of SES, and COVID-19 related clinical outcomes including hospitalization and all-cause mortality. This retrospective cohort study included 3528 patients with laboratory confirmed COVID-19 seen at a large New York City health system between March 1, 2020 and April 1, 2020. Data for neighborhood level poverty was acquired from the American Community Survey 2014-2018 and defined as the percent of residents in each ZIP code whose household income was below the federal poverty threshold (FPT): 0% to < 20% below FPT (low poverty) and > 20% below FPT (high poverty). COVID-19 positive patients who resided in high poverty areas were significantly younger, had a higher prevalence of comorbidities and were more likely to be of female gender or a racial minority when compared to individuals living in low poverty areas. Residence in a high poverty area was not associated with an increased risk of COVID-19 related hospitalization and was found to be associated with a decreased risk of in-hospital mortality. This study suggests the existence of an unequal socioeconomic gradient in the demographic and clinical presentation of COVID-19 patients including differences in age, gender and race between poverty groups. Further studies are needed to fully assess the intersectionality of SES with the COVID-19 pandemic.

Modern management of splenomegaly in patients with myelofibrosis.

Myelofibrosis (MF) is a chronic myeloproliferative neoplasm which can lead to massive splenomegaly secondary to extramedullary hematopoiesis. Patients frequently exhibit debilitating symptoms including pain and early satiety, in addition to cellular sequestration causing severe cytopenias. JAK 1/2 inhibitors, such as ruxolitinib and fedratinib, are the mainstay of therapy and produce significant and durable reductions in spleen volume. However, many patients are not eligible for JAK 2 inhibitor therapy or become refractory to treatment over time. Novel therapies are in development that can reduce the degree of splenomegaly for some of these patients. However, splenectomy, splenic irradiation, and partial splenic artery embolization remain valuable therapeutic options in select patients. In this review, we will discuss currently available pharmacologic therapies and describe promising drugs currently in development. We will also delve into the efficacy and safety concerns of splenectomy, splenic irradiation, and partial splenic artery embolization. Finally, we will propose a treatment algorithm to help guide clinicians in the management of symptomatic splenomegaly in patients with MF.

Reevaluating the role of ferritin in the diagnosis of adult secondary hemophagocytic lymphohistiocytosis.

BACKGROUND: The standard diagnostic criteria for hemophagocytic lymphohistiocytosis (HLH) include hyperferritinemia to >500 ng/mL. This ferritin threshold is based on pediatric data, and evidence for its application among adults with secondary HLH is lacking. OBJECTIVE AND METHODS: We conducted a retrospective study assessing the relationship between extreme hyperferritinemia and adult secondary HLH at our institution. All adult inpatients seen over a 10-year period, with serum ferritin >5000 ng/mL, were included. RESULTS: Among 1055 patients with serum ferritin >5000 ng/mL, there were 69 cases of HLH (HLH prevalence of 6.5%). Mean ferritin among HLH patients was 70 398 ng/mL (SD 122 908), median 40 019 ng/mL (IQR 16 051-68 326). The prevalence of HLH only reached 50% as serum ferritin approached 90 000 ng/mL. A variety of conditions were contributory to hyperferritinemia, most commonly bacterial sepsis (33%), hematologic malignancy (29%), renal failure (24%), and liver injury (18%). The optimal cutoff ferritin for diagnosis of HLH was 16 000 ng/mL (sensitivity 79.4%, specificity 79.2%, PPV 20.9%, and NPV 98.2%). CONCLUSIONS: The threshold ferritin levels used in diagnostic criteria for adult secondary HLH are too low to be clinically relevant, and efforts should be undertaken to revise them upward. Similar reappraisals should be taken of the other criteria used to diagnose adult HLH.

Soluble interleukin-2 receptor (sIL-2r) level is a limited test for the diagnosis of adult secondary hemophagocytic lymphohistiocytosis.

BACKGROUND: Soluble interleukin-2 receptor (sIL-2r) level is used as a diagnostic tool in hemophagocytic lymphohistiocytosis (HLH). However, evidence supporting its use among adults is inadequate. OBJECTIVE AND METHODS: We conducted a retrospective study to assess the performance characteristics of sIL-2r for the diagnosis of adult HLH. RESULTS: One hundred thirty-two adults with sIL-2r levels sent for evaluation of HLH over a ten-year period were included. Sixty-five (49%) met criteria for HLH. Mean sIL-2r was significantly higher among patients with HLH relative to all patients without HLH (12942U/ml vs. 6308 U/mL, P = .00311). However, when comparing mean sIL-2r in the HLH group to those in the non-HLH group with primary diagnoses of hematologic malignancy (8911 U/mL), sepsis (7127 U/mL), and rheumatologic disease (4624 U/mL), no significant differences were found (P = .241, P = .178, and P = .0607, respectively). There was only weak correlation between sIL-2r and diagnosis of HLH (r = .253). The standard cutoff sIL-2r > 2400 U/ml yielded a sensitivity of 89.2% and specificity of 38.8%. The area under the curve for the corresponding receiver-operator curve was 0.691, consistent with a poor discriminating ability for the diagnosis of HLH. CONCLUSIONS: sIL-2r is a limited test for the diagnosis of adult secondary HLH, and its role in this setting should be reevaluated.

Portal vein thrombosis patients harboring JAK2V617F have poor long-term outcomes despite anticoagulation.

Non-cirrhotic portal vein thrombosis (ncPVT) most often occurs in the setting of intraabdominal proinflammatory processes. Less often, ncPVT may result from primary hematologic thrombophilia (most commonly JAK2V617F). Although these etiologic categories are pathophysiologically distinct, they are treated similarly using anticoagulation. We conducted a retrospective assessment of outcomes among ncPVT patients harboring JAK2V617F, and compared them to outcomes among patients with other etiologies for ncPVT, to determine whether anticoagulation alone is adequate therapy for JAK2V617F associated PVT. Outcomes were complete radiographic resolution (CRR) of PVT, recanalization (RC) of occlusive PVT, and development of significant portal hypertension (SPH). Three-hundred-thirty ncPVT patients seen between 1/2000 and 1/2019, including 37 harboring JAK2V617F (JAK2), 203 with other evident etiology (OE) for PVT, and 90 with no evident etiology (NE) for PVT followed for a median 29 months (53, 21, and 32 months respectively). Outcomes among the JAK2 cohort were dismal relative to the other groups. CRR rates were 8%, 31%, and 55% for the JAK2, NE, and OE cohorts respectively (multivariable HR JAK2:OE = 0.15 (0.05, 0.49), p = 0.0016). RC rates were 16%, 33%, and 49% for the JAK2, NE, and OE cohorts respectively (multivariable HR for RC JAK2:OE = 0.24 (0.09, 0.63), p = 0.0036). SPH rates were 49%, 32%, and 17% for the JAK2, NE, and OE cohorts respectively (multivariable HR for SPH JAK2:OE = 1.23 (0.62, 2.42), p = 0.5492). Given the strikingly poor outcomes among patients harboring JAK2V617F, anticoagulation alone does not appear to be adequate therapy for this cohort. Further investigation into thrombolysis and/or thrombectomy as an adjunct to anticoagulation is merited in this high-risk group.