SARS-CoV-2 vaccination and ITP in patients with de novo or preexisting ITP.

Cases of de novo immune thrombocytopenia (ITP), including a fatality, following SARS-CoV-2 vaccination in previously healthy recipients led to studying its impact in preexisting ITP. In this study, 4 data sources were analyzed: the Vaccine Adverse Events Reporting System (VAERS) for cases of de novo ITP; a 10-center retrospective study of adults with preexisting ITP receiving SARS-CoV-2 vaccination; and surveys distributed by the Platelet Disorder Support Association (PDSA) and the United Kingdom (UK) ITP Support Association. Seventy-seven de novo ITP cases were identified in VAERS, presenting with median platelet count of 3 [1-9] ×109/L approximately 1 week postvaccination. Of 28 patients with available data, 26 responded to treatment with corticosteroids and/or intravenous immunoglobulin (IVIG), and/or platelet transfusions. Among 117 patients with preexisting ITP who received a SARS-CoV-2 vaccine, 19 experienced an ITP exacerbation (any of: ≥50% decline in platelet count, nadir platelet count <30 × 109/L with >20% decrease from baseline, and/or use of rescue therapy) following the first dose and 14 of 70 after a second dose. Splenectomized persons and those who received 5 or more prior lines of therapy were at highest risk of ITP exacerbation. Fifteen patients received and responded to rescue treatment. In surveys of both 57 PDSA and 43 UK patients with ITP, prior splenectomy was associated with worsened thrombocytopenia. ITP may worsen in preexisting ITP or be identified de novo post-SARS-CoV2 vaccination; both situations responded well to treatment. Proactive monitoring of patients with known ITP, especially those postsplenectomy and with more refractory disease, is indicated.

Rivaroxaban for Thromboprophylaxis in High-Risk Ambulatory Patients with Cancer.

BACKGROUND: Ambulatory patients receiving systemic cancer therapy are at varying risk for venous thromboembolism. However, the benefit of thromboprophylaxis in these patients is uncertain. METHODS: In this double-blind, randomized trial involving high-risk ambulatory patients with cancer (Khorana score of ≥2, on a scale from 0 to 6, with higher scores indicating a higher risk of venous thromboembolism), we randomly assigned patients without deep-vein thrombosis at screening to receive rivaroxaban (at a dose of 10 mg) or placebo daily for up to 180 days, with screening every 8 weeks. The primary efficacy end point was a composite of objectively confirmed proximal deep-vein thrombosis in a lower limb, pulmonary embolism, symptomatic deep-vein thrombosis in an upper limb or distal deep-vein thrombosis in a lower limb, and death from venous thromboembolism and was assessed up to day 180. In a prespecified supportive analysis involving the same population, the same end point was assessed during the intervention period (first receipt of trial agent to last dose plus 2 days). The primary safety end point was major bleeding. RESULTS: Of 1080 enrolled patients, 49 (4.5%) had thrombosis at screening and did not undergo randomization. Of the 841 patients who underwent randomization, the primary end point occurred in 25 of 420 patients (6.0%) in the rivaroxaban group and in 37 of 421 (8.8%) in the placebo group (hazard ratio, 0.66; 95% confidence interval [CI], 0.40 to 1.09; P = 0.10) in the period up to day 180. In the prespecified intervention-period analysis, the primary end point occurred in 11 patients (2.6%) in the rivaroxaban group and in 27 (6.4%) in the placebo group (hazard ratio, 0.40; 95% CI, 0.20 to 0.80). Major bleeding occurred in 8 of 405 patients (2.0%) in the rivaroxaban group and in 4 of 404 (1.0%) in the placebo group (hazard ratio, 1.96; 95% CI, 0.59 to 6.49). CONCLUSIONS: In high-risk ambulatory patients with cancer, treatment with rivaroxaban did not result in a significantly lower incidence of venous thromboembolism or death due to venous thromboembolism in the 180-day trial period. During the intervention period, rivaroxaban led to a substantially lower incidence of such events, with a low incidence of major bleeding. (Funded by Janssen and others; CASSINI ClinicalTrials.gov number, NCT02555878.).

Phase 2 study of efgartigimod, a novel FcRn antagonist, in adult patients with primary immune thrombocytopenia.

Primary immune thrombocytopenia (ITP) is an acquired autoimmune bleeding disorder, characterized by a low platelet count (<100 × 109 /L) in the absence of other causes associated with thrombocytopenia. In most patients, IgG autoantibodies directed against platelet receptors can be detected. They accelerate platelet clearance and destruction, inhibit platelet production, and impair platelet function, resulting in increased risk of bleeding and impaired quality of life. Efgartigimod is a human IgG1 antibody Fc-fragment, a natural ligand of the neonatal Fc receptor (FcRn), engineered for increased affinity to FcRn, while preserving its characteristic pH-dependent binding. Efgartigimod blocks FcRn, preventing IgG recycling, and causing targeted IgG degradation. In this Phase 2 study, 38 patients were randomized 1:1:1 to receive four weekly intravenous infusions of either placebo (N = 12) or efgartigimod at a dose of 5 mg/kg (N = 13) or 10 mg/kg (N = 13). This short treatment cycle of efgartigimod in patients with ITP, predominantly refractory to previous lines of therapy, was shown to be well tolerated, and demonstrated a favorable safety profile consistent with Phase 1 data. Efgartigimod induced a rapid reduction of total IgG levels (up to 63.7% mean change from baseline), which was associated with clinically relevant increases in platelet counts (46% patients on efgartigimod vs 25% on placebo achieved a platelet count of ≥50 × 109 /L on at least two occasions, and 38% vs 0% achieved ≥50 × 109 /L for at least 10 cumulative days), and a reduced proportion of patients with bleeding. Taken together, these data warrant further evaluation of FcRn antagonism as a novel therapeutic approach in ITP.

A Retrospective Study of the Combination of Rituximab, Cyclophosphamide and Dexamethasone for the Treatment of Relapsed/Refractory Warm Antibody Autoimmune Hemolytic Anemia.

The combination of rituximab, cyclophosphamide, and dexamethasone (RCD) is highly effective in the treatment of warm autoimmune hemolytic anemia (WAIHA) associated with chronic lymphocytic leukemia (CLL). We treated a cohort of patients with relapsed/refractory WAIHA, without CLL, with RCD. The primary objective was to evaluate the overall response (OR) of RCD therapy. Complete response (CR) was defined as a hemoglobin (Hgb) ≥12 g/dL. Partial response (PR) was defined as Hgb 10-11.9 g/dL or ≥2 g/dL increase in Hgb. Sustained response was defined as Hgb ≥10 g/dL with no treatment changes. A total of 16 patients with relapsed/refractory WAIHA received RCD (7 primary WAIHA, 9 secondary WAIHA) for a median of 4 cycles (range: 2-6). The median pretreatment Hgb was 10.0 g/dL (range: 4.3-12.2). The median best Hgb achieved was 12.5 g/dL (range: 10.6-15.1) with a median of 2 cycles until best Hgb response. The OR was 94% (11 CR, 4 PR). Two immunocompromised patients were admitted for infections during RCD treatment. There were no deaths during the treatment or follow-up period. Following a response to RCD, 4 patients received noncorticosteroid immune modulation therapy and 4 patients continued on corticosteroid therapy. Seven patients received no additional treatment.

Ethnic and racial difference in Helicobacter pylori infection in patients with immune thrombocytopenia treated at a major urban medical center.

Immune thrombocytopenia (ITP) is an autoimmune disorder with a complex immunopathology and pathogenesis characterized by thrombocytopenia and bleeding manifestations. The disorder is separated into primary (idiopathic) ITP and secondary ITP, when associated with other immune or lymphoproliferative disorders and certain chronic infections. Helicobacter pylori (H. pylori) is a recognized bacterial cause of ITP. In regions with high prevalence of infection, bacterial eradication has resulted in improvement in platelet count. However, the prevalence of H. pylori infection and response to antimicrobial therapy in North American ITP patients is reportedly low. We evaluated the prevalence of H. pylori infection in ITP patients diagnosed and treated at a large urban medical center. Eighty-two patients were screened for H. pylori, by stool antigen (n = 54), H. pylori breath test (n = 11), and H. pylori antibodies (n = 16), of which 15 (18.3%) were white non-Hispanic (WNH), 55 (67%) Hispanic (H), 8 (9.8%) Asian (A), and 4 (4.9%) African-American (AA). Of the screened patients, 36/82 (43.9%) tested positive for H. pylori. The prevalence of H. pylori infection within the represented ethnic groups was 2/15 (13%) WNH, 29/55 (52.7%) H, 3/8 (37.5%) A, and 2/4 (50%) AA. There was a significant difference in prevalence of infection comparing WNH and H patients (p = 0.007). There were 36 treated patients, with H. pylori eradication documented in 26 patients. Fifteen of the 26 patients were evaluable for response with 8 of 15 (53%) having clinical responses, 6 complete responses, and 2 partial responses. Our study demonstrates an increased prevalence of H. pylori infection in the Hispanic ITP population with a reasonable platelet response among patients with H. pylori eradication.

Predictors of Venous Thromboembolism and Early Mortality in Lung Cancer: Results from a Global Prospective Study (CANTARISK).

BACKGROUND: Patients with lung cancer are known to be at increased risk for venous thromboembolism (VTE). Venous thromboembolism is associated with increased risk for early mortality. However, there have been no studies performing a comprehensive assessment of risk factors for VTE or early mortality in lung cancer patients undergoing systemic chemotherapy in a global real-world setting. MATERIALS AND METHODS: CANTARISK is a prospective, global, noninterventional cohort study including patients with lung cancer initiating a new cancer therapy. Clinical data were collected until 6-month follow-up. The impact of patient-, disease-, and treatment-related factors on the occurrence of VTE and early mortality was evaluated in univariable and multivariable Cox regression analyses. A previously validated VTE risk score (VTE-RS) was also calculated (also known as Khorana score). RESULTS: Of 1,980 patients with lung cancer who were enrolled from 2011 to 2012, 84% had non-small cell lung cancer. During the first 6 months, 121 patients developed a VTE (6.1%), of which 47% had pulmonary embolism, 46% deep vein thrombosis, 3% catheter-associated thrombosis, and 4% visceral thrombosis. Independent predictors for VTE included female sex, North America location, leg immobilization, and presence of a central venous catheter. The VTE-RS was not significantly associated with VTE in either univariable or multivariable analysis in this population. During the study period, 472 patients died, representing 20%, 24%, 36%, and 25% with VTE-RS 1, 2, ≥3, or unknown, respectively (p < .0001). Significant independent predictors of early mortality include older age, current/former smoking, chronic obstructive pulmonary disease, Eastern Cooperative Oncology Group performance status ≥2, no prior surgery, and metastatic disease, as well as the VTE-RS. CONCLUSION: In this global, prospective, real-world analysis, several demographic, geographic, and clinical factors are independent risk factors for VTE and early mortality in patients with lung cancer. The VTE-RS represents a significant independent predictor of early mortality but not for VTE in lung cancer in the era of targeted therapy. IMPLICATIONS FOR PRACTICE: Multiple risk factors for both venous thromboembolism (VTE) and early mortality in patients with lung cancer receiving systemic chemotherapy should guide best practice by better informing clinical evaluation and treatment decision-making. The Khorana risk score is of value in assessing the risk of early all-cause mortality along with other clinical parameters in patients with lung cancer receiving systemic therapy. Further study is needed to fully evaluate the validity of the risk score in predicting the risk of VTE in the modern era of lung cancer therapy.

Comparison of two dosing schedules for subcutaneous injections of low-dose anti-CD20 veltuzumab in relapsed immune thrombocytopenia.

We compared two dosing schedules for subcutaneous injections of a low-dose humanized anti-CD20 antibody, veltuzumab, in immune thrombocytopenia. Fifty adults with primary immune thrombocytopenia, in whom one or more lines of standard therapy had failed and who had a platelet count <30×109/L but no major bleeding, initially received escalating 80, 160, or 320 mg doses of subcutaneous veltuzumab administered twice, 2 weeks apart; the last group received once-weekly doses of 320 mg for 4 weeks. In all dose groups, injection reactions were transient and mild to moderate; there were no other safety issues. Forty-seven response-evaluable patients had 23 (49%) objective responses (platelet counts ≥30×109/L and ≥2 × baseline) including 15 (32%) complete responses (platelets ≥100×109/L). Responses (including complete responses) and bleeding reduction occurred in all dose groups and were not dose-dependent. In contrast, response duration increased progressively with total dose, reaching a median of 2.7 years with the four once-weekly 320-mg doses. Among nine responders retreated at relapse, three at higher dose levels responded again, including one patient who was retreated four times. In all dose groups, B-cell depletion occurred after the first dose until recovery starting 12 to 16 weeks after treatment. Veltuzumab serum levels increased with dose group according to total dose administered, but terminal half-life and clearance were comparable. Human anti-veltuzumab antibody titers developed without apparent dose dependence in nine patients, of whom six responded including five who had complete responses. Subcutaneous veltuzumab was convenient, well-tolerated, and active, without causing significant safety concerns. Platelet responses and bleeding reduction occurred in all dose groups, and response durability appeared to improve with higher doses. Clinicaltrials.gov identifier: NCT00547066.

Life-threatening delayed hyperhemolytic transfusion reaction in a patient with sickle cell disease: effective treatment with eculizumab followed by rituximab.

BACKGROUND: Hyperhemolysis in sickle cell disease is a rare and potentially life-threatening complication of transfusion. STUDY DESIGN AND METHODS: In this article we report a case of delayed hemolytic transfusion reaction with resultant hyperhemolysis triggered by an anti-IH autoantibody with alloantibody behavior. RESULTS: The anti-IH was reactive at room temperature as well as 37 °C, but only weakly reactive with autologous red blood cells. Initial cold agglutinin titer was 512. The profound, life-threatening, intravascular hemolysis was rapidly and dramatically reduced with the Complement 5 (C5) inhibitory antibody, eculizumab. The auto/allo cold agglutinin was subsequently suppressed with rituximab treatment. CONCLUSIONS: Eculizumab, a potent C5 inhibitory antibody, can be a rapid and effective therapy for hyperhemolytic transfusion reactions when given in a sufficient dose to fully block the activation of complement C5.

Approach to the management of incidental venous thromboembolic events in patients with cancer.

Venous thromboembolism (VTE) is a frequent clinical complication of cancer and its treatment. Although much of the epidemiologic data regarding this complication have been based on symptomatic events, the use of multidetector row CT scanner technology has led to increased identification of VTE on scans ordered primarily for staging or restaging of malignancy. These incidentally discovered VTEs are variously referred to in the literature as incidental, asymptomatic, unexpected, or unsuspected VTE. A recent guidance paper by the Hemostasis and Malignancy Subcommittee of the International Society on Thrombosis and Haemostasis provided recommendations regarding this terminology (now termed incidental) and reporting of incidental VTE for clinical trials. A growing number of retrospective and case-controlled reports have described the prevalence, prognostic implications, and treatment options for these incidentally discovered VTE events, and have reported similar clinical outcomes for patients with incidental and symptomatic VTE. Because most reported patients with incidental VTE have been treated in a manner similar to those with symptomatic events, the present recommendations, except in rare circumstances, support the use of standard anticoagulation in the management of incidental deep vein thrombosis and pulmonary embolism.

Low-dose anti-CD20 veltuzumab given intravenously or subcutaneously is active in relapsed immune thrombocytopenia: a phase I study.

Low doses of the humanized anti-CD20 monoclonal antibody, veltuzumab, were evaluated in 41 patients with immune thrombocytopenia (ITP), including 9 with ITP ≤1 year duration previously treated with steroids and/or immunoglobulins, and 32 with ITP >1 year and additional prior therapies. They received two doses of 80-320 mg veltuzumab 2 weeks apart, initially by intravenous (IV) infusion (N = 7), or later by subcutaneous (SC) injections (N = 34), with only one Grade 3 infusion reaction and no other safety issues. Thirty-eight response-assessable patients had 21 (55%) objective responses (platelet count ≥30 × 10(9) /l and ≥2 × baseline), including 11 (29%) complete responses (CRs) (platelet count ≥100 × 10(9) /l). Responses (including CRs) occurred with both IV and SC administration, at all veltuzumab dose levels, and regardless of ITP duration. Responders with ITP ≤1 year had a longer median time to relapse (14·4 months) than those with ITP >1 year (5·8 months). Three patients have maintained a response for up to 4·3 years. SC injections resulted in delayed and lower peak serum levels of veltuzumab, but B-cell depletion occurred after first administration even at the lowest doses. Eight patients, including 6 responders, developed anti-veltuzumab antibodies following treatment (human anti-veltuzumab antibody, 19·5%). Low-dose SC veltuzumab appears convenient, well-tolerated, and with promising clinical activity in relapsed ITP.(Clinicaltrials.gov identifier: NCT00547066.).

Prediction and prevention of thromboembolic events with enoxaparin in cancer patients with elevated tissue factor-bearing microparticles: a randomized-controlled phase II trial (the Microtec study).

Elevated levels of circulating tissue factor-bearing microparticles (TFMP) have been associated with an increased risk of developing venous thromboembolism (VTE) in cancer patients. We performed a randomized phase II study to evaluate the cumulative incidence of VTE in advanced cancer patients with lower levels of TFMP not receiving thromboprophylaxis and those with higher levels of circulating TFMP randomized to enoxaparin or observation. The cumulative incidence of VTE at 2 months in the higher TFMP group randomized to enoxaparin (N = 23) was 5·6% while the higher TFMP group observation arm (N = 11) was 27·3% (Gray test P = 0·06). The cumulative incidence of VTE in the low TFMP was 7·2% (N = 32). No major haemorrhages were observed in the enoxaparin arm. The median survival for patients with higher levels of TFMP followed by observation was 11·8 months compared with 17·8 months on enoxaparin (P = 0·58). In a prospective randomized trial, increased numbers of circulating TFMP detected by impedance flow cytometry identified cancer patients with a high incidence of VTE. Enoxaparin demonstrated a clear trend towards reducing the rate of VTE in patients with elevated levels of TFMP, with an overall rate of VTE similar in magnitude to the lower TFMP group.

Predictive model of venous thromboembolism in endometrial cancer.

OBJECTIVE: To profile characteristics and survival of endometrial cancer patients who develop venous thromboembolism (VTE) and to establish a predictive model of VTE in endometrial cancer. METHODS: Cases were identified using an institutional database between 2000 and 2011. VTE was correlated to clinico-pathological information and survival outcomes. Frequency and odds ratio (OR) of VTE were examined in a predictive model based on combination patterns of independent risk factors for VTE. RESULTS: VTE was seen in 42 (8.1%, 95% CI 5.8-10.5) out of 516 cases subsequent to the diagnosis of endometrial cancer. Multivariate analysis identified 4 independent risk factors for VTE: elevated CA-125 (hazard ratio [HR] 5.38, p<0.001), extrauterine disease (HR 2.87, p=0.019), thrombocytosis (HR 2.11, p=0.04), and high risk histology (serous and clear cell, HR 2.09, p=0.049). VTE was the strongest variable for decreased progression-free survival (HR 4.28) and the second strongest variable for decreased overall survival (HR 5.65) in multivariate analysis. In a predictive model of VTE, the presence of multiple risk factors was associated with significantly increased risk of VTE: frequency of VTE, 1.4% if no risk factors, 0-9.3% (OR 1.0-4.2) if a single risk factor, 11.1-25.0% (OR 9.0-24.0) if two risk factors, and 42.9-46.2% (OR 54.0-61.7) if ≥3 risk factors. CONCLUSION: VTE represents a surrogate for aggressive disease in endometrial cancer. Multiple risk factors of VTE in our predictive model demonstrated exceedingly high risk of VTE, suggesting that there may be a certain population of endometrial cancer patients who would benefit from long-term anti-coagulant prophylaxis to improve survival outcome.

Rilzabrutinib versus placebo in adults and adolescents with persistent or chronic immune thrombocytopenia: LUNA 3 phase III study.

Background: Immune thrombocytopenia (ITP) is characterized by primarily autoantibody-mediated platelet destruction and impaired platelet production resulting in thrombocytopenia and an increased risk of bleeding. Other manifestations include increased risk of thrombosis and diminished quality of life. Current treatment approaches are directed toward lowering the rate of platelet destruction or stimulating platelet production to prevent bleeding. Rilzabrutinib is an oral, reversible, potent Bruton tyrosine kinase inhibitor that was specifically designed to treat immune-mediated diseases and mediates its therapeutic effect through a dual mechanism of action: (1) inhibiting B-cell activation and (2) interrupting antibody-coated cell phagocytosis by Fc gamma receptor in spleen and liver. A 24-week dose-finding phase I/II study of rilzabrutinib in patients with ITP showed a 40% platelet response (⩾2 consecutive platelet counts of ⩾50 × 109/L and increase from baseline ⩾20 × 109/L without rescue medication use) and a well-tolerated safety profile with only grade 1/2 transient adverse events across dose levels. Objectives: Assess the efficacy and safety of oral rilzabrutinib in adult and adolescent patients with persistent or chronic ITP. Design: Rilzabrutinib 400 mg BID is being evaluated in the ongoing LUNA 3 multicenter, double-blind, placebo-controlled phase III study. Methods and analysis: The primary endpoint is durable platelet response, defined as achieving platelet counts of ⩾50 × 109/L for at least two-thirds of ⩾8 available weekly scheduled platelet measurements during the last 12 weeks (including ⩾2 available measurements within the last 6 weeks) of the 24-week blinded treatment period in the absence of rescue therapy. Ethics: Ethical guidelines and informed consent are followed. Discussion: The LUNA 3 trial will further investigate rilzabrutinib's safety and efficacy in adult and adolescent patients, with the primary goal of addressing a major objective in treating patients with ITP: durability of platelet response. Trail Registration: ClinicalTrials.gov NCT04562766: https://clinicaltrials.gov/ct2/show/NCT04562766; EU Clinical Trials Register EudraCT 2020-002063-60: https://www.clinicaltrialsregister.eu/ctr-search/search?query=2020-002063-60.

The ITP syndrome: pathogenic and clinical diversity.

Immune thrombocytopenia (ITP) is mediated by platelet autoantibodies that accelerate platelet destruction and inhibit their production. Most cases are considered idiopathic, whereas others are secondary to coexisting conditions. Insights from secondary forms suggest that the proclivity to develop platelet-reactive antibodies arises through diverse mechanisms. Variability in natural history and response to therapy suggests that primary ITP is also heterogeneous. Certain cases may be secondary to persistent, sometimes inapparent, infections, accompanied by coexisting antibodies that influence outcome. Alternatively, underlying immune deficiencies may emerge. In addition, environmental and genetic factors may impact platelet turnover, propensity to bleed, and response to ITP-directed therapy. We review the pathophysiology of several common secondary forms of ITP. We suggest that primary ITP is also best thought of as an autoimmune syndrome. Better understanding of pathogenesis and tolerance checkpoint defects leading to autoantibody formation may facilitate patient-specific approaches to diagnosis and management.

Corticosteroid overuse in adults with immune thrombocytopenia: Cause for concern.

Corticosteroids remain a crucial component of first-line therapy for immune thrombocytopenia (ITP) due to low cost, high initial response rates, and acceptable short-term tolerability. However, extended and recurrent use of corticosteroids is associated with substantial toxicity. Survey studies indicate that >95% of patients with ITP treated with corticosteroids report adverse effects, more than one-third of whom require reduction or discontinuation of treatment. In light of the heavy treatment burden of prolonged corticosteroid exposure, clinical practice guidelines recommend limiting corticosteroid treatment to no more than 6 weeks in adults with ITP receiving initial therapy. For patients who require subsequent therapy, clinical practice guidelines recommend treatments more suitable for long-term disease control such as thrombopoietin receptor agonists, rituximab, other immune-modulating medications, or splenectomy, rather than repeated courses of corticosteroids. Despite these recommendations, real-world evidence suggests that corticosteroids remain the most frequently used treatment for adults with ITP, not only in the first line, but also in the second and third line. In this review, we summarize evidence on the efficacy, safety, and tolerability of corticosteroids; discuss the problem of overuse; and suggest strategies for curtailing the excessive use of corticosteroids in adults with ITP.

Understanding Immune Thrombocytopenia: Looking Out of the Box.

The pathogenesis of immune thrombocytopenia (ITP) is increasingly being elucidated, and its etiology is becoming more frequently identified, leading to a diagnostic shift from primary to secondary ITP. The overlap between autoimmunity, immunodeficiency, and cancer is evident, implying more interdisciplinarity in daily care. This mini-review is based on an expert meeting on ITP organized by the Intercontinental Cooperative ITP Study Group and presents the challenges of hematologists in understanding and investigating "out of the box" concepts associated with ITP.

Tapering thrombopoietin receptor agonists in primary immune thrombocytopenia: Expert consensus based on the RAND/UCLA modified Delphi panel method.

BACKGROUND: Thrombopoietin receptor agonists (TPO-RAs) are used to treat primary immune thrombocytopenia (ITP). Some patients have discontinued treatment while maintaining a hemostatic platelet count. OBJECTIVES: To develop expert consensus on when it is appropriate to consider tapering TPO-RAs in ITP, how to taper patients off therapy, how to monitor patients after discontinuation, and how to restart therapy. METHODS: We used a RAND/UCLA modified Delphi panel method. Ratings were completed independently by each expert before and after a meeting. Second-round ratings were used to develop the panel's guidance. The panel was double-blinded: The sponsor and nonchair experts did not know each other's identities. RESULTS: Guidance on when it is appropriate to taper TPO-RAs in children and adults was developed based on patient platelet count, history of bleeding, intensification of treatment, trauma risk, and use of anticoagulants/platelet inhibitors. For example, it is appropriate to taper TPO-RAs in patients who have normal/above-normal platelet counts, have no history of major bleeding, and have not required an intensification of treatment in the past 6 months; it is inappropriate to taper TPO-RAs in patients with low platelet counts. Duration of ITP, months on TPO-RA, or timing of platelet response to TPO-RA did not have an impact on the panel's guidance on appropriateness to taper. Guidance on how to taper patients off therapy, how to monitor patients after discontinuation, and how to restart therapy is also provided. CONCLUSION: This guidance could support clinical decision making and the development of clinical trials that prospectively test the safety of tapering TPO-RAs.

Venous Thromboembolism Prophylaxis and Treatment in Patients With Cancer: ASCO Clinical Practice Guideline Update.

PURPOSE: To provide updated recommendations about prophylaxis and treatment of venous thromboembolism (VTE) in patients with cancer. METHODS: PubMed and the Cochrane Library were searched for randomized controlled trials (RCTs) and meta-analyses of RCTs published from August 1, 2014, through December 4, 2018. ASCO convened an Expert Panel to review the evidence and revise previous recommendations as needed. RESULTS: The systematic review included 35 publications on VTE prophylaxis and treatment and 18 publications on VTE risk assessment. Two RCTs of direct oral anticoagulants (DOACs) for the treatment of VTE in patients with cancer reported that edoxaban and rivaroxaban are effective but are linked with a higher risk of bleeding compared with low-molecular-weight heparin (LMWH) in patients with GI and potentially genitourinary cancers. Two additional RCTs reported on DOACs for thromboprophylaxis in ambulatory patients with cancer at increased risk of VTE. RECOMMENDATIONS: Changes to previous recommendations: Clinicians may offer thromboprophylaxis with apixaban, rivaroxaban, or LMWH to selected high-risk outpatients with cancer; rivaroxaban and edoxaban have been added as options for VTE treatment; patients with brain metastases are now addressed in the VTE treatment section; and the recommendation regarding long-term postoperative LMWH has been expanded. Re-affirmed recommendations: Most hospitalized patients with cancer and an acute medical condition require thromboprophylaxis throughout hospitalization. Thromboprophylaxis is not routinely recommended for all outpatients with cancer. Patients undergoing major cancer surgery should receive prophylaxis starting before surgery and continuing for at least 7 to 10 days. Patients with cancer should be periodically assessed for VTE risk, and oncology professionals should provide patient education about the signs and symptoms of VTE.Additional information is available at www.asco.org/supportive-care-guidelines.

Recognizing and treating secondary immune thrombocytopenic purpura associated with lymphoproliferative disorders.

Immune thrombocytopenic purpura (ITP), a condition of low platelets, can occur from primary causes, often referred to as idiopathic thrombocytopenic purpura, or secondary to an underlying disease, such as an autoimmune disorder or an infection. Secondary ITP can also occur with lymphoproliferative malignancies, such as chronic lymphocytic leukemia (CLL), Hodgkin's disease (HD), and non-Hodgkin's lymphomas (NHL). ITP associated with lymphoproliferative disorders has the same mechanism of platelet destruction as in idiopathic or primary ITP. The current treatment paradigm for secondary ITP varies according to the underlying condition. Standard treatments for primary ITP, which include corticosteroids, intravenous immunoglobulin (IVIg), anti-D, and splenectomy, are often successful in secondary ITP. However, in most situations with secondary ITP, treatment should focus on resolving the underlying disorder before treating the shortage of platelets, and, in the circumstances of ITP developing in patients with lymphoproliferative disorders, responses are frequently linked to remission of the primary malignancy.