Relapsed adult acute lymphoblastic leukemia (ALL) is associated with high reinduction mortality, chemotherapy resistance, and rapid progression leading to death. Vincristine sulfate liposome ...injection (VSLI), sphingomyelin and cholesterol nanoparticle vincristine (VCR), facilitates VCR dose-intensification and densification plus enhances target tissue delivery. We evaluated high-dose VSLI monotherapy in adults with Philadelphia chromosome (Ph) -negative ALL that was multiply relapsed, relapsed and refractory to reinduction, and/or relapsed after hematopoietic cell transplantation (HCT).
Sixty-five adults with Ph-negative ALL in second or greater relapse or whose disease had progressed following two or more leukemia therapies were treated in this pivotal phase II, multinational trial. Intravenous VSLI 2.25 mg/m(2), without dose capping, was administered once per week until response, progression, toxicity, or pursuit of HCT. The primary end point was achievement of complete response (CR) or CR with incomplete hematologic recovery (CRi).
The CR/CRi rate was 20% and overall response rate was 35%. VSLI monotherapy was effective as third-, fourth-, and fifth-line therapy and in patients refractory to other single- and multiagent reinduction therapies. Median CR/CRi duration was 23 weeks (range, 5 to 66 weeks); 12 patients bridged to a post-VSLI HCT, and five patients were long-term survivors. VSLI was generally well tolerated and associated with a low 30-day mortality rate (12%).
High-dose VSLI monotherapy resulted in meaningful clinical outcomes including durable responses and bridging to HCT in advanced ALL settings. The toxicity profile of VSLI was predictable, manageable, and comparable to standard VCR despite the delivery of large, normally unachievable, individual and cumulative doses of VCR.
Anemia is very commonly encountered in general clinical practice among all age groups. The more commonly used way to classify anemia has been to categorize it as being microcytic (mean corpuscular ...volume MCV <80 fL), normocytic (MCV 80-100 fL), or macrocytic (MCV >100 fL), which in turn allows for a more practical way to attempt to come up with a cause for any decrease in hemoglobin. Microcytic anemias are usually due to iron deficiency (in turn, a result of a number of different etiologies ranging from decreased intake, malabsorption, or blood loss), hemoglobinopathies (thalassemic syndromes), and some cases of severe anemia resulting from chronic disease. Normocytic anemia is often a result of anemia of chronic disease, hemolysis, or secondary to bone marrow failure. Macrocytic anemias are frequently caused by deficiencies of folic acid and/or Vitamin B12, exposure to toxic agents like drugs that interfere with DNA metabolism and alcohol, as also bone marrow failure states, such as from myelodysplastic syndrome. A comprehensive history, physical examination, and directed laboratory evaluation will help to identify a specific cause for anemia.
Biological and non-biological variables unrelated to acute myeloid leukemia (AML) preclude standard therapy in many settings, with "real world" patients under-represented in clinical trials and ...prognostic models. Here, using a case-based format, we illustrate the impact that socioeconomic and anthropogeographical constraints can have on optimally managing AML in 4 different healthcare systems. The granular details provided, emphasize the need for the development and targeting of socioeconomic interventions that are commensurate with the changing landscape of AML therapeutics, in order to avoid worsening the disparity in outcomes between patients with biologically similar disease.
Men with hemophilia were initially thought to be protected from cardiovascular disease (CVD), but it is now clear that atherothrombotic events occur. The primary objective of the CVD in Hemophilia ...study was to determine the prevalence of CVD and CVD risk factors in US older men with moderate and severe hemophilia and to compare findings with those reported in age-comparable men in the Atherosclerosis Risk in Communities (ARIC) cohort. We hypothesized if lower factor levels are protective from CVD, we would see a difference in CVD rates between more severely affected and unaffected men. Beginning in October 2012, 200 patients with moderate or severe hemophilia A or B (factor VIII or IX level ≤ 5%), aged 54 to 73 years, were enrolled at 19 US hemophilia treatment centers. Data were collected from patient interview and medical records. A fasting blood sample and electrocardiogram (ECG) were obtained and assayed and read centrally. CVD was defined as any angina, any myocardial infarction by ECG or physician diagnosis, any self-reported nonhemorrhagic stroke or transient ischemic attack verified by physicians, or any history of coronary bypass graft surgery or coronary artery angioplasty. CVD risk factors were common in the population. Compared with men of similar age in the ARIC cohort, patients with hemophilia had significantly less CVD (15% vs 25.8%; P < .001). However, on an individual patient level, CVD events occur and efforts to prevent cardiovascular events are warranted. Few men were receiving secondary prophylaxis with low-dose aspirin, despite published opinion that it can be used safely in this patient population.
•CV risk factors are common in older men with hemophilia.•Although older men with hemophilia have less CV disease than comparable unaffected men, CV events do occur and require treatment.
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Background:
Herediatry Hemorrhagic Telangiectasia (HHT), is also known as Osler-Weber-Rendu syndrome is an inherited familial disorder of vascular dysplasia with a variety of clinical manifestations ...including arteriovenous malformations of hepatic, pulmonary, cerebral circulation and with characteristic mucocutaneous telangiectasias. The underlying arteriovenous malformation may lead to recurrent and sometimes severe bleeding, of which epistaxis is the the most common. Excessive bleeding may in turn contribute to the development of severe iron deficiency anemia. Current management of excessive bleeding can be local therapy such as nasal cauterization versus systemic treatment in the form of iron infusions, red blood cell transfusions and angiogenesis inhibitors. Currently, there is no cure for HHT. Despite screening measures, most patients with HHT are unaware of their diagnosis. The incidence of HHT has also been subject to under-reporting. Currently, the United States lacks a formal registry for pateints with HHT. Other countries have initiated a registry to understand HHT in their institution. Given the significant morbidity associated with HHT, the purpose of this single institution, multidisciplinary study is to understand the prevelance and clinical characteristics of HHT and thus facilitate better treatment measures and continuity of care for patients with HHT.
Methods:
A retrospective study was made of all patients diagnosed with HHT at our institution from 2008 to 2014. Epidemilogical data, presence or absence of first degree relatives with HHT, visceral involvement, severity of epistaxis using a validated epistaxis severity scoring system, genetic testing for ENG or ACVRL1 gene mutation, and current local or systemic treatment were evaluated.
Results:
27 patients ranging from age of 11 to 78 years were diagnosed as HHT. Median age was 52. 15 patients were male and 12 patients were female. 6 pateints had ENG gene mutation and 1 patient had ACVRL1 gene mutation. 3 out of 6 patients with ENG gene mutation did not have significant iron deficiency anemia. 11 patients had more than one first degree relative with HHT. All patients had symptoms of epistaxis. 8 patients had more than 1 visceral involvement with gastrointestinal and pulmonary manifestations being the most common. 11 patients had pulmonary arteriovenous malformations, 4 had cerebral arteriovenous malformations, and 8 had gastrointestinal manifestaions. Majority of patients had nasal cauterization to control their nasal bleeding. Of the local treatments, 1 patient used intranasal bevacizumab. Of the systemic treatments, 1 patient used estrogen and 1 used tamoxifen and 1 used thalidomide. 8 patients received intravenous iron therapy with significant improvement in their symptoms. 7 patients has multiple red blood cell transfusions. The most common discipline to evaluate patients with HHT was otolaryngology, hematology and genetics department.
Conclusion:
This is the first single institution, multidisciplinary registry created to decribe the occurrence of HHT in our institution and to identify and understand the clinical presentation of HHT. This data will help improve better screening measures, diagnosis, treatment options and improve clinical care and outcomes for patients with HHT in our institution and also help facilitate a future multicenter registry.
No relevant conflicts of interest to declare.
Background:
The incidence of coronary artery disease is increasing in hemophilia patients as their life expectancy improves. However, there are limited evidence-based studies available, and most ...current guidelines for antiplatelet therapy in patients with hemophilia are largely based on expert opinions. The assessment of benefit and risk of using antiplatelet therapy in these patients remains a clinical challenge.
Aim:
This study reports our institution's clinical outcome of patients with inherited hemophilia who underwent antiplatelet therapy for percutaneous coronary intervention in the last 10 years.
Methods:
Retrospective chart review from a single hospital for 10 calendar years of patients with inherited hemophilia A or B and a diagnosis of coronary artery disease who received oral antiplatelet agents.
Results:
See data Table 1 below.
Conclusions:
The usage of antiplatelet therapy for coronary artery disease as well as dual-antiplatelet therapy post percutaneous coronary intervention in patients with Hemophilia A or B carries a realistic risk of bleeding. However, outside of one patient with traumatic laceration of the liver, we did not identify any life threatening bleeding events in our patients who were placed on antiplatelet therapy. Since all subjects had no more than mild to moderate factor deficiency, it would be important to see how patients with severe deficiency would do on such therapy. Further studies are needed in the future to provide evidence and clarify the overall risk versus benefit of antiplatelet therapy in hemophilia patients with coronary artery disease.
No relevant conflicts of interest to declare.
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