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.
Introduction
Risk stratification in Multiple Myeloma according to cytogenetic abnormalities has been utilized clinically to guide understanding of prognosis. Specific cytogenetics abnormalities such ...as deletion 17p, t(14,16) and t(4,14) have been associated with more aggressive disease and poor outcome1. It has been postulated that genetic aberrations evolve in a temporal pattern in non-hyperploid multiple myeloma such that 13q deletion and t14q32 tend to be early events while chromosome 1 and 17 abnormalities occur as later events 2. Furthermore, other studies have suggested higher frequencies of high risk cytogenetic abnormalities (such as deletion 17p and gain of 1q) at relapse after upfront autologous stem cell transplant 3. Our study examined the cytogenetic profile of patients treated at a tertiary health system at the time of diagnosis and at first relapse, irrespective of bone marrow transplant and treatment
Methods
This is a retrospective study of patients treated at Henry Ford Cancer Institute/Henry Ford Health System. Subjects were adults diagnosed with multiple myeloma with relapse confirmed by a bone marrow biopsy between January 2014 and January 2019. The cytogenetic profile at time of diagnosis and relapse for each patient was reviewed. Exclusion criteria included history or current diagnosis of another malignancy. 145 cases were identified, of which 112 cases were excluded: 19 cases with plasmacytoma but no bone marrow relapse, 32 with other malignancy, 21 with relapse before study period, 5 with relapse after study period, and 35 with bone marrow biopsy or cytogenetics not available for review. As such, we analyzed the remaining 33 cases
Results
26 of the 33 cases underwent a bone marrow transplant. A third of the patients (11) developed new mutations, which included 17p deletion (3), 13q deletion (1), chromosome 1 abnormality (1), new trisomies (5), t(11,14) (4), hypoploidy (1), and IgH/CCDN1 changes (1).
Conclusion
Though cytogenetic evolution in multiple myeloma has been studied, not all patients undergo a bone marrow biopsy and cytogenetic evaluation at relapse, which limits this assessment. Despite our sample size being limited as a majority of the study population did not have cytogenetics recorded at relapse, our study reveals that new mutations can arise in a significant proportion of patients at relapse, some of which are known to be associated with poor prognosis. This can be potentially prognostic, as presence of new high-risk mutations could alter the presumed disease trajectory, and these could also have therapeutic consequences. While further studies with a larger sample size are needed to determine the frequencies of each mutation, our study underscores the importance of dedicated monitoring of cytogenetics at each relapse in multiple myeloma.
References
1.Palumbo, A., et al., Revised International Staging System for Multiple Myeloma: A Report From International Myeloma Working Group. J Clin Oncol, 2015. 33(26): p. 2863-9.2.Jimenez-Zepeda, V.H., E. Braggio, and R. Fonseca, Dissecting karyotypic patterns in non-hyperdiploid multiple myeloma: an overview on the karyotypic evolution. Clin Lymphoma Myeloma Leuk, 2013. 13(5): p. 552-8.3.Merz, M., et al., Longitudinal fluorescence. Haematologica, 2017. 102(8): p. 1432-1438.
No relevant conflicts of interest to declare.
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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9016 Background: The aim ofour study was to explore the characteristics, aspirations, and factors influencing career choices among adult Hematology/Oncology (HO) fellows, as well as their ...post-fellowship perspectives. Methods: An anonymous 25-question survey was distributed online to adult HO fellowship programs in the United States. The survey collected data on demographics, educational background, career plans, and specific factors influencing career choices. Results: Of the 56 fellows completing the survey, 54% identified as male, and 46% as female. The majority were White (40%), followed by Asian (34%), Middle Eastern (12%), Hispanic (7%), and Black (3%). Most fellows (79%) were aged 30-34 years, and 68% were MD graduates of US/Caribbean schools. A significant proportion expressed certainty (80%) during residency about pursuing adult HO as a career. Thirty eight percent of the respondents planned to practice both hematology and Oncology. While 39% hoped to work in an academic/university setting, 41% planned to stay within the community. Geographically, 45% preferred suburban, and 39% urban areas. Only 3% of respondents had plans to pursue a career in classical hematology. Factors influencing career choice included clinical interest in the field (98%), previous research experience in HO (54%), career mentorship (70%), lifestyle considerations (66%), and perceived job market (60%) (Table). Almost all respondents (97%) expressed a high likelihood of pursuing adult HO fellowship if they had to choose again. Fellows were confident about finding positions aligned with their interests, including clinical (72%), providing research opportunities (43%), and those offering intellectual stimulation (73%). While the majority were confident in achieving work-life balance (84%), 16% expressed some concerns. Conclusions: This study offers valuable insights into the factors influencing career choices among adult HO fellows. The findings emphasize the necessity of adjusting strategies to align with the evolving needs and aspirations of prospective fellows. Key initiatives could include fortifying career mentorship programs, providing increased support for those interested in classical hematology, fostering research experiences during residency training, and actively promoting a diverse and inclusive environment. Understanding these aspects and results is crucial for program directors, educators, and policymakers to optimize training programs and support the diverse needs of future practitioners in the field. Table: see text
9015 Background: We aimed to investigate the timing and influence of factors behind career choices in hematology and medical oncology, assess levels of job satisfaction, and identify factors ...contributing to professional retention and the prevention of attrition. Methods: An anonymous survey with 13 questions was distributed to practicing hematologists and oncologists who were members of the American Society of Clinical Oncology and/or American Society of Hematology. The respondents encompassed diverse areas of primary focus within the field, varied practice settings, and all geographical regions. Results: Out of 423 respondents, 66% were male and 32% female. The majority identified as White (69%), followed by Asian (19%), Middle Eastern (4%), Hispanic (3%), and Black (1%). Most were practicing either Medical Oncology (43%) or combined Hematology/Oncology (36%), with 46% working in an academic/university setting and 57% located in an urban region. In terms of timing, about a third had decided on their career choice in medical school, with the majority of the remaining having decided by residency. While most of those surveyed were practicing in the area they had hoped to, about one-sixth (17.5%) appeared to be working in an area they hadn't planned on. Most said they would choose their current profession again (67% definitely yes, 24% likely yes). Science and academic interest (81%) ranked the highest when combining the top two responses for factors influencing choice, followed by mentor influence (47%), with work/life balance (19%) and financial considerations (6%) being less frequently cited. Satisfaction levels were generally high across key dimensions (Table), with intellectual fulfillment receiving the highest satisfaction (63.1% very satisfied, 26% satisfied). Importantly, better work/life balance (37% respondents), fewer non-medical tasks (35%), and a higher salary (20%) were key considerations to deter professional attrition. Conclusions: This study offers valuable insights into the career perspectives of Hematologists and Medical Oncologists, providing a foundation for developing strategies for career development and retention initiatives within the specialty. Efforts should be undertaken to enhance participation from different minorities within Hematology/Oncology and physicians practicing Classical Hematology to identify specific support and retention needs for these areas. Table: see text
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.
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