Clinical experience with frontline Hyper-CVAD-based regimens, including Hyper-CVAD plus ponatinib, in patients with acute lymphoblastic leukemia treated at a comprehensive cancer center.

BACKGROUND: Hyper-CVAD is an established regimen for adult ALL that was developed at the MD Anderson Cancer Center (MDACC). However, results can vary across different institutions given the heterogeneity of patient populations and institutional practices. Moreover, while a MDACC study demonstrated that the combination of ponatinib plus hyper-CVAD produced remarkable activity in untreated Ph+ ALL, it remains to be externally validated. We sought to validate those findings in previously untreated adult patients with Ph+ ALL. METHODS: This was a retrospective study analyzing the outcomes of previously untreated adult ALL patients treated with hyper-CVAD, with a focus on Ph+ ALL patients treated with ponatinib plus hyper-CVAD. RESULTS: 82 patients were included. The median age was 51 years. The median follow-up was 2.62 years. The 5-year overall survival (OS) and event-free survival (EFS) were 39.5 % and 28.2 %, respectively. For Ph+ ALL patients (n = 13) receiving ponatinib plus hyper-CVAD, 3-year OS and EFS were both 92.3 %. Univariate analysis showed a high WBC and poor-risk cytogenetics to be associated with inferior outcomes, while CD20 + predicted favorable outcomes in B-ALL patients. On multivariate analysis, CD20 + retained significance for Philadelphia-negative (Ph-) ALL. For Ph+ ALL, ponatinib was associated with better OS and EFS on univariate and multivariate analysis. CONCLUSION: Our data supports the use of ponatinib plus hyper-CVAD as a standard of care regimen for Ph+ ALL. Our outcomes for Ph-ALL and T-cell ALL (T-ALL) show that advances are still needed in the frontline setting, and clinical trial enrollment is recommended.

A New High Affinity Hemoglobin Variant: Hb San Francisco-KP (HBB: c.104T>C).

The evaluation of erythrocytosis can fail to detect hemoglobin (Hb) variants if a thorough and systemic investigation is not undertaken. Here we report the identification of a novel high-oxygen affinity Hb that was previously misclassified as polycythemia vera (PV). Given that treatment recommendations can vary significantly based on the etiology of erythrocytosis, familiarity with reference laboratories and their methodologies is of crucial importance to conducting a precise consultation, as in the case of our Hb variant, named Hb San Francisco-KP [ß34(B16)Val→Ala, HBB: c.104T>C] for the city and medical center where it was discovered. The Mayo Clinic's (Rochester, MN, USA) Erythrocytosis Evaluation (REVE) panel was instrumental in establishing a final diagnosis. Of note, the patient's clinical response to phlebotomy distinguishes this subtype from many of the other high affinity Hbs where the erythrocytosis is primarily compensatory and not in need of venesection.

Atypical manifestations of coronavirus disease 2019 (COVID-19)-associated autoimmune thrombotic thrombocytopenic purpura.

Patients with coronavirus disease 2019 (COVID-19) infection can have various abnormal hematologic parameters. This report illustrates a case with unusual presentation of COVID-19-associated thrombotic thrombocytopenic purpura, in which the patient did not develop any typical respiratory signs or symptoms.

Splenectomy and the incidence of venous thromboembolism and sepsis in patients with autoimmune hemolytic anemia.

INTRODUCTION: The impact of splenectomy on venous thrombosis (VTE), abdominal thrombosis (abVTE) and sepsis in autoimmune hemolytic anemia (AIHA) is unclear. METHODS: Using the California Discharge Dataset 1991-2014, 4756 AIHA patients were identified. Cumulative incidences (CI) of VTE, abVTE, and sepsis were determined in patients with and without splenectomy. Using propensity score matching adjusted for competing risk of death, the association between VTE, abVTE and sepsis with splenectomy was determined. RESULTS: In those without splenectomy, the CIs of VTE, abVTE, and sepsis were 1.4%, 0.2%, and 4.3% respectively, compared to 4.4%, 3.0% and 6.7% with splenectomy. Splenectomy was associated with increased risk for VTE in immediate (HR 2.66, CI 1.36-5.23) and late (HR 3.29, CI 2.10-5.16) post-operative periods. AbVTE was increased in immediate post-operative period (HR 34.11, CI 4.93-236.11). Sepsis was only increased in late post-operative period (HR 2.20, CI 1.75-2.77). In multivariate models, older age, having >1 comorbidity and having VTE, abVTE, and sepsis were associated with increased mortality. Splenectomy was not associated with increased mortality. DISCUSSION: Splenectomy in AIHA was associated with significant early thrombotic risk and long-term morbidity. Future research should evaluate the role of splenectomy in AIHA patients, and potential long-term thrombotic and antibiotic prophylaxis.

Decreased early mortality associated with the treatment of acute myeloid leukemia at National Cancer Institute-designated cancer centers in California.

BACKGROUND: To the authors' knowledge, few population-based studies to date have evaluated the association between location of care, complications with induction therapy, and early mortality in patients with acute myeloid leukemia (AML). METHODS: Using linked data from the California Cancer Registry and Patient Discharge Dataset (1999-2014), the authors identified adult (aged ≥18 years) patients with AML who received inpatient treatment within 30 days of diagnosis. A propensity score was created for treatment at a National Cancer Institute-designated cancer center (NCI-CC). Inverse probability-weighted, multivariable logistic regression models were used to determine associations between location of care, complications, and early mortality (death ≤60 days from diagnosis). RESULTS: Of the 7007 patients with AML, 1762 (25%) were treated at an NCI-CC. Patients with AML who were treated at NCI-CCs were more likely to be aged ≤65 years, live in higher socioeconomic status neighborhoods, have fewer comorbidities, and have public health insurance. Patients treated at NCI-CCs had higher rates of renal failure (23% vs 20%; P = .010) and lower rates of respiratory failure (11% vs 14%; P = .003) and cardiac arrest (1% vs 2%; P = .014). After adjustment for baseline characteristics, treatment at an NCI-CC was associated with lower early mortality (odds ratio, 0.46; 95% confidence interval, 0.38-0.57). The impact of complications on early mortality did not differ by location of care except for higher early mortality noted among patients with respiratory failure treated at non-NCI-CCs. CONCLUSIONS: The initial treatment of adult patients with AML at NCI-CCs is associated with a 53% reduction in the odds of early mortality compared with treatment at non-NCI-CCs. Lower early mortality may result from differences in hospital or provider experience and supportive care. Cancer 2018;124:1938-45. © 2018 American Cancer Society.

Early mortality and complications in hospitalized adult Californians with acute myeloid leukaemia.

Few studies have evaluated the impact of complications, sociodemographic and clinical factors on early mortality (death ≤60 days from diagnosis) in acute myeloid leukaemia (AML) patients. Using data from the California Cancer Registry linked to hospital discharge records from 1999 to 2012, we identified patients aged ≥15 years with AML who received inpatient treatment (N = 6359). Multivariate logistic regression analyses were used to assess the association of complications with early mortality, adjusting for sociodemographic factors, comorbidities and hospital type. Early mortality decreased over time (25·3%, 1999-2000; 16·8%, 2011-2012) across all age groups, but was higher in older patients (6·9%, 15-39, 11·4%, 40-54, 18·6% 55-65, and 35·8%, >65 years). Major bleeding [Odds ratio (OR) 1·5, 95% confidence interval (CI) 1·3-1·9], liver failure (OR 1·9, 95% CI 1·1-3·1), renal failure (OR 2·4, 95% CI 2·0-2·9), respiratory failure (OR 7·6, 95% CI 6·2-9·3) and cardiac arrest (OR 15·8, 95% CI 8·7-28·6) were associated with early mortality. Higher early mortality was also associated with single marital status, low neighbourhood socioeconomic status, lack of health insurance and comorbidities. Treatment at National Cancer Institute-designated cancer centres was associated with lower early mortality (OR 0·5, 95% CI 0·4-0·6). In conclusion, organ dysfunction, hospital type and sociodemographic factors impact early mortality. Further studies should investigate how differences in healthcare delivery affect early mortality.

Inferior vena cava filters in patients with cancer and venous thromboembolism (VTE) does not improve clinical outcomes: A population-based study.

BACKGROUND: There are few studies that have determined clinical outcomes following inferior vena cava filter (IVCF) insertion in cancer patients hospitalized for acute deep-vein-thrombosis (DVT) or pulmonary embolism (PE). METHODS AND RESULTS: We analyzed hospital discharge records of all patients with active cancer who were admitted to a California hospital specifically for acute DVT or PE between 2005 through 2009. Propensity and competing risk methodology were used to determine if IVCF-use lowered either 30-day mortality or the risk of recurrent PE, DVT, and major bleeding within 180days. Among 14,000 patients, an IVCF was placed in 2747 (19.6%), but only 577 (21%) of these IVCF patients had an apparent indication for filter use because of acute bleeding or undergoing major surgery. Data on anticoagulation use was not available. Filter-use provided no reduction in either 30-day mortality (HR=1.12, 95% CI: 0.99-1.26, p=0.08) or the adjusted 180-day risk of subsequent PE (±DVT) (HR=0.81, 95% CI: 0.52-1.27, p=0.36). Filter use was, however, associated with an increase in the adjusted180-day risk of recurrent DVT (HR=2.10, 95% CI: 1.53-2.89, p<0.0001). CONCLUSIONS: We conclude that in this population-based study, approximately 20% of cancer patients with acute VTE received an IVCF, but only 21% of these had an indication for IVCF use. Overall, IVCF use provided neither a short-term survival benefit nor a reduction in risk of recurrent PE, but IVCF use was associated with a higher risk of recurrent DVT.

Inferior vena cava filters in patients with cancer and venous thromboembolism (VTE): patterns of use and outcomes.

BACKGROUND: Few studies have evaluated the use and outcomes of inferior vena cava filters (IVCF) insertion in cancer patients with deep venous thrombosis (DVT) or pulmonary embolism (PE). METHODS: Hospital records of patients with a principal diagnosis of lower extremity DVT and/or PE and cancer in California between January 1, 2005 and December 31, 2009 were analyzed. Multivariable logistic regression analysis was used to identify variables associated with IVCF use and propensity matched methodology was used to determine the effect of IVCF insertion on clinical outcomes. RESULTS: An IVCF was placed in 19.6% of 14,000 cancer patients and VTE. This varied widely across hospitals, from 0% to 52%, and by cancer type. The strongest predictors of IVCF use were a diagnosis of brain cancer (OR=4.6, CI: 3.7-5.6), undergoing major surgery (OR=4.9, CI: 3.9-6.1), and bleeding (OR=2.7, CI: 2.0-3.5). Only 21% of patients with IVCF had a strong contraindication to anticoagulation (bleeding or major surgery). There was no benefit for 30-day mortality and no reduction in subsequent PE (+/-DVT). Additionally, there was 60% increased risk of recurrent DVT and 20% increased risk of subsequent bleeding when an IVCF was placed. CONCLUSIONS: An IVCF was placed in approximately 20% of acute VTE patients with cancer and use varied widely between hospitals and cancer types. Most patients did not have a contraindication for anticoagulation. There was no benefit in short-term mortality or risk of PE; there was increased risk of DVT and subsequent bleeding.

Vena cava filter use in cancer patients with acute venous thromboembolism in California.

BACKGROUND: Few studies have evaluated the use of vena cava filters (VCF) in cancer patients with acute venous thromboembolism (VTE). METHODS: Hospital discharge records of patients who were admitted with a principal diagnosis of lower extremity deep-vein thrombosis or pulmonary embolism and cancer in California between January 1, 2005 and December 31, 2009 were analyzed. Multivariable logistic regression analysis was used to identify variables associated with VCF use. RESULTS: A VCF was placed in 2747 (19.6%) of 14,000 cancer patients. The percentage of patients treated with a VCF varied widely across hospitals, from 0% to 52% (mean=19.2%, median=17.2%), and by cancer type, ranging from 8% for lip/oral to 43% for brain. Using multivariable analysis, the strongest predictors of VCF use were a diagnosis of brain cancer (OR=4.6, CI: 3.7 -5.6), undergoing major surgery (OR=4.9, CI: 3.9 -6.1), and bleeding (OR=2.7, CI: 2.0-3.5). Other factors significantly associated with VCF insertion included hospital characteristics (larger, urban and private), and greater severity-of-illness at the time of admission. Only 1083 (7.7%) of patients had an absolute contraindication to anticoagulation (bleeding or surgery). CONCLUSIONS: A VCF was deployed in approximately 20% of acute VTE patients with cancer, but use varied widely between hospitals and cancer types. The strongest risk factors were undergoing surgery, active bleeding, and having brain cancer. Only 21% of VCF treated cancer patients had a strict contraindication to anticoagulation therapy. Further research is needed to determine if VCF use is of any benefit in cancer patients with acute VTE.

Biomarkers of tobacco smoke exposure and asthma severity in adults.

BACKGROUND: Tobacco biomarkers including serum cotinine and urinary 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) have been used in research settings. PURPOSE: The goal of the study was to examine the association of cotinine and NNAL with asthma outcomes in the U.S. adult population. METHODS: A cross-sectional design was used, using data from the National Health and Nutrition Examination Survey, 2007-2008, with participants aged >20 years with self-reported asthma (N=456). Past-year asthma exacerbations and emergency room/urgent care visits for asthma were examined. Analyses were conducted in 2013. RESULTS: Among adult asthmatics, 50.3% reported a past-year asthma attack (61.8% smokers, 46.6% nonsmokers, p=0.029). Among these, 24.7% reported a past-year emergency/urgent visit for asthma (34.7% smokers, 20.1% nonsmokers, p=0.034). Median concentrations of cotinine and creatinine-adjusted NNAL (NNAL/Cr) were significantly higher in those with a past-year asthma attack (0.43 ng/mL and 7.28 pg/mL) than in those without (0.06 ng/mL and 2.26 pg/mL), and highest in those with past-year emergency/urgent visits (0.93 ng/mL and 28.14 pg/mL). Among nonsmokers, increasing levels of log cotinine or log NNAL/Cr, adjusted for demographics, were significantly associated with past-year asthma exacerbation (log cotinine OR=1.46 [95% CI=1.1, 1.92]; log NNAL/Cr OR=1.42 [95% CI=1.07, 1.88]) and past-year emergency/urgent visit (log cotinine OR=1.95 [95% CI=1.32, 2.88]; log NNAL/Cr OR=1.58 [95% CI=1.23, 2.02]). Among smokers, increasing biomarker levels were not significantly associated with either outcome. CONCLUSIONS: In a population-based cross-sectional analysis, increased cotinine and NNAL were found to be associated with asthma exacerbation and healthcare use in nonsmokers with asthma. If these findings are confirmed in prospective studies, these biomarkers might be candidates for clinical indicators of risk of asthma.