scholarly journals Cerebral Sinovenous Thrombosis in Greek Children: A Single Centre Experience

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4251-4251
Author(s):  
Athina Dettoraki ◽  
Aikaterini Michalopoulou ◽  
Maria Gavra ◽  
Loukia Ioannidou ◽  
Zoey Kapsimali ◽  
...  
Keyword(s):  
Risk Factors ◽  
Otitis Media ◽  
Oral Contraceptives ◽  
Research Funding ◽  
Sigmoid Sinus ◽  
Categorical Variables ◽  
Homogeneity Test ◽  
Cerebral Sinovenous Thrombosis ◽  
Sinovenous Thrombosis

Abstract Introduction: Cerebral sinovenous thrombosis (CSVT) in children is a rare, often underdiagnosed but serious event. The risk factors in children include head or neck infections, prothrombotic agents such as oral contraceptives and a chronic systemic illness. In the present study, we aimed to investigate the clinical manifestations, neuroimaging findings, risk factors and treatment of children suffering from CSVT in a reference paediatric centre for thrombosis. In addition, we assessed outcomes after CSVT. Methods: Data were retrospectively collected for children with CSVT, referred between 2010 and 2020 to our hospital. There were 103 children that were used as controls concerning thrombophilic factors. The categorical variables were described by frequency distributions and compared with x2-homogeneity test. Results: Sixty-five patients were included in the study (58% males). The mean age of the children at the time of diagnosis was 6.2 years (SD 4 years, range 1 month to 16 years). The most common presenting symptoms were headache (43%), decreased consciousness (32%), vomiting (12%), seizures (15%), diplopia (6%) and torticollis (5%). Papilloedema was found in 14 children (21.5%) and intracerebral haemorrhage in one. The most frequent risk factors were infections (74%), mainly acute otitis media with or without mastoiditis (55% και 19% respectively) and chronic medical conditions, such as polycythemia vera, nephrotic syndrome, arteriovenous malformation, ulcerative colitis-3% each. The use of oral contraceptives was not documented. For the diagnostic evaluation MRI/Magnetic Resonance Venography was performed in 72.3% of children. CT was diagnostic in 24.6% of patients and one infant underwent Power Doppler Ultrasound. Thrombosis was detected in 46% of children on left side, in 34% on right side and in 20% bilaterally. The deep venous system (straight venous, vein of Galen, transverse and sigmoid sinus, jugular veins) was more commonly affected (75%). Notably, sigmoid sinus thrombosis (40%) was predominantly involved, followed by transverse (31%), while extension to ipsilateral jugular vein occurred in 32%. Multiple sinus involvement was found in 64% of patients. Interestingly, simultaneous localization in the transverse and sigmoid sinuses had an increased probability of being accompanied by papilloedema (p <0.05). Venous infarctions were noticed in two children, while one child with hypoplastic venous sinus had an abdominal peritoneal CNS drain. Laboratory investigations for prothrombotic risk factors were available for all patients. One or more prothrombotic risk factor were found in 18 of the 65 (28%) children. To be more accurate, heterozygosity for FVLeiden and FII20210A mutations were found in 8% and 5% of patients, respectively and homozygosity for MTHFR-C776T in 15% (without raised homocysteine). Thrombophilic factors did not attain statistically significant results, apart from a trend for heterozygosity for FVLeiden and FII20210A mutations in patients (in controls 5% and 3% respectively). All patients received anticoagulation (68% coumarin anticoagulants, 32% Low Molecular Weight Heparin) for a mean duration of 7.5 ±3.3 months and 18.8 ±32.4 months respectively, while 7 children still receive anticoagulation. The duration of anticoagulation therapy was based on clinical outcome and follow-up investigations. No patient developed hemorrhagic events during the therapy. Follow-up imaging studies were available in most of the children. Six children showed no recanalization on 3.5 ±0.5 months, 19 children showed partial recanalization on 5±3 months and 20 children showed complete recanalization on 7± 5 months. No child died or had persisting neurological sequelae, apart from signs of attention deficit disorder, during a median follow-up of 4±3 years. One patient underwent remission of thrombosis in other site (pulmonary emboli) in adulthood. Conclusions: Physicians should be suspicious of CSVT in children with otitis media/mastoiditis or chronic diseases, when referred for headache or other neurological signs. In a quarter of the cases a thrombophilic factor had eventually some contribution to the event. Longer follow-up may reveal the incidence of cognitive or behavioral disabilities due to CSVT. Disclosures Kattamis: Novartis: Consultancy, Honoraria, Research Funding; CRISPR/Vertex: Consultancy, Honoraria; Chiesi: Honoraria; BMS/Celgene: Consultancy, Honoraria, Research Funding; Agios Pharmaceuticals: Consultancy; IONIS: Consultancy; VIFOR: Consultancy; Amgen: Consultancy.

scholarly journals The Burden of Atrial Fibrillation in Sickle Cell Disease

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3119-3119
Author(s):  
Chinonso Ukeje ◽  
Bahaa Al-Azzam ◽  
Santosh L. Saraf ◽  
Dawood Darbar ◽  
David Tofovic
Keyword(s):  
Risk Factors ◽  
Life Expectancy ◽  
Board Of Directors ◽  
Research Funding ◽  
Observation Time ◽  
Hemoglobin Level ◽  
Categorical Variables ◽  
Cell Disease ◽  
Advisory Committees

Abstract Introduction Life expectancy amongst individuals with sickle cell disease (SCD) has plateaued, with cardiopulmonary complications now becoming a leading cause of death (Fitzhugh et al. Am. J. Hematology 2010). Indeed, SCD is associated with increased rates of pulmonary hypertension (pHTN) and diastolic dysfunction (Sachdev et al. Blood 2005). In the general population, atrial fibrillation (AF) is associated with an increased mortality in the setting of either pHTN or diastolic dysfunction. Although cardiac structural and biochemical changes likely create an electrophysiological substrate for AF in SCD, the prevalence and risk factors for AF in SCD remain unclear. We determined the prevalence, incidence, and clinical characteristics of AF in a large cohort of patients with SCD. Methods We conducted a retrospective, longitudinal cohort study of all adult patients with SCD seen at our large, urban single center from January 2008 to December 2017. SCD patients were identified using a previously described semi-automated system with a subset with direct chart review (Srisuwananukorn et al. Blood Advances 2020). We performed manual review of ~17,000 available electrocardiograms of all enrolled subjects to look for AF. For univariate analyses, the associations of linear and categorical variables with AF were assessed using the Kruskal-Wallis test and Pearson's χ 2 test, respectively. We used Bonferroni correction for categorical variables with greater than two groups. Logistic regression analysis with stepwise addition of variables (p>0.15) was used to evaluate for the effects of previously described AF risk factors, degree of anemia, hydroxyurea use, and genotype on AF development. Results Our cohort consisted of 763 adult SCD patients with a median age of 27.95 years, 59.50% female, 72.4% with Hb SS or Sβ 0-thalassemia genotype, and 61.2% were prescribed hydroxyurea. Mean observation time for the cohort was 8.3 ± 6.3 yrs. We identified AF in 30 out of 763 adult SCD individuals with a mean age onset of 51 ± 10 years (median age 52 years). The period prevalence of AF was 3.93% and the incidence density was 3.02 per 1000 patient years observed. Individuals with AF tended to be older at initial (40 vs. 25 years, p<0.0001) and follow-up (53 vs. 35 years, p<0.0001) visits and were observed for a longer period (13.3 vs. 9.5 years, p=0.0014). There was no difference in gender (p=0.7), ethnicity (p=0.5), or SCD genotype (p=0.03) between groups (see Table 1). Those with AF were more likely to carry diagnoses of chronic obstructive pulmonary disease (p=0.0004), hypertension (p<0.0001), chronic kidney disease (p<0.0001), type 2 diabetes (p<0.0001), and any cancer (p=0.04). However, hydroxyurea use was not associated with AF development (p=0.3). SCD patients with AF were more likely to receive diuretics, atrioventricular nodal blocking agents, antihypertensives, antiplatelets, and statin therapies (see Table 1). AF was associated with worse anemia and reduced renal function. Regression analysis identified significant odds ratios (ORs) for age at initial visit (OR 1.06, p=0.03), serum creatinine per 1 mg/dL increase (OR 2.34, p=0.02), hemoglobin level per 1 g/dL increase (OR 0.52, p=0.0009), fetal hemoglobin level per 1% increment (OR 0.81, p=0.008), and total observation time per year follow up (OR 1.26, p=0.0006). Conclusion We showed that the prevalence and incidence of AF is high in patients with SCD with the median age of onset occurring 1-2 decades earlier than in the general populace (Feinberg et al. JAMA Internal Medicine 1995). AF in patients with SCD is associated with advanced age, worse renal function, a higher degree of anemia, and greater usage of cardio- and nephro-active medications. The high incidence of AF in patients with SCD may contribute to the plateauing of life expectancy and identifying the causative risk factors and the underlying mechanisms may not only improve life expectancy but also the quality of life. Further study is warranted. Figure 1 Figure 1. Disclosures Saraf: Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Research Funding.

scholarly journals Neonatal Cerebral Sinovenous Thrombosis: A Rare Case Report and Literature Review

2020 ◽  
Vol 5 (2) ◽  
Keyword(s):  
Risk Factors ◽  
Early Recognition ◽  
Brain Mri ◽  
Correct Diagnosis ◽  
Anticoagulation Therapy ◽  
Brain Magnetic Resonance Imaging ◽  
Neurological Deficits ◽  
Cerebral Sinovenous Thrombosis ◽  
Sinovenous Thrombosis

Neonatal cerebral sinovenous thrombosis is a rare and potentially life-threatening disorder associated with various longterm neurological deficits. The pathogenesis of cerebral sinovenous thrombosis in neonates is still unclear. Many potential risk factors have been identified, such as gestational or delivery complications or neonatal comorbid conditions including dehydration, sepsis, or cardiac defects. A correct diagnosis is often delayed due to the subtle presentation of the disorder, leading to delayed treatment with poor outcomes. Herein, we report a preterm female neonate who was born only with the presentation of intrapartum maternal fever. Routine brain sonography showed intraventricular hemorrhage. In a further study, brain magnetic resonance imaging revealed neonatal multiple sinovenous thrombosis. To prevent potential thrombosis development and ameliorate possible thrombosis-related problems, the infant immediately received anticoagulation therapy. At the 3-month follow-up, developmental milestones were within the normal range, and the follow-up brain MRI scans also showed normal results. In conclusion, early recognition and proper treatment may yield a better prognosis for neonatal cerebral sinovenous thrombosis, especially when patients exhibit any possible risk factors, which should alert healthcare professionals.

Mortality and Morbidities During Long-Term Follow-up After Recovery From Thrombotic Thrombocytopenic Purpura (TTP)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 362-362 ◽  
Author(s):  
Jessica A. Reese ◽  
Zayd L. Al-Nouri ◽  
Cassandra C. Deford ◽  
Lauren M. Stewart ◽  
Deirdra R. Terrell ◽  
...  
Keyword(s):  
Risk Factors ◽  
Clinical Trial ◽  
Relative Frequency ◽  
Research Funding ◽  
Population Data ◽  
Term Survival ◽  
The Us ◽  
Initial Episode

Abstract Abstract 362 Introduction Since recovery from an acute episode of TTP is typically assumed to be complete, subsequent survival has been commonly assumed to be normal except for the risk of death with relapse. However we have observed unexpectedly high mortality among patients in the Oklahoma TTP-HUS Registry who had recovered from their initial episode of TTP. Therefore we documented long-term survival and compared the mortality of our patients to the US population data. To investigate possible risk factors for increased mortality, we documented the frequency of common risk factors for poor health outcomes: abnormal renal function, increased body mass index (BMI), hypertension (HTN) and diabetes (DM). Methods We included all 68 Oklahoma TTP-HUS Registry patients whose initial episode was associated with severe ADAMTS13 deficiency (<10%), 1995–2010. Health outcome measures for renal function were glomerular filtration rate (GFR) and urine albumin-creatinine ratio (ACR). BMI and HTN and DM preceding TTP were documented at the time of the initial episode. HTN, DM, GFR, and ACR were documented on patients who survived their initial episode at the time of their last follow-up. HTN and DM were documented by the use of regularly prescribed medication. GFR was estimated by the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation. ACR was quantified on a random urine sample. Population data were obtained from the National Health and Nutrition Examination Survey (NHANES); we calculated expected proportions based on the age, race, and gender composition of our patient group. We used survival data analysis to compare the mortality of the patients to the U.S. population; we used one way chi-square to compare the relative frequency of BMI, GFR, ACR, HTN and DM of the patients to the expected proportions from the US population. Results Fifty-five of the 68 consecutive patients survived their initial episode of TTP. At the time of their initial episode, the median age of the 55 patients was 39 years (range 9–71); 44 (80%) were women; 20 (36%) were black. Median follow-up to August 1, 2012 was 9.5 years (range, 2.3–16.7 years). At the time of their initial episode, BMI was significantly greater than the US population (p<0.001); in 15 (27%) of the 55 patients, BMI was >40 kg/m2, indicating morbid obesity. Although the relative frequency of hypertension (16%) and diabetes (9%) was not different from the US population preceding the initial episode of TTP, the relative frequencies were significantly greater than the US population at the time of their last follow-up (hypertension, 47%, p<0.001; diabetes, 22%, p=0.003). The GFR (measured in all 55 patients) and ACR (measured in 37 patients) were not different from the US population (p=0.374 and p=0.053). Nineteen (35%) patients have had 1–4 subsequent episodes of TTP. Eleven (20%) of the 55 patients have died (median age at death, 51 years; range, 41–82), a mortality proportion significantly greater than the age/race/gender matched U.S. population (Table). Two of the 11 patients died during their first relapse. Although relapsed TTP was not an apparent cause of death in the remaining 9 patients, 2 deaths were sudden and unexpected; 7 followed prolonged illnesses: congestive heart failure/myocardial infarction (3), sepsis (2), respiratory failure, ovarian cancer. Conclusion Long-term survival after recovery from an acute episode of TTP is significantly less than the age/race/gender-matched US population. Although relapse contributes to increased mortality, the significantly increased relative frequency of hypertension and diabetes are important and previously unrecognized risk factors for poor health outcomes in TTP survivors. Disclosures: Terrell: Baxter, Inc.: Consultancy; Amgen, Inc.: Consultancy. Kremer Hovinga:Baxter Healthcare: Consultancy, Research Funding. George:Alexion, Inc.: Consultancy; Baxter, Inc.: Consultancy; Amgen, Inc.: Consultancy, PI for clinical trial involving romiplostim, PI for clinical trial involving romiplostim Other, Research Funding.

Obesity and Hepatitis B Infection and Risk Of Primary CNS Lymphoma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4298-4298
Author(s):  
Chia-Ching J. Wang ◽  
Paige M Bracci ◽  
James L. Rubenstein
Keyword(s):  
Risk Factors ◽  
Hepatitis B ◽  
Research Funding ◽  
Hbv Infection ◽  
Cns Lymphoma ◽  
High Dose ◽  
Hepatitis B Infection ◽  
Dose Methotrexate ◽  
Hep B

Abstract Introduction The incidence of primary central nervous system lymphoma (PCNSL) has markedly increased during the past three decades. Advanced HIV disease, as well as congenital and iatrogenic immunodeficiency states are the only established risk factors. While the incidence of PCNSL continues to rise among older patients (>60), the vast majority of newly-diagnosed PCNSL patients are not overtly immune suppressed. The goal of this study is to identify novel risk factors for PCNSL that may explain the continued rise in incidence among non-HIV infected, immunocompetent populations. Methods A cohort of 72 HIV-negative patients diagnosed with primary and secondary CNS lymphoma who received ambulatory follow-up evaluation at University of California at San Francisco between 2009-2013 were frequency-matched to Bay Area population-based controls by age-group, sex and race with 1:4 case:control ratio. We regarded HBsAg positivity at baseline as evidence of chronic HBV infection, and HBcAb positivity at baseline as prior HBV infection. Body mass index (BMI) was modeled as normal (reference,<25), overweight (25-30) and obese (30+). Multivariable unconditional logistic regression was used to compute odds ratios (OR) as estimates of relative risk. Models were adjusted for matching factors and statistical significance was based on a two-sided p<0.05. Having been born in a country with a high prevalence of HBV was assessed as a potential confounder. Results 64 patients with PCNSL were identified. Among these, 28 (44%) were male, 69% Caucasian, median age at diagnosis was 61.5 years, 6 (10%) died during the follow-up period, and 7 (11%) had intraocular involvement. HBV infection (chronic or prior) and increased BMI were independently associated with increased risk of PCNSL; HBV infection: OR=14.8 (5.0-44), p<0.0001; BMI: obese vs. normal, OR=2.8 (1.2-6.5), p for trend=0.04. There was no evidence of confounding and no statistical interaction between HBV and BMI (p=0.72). HCV positivity also was assessed but analysis was constrained as only 3 patients were HCV antibody positive (1 also HBV positive). Results from descriptive analyses of intraocular involvement provided some evidence that these PCNSL patients were more likely to have been born in a country with moderate/high HBV prevalence (chi-square p=0.006). Obese PCNSL patients were statistically significantly younger (median age 54) than other patients (overweight median age 64.5, normal 63). Interestingly the Asian patients were younger (median age 57) than Caucasian (median age 62). Hep B patients were older (median age 66) compared with non Hep B (median age 56) but the difference was not statistically significant. All PCNSL patients were treated with high dose methotrexate-based systemic chemotherapy. 37 (58%) were determined to be in complete remission at the end of the follow-up period. For B-cell PCNSL patients who were treated with high-dose methotrexate (n=55), those who were obese had improved progression-free survival (PFS) compared to non-obese (P<0.04; HR 0.3). In contrast, a history of hepatitis B infection was associated with shorter PFS (P=0.04; HR 2.7). Notably, the apparent risk factors of obesity and/or hepatitis B impact approximately half of the 55 non-HIV-infected PCNSL patients in this analysis. Conclusions We believe this to be the first report of associations among obesity, hepatitis B infection and PCNSL. These findings may partly explain the increasing incidence of this subtype of NHL. We hypothesize that both hepatitis B infection as well as obesity may each promote inflammatory states that contribute to CNS lymphomagenesis. Further studies are warranted to confirm these findings and to explore underlying mechanisms of pathogenesis. Supported by Leukemia and Lymphoma Society and NIH R01CA139-83-01A1. Disclosures: Rubenstein: Genentech: Research Funding; Celgene: Research Funding.

Antithrombotic Treatment and Outcomes of Splanchnic Vein Thrombosis in an International Prospective Registry: Results of 2-Year Follow-up

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 592-592
Author(s):  
Walter Ageno ◽  
Nicoletta Riva ◽  
Sam Schulman ◽  
Jan Beyer-Westendorf ◽  
Soo-Mee Bang ◽  
...  
Keyword(s):  
Risk Factors ◽  
Major Bleeding ◽  
Research Funding ◽  
Bleeding Events ◽  
Primary Analysis ◽  
Vascular Events ◽  
Vein Thrombosis ◽  
Cirrhotic Patients

Abstract Background: Little information is available on the long-term clinical outcome of patients with splanchnic vein thrombosis (SVT). We aimed to assess incidence rates of bleeding, recurrence, and mortality in a large prospective cohort of SVT patients after a 2-year follow-up. Methods: Consecutive SVT patients were enrolled in a multicenter international registry, from 2008 to 2012. Information was gathered on baseline characteristics, risk factors and therapeutic strategies. Clinical outcomes (major bleeding; vascular events, defined as venous or arterial thrombosis, and mortality) during follow-up were collected and reviewed by a Central Adjudication Committee. Major bleeding was defined using the ISTH definition plus the need for hospitalization. The primary analysis was performed up to the first adjudicated major bleeding or thrombotic event. Results: 604 patients from 31 centers were enrolled in this study, 21 (3.5%) were lost to follow-up. Median follow-up duration was 2 years (IQR 1-2). Median age was 54 years (range 16-85); 62.6% were males. Most common risk factors were liver cirrhosis in 27.8% of patients and solid cancer in 22.3%. Portal vein was the most common site of thrombosis. 139 patients were not anticoagulated; 175 received parenteral anticoagulants only (median duration 5.8 months, IQR 3-12) and 290 were started on vitamin K antagonists (median duration 24 months, IQR 7-24). According to the primary analysis, 103 events occurred during follow-up: 35 major bleeding events (3.8/100 patient-years [pt-y]; 95%CI, 2.7-5.2), 2 of which were fatal bleeding, and 68 thrombotic events (7.3/100 pt-y; 95%CI 5.8-9.3), 9 of which were vascular deaths. All-cause mortality occurred in 106 patients (10.3/100 pt-y; 95% CI 8.5-12.5). The incidence of major bleeding events was 4.0/100 pt-y in patients on anticoagulant drugs and 3.4/100 pt-y in patients not receiving anticoagulants. The incidence of vascular events was 5.6/100 pt-y and 9.7/100 pt-y, respectively. Major bleeding and vascular event rates were highest in cirrhotic patients (10.0/100 pt-y and 11.3/100 pt-y, respectively), and lowest in the subgroup of non-malignant non-cirrhotic patients (1.8/100 pt-y and 5.6/100 pt-y, respectively). Conclusions: SVT patients have a non-negligible long-term risk of both bleeding and thrombotic events, but this risk varies according to the pathogenesis of SVT. Anticoagulant treatment is associated with a reduced incidence of thrombotic events without apparently resulting in an increased risk of bleeding. Funding: The study was funded by a grant from Pfizer Canada to ISTH Disclosures Ageno: Bayer Healthcare: Research Funding. Schulman:Bayer HealthCare: Consultancy, Honoraria, Research Funding; Boehringer Ingelheim: Consultancy, Honoraria, Research Funding. Beyer-Westendorf:Bayer: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Boehringer: Honoraria, Research Funding.

scholarly journals Low Bone Mass and Osteoporosis in Hispanic Acute Lymphoblastic Leukemia Survivors. Is It a Real Problem ?

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 5015-5015
Author(s):  
Alfonso Orozco ◽  
Juan Rangel-Patiño ◽  
Mayra Valdez-Carrizales ◽  
Roberta Demichelis
Keyword(s):  
Risk Factors ◽  
Bone Mineral Density ◽  
Acute Lymphoblastic Leukemia ◽  
Bone Mass ◽  
Bone Mineral ◽  
Research Funding ◽  
Lymphoblastic Leukemia ◽  
Mineral Density ◽  
High Prevalence

Abstract Introduction: The survival rates in children and adolescent or young adults with acute lymphoblastic leukemia (ALL) have improved in the last decades. Cancer survivors can have reduced bone mineral density (BMD) related both to the underlying disease and the treatment. This can persist for up to 20 years, increasing the risk of osteopenia / osteoporosis and the development of fractures that can generate disability and loss of function. The risk factors for the development of disorders of BMD in the adult ALL survivors has been little studied and there are no formal guideline recommendations on the long-term follow-up and treatment of these patients. We evaluated ALL-survivor patients in Mexico; both ALL and osteoporosis are more prevalent in Hispanic patients, therefore we implemented conducting a dual-energy x-ray absorptiometry (DXA) during follow-up. Primary objective: Our main objective was to know the prevalence of alterations in bone mineral density (BMD) in a cohort of Hispanic ALL-survivors. Secondary objectives: To identify risk factors and the incidence of complications associated with BMD alterations. Methods: An observational, case-control study in a cohort of adult ALL survivors with follow-up at a referral center´s acute leukemia clinic in Mexico City. We include patients with more than one year of elective cessation of treatment in whom a DXA was performed as the routine follow-up for survivors. We compared the characteristics of the cases (patients with alterations in BMD) with the controls (patients without alterations in BMD). We define alterations in BMD by the WHO and the International Society of clinical DXA: the term of low BMD was used for younger patients and osteoporosis/osteopenia for older. Results: 61 ALL survivors were identified, 86.9% had B-Cell ALL and 13.1% T-Cell ALL. The median age at diagnosis was 12 years (1-55 years) and at the time of the study, 27 years (20-69 years). The majority (78.8%) had less than 18 years-old at diagnosis. The median follow-up from treatment cessation to densitometry was 142 months (10-499 months). An alteration in BMD was found in 63.9% of the patients: 84.6% were classified as low BMD for age and 15.4% as osteopenia/osteoporosis. The most frequently affected site was the spine (40%) followed by the hip and spine (32.5%) and the hip (10%). The median T-score and Z-score by area are shown in Table 1. Table 2 shows the characteristics of ALL-survivors with or without alterations in BMD. The median follow-up time was not different between the 2 groups. Gender, age at diagnosis, the use of induction dexamethasone and other chemotherapeutic agents, vitamin D deficiency, and hypogonadism were not associated with an increased risk of alterations in BMD. Receiving induction chemotherapy between 8 and 18 years of age (age where the highest bone mass is acquired) does not affect in the BMD at follow-up. During follow-up, three patients developed fractures: one pathological and 2 associated with trauma. The patient with a pathological fracture is a man with ALL diagnosed at 8 years of age and had an ankle fracture at 12 years associated with osteoporosis. Discussion and Conclusions: Alterations in BMD are very frequent in our cohort of ALL-survivors despite being a very young population (90% are under 50 years of age). We could not replicate the classically associated risk factors for altered BDM. We only found a non-significant trend for hematopoietic-stem cell transplantation (HSCT) and radiotherapy. This was previously been associated with alterations in different hormonal axes. Despite the high-prevalence of alterations in BMD, the incidence of fractures is very low. This may be related to the fact that it is unknown how to interpret DXA in a group of patients who received chemotherapy/radiotherapy in growth stages. Despite the limitations (small number of patients, the time between treatment and densitometry is heterogeneous and hormonal axes are not measured in all patients), given the high prevalence of BMA alterations, a better understanding of DXA findings in this group of patients is needed. Figure 1 Figure 1. Disclosures Rangel-Patiño: Bristol: Consultancy; Abbvie: Speakers Bureau. Demichelis: AMGEN: Consultancy, Speakers Bureau; Novartis: Consultancy, Research Funding, Speakers Bureau; Astellas: Consultancy; Bristol/Celgene: Consultancy, Speakers Bureau; Jazz: Consultancy; ASH: Research Funding; Gilead: Consultancy; Abbvie: Consultancy, Speakers Bureau.

scholarly journals Risk Factors Associated with Richter's Transformation in Patients with Chronic Lymphocytic Leukemia

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1697-1697 ◽  
Author(s):  
Yasmin Ben-Dali ◽  
Mariam Hussein Hleuhel ◽  
Michael Asger Andersen ◽  
Christian Brieghel ◽  
Erik Clasen-Linde ◽  
...  
Keyword(s):  
Risk Factors ◽  
Chronic Lymphocytic Leukemia ◽  
Incidence Rate ◽  
Cumulative Incidence ◽  
Research Funding ◽  
Univariate Analysis ◽  
Lymphocytic Leukemia ◽  
Increased Risk ◽  
Binet Stage

Abstract Background Richter's transformation (RT) refers to the development of an aggressive lymphoma in patients with chronic lymphocytic leukemia (CLL) or small lymphocytic leukemia (SLL). Roughly, 2-10 % of patients with CLL develop RT most often as diffuse large B-cell lymphoma (DLBCL) or Hodgkin lymphoma (HL). Aim This study aimed to assess the incidence rate and risk factors for RT for patients with CLL in a nationwide cohort. Furthermore, we want to assess prognostic risk factors for patients with RT. Methods All patients diagnosed with CLL in Denmark between 2008 and 2016 were included in this study. Clinical data was retrieved from the Danish National CLL Registry (DCLLR), whereas all histologically verified DLBCL, HL and/or transformation diagnoses for patients with CLL were retrieved from the Danish National Pathology Registry. Patients were followed from date of CLL diagnosis until date of RT, death or end of follow-up, whichever came first. The time to RT was estimated as cumulative incidence considering death as a competing risk. Stepwise Cox analysis with backward elimination was applied to identify independent risk factors for RT in patients with CLL. Results A total of 3771 CLL patients were identified, and followed for 14165 person-years. With a median follow-up of 4.3 (IQR (2.4;6.6)) years, 120 (3%) CLL patients had a transformation diagnosis, of which 4 patients were excluded due to misdiagnosis. DLBCL accounted for 78/116 (67%) cases, HL for 15/116 (13%) cases and one patient presented with both DLBCL and HL. In the remaining 22/116 (19%) cases the subtype of the transformation was either unspecified or unclassified RT. The median time to RT was 3.4 (IQR (1.8;5.7)) years from CLL diagnosis and the median overall survival (OS) after development of RT was 4.9 (IQR (0.7;8.4)) years. The cumulative incidence of RT, calculated by Aalen-Johansen estimator, at 5 and 8 years post-CLL diagnosis were 3.3% and 7.9% respectively (Figure 1). The annual crude incidence rate of RT was approximately 0.7% per year for all CLL patients. In all, 918 (24%) patients received CLL-related treatment, of whom 59 (6.4%) patients developed RT, resulting in a cumulative incidence of RT of 7% after 5 years and 11% after 8 years. At the time of CLL diagnosis, patients treated for CLL prior to RT diagnosis had a worse median OS (1.49 years) compared to RT patients who were untreated for CLL (6.16 years). In the univariate analysis, RT was significantly associated with male gender, advanced Binet stage (B or C), unmutated IGHV status (CLL-U), elevated beta-2-microglobulin (>3.5 mg/L) and elevated lactate dehydrogenase (>205 U/L). Of cytogenic aberration, deletion 13q (del(13q)) had a protective effect on the risk of RT, whereas deletion 11q (del(11q)) and deletion 17p (del(17p)) increased the risk. In the multivariable model, advanced Binet stage (HR 2.86 (1.82;4.51), p<0.001), del(17p) ((HR 3.74 (2.12;6.61), p<0.001) and CLL-U ((HR 2.30 (1.46;3.63), p<0.001) showed an independent correlation with development of RT. ZAP70 and CD38 were excluded from statistical analyses due to incomplete data and high inter-laboratory variation. Among RT patients, CLL-U, trisomy 12 and del(17p) at CLL diagnosis as well as ECOG Performance Status (PS) (i.e. PS≥1) at time of RT diagnosis correlated with poor OS in univariate analysis. Both del(17p) and PS≥1 were independently associated with an increased risk of death in a multivariable analysis (HR 2.9, (1.1;7.7), p=0.04 and HR 3.0, (1.0;3.1), p=0.05, respectively). Conclusions To the best of our knowledge, we here report the largest study on RT assessing nationwide data of consecutive patients diagnosed with CLL. The incidence of RT in this unselected population was 3.3% after 5 years while the median OS for patients from time of RT was 4.9 years. Advanced Binet stage, del(17p) and CLL-U were significantly and independently associated with an increased risk of RT. Del(17p) at CLL diagnosis and PS≥1 at RT diagnosis were significant predictors for death for patients with RT. For patients diagnosed with RT prior to any CLL treatment, a less severe disease course with a median OS of 6.16 years was demonstrated. Contrary, the median OS for patients receiving prior CLL treatment was 1.49 years. Thus, assessment of different treatment options for patients developing RT based on whether they have received prior CLL treatment or not is warranted. Figure 1. Figure 1. Disclosures Ben-Dali: Rigshospitalet: Research Funding. Hleuhel:Rigshospitalet: Research Funding. Brieghel:Arvid Nilson's Fund: Research Funding; Rigshospitalet, Denmark: Research Funding. Niemann:Danish Cancer Society: Research Funding; Novo Nordisk Foundation: Research Funding; Janssen: Consultancy, Research Funding; Abbvie: Consultancy, Research Funding; Novartis: Consultancy; Roche: Consultancy; Gilead: Consultancy; AstraZeneca: Consultancy; CSL Behring: Consultancy.

scholarly journals Drug Persistence with Rivaroxaban Therapy in Atrial Fibrillation Patients Results from the Dresden NOAC registry

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4264-4264
Author(s):  
Jan Beyer-Westendorf ◽  
Kati Förster ◽  
Franziska Ebertz ◽  
Vera Gelbricht ◽  
Franziska Michalski ◽  
...  
Keyword(s):  
Risk Factors ◽  
Atrial Fibrillation ◽  
Research Funding ◽  
Treatment Discontinuation ◽  
Baseline Risk ◽  
Bleeding Complications ◽  
Event Analysis ◽  
Daily Care ◽  
Kaplan Meier

Abstract Aims: Worldwide, rivaroxaban is increasingly used for stroke prevention in atrial fibrillation (SPAF) but little is known about the rates of or reasons for rivaroxaban discontinuation in daily care. Using data from a prospective, non-interventional oral anticoagulation (NOAC) registry, we analysed rivaroxaban treatment persistence. Methods and results: Persistence with rivaroxaban in SPAF was assessed in an ongoing, prospective, non-interventional registry of >2600 NOAC patients from daily care using Kaplan-Meier time-to-first-event analysis. Reasons for and management of rivaroxaban discontinuation were assessed. Potential baseline risk factors for treatment discontinuation were evaluated using Cox regression analysis. Between October 2011 and April 2014, 2603 patients were enrolled in the registry. Of these, 1204 (46.3%) received rivaroxaban for SPAF, with 473 (39.3%) switched from VKA pretreatment to rivaroxaban and 731 (60.7%) newly anticoagulated rivaroxaban patients. As of 30 April 2014, follow-up information was available for all 1204 patients (100%). By that date, the median treatment duration with rivaroxaban was 544 days (25th and 75th percentile 444/639d) for all patients. During follow-up, the overall persistence with rivaroxaban therapy was 81.5% (223/1204 patients discontinued rivaroxaban) and similar for patients switched from VKA to rivaroxaban or newly treated rivaroxaban patients (82.0% vs 81.1%). In the intention-to-treat analysis, rates of treatment discontinuation per 100 patient-years were assessed as a Kaplan–Meier time-to-first-event analysis and found to be 13.6 [95% CI 11.8–15.4] for all patients and similar for newly treated rivaroxaban patients (14.1 [95% CI 11.9–16.7]) and patients switched from VKA to rivaroxaban (12.7 [95% CI 10.1–15.7]; p = 0.35; Figure 1a). This finding did not change if only patients with a completed 12-month follow-up were assessed (Figure 1b). Discontinuation rates were highest in the first 6 months of treatment (9.9% [95% CI 7.7–12.1%] for patients newly treated with rivaroxaban and 10% [95% CI 7.3–12.7%] for patients switched from VKA pretreatment to rivaroxaban) and declined similarly in both subgroups over time (for 6–12 months: 6% [95% CI 5.5–6.4%] and 3.9% [95% CI 3.5–4.4%], respectively; after 12 months: 4.4% [95% CI 3.9–5%) and 7.7% [95% CI 6.0–9.2%], respectively). Most common reasons for treatment discontinuations were bleeding complications (30% of all discontinuations), followed by other side-effects (24.2%) and diagnosis of stable sinus rhythm (9.9%). Within the group of 67 bleeding complications, according to the International Society on Thrombosis and Haemostasis bleeding definition, 14 were major and 53 were non-major clinically relevant bleeding events that led to treatment discontinuation. A history of chronic heart failure (HR 1.43; 95% CI 1.09-1.87; p=0.009) or diabetes (HR 1.39; 95% CI 1.06-1.82; p=0.018) were the only statistically significant baseline risk factors for rivaroxaban discontinuation. After discontinuation of rivaroxaban, patients received antiplatelet therapy (31.8%), VKA (24.2%), another NOAC (18.4%), heparin (9.9%) or nothing (15.7%). Conclusion: Our data indicate that overall persistence with rivaroxaban therapy is high, with a discontinuation rate of approximately 15% in the first year of treatment and few additional discontinuations thereafter. Non-major bleeding is the most common reason for riaroxaban discontinuation and nearly 50% of all discontinuing patients receive only antiplatelet or no antithrombotic treatment. Figure 1: Kaplan–Meier analysis of persistence to rivaroxaban treatment for all patients (left diagram) and for all patients who were observed for at least 12 months (right diagram), according to VKA pretreatment Figure 1:. Kaplan–Meier analysis of persistence to rivaroxaban treatment for all patients (left diagram) and for all patients who were observed for at least 12 months (right diagram), according to VKA pretreatment Disclosures Beyer-Westendorf: Bayer: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Boehringer Ingelheim: Honoraria, Research Funding. Weiss:Boehringer Ingelheim: Honoraria; Bayer: Honoraria.

Sign in / Sign up

Export Citation Format

Share Document