Disseminated adenovirus infections after allogeneic hematopoietic stem cell transplantation: incidence, risk factors and outcome

We analyzed the factors and outcome of patients with disseminated adenovirus infection (dAdV) after allogeneic hematopoeitic stem cell transplantation (HSCT). Thirty patients with dAdV were identified among 620 allogeneic HSCT recipients. Primary diseases were leukemia (n=17), Fanconi anemia (n=12) or others (n=1). Source of stem cells was unrelated in 28 and related in 2 patients. The graft consisted of peripheral blood (n=3), bone marrow (n=12) and unrelated cord-blood (UCB, n=15). Risk factors for dAdV in unrelated HSCT recipients were previous Fanconi disease (p=0.03) and GVHD (p=0.02) in children, and cord blood source of stem cells (p=0.029) and GVHD (0.024) in adults.     

Outcome and risk factors for late-onset complications 24 months beyond allogeneic hematopoietic stem cell transplantation

Objectives: The aim of this retrospective study was to assess the incidence of late complications occurring ≥2 years after allogeneic hematopoietic stem cell transplantation (HSCT) for malignant diseases using a T‐cell depletion strategy. Methods: Between 1984 and 2004, 142 patients were eligible for the study. Total body irradiation (TBI) was carried out in 85% of the patients and T‐cell depletion in 84%. Results: Non‐relapse mortality (NRM) was 3% (95% CI 0–11) at 10 years, and serious late events affected a substantial number of patients. The cumulative incidence (CI) of chronic graft‐versus‐host disease (cGvHD) was 30% (95% CI 23–40), and that of infectious complications was 17% (95% CI 11–23). Multivariate analysis showed a higher risk for late complications in patients with cGvHD (HR 1.9, 95% CI 1.2–3.2, P = 0.011) and patients receiving methylprednisolone during conditioning (HR 1.9, 95% CI 1.1–3.3, P = 0.019 1), patients with cGvHD also having a higher risk for NRM (HR 13.2, 95% CI 1.2–143, P = 0.03), as well as those receiving steroids for >3 months (HR 40.3, 95% CI 2.3–718, P = 0.02) and those receiving antithymocyte globulin (HR 9.6, 95% CI 0.8–68, P = 0.024). Conclusions: A significant proportion of long‐term survivors of HSCT had late complications. cGvHD remained an important risk factor for late complications despite T‐cell depletion resulting in immunosuppression and infectious complications.     

Early menopause, low body mass index, and smoking are independent risk factors for developing giant cell arteritis

OBJECTIVE: To assess female sex hormone related variables in a group of women with biopsy positive giant cell arteritis and a control group. METHODS: 49 women with biopsy positive giant cell arteritis, aged 50 to 69 years at the time of diagnosis, answered a questionnaire on hormonal and reproductive factors. The same questions were answered by a large population of women from the same geographical area in connection with routine mammograms. The results were tested statistically, using logistic regression analysis of each variable adjusted for age, and a multivariate logistic regression analysis including age and the variables which differed significantly between giant cell arteritis and controls. RESULTS: From the multivariate logistic regression analysis, three independent variables were associated with an increased risk of having giant cell arteritis: smoking and being an ex-smoker (odds ratio (OR) = 6.324 (95% confidence interval (CI), 3.503 to 11.418), p<0.0001); body mass index (a reduction of 1.0 kg/m2 increased the risk by 10% (OR = 0.898 (0.846 to 0.952), p = 0.0003); and menopause before the age of 43 (OR = 3.521 (1.717 to 7.220), p = 0.0006). CONCLUSIONS: There was a significant association between hormonal and reproduction related factors and the risk of developing giant cell arteritis in women given the diagnosis before the age of 70. The results suggest a possible role of oestrogen deficiency in the pathogenesis of giant cell arteritis. To confirm the results, an extended study will be needed, including women older than 70.     

Analysis of incidence,risk factors and clinical outcome of thromboembolic and bleeding events in 431 allogeneic hematopoietic stem cell transplantation recipients

Allogeneic hematopoietic stem cell transplantation recipients have an increasing risk of both hemorrhagic and thrombotic complications. However, the competing risks of two of these life-threatening complications in these complex patients have still not been well defined. We retrospectively analyzed data from 431 allogeneic transplantation recipients to identify the incidence, risk factors and mortality due to thrombosis and bleeding. Significant clinical bleeding was more frequent than symptomatic thrombosis. The cumulative incidence of a bleeding episode was 30.2% at 14 years. The cumulative incidence of a venous or arterial thrombosis at 14 years was 11.8% and 4.1%, respectively. The analysis of competing factors for venous thrombosis revealed extensive chronic graft-versus-host disease to be the only independent prognostic risk factor. By contrast, six factors were associated with an increased risk of bleeding; advanced disease, ablative conditioning regimen, umbilical cord blood transplantation, anticoagulation, acute III-IV graft-versus-host disease, and transplant-associated microangiopathy. The development of thrombosis did not significantly affect overall survival (P=0.856). However, significant clinical bleeding was associated with inferior survival (P<0.001). In allogeneic hematopoietic stem cell transplantation, significant clinical bleeding is more common than thrombotic complications and affects survival.     

Evaluating potentially modifiable risk factors for prevalent and incident nocturia in older adults

OBJECTIVES: To examine associations between nocturia and potentially modifiable risk factors in older adults. DESIGN: Secondary analysis of cross-sectional and longitudinal data. SETTING: Respondents were selected using population-based sampling, drawing from a single Michigan county in 1983. They were followed through 1990. PARTICIPANTS: Community-living adults aged 60 and older. MEASUREMENTS: Episodes of nocturia, development of nocturia at 2 years after baseline survey, age, sex, hypertension, diabetes mellitus, drinking fluids before bedtime, amount of fluid intake before bedtime, diuretic use, and 24-hour coffee intake. All measures were self-reported. RESULTS: Bivariate cross-sectional analysis revealed significant associations with two or more episodes of nocturia for hypertension (odds ratio (OR)=1.7, 95% confidence interval (CI)=1.37-2.1), diabetes mellitus (OR=1.51, 95% CI=1.1-2.0), diuretic use (OR=1.7, 95% CI=1.3-2.1), age (OR=1.05 per additional year over 60, 95% 1.03-1.06), and number of cups of coffee (OR=0.93 for each cup of coffee, 95% CI=0.89-0.97). In multivariate analysis, hypertension (OR=1.52, 95% CI=1.2-1.9), diuretic use (OR=1.3, 95% 95% CI=1.0-1.7), and age (OR=1.04 per additional year over 60, 95% 1.03-1.06) were independently associated with two or more nocturia episodes per night. No baseline factors predicted future development of nocturia (save for age, in one model). CONCLUSION: Hypertension, older age, and diuretic use were independently associated with two or more episodes of nocturia in cross-sectional analysis. No baseline factor was related to the development of nocturia over a 2-year interval in this sample. Nighttime fluid intake and coffee intake, practices providers commonly target in patients with nocturia, were not associated with nocturia in this population-based sample of community-living older adults.     

B cell lymphoproliferative disorders following hematopoietic stem cell transplantation: risk factors, treatment and outcome

Twenty-six cases of B cell lymphoproliferative disorder (BLPD) were identified among 2395 patients following hematopoietic stem cell transplants (HSCT) for which an overall incidence of BLPD was 1.2%. The true incidence was probably higher, since 9/26 of the diagnoses were made at autopsy. No BLPD was observed following autologous HSCT, so risk factor analyses were confined to the 1542 allogeneic HSCT. Factors assessed were HLA-mismatching (> or = 1 antigen), T cell depletion (TCD), presence of acute GvHD (grades II-IV), donor type (related vs unrelated), age of recipient and donor, and underlying disease. Factors found to be statistically significant included patients transplanted for immune deficiency and CML, donor age > or = 18 years, TCD, and HLA-mismatching, with recipients of combined TCD and HLA-mismatched grafts having the highest incidence. Factors found to be statistically significant in a multiple regression analysis were TCD, donor age and immune deficiency, although 7/8 of the patients with immunodeficiencies and BLPD received a TCD graft from a haploidentical parent. The overall mortality was 92% (24/26). One patient had a spontaneous remission, but subsequently died >1 year later of chronic GVHD. Thirteen patients received therapy for BLPD. Three patients received lymphocyte infusions without response. The only patients with responses and longterm survival received alpha interferon (alphaIFN). Of seven patients treated with alphaIFN there were four responses (one partial and three complete). These data demonstrate that alphaIFN can be an effective agent against BLPD following HSCT, if a timely diagnosis is made.     

Clinical features and risk factors of pure red cell aplasia following major ABO-incompatible allogeneic hematopoietic stem cell transplantation

The objective of this paper was to study the incidence, risk factors, clinical outcome, management and prevention of pure red cell aplasia (PRCA) following major ABO-incompatible allogeneic hematopoietic stem cell transplantation (allo-HSCT). We retrospectively analyzed 11 cases of PRCA from a series of 42 patients undergoing major ABO-incompatible allo-HSCT from April 1997 to December 2005. Eleven out of the 42 patients developed PRCA (26.1%). All the 11 cases of PRCA were in blood group O recipients of grafts from blood group A donor (n = 9) or blood group B donor (n = 2). The following factors were associated with an increased risk of PRCA: (1) blood group O recipient; (2) blood group A donor; and (3) blood group O/A in recipient/donor pair. Only blood group a/A in recipient/donor pair was identified as being significantly associated with the occurrence of PRCA by multivariate analysis. Six patients who received donor-type plasma exchange did not develop PRCA and among them 5 cases were the blood group O recipients. Eight patients obtained spontaneous remission and in the remaining 3 patients 2 with long-lasting PRCA were successfully treated with plasma exchange with donor-type plasma replacement and the other one who was also complicated by EBV-associated lymphoproliferative disorder (EBV-PTLD) responded rapidly to anti-CD20 monoclonal antibody and achieved complete resolution of clinical finding and symptom of both EBV-PTLD and PRCA. We conclude that blood group A/O in donor/recipient pair is identified as being significantly associated with the occurrence of PRCA by multivariate analysis. Donor-type plasma exchange and anti-CD20 monoclonal antibody is an effective approach for the treatment of PRCA. PRCA could be prevented by plasma exchange prior to transplantation.     

Clinical features and risk factors of pure red cell aplasia following major ABO-incompatible allogeneic hematopoietic stem cell transplantation

The objective of this paper was to study the incidence, risk factors, clinical outcome, management and prevention of pure red cell aplasia (PRCA) following major ABO-incompatible allogeneic hematopoietic stem cell transplantation (allo-HSCT). We retrospectively analyzed 11 cases of PRCA from a series of 42 patients undergoing major ABO-incompatible allo-HSCT from April 1997 to December 2005. Eleven out of the 42 patients developed PRCA (26.1%). All the 11 cases of PRCA were in blood group O recipients of grafts from blood group A donor (n = 9) or blood group B donor (n = 2). The following factors were associated with an increased risk of PRCA: (1) blood group O recipient; (2) blood group A donor; and (3) blood group O/A in recipient/donor pair. Only blood group O/A in recipient/donor pair was identified as being significantly associated with the occurrence of PRCA by multivariate analysis. Six patients who received donor-type plasma exchange did not develop PRCA and among them 5 cases were the blood group O recipients. Eight patients obtained spontaneous remission and in the remaining 3 patients 2 with long-lasting PRCA were successfully treated with plasma exchange with donor-type plasma replacement and the other one who was also complicated by EBV-associated lymphoproliferative disorder (EBV-PTLD) responded rapidly to anti-CD20 monoclonal antibody and achieved complete resolution of clinical finding and symptom of both EBV-PTLD and PRCA. We conclude that blood group A/O in donor/recipient pair is identified as being significantly associated with the occurrence of PRCA by multivariate analysis. Donor-type plasma exchange and anti-CD20 monoclonal antibody is an effective approach for the treatment of PRCA. PRCA could be prevented by plasma exchange prior to transplantation.     

Colonization with multidrug-resistant bacteria increases the risk of complications and a fatal outcome after allogeneic hematopoietic cell transplantation

Composition of the gut microbiota seems to influence early complications of allogeneic hematopoietic cell transplantation (HCT) such as bacterial infections and acute graft-versus-host disease (GVHD). In this study, we assessed the impact of colonization with multidrug-resistant bacteria (MDRB) prior to HCT and the use of antibiotics against anaerobic bacteria on the outcomes of HCT. We retrospectively analyzed the data of 120 patients who underwent HCT for hematologic disorders between 2012 and 2014. Fifty-one (42.5%) patients were colonized with MDRB and 39 (32.5%) had infections caused by MDRB. Prior colonization was significantly correlated with MDRB infections (P?<?0.001), especially bacteremia (P?=?0.038). A higher incidence of MDRB infections was observed in patients with acute (P?=?0.014) or chronic (P?=?0.002) GVHD and in patients aged >?40 years (P?=?0.002). Colonization had a negative impact on overall survival (OS) after HCT (64 vs. 47% at 24 months; P?=?0.034) and infection-associated mortality (P?<?0.001). Use of metronidazole was correlated with an increased incidence of acute GVHD (P?<?0.001) and lower OS (P?=?0.002). Patients colonized with MDRB are more susceptible to life-threatening infections. Colonization with virulent flora is the most probable source of neutropenic infection; therefore, information about prior positive colonization should be crucial for the selection of empiric antibiotic therapy. The use of metronidazole, affecting the biodiversity of the intestinal microbiome, seems to have a significant impact on OS and acute GVHD.     

Nutritional risk in allogeneic stem cell transplantation: rationale for a tailored nutritional pathway

Hematopoietic stem cell transplantation carries nutrition-related risks. Therefore, nutritional therapy needs to be initiated before transplantation even takes place. We assessed nutritional risk among patients who underwent allogeneic stem cell transplantation. We assessed nutrient supply (calorie supply and protein supply) by chart review. Assessments were made from the pretreatment phase of transplantation to after the end of parenteral nutrition in 51 patients who underwent allogeneic stem cell transplantation at Shizuoka Cancer Center between 2007 and 2012. We compared nutrition-related adverse events and parameters between two groups: those in whom % loss of body weight was ≥7.5 and those in whom % loss of body weight was <7.5. A correlation was observed between changes in weight and skeletal muscle mass (r = 0.89; P < 0.0001). A weak correlation was observed between % loss of body weight and nutrient supply of calories (r = 0.517; P = 0.0001). There were significant differences between the % loss of body weight ≥7.5 group and the % loss of body weight <7.5 group in the following variables: % loss of body weight, nutrient supply from calories and protein; orally ingested nutrient supply from calories and protein; start day of oral intake; and acute graft-versus-host disease. Orally ingested calories were negatively correlated with nutrition-related adverse events in both groups. Early and customized nutritional intervention may be optimal for all patients who undergo allogeneic stem cell transplantation to ameliorate body weight loss associated with nutrition-related adverse events.     

Incidence, characteristics and risk factors of marked hyperbilirubinemia after allogeneic hematopoietic cell transplantation with reduced-intensity conditioning

To analyze the incidence, characteristics and risk factors of hyperbilirubinemia after allogeneic hematopoietic cell transplantation with reduced-intensity conditioning (allo-RIC), we conducted a retrospective study in three Spanish centers. We analyzed 452 consecutive patients receiving allo-RIC. Of these, 92 patients (20%) developed marked hyperbilirubinemia (>4?mg/day or >68.4?μM) after allo-RIC. The main causes of marked hyperbilirubinemia after transplant were cholestasis due to GVHD or sepsis (n=57, 62%) and drug-induced cholestasis (n=13, 14%). A total of 22 patients with marked hyperbilirubinemia (24%) underwent liver biopsy. The most frequent histological finding was iron overload alone (n=6) or in combination with other features (n=6). In multivariate analysis, the risk factors for marked hyperbilirubinemia after allo-RIC were non-HLA-identical sibling donors (hazard ratio (HR) 2.2 (95% confidence interval (CI) 1.4-3.6) P=0.001), female donors to male recipients (HR 2.1 (95% CI 1.3-3.3) P=0.003) and high levels of bilirubin and γ-glutamyl transpeptidase before transplant (HR 4.5 (95% CI 2.5-8.4) P<0.001 and HR 4.6 (95% CI 2.6-8.1) P<0.001, respectively). Patients with marked hyperbilirubinemia showed higher 4-year nonrelapse mortality (HR 1.3 (95% CI 1-1.7), P=0.02) and lower 4-year OS (HR 1.4 (95%CI 1.3-1.7), P<0.001) than patients without. In conclusion, we confirm that marked hyperbilirubinemia is frequent and diverse after allo-RIC. Development of marked hyperbilirubinemia after allo-RIC is associated with worse outcome of the procedure.     

Incidence,etiology, and outcome of pleural effusions in allogeneic hematopoietic stem cell transplantation

Pleural effusion is a known entity in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT); however, the incidence, risk factors, and morbidity?mortality outcomes associated with pleural effusions remain unknown. We retrospectively evaluated pleural effusions in 618 consecutive adult patients who underwent allogeneic HSCT from January 2008 to December 2013 at our institution. Seventy one patients developed pleural effusion at a median of 40 days (range, 1 ? 869) post‐HSCT with the cumulative incidence of 9.9% (95% CI, 7.7 ? 12.5%) at 1 year. Infectious etiology was commonly associated with pleural effusions followed by volume overload and serositis type chronic GVHD. In multivariate analysis, higher comorbidity index (P = 0.03) and active GVHD (P = 0.018) were found to be significant independent predictors for pleural effusion development. Higher comorbidity index, very high disease risk index, ≤7/8 HLA matching, and unrelated donor were associated with inferior overall survival (OS) (P < 0.03). More importantly, patients with pleural effusion were noted to have poor OS in comparison to patients without pleural effusion (P < 0.001). Overall, pleural effusion is a frequently occurring complication after allogeneic HSCT, adding to morbidity and mortality and hence, early identification is required. Am. J. Hematol. 91:E341–E347, 2016. © 2016 Wiley Periodicals, Inc.     

Body mass index, other cardiovascular risk factors, and hospitalization for dementia

BACKGROUND: Previous studies have shown that risk factors commonly associated with coronary disease, stroke, and other vascular disorders also predict dementia. We investigated the longitudinal relationship between body mass index (BMI, calculated as weight in kilograms divided by the square of height in meters) and risk of hospital discharge or death certificate diagnosis of dementia. METHODS: A total of 7402 men who were 47 to 55 years old in 1970 to 1973, without prior stroke or myocardial infarction, derived from a population sample of 9998 men were prospectively followed up until 1998. Two hundred fifty-four men (3.4%) had a hospital discharge diagnosis or a death certificate diagnosis of dementia: 176 with a primary diagnosis or cause of death and 78 with a secondary diagnosis. RESULTS: The relationship between BMI and dementia as a primary diagnosis was J-shaped, and men with a BMI between 20.00 and 22.49 had the lowest risk. Subsequently, after adjustment for smoking, blood pressure, serum cholesterol level, diabetes mellitus, and social class, the risk increased linearly in men who had a BMI of 22.50 to 24.99 (multiple-adjusted hazard ratio [HR], 1.73; 95% confidence interval [CI], 0.92-3.25), 25.00 to 27.49 (HR, 1.93; 95% CI, 1.03-3.63), 27.50 to 29.99 (HR, 2.30; 95% CI, 1.18-4.47), and 30.00 or greater (HR, 2.54; 95% CI, 1.20-5.36) (P for linear trend = .03). Men with a BMI less than 20.00 had a nonsignificantly elevated risk (HR, 2.19; 95% CI, 0.77-6.25). CONCLUSIONS: A J-shaped relationship was observed between BMI and dementia, such that a BMI less than 20 and an increasing BMI of 22.5 or greater were associated with increased risk from midlife to old age of a primary hospital diagnosis of dementia. Overweight and obesity could be major preventable factors in the development of dementia.     

Body mass index and metabolic risk factors for coronary heart disease in women.

AIMS: Prospective epidemiological studies demonstrate an increase in coronary heart disease mortality in women beginning at values of body mass index > or = 22 kg. m(-2). However, the metabolic basis for this observation has not been adequately studied in women. Our aim was to examine the association between body mass index, metabolic coronary heart disease risk factors and a predicted 10-year coronary heart disease risk score in a large occupational cohort of women in the U.K. METHODS AND RESULTS: We carried out a cross-sectional survey of cardiovascular risk factors in 14 077 women, aged 30-64 years. The main outcome measures were systolic and diastolic blood pressure, serum total cholesterol, HDL cholesterol, total cholesterol/HDL cholesterol ratio, LDL-cholesterol, triglycerides, apolipoprotein A1, apolipoprotein B, lipoprotein(a), fasting blood glucose and a predicted 10-year coronary risk score. Across seven categories of body mass index, i.e. < 20, 20-, 22-, 24-, 26-, 28- and > or = 30 kg. m(-2), there were highly significant age-adjusted increases in the risk factors (all P < 0.001), except for a decrease in HDL cholesterol and ApoA1 (all P<0.001) and no relationship with lipoprotein(a) (P = 0.05). Based on a multifactorial 10-year coronary heart disease risk estimate, odds ratios for being in the highest quintile of risk for each category of body mass index, were 1 (< 20 kg. m(-2)), 0.91, 1.56, 2.18, 2.97, 3.83 and 4.21 (> or = 30 kg. m(-2)). CONCLUSION: The significant rise in metabolic coronary heart disease risk at 22 kg. m(-2)observed in this study is consistent with prospective epidemiological studies in women which have reported an increase in coronary heart disease mortality starting at 22 kg. m(-2). However, body mass index was a poor discriminator of women at different levels of coronary heart disease risk. The primary goal of weight loss in individuals should be the correction of dysmetabolism, irrespective of the level of body mass index.