Kinetics of peripheral blood mononuclear cell mobilization with chemotherapy and/or granulocyte-colony-stimulating factor: implications for yield of hematopoietic progenitor cell collections

BACKGROUND: Peripheral blood progenitor cells (PBPCs) are commonly collected and used to reconstitute hematopoiesis after high-dose chemotherapy. However, strategies for optimal collection and assessment of leukapheresis components are not standardized. STUDY DESIGN and METHODS: Hematopoietic progenitor cell assays were performed on 369 leukapheresis components collected from 95 patients who had received doxorubicin-based chemotherapy and/or granulocyte-colony-stimulating factor (G-CSF). Precollection patient hematologic values, leukapheresis collection values, component hematopoietic progenitor cell assays, and patient outcome measures were summarized. The kinetics of mononuclear cell (MNC) and PBPC mobilization were assessed among four patient groups. RESULTS: Patient group was a significant predictor of the peripheral blood MNC count on the day of collection (p<0.0001), and that value was a significant predictor of granulocyte-macrophage– colony-forming unit (CFU-GM) yield (p<0.0001). This relationship between the peripheral blood MNC count on the day of collection and CFU- GM yield differed according to patient group (p<0.0001). CFU-GM made up a larger fraction of peripheral blood MNCs collected from patients who received chemotherapy plus G-CSF than collected from those who received G-CSF alone. Moreover, the peripheral blood MNC count and the corresponding CFU-GM yield increased significantly on consecutive days of collection in patient groups receiving chemotherapy and G-CSF but were unchanged or decreased in patients receiving G-CSF alone. CONCLUSION: The relationship between peripheral blood MNC count and leukapheresis component CFU-GM yield differed significantly between patients who received chemotherapy and G-CSF and those who received G- CSF alone for the mobilization of PBPCs. Patient peripheral blood MNC count and component CFU-GM yield are useful for both assessing and suggesting revisions to PBPC mobilization and collection strategies.     

Predicting oxygen uptake for men and women with moderate to severe chronic obstructive pulmonary disease

OBJECTIVE: To develop regression equations for estimating peak oxygen consumption (Vo(2)) for men and women with moderate to severe chronic obstructive pulmonary disease (COPD) from the 6-minute walk test (6MWT). DESIGN: Multivariate analysis of patient pulmonary function and exercise gas exchange indices to 2 outcomes for the 6MWT (distance ambulated, calculated work [6M(WORK)]). SETTING: A university hospital and clinics. PARTICIPANTS: A total of 124 patients (90 men 34 women; age range, 45\N81y), from the community, with moderate to very severe COPD. Forced expiratory volume in 1 second (FEV(1)) ranged from.70 to 2.79L/min, forced vital capacity (FVC) ranged from 1.73 to 5.77L, and FEV(1)/FVC ranged from 24% to 69%. All patients were in stable condition at the time of testing and were on a stable drug regimen. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Pulmonary function testing was completed according to American Thoracic Society criteria. Cycle ergometry with gas exchange, by using a ramp protocol, was completed. The 6MWT was done in the hospital corridor, with distances recorded after each minute. Work capacity by each method was reduced from the normal predicted. RESULTS: Peak oxygen uptake (Vo(2)) averaged 1184+/-302mL/min for men and 860+/-256mL/min for women (58%, 68% of predicted, respectively). Ventilatory reserve was limited at an achieved peak ventilation (Ve) of 79.9%+/-19.1% of predicted. Borg scores for dyspnea and leg fatigue were equivalent for each test modality, with leg fatigue being slightly higher for each gender. 6M(WORK) for the 6MWT was the strongest independent predictor of peak Vo(2) (r=.81, P<.0001), whereas that for distance ambulated was correlated at r equal to.54 (P<.0001). This is a 36% improvement in the variance accounted for by the application of 6M(WORK) as the outcome for the 6MWT. Generalized regression modeling was then used to develop equations for the estimation of peak Vo(2) for the 6MWT. Additional variables included in the model were diffusing capacity of lung for carbon dioxide, FVC, maximal inspiratory pressure, weight (in kilograms), and age, with their appropriate interactions. This derived regression model accounted for 79% on the variance for estimation of peak Vo(2) in the patients studied. CONCLUSION: Peak Vo(2) can be estimated for men and for women by using the generalized equations presented. The calculation of 6M(WORK) is an improvement over distance ambulated as the 6MWT outcome. These data build on the existing body of knowledge for the 6MWT and extend its application for patients with COPD. Knowledge of the peak Vo(2) can be used for patient assessment, serial monitoring, evaluating disability, and as a common index of function across modalities. The calculation of 6M(WORK) outperformed distance ambulated and is easily converted to other indices of caloric expenditure that are commonly used in the laboratory and clinical settings.     

Prenatal identification of potential donors for umbilical cord blood transplantation for Fanconi anemia

Reported here are studies of Fanconi anemia fetal cells that led to the first use of umbilical cord blood for hematopoietic reconstitution in a clinical trial. Prenatal diagnosis and HLA typing were performed in fetuses at risk for Fanconi anemia (FA) to identify, prior to birth, those that were unaffected with the syndrome and were HLA-identical to affected siblings. Umbilical cord blood was harvested at the delivery of these infants; assays of progenitor cells indicated the presence of colony-forming units-granulocyte-macrophage (CFU-GM) in numbers similar to those of bone marrow CFU-GM that are associated with successful engraftment in HLA-matched allogeneic bone marrow transplantation. The possibility that umbilical cord blood from a single individual can be used as an alternative to bone marrow for hematopoietic reconstitution has now been demonstrated by the successful engraftment of two patients with FA. Progenitor cell assays of umbilical cord blood collected at the birth of a child affected with FA, who had been misdiagnosed on the basis of chorionic villus sampling (CVS) studies, indicated a profound deficiency in colony formation, consistent with previously reported abnormalities in the growth of FA cells in vitro. These results suggest that the hematopoietic disorder in FA is related to an underlying problem with cell proliferation.     

Aspirin in Alzheimer's disease (AD2000): a randomised open-label trial

BACKGROUND: Cardiovascular risk factors and a history of vascular disease can increase the risk of Alzheimer's disease (AD). AD is less common in aspirin users than non-users, and there are plausible biological mechanisms whereby aspirin might slow the progression of either vascular or Alzheimer-type pathology. We assessed the benefits of aspirin in patients with AD. METHODS: 310 community-resident patients who had AD and who had no potential indication or definite contraindication for aspirin were randomly assigned to receive open-label aspirin (n=156; one 75-mg enteric-coated tablet per day, to continue indefinitely) or to avoid aspirin (n=154). Primary outcome measures were cognition (assessed with the mini-mental state examination [MMSE]) and functional ability (assessed with the Bristol activities of daily living scale [BADLS]). Secondary outcomes were time to formal domiciliary or institutional care, progress of disability, behavioural symptoms, caregiver wellbeing, and care time. Patients were assessed at 12-week intervals in the first year and once each year thereafter. Analysis of the primary outcome measures was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN96337233. FINDINGS: Patients had a median age of 75 years; 156 patients had mild AD, 154 had moderate AD, and 18 had concomitant vascular dementia. Over the 3 years after randomisation, in patients who took aspirin, mean MMSE score was 0.10 points higher (95% CI -0.37 to 0.57; p=0.7) and mean BADLS score was 0.62 points lower (-1.37 to 0.13; p=0.11) than in patients assigned to aspirin avoidance. There were no obvious differences between the groups in any other outcome measurements. 13 (8%) patients on aspirin and two (1%) patients in the control group had bleeds that led to admission to hospital (relative risk=4.4, 95% CI 1.5-12.8; p=0.007); three (2%) patients in the aspirin group had fatal cerebral bleeds. INTERPRETATION: Although aspirin is commonly used in dementia, in patients with typical AD 2 years of treatment with low-dose aspirin has no worthwhile benefit and increases the risk of serious bleeds.     

A study on the association with hepatitis B and hepatitis C in 1557 patients with lichen planus

Background Previous reports have demonstrated contradicting results on the association between lichen planus and hepatitis. Objectives The aim of this study was to investigate the association between lichen planus and viral hepatitis. Methods Patients with lichen planus were compared with controls regarding the prevalence of viral hepatitis in a case‐control study using logistic multivariate regression models. The study was performed utilizing the medical database of Clalit Health Services. Results The study included 1557 lichen planus patients over the age of 20 years and 3115 age‐ and gender‐matched controls. The prevalence of hepatitis C in patients with lichen planus was higher than that in the control group (1.9%, 0.4% respectively, P < 0.001). In a multivariate analysis, lichen planus was associated with hepatitis C (OR 4.19, 95% CI 2.21; 7.93). The prevalence of hepatitis B in patients with lichen planus was similar to that in the control group (0.9%, 0.5% respectively, P = 0.12). A multivariate analysis revealed that lichen planus was not associated with hepatitis B (OR 1.69, 95% CI 0.82; 3.47). Conclusion Lichen planus is associated with hepatitis C but not with hepatitis B. Physicians who care for patients with lichen planus should consider screening patients with lichen planus for hepatitis C.     

Two year cumulative incidence of trunk abnormalities in a schoolpopulation in Rotterdam, The Netherlands

We conducted a study of the 2 year cumulative incidence of trunkabnormalities in a cohort of 3,071 11 year old children (1,621boys, 1,450 girls). The following data were recorded: height,weight, signs of puberty and menarche. Trunk abnormality wasassessed in the erect child (asymmetry of shoulders and waistline,imbalance of the trunk, scoliosis, lordosis, kyphosis, swaybackand flexibility) and by the forward bending test (FBT) (ribhump or lumbar prominence, persisting scoliosis, kyphosis anddeviant lateral aspect). A normal FBT both at baseline and atfollow-up was found in 84% of the boys and in 79% of the girls.The 2 year cumulative incidence of an abnormal FBT was 10% inboys and 13% in girls.     

Percutaneous computed-tomography-stabilization of pelvic fractures: preliminary report

The authors performed percutaneous computed-tomography (CT)-guided stabilization of reproduced pelvic fractures in eight cadaver studies and in three additional clinical cases. The details of the technique are illustrated in this article. The authors conclude that percutaneous CT-guided stabilization of pelvic fractures in selected cases can be performed safely, rapidly, and with less associated morbidity than conventional open methods presently used. Clinical studies are currently being expanded.