Association between overcrowded households, multigenerational households, and COVID-19: a cohort study.

OBJECTIVES: The role of overcrowded and multigenerational households as a risk factor for COVID-19 remains unmeasured. The objective of this study is to examine and quantify the association between overcrowded and multigenerational households and COVID-19 in New York City (NYC). STUDY DESIGN: Cohort study. METHODS: We conducted a Bayesian ecological time series analysis at the ZIP Code Tabulation Area (ZCTA) level in NYC to assess whether ZCTAs with higher proportions of overcrowded (defined as the proportion of the estimated number of housing units with more than one occupant per room) and multigenerational households (defined as the estimated percentage of residences occupied by a grandparent and a grandchild less than 18 years of age) were independently associated with higher suspected COVID-19 case rates (from NYC Department of Health Syndromic Surveillance data for March 1 to 30, 2020). Our main measure was an adjusted incidence rate ratio (IRR) of suspected COVID-19 cases per 10,000 population. Our final model controlled for ZCTA-level sociodemographic factors (median income, poverty status, White race, essential workers), the prevalence of clinical conditions related to COVID-19 severity (obesity, hypertension, coronary heart disease, diabetes, asthma, smoking status, and chronic obstructive pulmonary disease), and spatial clustering. RESULTS: 39,923 suspected COVID-19 cases were presented to emergency departments across 173 ZCTAs in NYC. Adjusted COVID-19 case rates increased by 67% (IRR 1.67, 95% CI = 1.12, 2.52) in ZCTAs in quartile four (versus one) for percent overcrowdedness and increased by 77% (IRR 1.77, 95% CI = 1.11, 2.79) in quartile four (versus one) for percent living in multigenerational housing. Interaction between both exposures was not significant (ßinteraction = 0.99, 95% CI: 0.99-1.00). CONCLUSIONS: Overcrowdedness and multigenerational housing are independent risk factors for suspected COVID-19. In the early phase of the surge in COVID cases, social distancing measures that increase house-bound populations may inadvertently but temporarily increase SARS-CoV-2 transmission risk and COVID-19 disease in these populations.

Variability in sleep disturbance, physical activity and quality of life by level of depressive symptoms in women with Type 2 diabetes.

AIMS: To examine (1) the prevalence of depressive symptoms in women with Type 2 diabetes, (2) the associations between depressive symptoms and the following dependent variables: sleep disturbance; physical activity; physical health-related; and global quality of life, and (3) the potential moderating effects of antidepressants and optimism on the relationship between depressive symptoms and dependent variables. METHODS: Participants in the Women's Health Initiative who had Type 2 diabetes and data on depressive symptoms (N=8895) were included in the analyses. In multivariable linear regression models controlling for sociodemographic, medical and psychosocial covariates, we examined the main effect of depressive symptoms, as well as the interactions between depressive symptoms and antidepressant use, and between depressive symptoms and optimism, on sleep disturbance, physical activity, physical health-related quality of life; and global quality of life. RESULTS: In all, 16% of women with Type 2 diabetes reported elevated depressive symptoms. In multivariable analyses, women with depressive symptoms had greater sleep disturbance (P<0.0001) and lower global quality of life (P<.0001). We found evidence of significant statistical interaction in the models for quality-of-life outcomes: the increased risk of poor physical health-related quality of life associated with antidepressant use was stronger in women without vs with depressive symptoms, and the association between greater optimism and higher global quality of life was stronger in women with vs without depressive symptoms. CONCLUSIONS: To improve health behaviours and quality of life in women with Type 2 diabetes, sociodemographic and medical characteristics may identify at-risk populations, while psychosocial factors including depression and optimism may be important targets for non-pharmacological intervention.

Associations of coagulation factors IX and XI levels with incident coronary heart disease and ischemic stroke: the REGARDS study.

Essentials Coagulation factors (F) IX and XI have been implicated in cardiovascular disease (CVD) risk. We studied associations of FIX and FXI with incident coronary heart disease (CHD) and stroke. Higher FIX antigen was associated with incident CHD risk in blacks but not whites. Higher levels of FIX antigen may be a CHD risk factor among blacks. SUMMARY: Background Recent studies have suggested the importance of coagulation factor IX and FXI in cardiovascular disease (CVD) risk. Objectives To determine whether basal levels of FIX or FXI antigen were associated with the risk of incident coronary heart disease (CHD) or ischemic stroke. Patients/Methods The REasons for Geographic And Racial Differences in Stroke (REGARDS) study recruited 30 239 participants across the contiguous USA between 2003 and 2007. In a case-cohort study within REGARDS, FIX and FXI antigen were measured in participants with incident CHD (n = 609), in participants with incident ischemic stroke (n = 538), and in a cohort random sample (n = 1038). Hazard ratios (HRs) for CHD and ischemic stroke risk were estimated with Cox models per standard deviation higher FIX or FXI level, adjusted for CVD risk factors. Results In models adjusting for CHD risk factors, higher FIX levels were associated with incident CHD risk (HR 1.19; 95% confidence interval [CI] 1.01-1.40) and the relationship of higher FXI levels was slightly weaker (HR 1.15; 95% CI 0.97-1.36). When stratified by race, the HR of FIX was higher in blacks (HR 1.39; 95% CI 1.10-1.75) than in whites (HR 1.06; 95% CI 0.86-1.31). After adjustment for stroke risk factors, there was no longer an association of FIX levels with ischemic stroke, whereas the association of FXI levels with ischemic stroke was slightly attenuated. Conclusions Higher FIX antigen levels were associated with incident CHD in blacks but not in whites. FIX levels may increase CHD risk among blacks.

Hemostasis biomarkers and risk of sepsis: the REGARDS cohort.

Essentials Few studies have investigated the risk of sepsis by baseline hemostasis biomarkers measures. Baseline hemostasis biomarkers and risk of sepsis was examined using case-control study design. Increased fibrinogen, factor IX, and factor XI levels may be associated with risk of sepsis. Hemostasis biomarkers may provide a target for sepsis mitigation or prevention. SUMMARY: Background Sepsis is a major public health concern, responsible for more than 750 000 hospitalizations and 200 000 annual deaths in the USA. Few studies have investigated the association between baseline measurements of hemostasis biomarkers and the future risk of sepsis. Objective To determine whether hemostasis biomarkers levels measured at baseline in a cohort of community-dwelling participants are associated with the risk of future sepsis events. Methods We performed a nested case-control study within the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort. We identified sepsis hospitalizations occurring over a 10-year period. There were 50 incident sepsis cases with baseline measurements of hemostasis (fibrinogen, factor VIII, FIX, FXI, protein C, and D-dimer). Using incidence density sampling, we matched the 50 sepsis cases with 200 controls by age, sex, and race. We used conditional logistic regression to evaluate the association between baseline hemostasis biomarkers and future sepsis events. Results Comparison of 50 sepsis cases with 200 non-sepsis controls showed that sepsis cases had lower education and income, were more likely to live in the stroke belt, had chronic lung disease, and had higher albumin level/creatinine level ratios (ACRs). Individuals with higher baseline fibrinogen levels (adjusted odds ratio [OR] per standard deviation: 1.40, 95% confidence interval [CI] 1.01-1.94), FIX levels ([OR] 1.46, 95% [CI] 1.03-2.07) and FXI levels ([OR]1.52, 95% [CI] 1.04-2.23) were more likely to experience a sepsis event. Conclusion Baseline fibrinogen, FIX and FXI levels are associated with future episodes of sepsis. Hemostasis biomarkers may provide targets for sepsis mitigation or prevention.

Hospital-onset Clostridium difficile infection among solid organ transplant recipients.

Clostridium difficile infection (CDI) is a considerable health issue in the United States and represents the most common healthcare-associated infection. Solid organ transplant recipients are at increased risk of CDI, which can affect both graft and patient survival. However, little is known about the impact of CDI on health services utilization posttransplantation. We examined hospital-onset CDI from 2012 to 2014 among transplant recipients in the University HealthSystem Consortium, which includes academic medical center-affiliated hospitals in the United States. Infection was five times more common among transplant recipients than among general medicine inpatients (209 vs 40 per 10 000 discharges), and factors associated with CDI among transplant recipients included transplant type, risk of mortality, comorbidities, and inpatient complications. Institutional risk-standardized CDI varied more than 3-fold across high-volume hospitals (infection ratio 0.54-1.82, median 1.04, interquartile range 0.78-1.28). CDI was associated with increased 30-day readmission, transplant organ complications, cytomegalovirus infection, inpatient costs, and lengths of stay. Total observed inpatient days and direct costs for those with CDI were substantially higher than risk-standardized expected values (40 094 vs 22 843 days, costs $198 728 368 vs $154 020 528). Further efforts to detect, prevent, and manage CDI among solid organ transplant recipients are warranted.

Risk of hospitalized bacterial infections associated with biologic treatment among US veterans with rheumatoid arthritis.

OBJECTIVE: The comparative risk of infection associated with non-anti-tumor necrosis factor (anti-TNF) biologic agents is not well established. Our objective was to compare risk for hospitalized infections between anti-TNF and non-anti-TNF biologic agents in US veterans with rheumatoid arthritis (RA). METHODS: Using 1998-2011 data from the US Veterans Health Administration, we studied RA patients initiating rituximab, abatacept, or anti-TNF therapy. Exposure was based upon days supplied (injections) or usual dosing intervals (infusions). Treatment episodes were defined as new biologic agent use. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for hospitalization for a bacterial infection were estimated from Cox proportional hazards models, adjusting for potential confounders. RESULTS: Among 3,152 unique RA patients contributing 4,158 biologic treatment episodes to rituximab (n = 596), abatacept (n = 451), and anti-TNF agents (n = 3,111), the patient mean age was 60 years and 87% were male. The most common infections were pneumonia (37%), skin/soft tissue (22%), urinary tract (9%), and bacteremia/sepsis (7%). Hospitalized infection rates per 100 person-years were 4.4 (95% CI 3.1-6.4) for rituximab, 2.8 (95% CI 1.7-4.7) for abatacept, and 3.0 (95% CI 2.5-3.5) for anti-TNF. Compared to etanercept, the adjusted rate of hospitalized infection was not different for adalimumab (HR 1.4, 95% CI 0.9-2.2), abatacept (HR 1.1, 95% CI 0.6-2.1), or rituximab (HR 1.4, 0.8-2.6), although it was increased for infliximab (HR 2.3, 95% CI 1.3-4.0). Infection risk was greater for those taking prednisone >7.5 mg/day (HR 1.8, 95% CI 1.3-2.7) and in the highest quartile of C-reactive protein (HR 2.3, 95% CI 1.4-3.8) and erythrocyte sedimentation rate (HR 4.1, 95% CI 2.3-7.2) compared to the lowest quartile. CONCLUSION: In older, predominantly male US veterans with RA, the risk of hospitalized bacterial infections associated with rituximab or abatacept was similar to etanercept.

Association of pain with HbA1c in a predominantly black population of community-dwelling adults with diabetes: a cross-sectional analysis.

AIMS: To assess the relationship between pain and HbA(1c) levels in a predominantly black population with diabetes, and to determine whether self-management behaviours (exercise and diet) and symptoms of depression mediate this relationship. METHODS: We analysed cross-sectional data from 417 community-dwelling individuals with diabetes in rural Alabama, USA. Binary logistic regression was used to analyse the relationship between pain and HbA(1c) levels, defined as relatively good [≤ 64 mmol/mol (≤ 8.0%)] and relatively poor [> 64 mmol/mol (> 8.0%)], after adjusting for sociodemographics, insulin use, medication count, cigarette smoking history and body mass index (BMI). We examined the mediating roles of exercise, diet, and symptoms of depression using bootstrapping. RESULTS: Participants were primarily black (86.6%), female (76.1%) and reported an annual income of ≤$20,000 (52.7%). Their mean (sd) age was 59.6 (12.8) years. The majority of the participants reported moderate to extreme pain (71.5%). Participants reporting pain were more than twice as likely to have HbA(1c) levels > 64 mmol/mol (8.0%) in the fully adjusted model (odds ratio 2.33 [95% CI 1.28-4.24]; P < 0.05). Diet significantly mediated the relationship between pain and HbA(1c) control (ß = 0.06; 95% CI: 0.01-0.17), but only in the unadjusted model. Exercise and symptoms of depression were not significant mediators. CONCLUSIONS: A significant independent relationship between pain and HbA(1c) control was found in this mainly black population, which was not explained by self-management behaviours or symptoms of depression. Future research is needed to delineate the mechanism by which pain influences HbA(1c) control, especially among black people with diabetes on low incomes.

Dental risk factors for osteonecrosis of the jaws: a CONDOR case-control study.

BACKGROUND: Reports of osteonecrosis of the jaw (ONJ) have associated this lesion to treatment with bisphosphonates (BPs) and dental procedures. In this study, we investigated the association of specific dental diagnoses and procedures with ONJ among patients with past BP use. METHODS: Dentists from three practice-based research networks provided ONJ cases and controls (1:3). Data gathered from patients and dental offices with two respective standard questionnaires included demographic, medical, pharmaceutical, and dental information. Diagnoses and procedures up to 3 years prior to ONJ (prior to interview for controls) were analyzed within risk strata, defined by BP use and cancer status, using interaction terms within conditional logistic regression models. RESULTS: We enrolled 191 ONJ cases and 573 controls from 119 dental offices. Among participants who had used only oral BP, extraction was the only dental risk factor for ONJ (odds ratio (OR) = 12, p = 0.01). Suppuration was also more prevalent in cases (18 %) than in controls (9 %), but not statistically significant (OR = 9, p = 0.06). Among participants who had not used either oral or IV BP (a majority of whom received radiation therapy to the head and neck), suppuration was the only dental risk factor for ONJ (prevalence = 34 % for cases and 8 % for controls; OR = 7, p = 0.01). The prevalence of extractions in this group was also higher, but not statistically significant (44 vs 10 %; OR = 3). Limited power precludes definitive findings among participants exposed to IV BP. CONCLUSIONS: Among patients taking oral BP, extraction was the only dental procedure associated with subsequent ONJ development CLINICAL RELEVANCE: Results of this study suggest that routine dental procedures are not associated with development of ONJ in patients exposed to BPs.

Physicians' participatory decision-making and quality of diabetes care processes and outcomes: results from the triad study.

OBJECTIVES: In participatory decision-making (PDM), physicians actively engage patients in treatment and other care decisions. Patients who report that their physicians engage in PDM have better disease self-management and health outcomes. We examined whether physicians' diabetes-specific treatment PDM preferences as well as their self-reported practices are associated with the quality of diabetes care their patients receive. METHODS: 2003 cross-sectional survey and medical record review of a random sample of diabetes patients (n=4198) in 10 US health plans across the country and their physicians (n=1217). We characterized physicians' diabetes care PDM preferences and practices as 'no patient involvement,' 'physician-dominant,' 'shared,' or 'patient-dominant' and conducted multivariate analyses examining their effects on the following: (1) three diabetes care processes (annual hemoglobin A1c test; lipid test; and dilated retinal exam); (2) patients'satisfaction with physician communication; and (3) whether patients' A1c, systolic blood pressure (SBP), and low-density lipoprotein cholesterol (LDL) were in control. RESULTS: Most physicians preferred 'shared' PDM (58%) rather than 'no patient involvement' (9%), 'physician-dominant' (28%) or 'patient dominant' PDM (5%). However, most reported practicing 'physician-dominant' PDM (43%) with most of their patients, rather than 'no patient involvement' (13%), 'shared' (37%) or 'patient-dominant' PDM (7%). After adjusting for patient and physician-level characteristics and clustering by health plan, patients of physicians who preferred 'shared' PDM were more likely to receive A1c tests [90% vs. 82%, AOR: 2.05, 95% CI: 1.03-3.07] and patients of physicians who preferred 'patient-dominant' treatment decision-making were more likely to receive lipid tests [60% vs. 50%, AOR: 1.58, 95% CI: 1.04-2.39] than those of providers who preferred 'no patient involvement' in treatment decision-making. There were no differences in patients' satisfaction with their doctor's communication or control of A1c, SBP or LDL depending on their physicians' PDM preferences. Physicians' self-reported PDM practices were not associated with any of the examined aspects of diabetes care in multivariate analyses. CONCLUSIONS: Patients whose physicians prefer more patient involvement in decision-making are more likely than patients whose physicians prefer more physician-directed styles to receive some recommended risk factor screening tests, an important first step toward improved diabetes outcomes. Involving patients in treatment decision-making alone, however, appears not to be sufficient to improve biomedical outcomes.

Insulin resistance and weight gain in postmenopausal women of diverse ethnic groups.

OBJECTIVE: This study was conducted to examine the influence of insulin resistance on weight change in postmenopausal women of various ethnic groups. SUBJECTS: Data were obtained from 3389 women (60% White, 20% Black, 12% Hispanic, and 8% Asian/Pacific Islander), ages 50-79, enrolled in either the Women's Health Initiative Clinical trial or Observational Study, whose blood samples were selected randomly from the full cohort of 161 809 women for analyses. MEASUREMENTS: Glucose, insulin, and lipids were measured on fasting serum samples drawn at baseline and after 3 y of follow-up. Weight, height, waist circumference, and blood pressure were measured. Physical activity and energy intake were assessed via questionnaire. Insulin resistance was estimated using the HOMA (homeostasis model) calculation. RESULTS: Average age was 62 y, average BMI (body mass index) was 27.4 kg/m2, and average weight change was a gain of 0.4 kg in 3 y. In a multivariate analysis, insulin resistance and insulin concentrations were independent predictors of increases in weight in White women (P=0.002 and 0.004, respectively) and in the combined group (P=0.027 and 0.039). For the whole group, after adjustment for other covariates, those in the highest quartile of insulin resistance gained 0.4 kg in 3 y, whereas those in the lowest quartile lost 0.06 kg. Similar trends were found for insulin resistance and weight gain in Hispanic and Asian/Pacific Islander women, but they did not reach statistical significance. In Black women, no relation was seen between either insulin or insulin resistance and weight change. A significant interaction between obesity and insulin resistance was observed (P=0.002 for White women and 0.032 for the whole group), so that there is weight gain with increasing insulin resistance in the leaner women, but weight loss with increasing insulin resistance in the most obese. CONCLUSION: Insulin resistance appears to be a predictor of weight gain in postmenopausal women, except for the most obese women. The effect is more pronounced in women who have a lower BMI, and the effect was not seen in the Black women who as a group had a higher BMI.

Performance status of health care facilities changes with risk adjustment of HbA1c.

OBJECTIVE: To develop a risk adjustment method for HbA1c, based solely on administrative data and to determine the extent to which risk-adjusted HbA1c changes the identification of high- or low-performing medical facilities. RESEARCH DESIGN AND METHODS: Through use of pharmacy records, 204,472 diabetic patients were identified for federal fiscal year 1996 (FY96). Complete information (HbA1c levels, demographic data, inpatient records, outpatient pharmacy utilization records) was available on 38,173 predominantly male patients from 48 Veterans Health Administration (VHA) medical facilities. Hierarchical mixed-effects models were used to estimate risk-adjusted unique facility-level HbA1c. RESULTS: Predicted HbA1c demonstrated expected patterns for major factors known to influence glycemic control. Poorer glycemic control was seen in minorities and patients with greater disease severity, longer duration of disease (using treatment type or presence of amputation as surrogates), and more extensive comorbidity (measured by an adapted Charlson index). Better glycemic control was seen in Caucasians, older diabetic patients, and patients with higher outpatient utilization. The number of performance outliers was reduced as a result of risk adjustment. For mean HbA1c levels, 7 facilities that were initially identified as statistically significant outliers were no longer outliers after risk adjustment. For high-risk HbA1c (>9.5%) rates, 12 facilities that were initially identified as statistically significant outliers were no longer outliers after risk adjustment. CONCLUSIONS: Risk adjustment using only administrative data resulted in substantial changes in identification of high or low performers compared with non-risk-adjusted HbA1c. Although our findings are exploratory, risk adjustment using administrative data may be a necessary and achievable step in quality assessment of diabetes care measured by rates of high-risk HbA1c (>9.5%).

Oral soft tissue manifestations in HIV-positive vs. HIV-negative children from an inner city population: a two-year observational study.

PURPOSE: Data accrued after two years of longitudinal observation of oral soft tissue lesions in a cohort of HIV-infected children and comparisons to a group of uninfected controls is presented. SUBJECTS AND METHODS: One hundred and four HIV-positive subjects were enrolled from an inner city pediatric HIV clinic and HIV-negative household peers served as control. Oral exams were performed at six-month intervals while laboratory data of interest were obtained from the children's medical records. RESULTS: HIV-positive children had significantly more oral soft tissue lesions than their HIV-negative peers. In particular, the prevalence of candidiasis, linear gingival erythema and median rhomboid glossitis were high. However, oral lesions were not good predictors of mortality and only candidiasis was associated with a low CD4 count. CONCLUSIONS: Oral soft tissue lesions were common among HIV-positive children. While candidiasis was correlated with advanced disease, oral lesions were not good predictors of mortality.

Oral cancer and oral effects of anticancer therapy.

The term "oral cancer" generally refers to squamous cell carcinoma of oral mucosal origin, which accounts for more than 90% of all malignancies of this location. Although a relatively uncommon disease in the United States, this malignancy is nonetheless important, as it accounts for significant morbidity and mortality. Approximately half of the estimated 30 thousand cases diagnosed annually in this country have a fatal outcome. Survivors of the surgical and medical management may suffer from sequelae of treatment ranging from pain and infection to partial or total disfigurement and loss of stomatognathic function. Such high morbidity and mortality are truly regrettable, since many of these malignancies are preventable. This article will review recent developments in the epidemiology, treatment and chemoprevention of oral squamous cell carcinoma as they relate to early diagnosis, and management of the oral cancer patient.

JAK3: expression and mapping to chromosome 19p12-13.1.

We cloned JAK3, the most recently described member of the JAK family of intracellular tyrosine kinases, from normal human CD34+ RNA. JAK3 is involved in the signal transduction pathways of the IL-2, IL-4, IL7, IL-9, and IL-15 receptors by association with their common gamma-chain (gamma[c]). JAK3 is critical to lymphoid development, as recently established by the linking of mutations in JAK3 to a subgroup of patients with SCID and the generation of JAK3-null mice with severe disruptions in normal lymphocytic development. However, JAK3 expression is not restricted to the lymphocytic compartment of bone marrow but is found in a wide range of tissues of both hematopoietic and non-hematopoietic origin. Northern blot analysis indicates that JAK3 is also expressed in adult placenta, lung, liver, kidney, pancreas, spleen, thymus, ovary, and small intestine. RNAse protection assays and RT-PCR indicate that JAK3 is expressed in a variety of leukemic-derived hematopoietic cell lines with myeloid and/or lymphoid phenotypes. In normal human bone marrow, JAK3 is expressed in the CD34+/lineage- fraction, which is highly enriched in hematopoietic stem/progenitor cells. In addition, we found a splice variant of JAK3 which is formed by the splicing of JAK3 with exon II of the leydig insulin-like (LEY I-L) hormone. RT-PCR and RNAse protection assay analyses indicate that this variant (termed I-JAK3) is normally expressed in almost all hematopoietic and non-hematopoietic tissues shown to express JAK3. Using fluorescence in situ hybridization we have localized JAK3 to 19p12-13.1, the same region of chromosome 19 to which the LEY I-L hormone maps (19p12-13.2).

Management of oral pain in patients with malignant diseases.

Painful oral complications are common in patients undergoing treatment for malignant diseases. Correct diagnosis of painful oral lesions, as well as identification of etiological factors and appropriate therapy, are imperative for this group of patients. Oral mucosites, infections, and graft-versus-host disease and their respective current and prospective methods of management are reviewed.

Flow cytometric characterization of acute myeloid leukemia: IV. Comparison to the differentiation pathway of normal hematopoietic progenitor cells.

Gradual increase of CD38 on cells expressing CD34 characterizes the early cell differentiation pathway of normal human hematopoietic progenitors. In this study the coordinated expression pattern of CD34 and CD38 was assessed on leukemic blasts from bone marrow aspirates of 95 patients with newly diagnosed acute myeloid leukemia (AML). Expression was divided into six categories analogous to the differentiation pathway of normal bone marrow. The CD38 antigen was expressed on the leukemic cells of all patients and CD34+ leukemic cells were found in 79 patients (83%). In 93 patients, the leukemic cells were found along the differentiation pathway defined by CD34 and CD38. In 33 of the 93 patients, a part of the CD34+ cells did not express the CD38 antigen (categories 1 and 2). In another 33 patients, all CD34+ cells expressed CD38 (categories 3 and 4). In the remaining 27 patients, only cells were found which dimly expressed CD34 or did not express CD34 (categories 5 and 6). Of the 93 patients, 88 were treated with intensive chemotherapy according to the protocol of the German AML Cooperative Group. Of these, 21 died early and were not evaluable for treatment response. Complete remission was achieved in 14 of 22 patients (64%) in categories 1 and 2, in 19 of 26 patients (73%) in categories 3 and 4, and in 18 of 19 patients (95%) in categories 5 and 6. The event-free survival was significantly longer in patients of categories 5 and 6 compared to patients in categories 1 and 2 (p less than 0.01) and categories 3 and 4 (p less than 0.05), respectively. We conclude that in the majority of AML patients the immunophenotype of leukemic cells follows the early cell differentiation pathways defined by coordinated expression of CD34 and CD38 similar to that of normal hematopoietic progenitors. The presence of cells in the late cell differentiation stages (CD34+/-, CD38 /+) identifies patients with a higher complete remission rate and longer complete remission duration.

Flow cytometric characterization of acute myeloid leukemia. Part II. Phenotypic heterogeneity at diagnosis.

The frequency and distribution of aberrant antigen expression are analyzed on bone marrow aspirates from 80 patients with newly diagnosed acute myeloid leukemia (AML) by multidimensional flow cytometry. Parameters examined are the light scatter profile of the leukemic cells and the correlative expression of different combinations of the CD2, 4, 5, 7, 11b, 11c, 13, 14, 15, 16, 33, 34, 38, and HLA-DR antigens. Antigen expression on leukemic cells in bone marrow is described by characteristic antigen expression patterns describing: (i) the percentage of cells expressing the antigen; (ii) the antigen density; and (iii) the distribution of the antigen on the leukemic cells. Typically the non-myeloid antigens are homogeneously expressed by the leukemic cells, whereas the myeloid associated antigen CD11b, CD11c, CD14, and CD15 are heterogeneously expressed. Comparison of the antigenic profiles of 80 bone marrow aspirates revealed an extreme interclonal heterogeneity. Comparison of the antigen expression patterns found in AML patients with the antigen expression in normal bone marrow revealed four patterns of aberrant antigen expression in AML: (i) expression of nonmyeloid antigens (i.e. CD2, CD5, and CD7 were present in 57, 60, and 37% of the patients, respectively); (ii) asynchronous expression of myeloid associated antigens (i.e. co-expression of CD34 and CD15 in 25% of the patients and expression of CD16 on immature myeloid cells in 15% of the cases); (iii) over-expression of myeloid associated antigens (e.g. CD34 in 16% of the cases and CD14 on neutrophilic cells in 19% of all patients); and (iv) absence of expression of myeloid associated antigens (e.g. lack of CD33 in 21% of the cases and lack of both CD11b and CD15 in 6% of all patients. Multidimensional flow cytometric analysis of bone marrow aspirates of AML patients disclosed that the leukemic cells of each AML patient had a unique antigenic profile and could be discriminated from their normal counterparts based on aberrant antigen expression and typical light scatter profiles. The ability to distinguish leukemic cells from normal cells allows the detection of residual leukemic cells during and after chemotherapy.