Biomedical subjects

Andrew S Artz

Publications and source records attributed to Andrew S Artz.

8 recordsLinked to original sources

PubMed2026

Azacitidine-Venetoclax or Induction Chemotherapy for Acute Myeloid Leukemia.

BACKGROUND: Induction chemotherapy has long been a key component of curative therapy for fit patients with acute myeloid leukemia (AML), despite its frequently severe side effects and substantial health care utilization. For patients who are ineligible for induction chemotherapy, hypomethylating therapy plus venetoclax is the standard treatment owing to its efficacy and side-effect profile. METHODS: In this multicenter, phase 2 trial, we randomly assigned, in a 1:1 ratio, previously untreated adults with AML who were eligible for induction chemotherapy to receive either azacitidine plus venetoclax or induction chemotherapy. Patients with core binding factor fusions, mutations in the gene encoding FMS-like tyrosine kinase 3 (FLT3), or mutations in the gene encoding nucleophosmin-1 (NPM1; unless the patient was ≥60 years of age) were excluded. The primary end point was event-free survival. RESULTS: A total of 172 patients underwent randomization, with 86 patients assigned to each group. The median age of the patients was 64 years. A total of 72% of the patients had adverse-risk disease according to the European LeukemiaNet 2022 classification. At a median follow-up of 21.9 months, the median event-free survival was 14.5 months (95% confidence interval [CI], 10.4 to 24.4) in the azacitidine-venetoclax group, as compared with 6.2 months (95% CI, 4.1 to 10.1) in the induction chemotherapy group, corresponding to a hazard ratio for event or death of 0.57 (95% CI, 0.39 to 0.84; P = 0.002 by the stratified log-rank test). Infection of grade 3 or higher occurred in 28% of the patients (95% CI, 19 to 39) receiving azacitidine-venetoclax and in 41% of those (95% CI, 30 to 52) receiving induction chemotherapy; hemorrhage of grade 3 or higher occurred in 2% (95% CI, 0.3 to 8) and 12% (95% CI, 6 to 20), respectively. CONCLUSIONS: In this phase 2, randomized trial, azacitidine-venetoclax therapy led to significantly longer event-free survival than induction chemotherapy among induction-eligible patients with AML. (Funded by AbbVie and others; PARADIGM ClinicalTrials.gov number, NCT04801797.).

Adult↗

PubMed2006

Issues of aging and geriatric medicine: relevance to cancer treatment and hematopoietic reconstitution.

Aging is not a disease. Nevertheless, diseases, including most malignancies, increase in frequency with advancing age. Although there are many reasons why this might be the case, perhaps most important is that it takes time to progress through the many steps of carcinogenesis and growth to reach a threshold for diagnosis. Other factors, including accumulated nonlethal damage to DNA (eg, by free radicals), increased proinflammatory factors, and age-associated declines in DNA repair and immune competence, are to some degree important. The median age for all cancer is approximately 70 years and will become even older over the next several decades. Myelodysplasia and hematologic malignancies, including lymphoma, myeloma, and leukemia, can be effectively treated in older age groups, but advanced age presents a number of additional challenges. With appropriate pretreatment assessment of organ reserve, physical performance, and cognitive function, individualized (tailored) therapy may ultimately prove to offer the greatest chance for successful outcomes. Such assessment would also identify those who are likely to benefit from more aggressive treatments, including bone marrow or stem cell transplantation.

Aged↗

PubMed2006

Performance status and comorbidity predict transplant-related mortality after allogeneic hematopoietic cell transplantation.

Comorbidity measurements have recently been used to improve estimation of tolerance to allogeneic hematopoietic cell transplantation (HCT). We sought to determine the independent effect of comorbidity and performance status on HCT outcome and to devise a simple risk classification system for transplant-related mortality. We analyzed 105 consecutively enrolled patients who underwent HCT and received reduced intensity conditioning with fludarabine, melphalan, and alemtuzumab. Comorbid conditions were tabulated using 2 scales, the Charlson Comorbidity Index (CCI) and the Kaplan-Feinstein Scale (KFS). Comorbid conditions were found in 47% of patients by the KFS and in 27% by the CCI (P < .001). Using the Eastern Cooperative Oncology Group Performance Status (PS) scale, 34% had a PS score >0 (range, 0-2). A simple scale combining the KFS and PS enabled separation of high- from low-risk patients, with 6-month cumulative incidences 50% and 15%, respectively for transplant-related mortality (P = .001) and enhanced prognostic power over the CCI alone (P = .018). Prospective studies evaluating more comprehensive functional and comorbidity measurements are warranted.

Adult↗

PubMed2006

Order of patient entry influences outcome for metastatic renal cell cancer after non-myeloablative allogeneic stem cell transplantation.

Allogeneic transplantation for renal cell carcinoma has shown encouraging preliminary results. We reviewed the published literature to evaluate the impact of patient selection. Most studies did not include information on prognostic factors. We used patient entry rank within individual studies as a novel surrogate for patient selection, motivated by our own experience of an apparent impact of entry rank. One hundred patients were identified from nine studies. Twenty-six per cent of patients demonstrated either a partial or complete response. Median overall survival was 12.3 months. Grade 2-4 acute graft-versus-host disease correlated with an increased likelihood of response (odds ratio: 5.4, 95% confidence interval: 1.6-18.1, P = 0.006) but not survival. Earlier patient entry rank on each trial was associated with a higher probability of response (P = 0.004) and superior survival (P = 0.004). Patient entry rank served as a powerful prognostic factor, suggesting bias in patient selection that evolved over the course of the study. Further studies are warranted to determine the influence of order of patient entry in other early clinical trial settings.

Acute Disease↗

PubMed2005

Serum erythropoietin and aging: a longitudinal analysis.

OBJECTIVES: To determine the changes in serum erythropoietin with age in patients with and without anemia and to assess the importance of certain comorbidities on changes in erythropoietin level and the development of anemia. DESIGN: Clinical history, hematological parameters, and serum erythropoietin levels were examined at 1- to 2-year intervals for 8 to 30 years. SETTING: Baltimore Longitudinal Study on Aging (BLSA), National Institute on Aging. PARTICIPANTS: One hundred forty-three BLSA participants. MEASUREMENTS: Complete blood count and serum chemistries were performed at the time of each visit, and archived serum samples were used for erythropoietin level. RESULTS: Although all subjects were healthy and without anemia at the time of initial evaluation, some developed chronic illness-most notably hypertension and diabetes mellitus. Erythropoietin levels rose significantly for the group as a whole, and the slope of the rise was found to be greater for those who did not have associated diabetes mellitus or hypertension. During the subsequent years, subjects who developed anemia but did not have hypertension or diabetes mellitus had the greatest slope in erythropoietin rise over time, whereas those with hypertension or diabetes mellitus and anemia had the lowest erythropoietin slope. CONCLUSION: The increase in serum erythropoietin with aging may be compensation for subclinical blood loss, increased red blood cell turnover, or increased erythropoietin resistance of red cell precursors. It is suspected that, with very advanced age, or in those with compromised renal function (e.g., diabetes mellitus or hypertension), the compensatory mechanism becomes inadequate and anemia results.

Adult↗

PubMed2004

Mechanisms of unexplained anemia in the nursing home.

OBJECTIVES: To characterize anemia in elderly nursing home residents. DESIGN: Prospective multiinstitutional cohort study. SETTING: Five nursing homes. PARTICIPANTS: From retrospective analysis, residents found to be anemic using chart review were prospectively randomized. Of the 81 residents enrolled, 60 were anemic. MEASUREMENTS: Chart review for medical history and factors related to treatment or history of anemia, extensive laboratory evaluation for causes of anemia, and classification of anemia by two hematologists. RESULTS: Among the 60 anemic residents, the causes of anemia were idiopathic (n=27), iron-deficiency (n=14), anemia associated with chronic disease (n=8), anemia of renal insufficiency (n=6), and other (n=5). The eryrthropoietin (EPO) response to anemia was lower in residents with idiopathic anemia (IA) than in those with iron-deficiency anemia, and this correlated with renal function as estimated using calculated creatinine clearance. In this elderly population, advancing age was not correlated with lower EPO response. CONCLUSION: IA is common in nursing home residents. A lower EPO response contributes to the high prevalence of anemia in this setting and may be due, in part, to occult renal dysfunction.

Aged↗

PubMed2003

Pneumococcal vaccination and revaccination of older adults.

As individuals advance in age, the risk of infection, bacteremia, and mortality caused by Streptococcus pneumoniae rises. Retrospective data demonstrate that the licensed penumococcal polysaccharide vaccine (PPV) is effective in older persons in reducing serotype-specific invasive disease. PPV demonstrates good immunogenicity in older adults, generally comparable to that in younger subjects, although certain cohorts respond less well. The response to PPV is T cell independent, however, and does not elicit immunologic memory. The duration of the anti-capsular polysaccharide antibody response appears to wane as early as 3 years after vaccination. In older persons, revaccination induces an antibody response, although it may not be as strong as that from the initial vaccine. While revaccination of older adults has been recommended, clinical efficacy has not yet been proven. Measures of antibody function may be at least as important in determining protection as are quantitative antibody levels. Additional studies of immunogenicity, particularly regarding revaccination, will facilitate the design of an optimal pneumococcal vaccination policy. Research into conjugate- and protein-based pneumococcal vaccines, which elicit T-cell-dependent responses and induce immunologic memory, is needed in older persons. In the meantime, administering to PPV to recommended groups should be a public health priority.

Adult↗

PubMedDate not supplied

Prevalence of anemia in skilled-nursing home residents.

Anemia is a frequent problem among older persons, the prevalence of which may be particularly high in skilled-nursing facilities but recent data in this regard is lacking. The purpose of this study was to define the prevalence of anemia and its association with hospitalization in skilled-nursing home residents. We retrospectively reviewed randomly selected charts among five skilled-nursing facilities within the National Geriatrics Research Consortium (NGRC). Among 900 chronically residing patients with completed chart information, the mean and median ages were 79 years and 82 years, respectively. Eighty-seven percent of patients were 65 years or greater. Applying the World Health Organization criteria for anemia (hemoglobin <12 g/dl for women and hemoglobin <13 g/dl for men), we found a 6-month point prevalence of 48%. The hospitalization rate was higher among those with more severe anemia. Few residents were treated with recombinant erythropoietin therapy or red blood cell transfusion. Anemia is very common in the nursing home, and despite being associated with increased morbidity; it is, for the most part, untreated in this setting. With an increased understanding of erythropoiesis and the availability of recombinant growth factors, future studies should evaluate the causes and potential benefits of treatment in terms of quality of life, reduced morbidity and health economics.

Aged↗