A randomized, double-blind, multicenter study in 181 afebrile cancer patients with ANC levels <500/μL receiving myelosuppressive chemotherapy was undertaken to compare sargramostim (yeast-derived ...recombinant human granulocyte-macrophage colony-stimulating factor, RhuGM-CSF) and filgrastim (bacteria-derived recombinant human granulocyte colony-stimulating factor, RhuG-CSF) in the treatment of chemotherapy-induced myelosuppression. Patients received daily subcutaneous (SC) injections of either agent until ANC levels reached at least 1500/μL. There was no statistical difference between treatment groups in the mean number of days to reach an ANC of500/μL, but the mean number of days to reach ANC levels of 1000/μL and 1500/μ L was approximately one day less in patients receiving filgrastim. Fewer patients in the sargramostim arm were hospitalized, and they had a shorter mean length of hospitalization, mean duration of fever, and mean duration of IV antibiotic therapy compared with patients who received filgrastim. Both growth factors were well tolerated. No patient was readmitted to the hospital after growth factor was discontinued. Sargramostim and filgrastim have comparable efficacy and tolerabil-ity in the treatment of standard-dose chemotherapy-induced myelosuppression in community practice.
Respiratory syncytial virus (RSV) is a major cause of hospitalisation in infants. The burden of RSV infection in healthy term infants has not yet been established. Accurate health-care burden data in ...healthy infants are necessary to determine RSV immunisation policy when RSV immunisation becomes available.
We performed a multicentre, prospective, observational birth cohort study in healthy term-born infants (≥37 weeks of gestation) in five sites located in different European countries to determine the health-care burden of RSV. The incidence of RSV-associated hospitalisations in the first year of life was determined by parental questionnaires and hospital chart reviews. We performed active RSV surveillance in a nested cohort to determine the incidence of medically attended RSV infections. The study is registered with ClinicalTrials.gov, NCT03627572.
In total, 9154 infants born between July 1, 2017, and April 1, 2020, were followed up during the first year of life and 993 participated in the nested active surveillance cohort. The incidence of RSV-associated hospitalisations in the total cohort was 1·8% (95% CI 1·6-2·1). There were eight paediatric intensive care unit admissions, corresponding to 5·5% of 145 RSV-associated hospitalisations and 0·09% of the total cohort. Incidence of RSV infection in the active surveillance cohort confirmed by any diagnostic assay was 26·2% (24·0-28·6) and that of medically attended RSV infection was 14·1% (12·3-16·0).
RSV-associated acute respiratory infection causes substantial morbidity, leading to the hospitalisation of one in every 56 healthy term-born infants in high-income settings. Immunisation of pregnant women or healthy term-born infants during their first winter season could have a major effect on the health-care burden caused by RSV infections.
Innovative Medicines Initiative 2 Joint Undertaking, with support from the EU's Horizon 2020 research and innovation programme and European Federation of Pharmaceutical Industries and Associations.
A phase III trial to compare PIXY321 with granulocyte-macrophage colony-stimulating factor (GM-CSF) following high-dose therapy and autologous bone marrow transplant (ABMT) was conducted to evaluate ...the time to hematopoietic recovery.
One hundred seventy-seven patients with non-Hodgkin's lymphoma (NHL) receiving ABMT were randomized to receive either PIXY321 750 micrograms/m2/d divided into two subcutaneous (SC) doses or GM-CSF 250 micrograms/m2/d as a 2-hour intravenous (IV) infusion starting on day 0 post-ABMT for a maximum of 28 days.
The median time to reach an absolute neutrophil count (ANC) > or = 500/microL in the PIXY321 group was 17 days versus 19 days in the GM-CSF group (P = .07) and the median time to reach platelet transfusion independence in the PIXY321 group was 25 days versus 23 days in the GM-CSF group (P = .30). The toxicity profiles of the two agents appeared to be equivalent with the exception of more patients in the PIXY321 group with a rash (64%) compared with the GM-CSF group (48%) (P = .028). A logistic regression model identified the use of a non-total-body irradiation (TBI) regimen and/or receipt of unpurged marrow and a body-surface area greater than 2.0 m2 as predictive of faster neutrophil engraftment, and those three factors, as well as the receipt of < or = two prior chemotherapy regimens as predictive for rapid platelet engraftment.
There was a trend toward a slight improvement in neutrophil engraftment post-ABMT with the PIXY321 administered by an SC route compared with GM-CSF administered by an IV route. However, no differences could be identified between the two agents with respect to the time to platelet transfusion independence. Patient, regimen, and graft characteristics were most predictive of the engraftment tempo.
To determine the antiemetic drug preferences of practicing adult oncologists and to estimate the frequency of use of marijuana smoke as an antiemetic agent.
Identical mailed questionnaire surveys on ...antiemetic preferences, distributed prior to approval of ondansetron.
Two groups of practicing clinical adult oncologists were surveyed. The first group (N = 120) consisted of every twentieth board-certified, American member of the American Society of Clinic Oncology culled from the 1990 ASCO membership directory in alphabetical order. The second group (N = 60) consisted of every adult clinical oncologist in metropolitan Washington, D.C.
Completed surveys were returned by 141 (78%) physicians; the responses from both groups were almost identical (Wilcoxon Rank Sum Test). Marijuana (either as marijuana smoke or oral tetrahydrocannabinol) ranked ninth in order of preference for the treatment of mild to moderate nausea and vomiting, and sixth for the treatment of more severe symptoms induced by chemotherapy. Most (94 or 65%) respondents reported having prescribed marijuana or oral THC 10 times or less; only 5 (3.5%) had prescribed such drugs more than 100 times which represented for them about 1% of their average lifetime clinical patient load. The respondents who had prescribed marijuana in any form thought that it had effectively relieved post-chemotherapy nausea or vomiting in 50% of patients. Unpleasant adverse effects were estimated to have occurred in 25% of treated patients. Only 8 (6%) respondents indicated that they would prescribe marijuana much more frequently--if there were no legal barriers associated with its medical use.
Marijuana in any form was believed to be efficacious for 50% of patients with pre- or post-chemotherapy nausea or vomiting. However, one of four patients who received it complained of bothersome adverse effects. At the time of the study, cannabis was prescribed or recommended relatively infrequently by American clinical oncologists (i.e., those who actually prescribed chemotherapy). Even if it was freely available and restrictions on its use liberalized, smokeable marijuana, according to responses given on this survey, would not be used much more frequently by American oncologists.
Abstract Context Quality care for patients with cancer is a national priority—for those with noncurable cancer, the stakes are even higher. Strategies to promote integration of palliative care into ...oncology practice may enhance quality. We have developed a model in which palliative care services are integrated into the private, office-based oncology practice setting. We have evaluated the feasibility and assessed outcomes for both the oncologists and the patients they serve. To our knowledge, an embedded clinic in an outpatient, private practice oncology clinic has not been described previously. Objective The primary outcomes assessed were 1) quality care outcomes through assessment of symptom burden and relief achieved through palliative care consultation, 2) provider satisfaction, 3) volume determined by number of palliative care consultations over time, and 4) time saved for the oncologist as a surrogate for the bottom line of the cancer practice. Methods Measurement of: symptom burden and relief with the Edmonton Symptom Assessment System (ESAS), physician acceptance of palliative care services through a provider satisfaction survey and volume of referrals, and billing data to determine potential oncologists' time saved. Results Palliative care consultation was associated with a reduction in symptom burden by 21%, evidenced by decrease in average total ESAS score from 49.3 to 39. Median provider satisfaction scores rating components of palliative care ranged from 8.5 to 9/10, with an overall provider satisfaction of 9/10. Over the study period, the “embedded” oncology group consultation requests increased 87% (67–120), with each individual oncology provider nearly doubled. The total time saved for the oncology practice in Year 2 was just over four weeks (9720 minutes; 162 hours). Conclusion An embedded palliative care clinic integrated into an office-based oncology practice is feasible and may improve the quality of care. Formal study of this service delivery model is warranted.
Fifty-three women with breast cancer were treated with a new 16-week dose-intense, chemotherapy regimen. Patients with operable breast cancer with 10 or more histologically positive axillary nodes ...were treated with this five-drug regimen that incorporated the concepts of weekly chemotherapy, sequential administration of antimetabolites, and continuous infusion of fluorouracil (5-FU). The chemotherapy regimen consisted of eight cycles (each of 2 wk duration) of 100 mg of cyclophosphamide/m2 orally on days 1-7, 40 mg of doxorubicin/m2 intravenous (IV) on day 1, 100 mg of methotrexate/m2 IV on day 1 with 10 mg of leucovorin rescue/m2 every 6 hours for six oral doses on day 2, 1 mg of vincristine IV on day 1, and 600 mg of 5-FU/m2 IV at hour 20 over 2 hours. A continuous infusion of 300 mg of 5-FU/m2 per day was given IV on days 8-9 of each 2-week cycle. The doses and schedule of drug administration were designed to minimize dosage reduction and treatment delay. At a median follow-up of 17 months, there have been eight relapses in the 53 patients. The actuarial 3-year disease-free survival is 80% (95% confidence interval, 62% to 90%). The major side effects were attributable to myelosuppression. Absolute neutrophil counts less than 250/microL were noted in 12 (23%) patients; seven patients (13%) required hospitalization for management of neutropenic fever. No treatment-related deaths occurred. Ninety-four percent of the planned doses were administered, and only 5% of the courses were delayed because of toxic reactions. The encouraging therapeutic data, manageable side effects, and our ability to deliver over 90% of the planned doses provide the rationale for a phase III comparison of this new dose-intense regimen and standard chemotherapy in patients with operable disease and positive axillary nodes.
A multicenter study of CA549, a marker for breast cancer, was conducted using sera from 1721 patients with benign and malignant conditions by an immunoradiometric assay, BRESMARQ. Acceptable assay ...performance was demonstrated by studies of intra-assay (2.2% to 12% coefficient of variation CV), interassay (4.1% to 11.8% CV), and interlaboratory (4.8% to 8.7% CV) precision; sensitivity (.3 kU/L); linearity; recovery; high-dose hook effect (up to 10,000 kU/L); and interferences (human antimouse antibodies; protein, bilirubin, hemoglobin levels; lipid and cancer therapeutic agents). A reference interval of 0-12.5 kU/L (women) and 0-11.9 kU/L (men) was established from 746 healthy persons. The distribution of values exceeding the reference range for benign conditions was as follows: pregnant and lactating women (2%); benign breast disease (5%); and seven other benign diseases, including liver (24%), lung (19%), prostate (14%), colon, endometrial, gastric, and ovarian (< 10%). For nonbreast cancers, the distribution was Hodgkin's (7%), colon (10%), endometrial (15%), gastric (15%), lymphoma (15%), prostate (20%), ovarian (39%), and liver (45%). For breast cancer, the distribution was stage I (5%), stage II (14%), stage III (32%), and stage IV (74%). The receiver-operating characteristic analysis demonstrated the usefulness of CA549 as a marker in stage IV breast cancer.
Acute erythroid leukemia (AEL) commonly involves both myeloid and erythroid lineage transformation. However, the mutations that cause AEL and the cell(s) that sustain the bilineage leukemia phenotype ...remain unknown. We here show that combined biallelic Cebpa and Gata2 zinc finger-1 (ZnF1) mutations cooperatively induce bilineage AEL, and that the major leukemia-initiating cell (LIC) population has a neutrophil-monocyte progenitor (NMP) phenotype. In pre-leukemic NMPs Cebpa and Gata2 mutations synergize by increasing erythroid transcription factor (TF) expression and erythroid TF chromatin access, respectively, thereby installing ectopic erythroid potential. This erythroid-permissive chromatin conformation is retained in bilineage LICs. These results demonstrate that synergistic transcriptional and epigenetic reprogramming by leukemia-initiating mutations can generate neomorphic pre-leukemic progenitors, defining the lineage identity of the resulting leukemia.
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•Biallelic C/EBPα and GATA-2 ZnF1 mutations synergize during leukemogenesis•GATA-2 ZnF1 mutation generates an erythroid-permissive chromatin state•C/EBPα and GATA-2 mutant NMPs show ectopic erythroid lineage potential•Transformed leukemic NMPs are bipotent neutrophil-erythroid leukemia-initiating cells
By combining biallelic C/EBPα and GATA-2 ZnF1 mutations, Di Genua et al. generate a mouse model of bilineage acute erythroid leukemia and identify a neutrophil-monocyte progenitor (NMP) that undergoes transcriptional and epigenetic reprogramming to express erythroid genes as the major leukemia-initiating cell.
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