Maximizing Breast Cancer Therapy with Awareness of Potential Treatment-Related Blood Disorders

In this review we summarize the impact of the various modalities of breast cancer therapy coupled with intrinsic patient factors on incidence of subsequent treatment-induced myelodysplasia and acute myelogenous leukemia (t-MDS/AML). It is clear that risk is increased for patients treated with radiation and chemotherapy at younger ages. Radiation is associated with modest risk, whereas chemotherapy, particularly the combination of an alkylating agent and an anthracycline, carries higher risk and radiation and chemotherapy combined increase the risk markedly. Recently, treatment with granulocyte colony-stimulating factor (G-CSF), but not pegylated G-CSF, has been identified as a factor associated with increased t-MDS/AML risk. Two newly identified associations may link homologous DNA repair gene deficiency and poly (ADP-ribose) polymerase inhibitor treatment to increased t-MDS/AML risk. When predisposing factors, such as young age, are combined with an increasing number of potentially leukemogenic treatments that may not confer large risk singly, the risk of t-MDS/AML appears to increase. Patient and treatment factors combine to form a biological cascade that can trigger a myelodysplastic event. Patients with breast cancer are often exposed to many of these risk factors in the course of their treatment, and triple-negative patients, who are often younger and/or BRCA positive, are often exposed to all of them. It is important going forward to identify effective therapies without these adverse associated effects and choose existing therapies that minimize the risk of t-MDS/AML without sacrificing therapeutic gain.

Implications for Practice

Breast cancer is far more curable than in the past but requires multimodality treatment. Great care must be taken to use the least leukemogenic treatment programs that do not sacrifice efficacy. Elimination of radiation and anthracycline/alkylating agent regimens will be helpful where possible, particularly in younger patients and possibly those with homologous repair deficiency (HRD). Use of colony-stimulating factors should be limited to those who truly require them for safe chemotherapy administration. Further study of a possible leukemogenic association with HRD and the various forms of colony-stimulating factors is badly needed.

     

Peripheral Vascular Complication from Coronary Angiography: a Case Report of Cholesterol Embolization

A 65-year-old man developed acute limb ischemia, severe abdominal wall and lower limb livedo reticularis following a coronary angiogram. The differential diagnoses of acute limb ischemia and multiple cholesterol emboli syndrome (MCES) are discussed. This work was performed at Long Island Jewish Medical Center, 270-05, 76^th Avenue, New Hyde Park, NY 11040.     

Sentinel health events surveillance in diabetes. Deaths among persons under age 45 with diabetes

The pilot study for a sentinel health events surveillance system for deaths among persons under age 45 with diabetes was conducted in six states in 1984 and 1985. Two hundred and thirty-three events were identified. Information from death certificates, physicians, and families revealed that 22% died from acute complications of diabetes and 53% from chronic complications. Blood pressure measurement and urinalysis testing had been performed in the last year for almost all of the decedents, but other preventive practices were reported less frequently. Hypertension was present in 57% and of those, was not controlled in 73%. Forty-four percent were cigarette smokers at the time of death. Agreement between physicians and families was generally higher for clinical conditions than for care practices. This surveillance system appears to yield information about the health care of persons with diabetes not readily available from other sources, although modifications may be necessary before implementation.     

1-乙基-6-氟-1,4-二氢-4-氧代-7-(4-芳酰硫代氨甲酰基-1-哌嗪基)-3-喹啉羧酸的合成及抗菌作用

Thirteen new 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(4-aroyl-thiocarbamoyl- 1 piperazinyl)-3-quinoline carboxylic acids were prepared, Their structures were characterized by elemental analysis, IR, HNMR and MS spectra.Preliminary pharmacological tests indicated that some of compounds Ia～m possess strong inhibiting activity against Escherichia coli, Bacillus subtilis and Proteus at concentration of 100 μg/ml.     

Changing attentional demands in left hemispatial neglect.

Seven variations of a letter cancellation test were used to examine how varying attentional demands affect hemispatial neglect in patients with right hemisphere lesions. While the 14 targets always remained in the same location, the number of distractors (zero, nine, 28, or 82) as well as their complexity (one letter or nine different letters) were varied. The percentage of targets canceled in the left hemispace was linearly related to the number of distractors. There were no differences between the complexity conditions. In a second study, the same 14 targets were presented but the distractors (zero, 14, or 41) were all placed on the right. Increasing the number of distractors on the right increased neglect on both sides of the space. Taken together, these results suggest that, while the limited attentional resources of the left hemisphere are biased toward the right hemispace, the absence of contralateral attentional demands allows these resources to be directed ipsilaterally.     

Recommendations for the evaluation and treatment of neonatal autoimmune and alloimmune thrombocytopenia. The Working Party on Neonatal Immune Thrombocytopenia of the Neonatal Hemostasis Subcommittee of the Scientific and Standardization Committee of the ISTH

The following recommendations of the Neonatal Hemostasis Subcommittee of the Scientific and Standardization Committee of the ISTH for the management of neonatal immune thrombocytopenia were prepared by the working party on neonatal immune thrombocytopenia. Evaluation, diagnosis, and treatment of the mother and neonate with alloimmune and autoimmune thrombocytopenia are discussed and current recommendations provided. This document is likely to require frequent future revision(s).     

Poverty and health. Prospective evidence from the Alameda County Study

To examine the reasons for the association between socioeconomic status and poor health, the authors examined the nine-year mortality experience of a random sample of residents aged 35 and over in Oakland, California. Residents of a federally designated poverty area experienced higher age-, race-, and sex-adjusted mortality over the follow-up period compared with residents of nonpoverty areas (relative risk = 1.71, 95 per cent confidence interval 1.20-2.44). This increased risk of death persisted when there was multivariate adjustment for baseline health status, race, income, employment status, access to medical care, health insurance coverage, smoking, alcohol consumption, physical activity, body mass index, sleep patterns, social isolation, marital status, depression, and personal uncertainty. These results support the hypothesis that properties of the sociophysical environment may be important contributors to the association between low socioeconomic status and excess mortality, and that this contribution is independent of individual behaviors.     

Platelet antibodies in systemic lupus erythematosus

In systemic lupus erythematosus (SLE), the precise cause of the thrombocytopenia is unknown. Since platelet associated IgG is increased in many patients, it has been suggested that the destruction of platelets might be dependent on specific antibodies. In nine patients with SLE, platelet associated immunoglobulins were found together with free serum antibody which bound to platelets from all normal subjects. Using an immunoblotting technique with membrane proteins from normal platelets incubated with patient sera, target antigens were localized on a band of mol wt 108,000 in two cases (B. and N.) and on a band of mol wt 66,000 in a third (M.). When the same technique was applied to autologous platelets of patient N., autoantibody binding to the protein of mol wt 108,000 was demonstrated. The antigenic determinants were not removed from the platelets by enzyme treatment or by disulphide bond reduction, and were localized in the cytoplasmic fraction of the platelets.