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.     

Utilities of the Post-anesthesia State derived by the Standard Gamble method in surgical patients

Background  

There are no published utilities for the post-anesthesia state obtained by the standard gamble method (SG).     

The effect of bracing on proprioception of knees with anterior cruciate ligament injury.

This paper is a comprehensive review on the effect of bandaging, bracing, and neoprene sleeves on knee proprioception following anterior cruciate ligament (ACL) injury and reconstruction with a focus on studies that have measured joint position sense and threshold to detection of passive knee motion. Disruption of the ACL does not appear to alter joint position sense soon after injury, although there is evidence that in some subjects deterioration may occur over time. An ACL tear creates a deficit in the threshold to detection of passive knee motion soon after injury and in those with chronic tears. The magnitude of worsening is less then 1.0 degree of movement in flexion-extension and of questionable concern from a clinical and functional perspective. Application of a functional brace or neoprene sleeve to the ACL-deficient limb does not improve the threshold to detection of passive knee motion; however, application of an elastic bandage to a knee with an ACL tear improves joint position sense. Reconstruction of a torn ACL is associated with a deficit in the threshold to detection of passive knee motion, and during the first year of healing the use of a neoprene sleeve provides improvement. Two years following ACL reconstruction there is no deficit in the threshold to detection of passive knee motion and the use of a brace has no effect on this outcome.     

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).     

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.