Progressive transfusion and growth factor independence with adjuvant sertraline in low risk myelodysplastic syndrome treated with an erythropoiesis stimulating agent and granulocyte-colony stimulating factor

AbstractRefractoriness to growth factor therapy is commonly associated with inferior outcome in patients with low-risk myelodysplastic syndrome (LR-MDS) who require treatment for cytopenias. However, the mechanisms leading to refractoriness are unknown. Here we describe a clinically depressed 74-year-old male with refractory cytopenia with multilineage dysplasia (RCMD) and documented growth factor refractory anemia after erythropoeisis stimulating agent (ESA) therapy, who attained transfusion and growth factor independence after the addition of sertraline to his medication regimen. Our case demonstrates hematological improvement-erythroid (HI-E) in growth factor refractory, low risk MDS and highlights a potential mechanistic link between common inflammatory diseases and LR-MDS

LIGAND BINDING TO HEME PROTEINS: AN EVALUATION OF DISTAL EFFECTS

Steric interactions between ligand molecules and the valine E11 methyl group of human hemoglobin and sperm whale myoglobin have been examined by high resolution NMR. The methyl proton resonances of this amino acid are shifted markedly upfield by the heme ring current. In all the proteins the position of the E11 valine resonance showed little change in going from bound CO to bound methyl and ethyl isocyanide. In alpha chains and myoglobin, the binding of n-propyl and n-butyl isocyanide produced marked downfield shifts of the valine resonance, indicating that the valine residue was forced away from the center of the heme ring. In beta subunits only tert-butyl isocyanide produced a marked decrease in the ring current shift of the valine methyl protons. New peaks observed in the isonitrile protein spectra were identified as ligand proton resonances by comparing the spectra of normal and deuterated isonitrile complexes. The magnitudes of the ring current shifts for the terminal methyl protons of ethyl isocyanide suggest a linear geometry for the Fe = C = N - Cl bonds in beta chains and a bent geometry for alpha chains. Myoglobin ethyl isocyanide complexes exhibit ligand ring current shifts intermediate to those observed for the hemoglobin subunits. Kinetic and equilibrium constants for the reactions of CO and the isonitriles with a large group of proteins and a model heme compound have been determined. Results were analyzed in terms of a 3 barrier model for ligand binding. The observed rate and equilibrium constants for the protein reactions showed a complex dependence on each individual step in the binding process. Pentacoordinate heme dissolved in soap served as a simple model for the proteins. When the protein equilibrium data are converted into free energy terms and the heme-soap results subtracted, the resulting value, (DELTA)G(,prot), describes the distal protein steric barrier. The results indicate that CO binds easily to all of the heme proteins while methyl isocyanide shows a large increase in (DELTA)G(,prot). This increase in steric hindrance has been attributed to the distal histidine residue. In most of the proteins, bound ethyl isocyanide exhibits about the same steric barrier as methyl isocyanide and the longer isonitriles show increasingly larger steric hindrance

Uncovering Clinical Features of De Novo Philadelphia Positive Myelodysplasia

Myelodysplastic syndrome (MDS) is cytogenetically heterogeneous and retains variable risk for acute myeloid leukemia transformation. Though not yet fully understood, there is an association between genetic abnormalities and defects in gene expression. The functional role for infrequent cytogenetic alteration remains unclear. An uncommon chromosomic abnormality is the presence of the Philadelphia (Ph) chromosome. Here, we report a patient with Ph+ MDS treated with low dose Dasatinib who achieved hematologic response for 7 months. In addition, we also examined the English literature on all de novo Ph + MDS cases between 1996 and 2015 to gain insight into clinical features and outcome

Balancing Work and Cancer Care: Challenges Faced by Employed Informal Caregivers

Individuals with cancer commonly rely on their informal caregivers (e.g., spouse/partner, family member, close friend) to help them manage the demands of the disease and its treatment. Caregiving, including helping with patient care, performing household chores, and providing emotional and practical support, can be particularly demanding for employed caregivers, who must juggle their work responsibilities while providing care. Although a burgeoning literature describes the toll that balancing these oft-competing demands can exact, few resources exist to support employed cancer caregivers. To address this gap, we conducted a narrative review of the impacts of cancer on employed caregivers. We found that employed caregivers experience significant financial impacts in terms of lost time and income. They also experience a variety of work-related (e.g., reduced productivity, absenteeism) and mental health (e.g., stress, burden) impacts. Going forward, prospective studies are needed to characterize changes in caregiver support needs and preferences at different time points along the cancer care continuum (e.g., at diagnosis, during treatment, end-of-life) so that appropriate workplace accommodations can be provided. More population-based studies are also needed to develop models for identifying caregivers who are at increased risk for poor employment or mental health outcomes so that more targeted support programs can be developed. Ultimately, a multipronged effort on behalf of employers, healthcare, and community-based organizations may be needed to support and empower this vulnerable subgroup