Relapsing-remitting multiple sclerosis and chronic idiopathic neutropenia: a challenging combination.

We report the challenges of treating relapsing-remitting multiple sclerosis (MS) in a 31-year-old woman with long-standing chronic idiopathic neutropenia. The treatment with the disease-modifying therapy interferon-ß was significantly complicated by a further fall in her generally low neutrophil count, to values below 0.5×10(9)/l, although this recovered rapidly when the treatment was stopped. We discuss the difficulties of balancing the risk of neutropenia with a risk of MS relapse.

Spontaneous mediastinal haemorrhage linked with thymic carcinoma and myelodysplasia: a case report.

We report an unusual sequence of clinico-pathological manifestations of myelodysplastic syndrome and thymic squamous cell carcinoma. A 77-year-old man with a two-month history of myelodysplastic syndrome was admitted with acute chest pain and shortness of breath. Radiological investigations revealed an anterior mediastinal mass, associated with mediastinal haemorrhage. The mass was excised via a standard median sternotomy and was found to be an infiltrating squamous cell carcinoma, which arose from a multilocular thymic cyst.

Isolated neutropenia during ABVD chemotherapy for Hodgkin lymphoma does not require growth factor support.

We reviewed the outcome of 24 patients with early and advanced stage Hodgkin lymphoma (HL) treated with ABVD chemotherapy (263 treatment deliveries) without the use of G-CSF over a 3-year period. Patients received full dose ABVD regardless of the absolute neutrophil count (ANC) on the day of treatment if there were no other cytopenias or toxicities. Forty-eight percent of treatment deliveries were given with an ANC <1.0 x 10(9)/L and 18% with an ANC <0.5 x 10(9)/L. Four patients required drug omissions (vinblastine or bleomycin) due to non-hematological side-effects. The rate of neutropenic sepsis was 0.76%. At a median follow up of 17.5 months, one patient had progressive disease requiring intensive treatment and the remainder were in remission post-treatment. Overall survival and event-free survival were 95.8% and 91.7%, respectively. We estimate a saving of 60,000 pounds in pharmaceutical and nursing expenditure related to G-CSF; a saving of 2000 pounds per patient. We conclude that full dose ABVD can be administered to patients with early and advanced stage HL irrespective of isolated neutropenia on the planned treatment day without prophylactic G-CSF or antibiotics and that this practise is safe, efficacious and cost-saving.

Hepatocellular carcinoma and the penetrance of HFE C282Y mutations: a cross sectional study.

BACKGROUND: Although most patients with hereditary haemochromatosis have HFE C282Y mutations, the lifetime risk to HFE C282Y homozygotes of developing fatal diseases such as hepatocellular carcinoma is uncertain. We have carried out a cross-sectional study to determine the proportion of diagnosed hepatocellular carcinoma patients who are homozygous for the HFE C282Y mutation; and to estimate the penetrance of this genotype with respect to hepatocellular carcinoma in East Anglia. METHODS: Tissue biopsies were analysed from 144 cases of hepatocellular carcinoma for HFE C282Y mutations; the data produced were compared with the frequency of HFE mutations in a large sample of the local population. Data were also retrieved from the East Anglian Cancer Intelligence Unit to determine the annual incidence of hepatocellular carcinoma; and from appropriate life tables. RESULTS: Eight out of 144 of the cases were homozygous for the HFE C282Y mutation, all 8 cases were male. 6 of these 8 cases had a previous diagnosis of hereditary haemochromatosis. Male HFE C282Y homozygotes were more likely to be diagnosed with hepatocellular carcinoma (odds ratio [OR] = 14, 95% confidence interval [CI] = 5-37). For this population, we estimate that the penetrance of the HFE C282Y homozygous genotype, with respect to hepatocellular carcinoma, was between 1.31 % and 2.1% for males and was zero for females. CONCLUSION: In this population, we found that only a very small proportion of homozygotes for the HFE C282Y mutation developed hepatocellular carcinoma. However, individuals with this genotype have a significantly increased risk of this rare disease relative to those who do not carry the mutations.

HFE mutations in the elderly.

Most individuals diagnosed with hereditary hemochromatosis have mutations in both copies of the HFE gene, with such mutations being common in populations of north European origin. The number of individuals currently diagnosed and treated for hemochromatosis is small relative to the number carrying two HFE mutations. Studies searching for undiagnosed hemochromatosis cases among disease cohorts have generally failed to find the number of cases that would be expected if disease were the commonest outcome for individuals with two C282Y HFE mutations. Our aim was to test the hypothesis that individuals with two HFE mutations would be under-represented in an elderly population because many would have died from disease caused by hemochromatosis before they reached old age. This is a cross-sectional study of elderly patients referred for full blood counts at the Norfolk and Norwich University Hospital. We screened blood samples from 1,000 elderly men (aged 85 and over) and women (aged 89 and over) for the C282Y, H63D, and S65C mutations of the HFE gene. We also analyzed any recent laboratory data relevant to signs of hemochromatosis. None of the ten possible genotypes was significantly under- or over-represented compared to the expected frequency calculated from the Hardy-Weinberg equation. Four C282Y homozygotes were found. There were few significant differences in the laboratory findings between the genotypes. Our data suggest that most people with HFE mutations survive to old age and do not suffer from signs of iron overload and hemochromatosis.