BACKGROUNDIt is unclear whether patients with early-stage Hodgkin's lymphoma and negative findings on positron-emission tomography (PET) after three cycles of chemotherapy with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) require radiotherapy. METHODSPatients with newly diagnosed stage IA or stage IIA Hodgkin's lymphoma received three cycles of ABVD and then underwent PET scanning. Patients with negative PET findings were randomly assigned to receive involved-field radiotherapy or no further treatment; patients with positive PET findings received a fourth cycle of ABVD and radiotherapy. This trial assessing the noninferiority of no further treatment was designed to exclude a difference in the 3-year progression-free survival rate of 7 or more percentage points from the assumed 95% progression-free survival rate in the radiotherapy group. RESULTSA total of 602 patients (53.3% male; median age, 34 years) were recruited, and 571 patients underwent PET scanning. The PET findings were negative in 426 of these patients (74.6%), 420 of whom were randomly assigned to a study group (209 to the radiotherapy group and 211 to no further therapy). At a median of 60 months of follow-up, there had been 8 instances of disease progression in the radiotherapy group, and 8 patients had died (3 with disease progression, 1 of whom died from Hodgkin's lymphoma); there had been 20 instances of disease progression in the group with no further therapy, and 4 patients had died (2 with disease progression and none from Hodgkin's lymphoma). In the radiotherapy group, 5 of the deaths occurred in patients who received no radiotherapy. The 3-year progression-free survival rate was 94.6% (95% confidence interval [CI], 91.5 to 97.7) in the radiotherapy group and 90.8% (95% CI, 86.9 to 94.8) in the group that received no further therapy, with an absolute risk difference of −3.8 percentage points (95% CI, −8.8 to 1.3). CONCLUSIONSThe results of this study did not show the noninferiority of the strategy of no further treatment after chemotherapy with regard to progression-free survival. Nevertheless, patients in this study with early-stage Hodgkin's lymphoma and negative PET findings after three cycles of ABVD had a very good prognosis either with or without consolidation radiotherapy. Original ArticleThe New England Journal of Medicine also emerged. Thus, it was increasingly apparent that cure was bought at a high price and that less damaging therapies were required. Studies were therefore performed to evaluate fewer cycles of less toxic chemotherapy combined with smaller fields or doses of radiotherapy 13,14 ; as a result, for the treatment of patients with favorable prognostic features, 14,15 two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) 16,17 followed by 20 Gy of involved-field radiotherapy is now commonly used. 15In moving toward the goal of maximizing cure while minimizing toxic effects, greater individualization of therapy is appealing. Positron-emission tomography (PET) can be used to predict the...

SummaryGuidelines for the prevention and treatment of infection in patients with an absent or dysfunctional spleen were first published by the British Committee for Standards in Haematology (BCSH) in 1996 and formally reviewed in 2002. Although the guidelines originated from discussion within the BCSH, the intended readership is wide given the multidisciplinary nature of the management of hyposplenism.

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The aim of the present study was to assess whether patients with pulmonary embolism (PE) could be managed as outpatients after early discharge from hospital using low molecular weight heparin instead of remaining as in-patients until effective oral anticoagulation was achieved.Phase 1 of the study identified criteria for the safe discharge of selected patients; phase 2 treated a cohort of low-risk patients with PE as outpatients with tinzaparin using existing deep venous thrombosis services.In phase 1, 127 (56.4%) of 225 patients were considered unsuitable for outpatient management. Reasons included: admission for another medical reason; additional monitoring or requirement for oxygen; bleeding disorders; previous PE/further PE while on warfarin; co-existing major deep venous thrombosis; likelihood of poor compliance; significant immobility; and pregnancy. In phase 2, 157 patients with PE received outpatient anticoagulation therapy. There were no deaths, bleeding or recurrent thromboembolic events during acute treatment with low molecular weight heparin. The median (range) length of hospital stay was 1.0 (1-4) day, with a median saving of 5.0 (1-42) bed-days per patient.Patients were highly satisfied with outpatient management; 144 (96.6%) indicated that they would prefer treatment as outpatients for a subsequent pulmonary embolism. Early discharge and outpatient management of pulmonary embolism appears safe and acceptable in selected low-risk patients, and can be implemented using existing outpatient deep venous thrombosis services.

Serum prohepcidin concentration: no association with iron absorption in healthy men; and no relationship with iron status in men carrying HFE mutations, hereditary haemochromatosis patients undergoing phlebotomy treatment, or pregnant women Hepcidin plays a major role in iron homeostasis, but understanding its role has been hampered by the absence of analytical methods for quantification in blood. A commercial ELISA has been developed for serum prohepcidin, a hepcidin precursor, and there is interest in its potential use in the clinical and research arena. We investigated the association between serum prohepcidin concentration and iron absorption in healthy men, and its relationship with iron status in men carrying HFE mutations, hereditary haemochromatosis patients, and pregnant women. Iron absorption was determined in thirty healthy men (fifteen wild-type, fifteen C282Y heterozygote) using the stable isotope red cell incorporation technique. Iron status was measured in 138 healthy men (ninety-one wild-type, forty-seven C282Y heterozygote), six hereditary haemochromatosis patients, and thirteen pregnant women. Mean serum prohepcidin concentrations were 214 (SD 118) ng/ml [208 (SD 122) ng/ml in wild-type and 225 (SD 109) ng/ml in C282Y heterozygotes] in healthy men, 177 (SD 36) ng/ml in haemochromatosis patients, and 159 (SD 59) ng/ml in pregnant women. There was no relationship between serum prohepcidin concentration and serum ferritin in any subject groups, nor was it associated with efficiency of iron absorption. Serum prohepcidin is not a useful biomarker for clinical or research purposes. Hepcidin plays a major role in iron homeostasis, but full characterisation of its role in healthy humans and patients has been hindered by the absence of analytical methods to quantify circulating levels in the blood. Quantification of mRNA in the liver has been undertaken using reverse transcription and the polymerase chain reaction (Bridle et al. 2003;Gehrke et al. 2003), and polyclonal antibodies to refolded synthetic hepcidin have been produced and used for quantification in urine (Nemeth et al. 2003). Attempts to produce correctly folded synthetic hepcidin have proved difficult because the sequence contains eight cysteine residues that constrain the hepcidin molecule in a hairpin structure (Hunter et al. 2002). Hepcidin in urine has also been quantified using mass spectrometry methods (Kemna et al. 2005;Liang et al. 2006;Tomosugi et al. 2006).Prohepcidin, the sixty-amino-acid product of cleavage of the signal peptide from the hepcidin precursor, is expressed at the basolateral membrane domain of hepatocytes and is found in blood (Kulaksiz et al. 2004). Serum prohepcidin concentrations are significantly lower in patients with hereditary haemochromatosis compared to healthy control subjects (Kulaksiz et al. 2004), increase with declining kidney function (Taes et al. 2004), and are correlated with haematocrit in chronic haemodialysis patients (Hsu et al. 2006), but it is currently unclear whether * Corresponding author: ...