Melphalan is widely used as a preparative agent in patients with multiple myeloma (MM) undergoing autologous stem cell transplantation (SCT). Although disease relapse is the major cause of death after a melphalan-conditioned autograft, the mechanism remains unclear. Melphalan produces a number of DNA adducts with the DNA interstrand crosslink (ICL) considered to be the critical cytotoxic lesion. By using a modification of the single-cell gel electrophoresis (Comet) assay, we have measured formation and repair of DNA ICL in plasma cells from melphalannaive and melphalan-treated patients (ie, those who have relapsed after a melphalan-conditioned autologous SCT or oral melphalan therapy). Similar levels of dosedependent DNA interstand crosslinking were observed in cells from both melphalan-naive and -treated patients. However, marked differences in ICL repair were observed: cells from naive patients showed no repair, whereas those from treated patients exhibited between 42% and 100% repair at 40 hours. In vitro sensitivity to melphalan in plasma cells was found to correlate with ICL repair. These findings suggest that ICL repair may be an important mechanism by which melphalan resistance emerges after autologous SCT or oral therapy. This mechanism may have implications for MM patients undergoing melphalan therapy. (Blood. 2002;100:224-229)

Venous thromboembolism (VTE) is a clinically important complication for both hospitalised and ambulatory cancer patients. In the current study, the frequency, demographics and risk (according to tumour site) of VTE were examined among patients seen at outpatient DVT (deep-vein thrombosis) clinics. Of 10,015 VTE cases, 1,361 were diagnosed with cancer, for an overall rate of cancer-associated VTE of 13.6% in this outpatient population. Patients with cancer-associated VTE were significantly older than cancer-free VTE cases (66.4 +/- 12.7 vs. 58.8 +/- 18.5 years; p<0.0001). The frequency of cancer-associated VTE peaked earlier among females than males, occurring in the sixth (137/639, 21.4% vs. 98/851, 11.3%; p<0.001) and seventh decades (213/980, 21.7% vs. 197/1096, 18%; p=0.036). VTE was described most frequently in common cancers - breast, prostate, colorectal and lung (56.1% of cases). The risk of VTE varied widely across 17 cancer types. Calculating odds ratios (OR) to assess the effect size of cancer type on VTE risk, the highest odds were observed for patients with pancreatic cancer (OR 9.65, 95% confidence interval [CI] (5.51-16.91). Tumours of the head and neck had higher odds than previously reported (OR 8.24, 95% CI 5.06-13.42). Reduced risk estimates were observed for skin cancers (melanoma and non-melanoma: OR 0.89, 95% CI 0.42-1.87; OR 0.74, 95% CI, 0.32-1.69, respectively). We conclude that outpatients have a similar rate of cancer-associated VTE as VTE patient populations previously reported, that cancer-associated VTE occurs in an older age group and earlier in females and that outpatients exhibit distinct tumour site-specific risk from that described among hospitalised cancer patients.

This study provides evidence of very high D-dimer levels in patients with cancer who do not have VTE. This suggests that elevated D-dimer levels in patients with VTE and malignancy are not solely due to presence of thrombus. High D-dimer levels in malignancy are likely to reflect the biology of the underlying tumour, with higher levels observed in breast, prostate and bowel cancers.

Summary:In common with other plasma cell dyscrasias in which a small tumour burden is associated with severe clinical symptoms (notably systemic AL amyloidosis) the possible benefits of dose intensification are yet to be fully explored in POEMS syndrome. One important issue is whether the toxicity of the procedure is significantly increased in this group. We report two The acronym POEMS aids recognition of the more common features of a rare multi-system disorder associated with an underlying plasma cell dyscrasia (polyneuropathy, organomegaly (hepatosplenomegaly, lymphadenopathy), endocrinopathy (diabetes mellitus, hypogonadism, hypothyroidism), monoclonal gammopathy and skin changes (most frequently hyperpigmentation)). 1,2 In only a minority of cases are all the criteria met. A constellation of other clinical manifestations may be present including peripheral oedema, ascites, pleural effusions, pulmonary hypertension, papilloedema, polycythaemia, thrombocytosis and fever. 3 Bone lesions are also common. Miralles et al 4 described 38 patients, of whom 36 had bone lesions. In 31 of these the lesions were sclerotic or mixed sclerotic/lytic rather than predominantly lytic. The pathophysiological basis of the polyneuropathy along with other features of the disorder remains unclear. There is only limited evidence to support a direct role of the monoclonal protein in the neuropathy, 5 but it remains apparent that a Correspondence: K Peggs,

Summary Qualitative d‐dimer results, together with clinical probability scores, are well established in the diagnosis of venous thromboembolism (VTE). The predictive value of quantitative d‐dimer levels for various clinical outcomes in VTE patients is not fully understood. d‐dimer levels obtained at presentation were analysed in 699 (360 men; 339 women) VTE patients for survival and occurrence of malignancy. Patients were followed for a median of 23 months. 17·2% patients had a d‐dimer level >8000 ng FEU/mlat presentation, which was associated with decreased overall survival (OS) (P < 0·001) and event‐free survival (EFS) (P < 0·001). 25·4% patients had malignancy and 4% subsequently developed malignancy following VTE. 29·9% of patients with VTE and malignancy had a d‐dimer level >8 mg/l when compared with 13·4% of patients with VTE without malignancy (P < 0·001). 50% of patients who developed subsequent malignancy following VTE had a presentation d‐dimer >8000 ng FEU/mlas compared with 13·3% of patients with VTE with out malignancy (P = 0·009). In conclusion, d‐dimer >8000 ng FEU/ml at presentation in patients with VTE is a marker of poor OS, EFS and underlying malignancy. Consideration of screening for malignancy is recommended in patients with VTE with a presentation d‐dimer >8000 ng FEU/ml and age >60 years.