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Background Plasma concentrations of oral busulfan (BU) were measured in multiple myeloma (MM) patients undergoing autologous peripheral blood stem cell transplantation (ASCT) with a double alkylating conditioning protocol in order to individualise doses of BU based on individual pharmacokinetic parameters and to reduce toxicities related to BU exposure. Patients and methods Forty-four consecutive patients with MM participating in the co-operative Spanish protocol were prospectively evaluated. Conditioning regimen prior to autologous infusion consisted of BU followed by melphalan. BU pharmacokinetic parameters were estimated for each patient after the first dose based on measured concentrations and subsequent doses were modified as necessary to achieve target exposure. Results Mean BU exposure (AUCss) (+/-DS) before dosage modification range from 3192 to 12 180 ng h/mL. Twenty-six out of 44 (59%) patients required dose adjustment. None of the patients developed hepatic veno-occlusive disease (VOD). Grade > or = II oropharyngeal mucositis was observed in the majority of patients (95%) and the severity of mucositis increased with increasing average steady-state BU plasma concentration. There were four treatment-related deaths: two patients died from multiorgan failure and two of respiratory infections. Of the remaining 40 patients, 15 were in complete remission with negative immunofixation, 21 in partial remission and four in stable disease 3 months after ASCT. Conclusions The results of the present study show the variability in BU pharmacokinetic parameters and suggest the possible relationship between toxicities and BU exposure. Individualising BU dosage in MM patients undergoing ASCT we observed the absence of VOD.

SummaryIntroduction Patients with persistent high levels of serum vitamin B12 were often referred to Hematology departments. In this study, characteristic of patients with serum vitamin B12 levels higher than 2500 pmol/L (high B12) were studied. Methods Prevalence of high B12 was evaluated during a 10-month period. Samples with high B12 were incubated with polyethylene glycol (PEG) and a new measurement of vitamin B12 was carried out using the supernatant. As a pilot study, 26 frozen samples with high B12 were evaluated for changes in vitamin B12 after PEG. Moreover, a prospective study was carried out during three consecutive months. Size exclusion chromatography was employed to demonstrate the presence of immune complexes (ICs) with plasma vitamin B12-binding proteins in some serum samples with high B12. Results Prevalence of high B12 was 1.3%. Results from 26 frozen samples and from a prospective study (28 cases) showed that undergoing vitamin B12 treatment was the main cause of high B12. However, ICs were detected in 10 frozen samples and in seven cases (25%) of the prospective study, respectively. Serum vitamin B12 decreased to normal values after precipitation with PEG, and size exclusion chromatography confirmed ICs. An association with autoimmune or hematological disorders was observed. Conclusions In patients with repeatedly high B12 levels, ICs were detected in approximately 25% of samples. Precipitation with PEG is an easy method to confirm the presence of ICs and to evaluate serum vitamin B12 levels in these patients.

Phenylacetic acid (PAA), a metabolite of phenylethylamine, has been found in the urine of depressed patients at lower levels than in control subjects. It has been suggested that the determination of PAA in urine could be used as a biological marker of the depressive condition. In this study the levels of PAA in urine were investigated by gas-liquid chromatography in 39 patients diagnosed as having major depression according to DSM-III criteria, and in 32 healthy subjects. The values found in the patients were markedly lower than in controls. No relationship was found between the decrease of PAA excretion and weight loss. Using a discriminant equation, a value of 69% was obtained for both sensitivity and specificity. The results suggest that the determination of urine PAA could be a biological parameter comparable to the dexamethasone suppression test.