Summary. Four hundred and twenty-nine patients received myeloablative chemotherapy for solid and haematological malignancies in a bone marrow transplantation unit. Regimens appropriate to the tumour type were administered and haemopoietic reconstitution was achieved with peripheral blood progenitor cells (PBPC; n 275), autologous bone marrow (auto-BMT; n 69) or allogeneic bone marrow (allo-BMT; n 85). World Health Organization (WHO) oral mucositis scores were collected prospectively from the start of chemotherapy (d 1) until d 28 or discharge. Oral mucositis (OM) was experienced by 425 (99%) patients and in 289 (67´4%) this was grade III or IV. Strong opiate analgesia was prescribed for a median of 6 d to 47% of patients. Univariate analysis suggested that the area under the OM curve (AUC; sum of daily mucositis grades, d 1±28) was associated with the myeloablative regimen, haemopoietic progenitor source (PBPC . allo-BMT . auto-BMT), use of myeloid growth factors and age. Multivariate analysis showed that the only independent risk factor for mucositis was the conditioning regimen (P , 0´00005). The mean OM AUC for high-dose melphalan (HDM) regimens (52 grade±days) exceeded busulphan (41), busulphan±cyclo-phosphamide (35), cyclophosphamide±total body irradiation (TBI) (34), cyclophosphamide±carmustine (BCNU) (20) and cyclophosphamide±etoposide±carmustine (CVB) (19). HDM regimens resulted in the highest mean peak OM (3´6), followed by busulphan regimens (2´6), cyclophosphamide/TBI (2´3) and cyclophosphamide±carmustine and CVB (1´4). Busulphan produced significantly delayed OM (median 3 d; P , 0´00005). There was a linear association between the area under the OM curve for each treatment group and the time to reach grade 3 OM (P , 0´00005), but no association with the time to reach grade 4 neutropenia (P 0´24) or thrombocytopenia (P 0´73), implying that haematological and mucosal toxicity are not associated. The cytotoxic regimen is the most significant determinant of OM. Studies investigating agents to ameliorate mucosal toxicity should be stratified according to cytotoxic regimen.

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Summary.Fluconazole is widely used as antifungal prophylaxis but it is ineffective against Aspergillus. Itraconazole has a broader spectrum of activity but the capsules give erratic bioavailability in neutropenic patients. We compared itraconazole oral solution (which has an improved pharmacokinetic profile) with fluconazole for antifungal prophylaxis.Adults with haematological malignancies receiving chemotherapy or bone marrow transplants were randomly allocated 5 mg/kg/d itraconazole (itra) solution (288 episodes) or 100 mg fluconazole suspension (flu) (293 episodes) from before the onset of neutropenia until neutrophil recovery or suspected fungal infection. Outcomes were assessed by independent reviewers unaware of the prophylaxis allocation.More proven systemic fungal infections occurred in flu (Aspergillus four, Candida tropicalis one, C. krusei one) than itra (C. albicans one) and more of these were fatal (four versus nil). This difference reached statistical significance when first study episodes were considered separately (six flu versus nil itra, P ¼ 0·03). Significantly more deaths of presumed fungal origin occurred in flu than itra (seven versus nil, P ¼ 0·024). There were significantly more cases of proven aspergillosis in flu than itra (six versus nil, P ¼ 0·038, 5/6 cases were fatal) if those occurring outside the study period are included. Significantly more patients receiving flu required amphotericin B (58 v 39, P ¼ 0·043) but this may have been affected by the fact that the study was not blinded. There were 11 proven mucosal candidal infections in flu and four in itra.Itraconazole solution and fluconazole provide effective prophylaxis against Candida but itraconazole affords greater protection against fatal aspergillosis.

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Summary Twelve patients with small cell lung cancer were treated with recombinant human granulocyte colony-stimulating factor, rhG-CSF, given by continuous infusion at doses ranging from 1 to 40 ig kg-'day-'. Patients received the rhG-CSF before the start of intensive chemotherapy and after alternate cycles of chemotherapy. Several in vitro assays were performed using peripheral blood neutrophils and marrow progenitor cells collected from patients prior to and after infusion of the growth factor. Peripheral blood neutrophils were tested for mobility and phagocytic activity. In addition, in vitro clonogenic assays of marrow haemopoietic progenitor cells and analysis of bone marrow trephines and aspirates were carried out. We found that rhG-CSF in vivo has at least two main effects: (a) an early fall in peripheral neutrophils, within the first hour, followed by a rapid influx of mature neutrophils into the circulatory pool; (b) stimulation of proliferation and differentiation of neutrophil precursors in the bone marrow. Neutrophils released into the circulation were normal in tests of their mobility and phagocytic activity.

Patients with poor prognostic features who received high-dose therapy and BPC rescue had a superior EFS. The survival differences observed in this study justify a formal comparison in a randomized study.

Summary. Bone marrow aspirates (BMA) and trephine biopsies (BMT) are commonly performed in the staging of patients with newly diagnosed Hodgkin's lymphoma (HL) but the value of these procedures is controversial. The purpose of this study was to evaluate the predictive value of the blood count and erythrocyte sedimentation rate (ESR) for bone marrow involvement (BMI) and the influence of BMI on stage and prognostic score. A retrospective analysis of 955 patients with newly diagnosed HL entered into clinical trials in a regional cancer centre between 1975 and 1999 was performed. BMI was identified by BMT in 50 patients (5AE2%) but in only five of these by BMA. The negative predictive values of a normal full blood count (FBC) and ESR for absence of BMI were 98AE8% and 97AE3%, respectively, and the positive predictive value of an abnormal FBC and ESR for presence of BMI were both 6AE7%. BMT did not alter initial patient management in a single case but provided valuable prognostic information in certain subgroups of patients. BMA gave no additional staging information over BMT and abnormalities of blood count and ESR were poor predictors of infiltration. We conclude that BMA should be abandoned for staging purposes in HL and BMT restricted to patients with stage IIB or III disease, for whom valuable prognostic information may be obtained.

Summary A total of 142 patients With multiple myeloma received VAD as remission induction therapy. Seventy-five were previously untreated and 67 had relapsed (31) or refractory disease (36). Vincristine al., 1984). We reported the early results of a modified VAD regimen given to newly diagnosed, relapsed and refractory patients in 1987. The response rate was 80% for previously untreated patients and 50% for relapsed or refractory patients (Anderson et al.. 1987). From 1984 the VAD regimen has become our standard remission induction therapy for multiple myeloma.The aim of this paper is to report the results of the treatment of multiple myeloma using VAD as remission induction therapy in this institution. Materials and medsAll patients with multiple myeloma referred to our unit were treated with VAD unless serious concurrent medical conditions precluded the use of high-dose dexamethasone (uncontrolled cardiac failure, unstable diabetes or chronic chest infection, e.g. bronchiectasis).The staging tests for myeloma included a modified skeletal survey and bone marrow examination. Serum was taken for protein and immunoelectrophoresis and quantification of immunoglobulins. A 24 h urine specimen was collected for quantification of light chains, total protein excretion and creatinine clearance. In all cases the pathology was reviewed. Myeloma was staged according to the Durie and Salmon (1975) classification.