Melphalan-Induced Pulmonary Fibrosis in Osteosclerotic Myeloma

G.J. Mufti, T.J. Hamblin, J. Gordon, Royal Victoria Hospital, Bournemouth, Dorset (UK) To the Editors, Patients with multiple myeloma and osteosclerotic bony lesions on presentation have been described although the occurrence is rare and the pathogenesis is unknown∏]. In this report we document a patient with osteosclerotic myeloma and a very high alkaline phosphatase (AP) on presentation who developed pulmonary fibrosis following treatment with mel-phalan. A 57-year-old retired dress machinist presented with a 3-month history of tiredness. On examination abnormal findings were pallor and 2 cm hepatomegaly. Investigations revealed Hb 8.7 g/dl, WBC 13 × 10Yl, platelets 140× 10Vl, ESR 84 mm in the first hour. Blood film showed neutrophils 34%, lymphocytes 54%, monocytes 9%, eosinophils 3%, 9 nucleated red cells/100 WBC. Liver function tests showed bilirubin 9 μmol/l (NR < 17), AST 24 IU/1 (NR < 18), LDH 237 IU/1 (NR 30-90), AP 1,580 IU/1 (NR 20-90), 5-nucleotidase 10 IU/1 (NR 1-15), total protein 71 g/l (NR 60-80), albumin 25 g/l (NR 35-47). Immunoglobins were IgG 30 g/l (NR 7.2-18), IgA 0.2 g/l (NR 1.03.6), IgM 0.2 g/l ‘(NR 1.2-2.5), IgG kappa monoclonal band was detected on immunoelectrophoresis. Urinary protein excretion was 0.6 g in 24 h and concentrated urine electro-phoresis showed free K light chains. Appearances of the bone marrow trephine biopsy, skeletal survey and “Tc bone scan were consistent with the diagnosis of osteosclerotic myeloma. Serum calcium, phosphate and urate were normal. Chest Xray was reported and has since been reviewed as normal. She was commenced on 6-weekly courses of mel-phalan and prednisolone. After two courses of treatment and despite a satisfactory blood count, she complained of breathlessness. There was little abnormal on physical examination. Chest X-rays revealed reticular shadowing at the bases. Lung function studies showed a marked diffusion defect. The transfer factor was reduced at 10 ml/min/mm Hg (predicted 21.5) and respiratory function tests were consistant with restrictive lung disease. After six courses of chemotherapy she was breathless on moderate exertion. However, her Hb stabilised without further transfusions at 14 g/dl, the platelet count rose to 168 × 10Vl, ESR fell to 15 mm in the first hour. The AP fell to 293 IU/1, IgG to 20.6 g/l, LDH to 90 IU/1 and AST to 10