H. Mouas

Voriconazole for Invasive Bone Aspergillosis: A Worldwide Experience of 20 Cases

UNLABELLED BACKGROUND; Bone aspergillosis remains a rare but potentially devastating fungal disease. Although voriconazole is effective for invasive pulmonary aspergillosis, evidence of its efficacy for aspergillosis located in bone is limited. METHODS We report our experience with voriconazole in 4 cases of invasive bone aspergillosis. In addition, all cases of probable and definite bone aspergillosis from the Pfizer clinical database were reviewed and analyzed to determine the safety and efficacy of voriconazole treatment. Global response was evaluated at the end of therapy on the basis of a composite assessment of overall clinical, radiological, and mycological responses. RESULTS Twenty patients are described, of whom 18 had definite bone involvement diagnosed (spondylodiskitis in 9, sternum/rib osteomyelitis in 6, and peripheral bone involvement in 5). Of 20 patients, 14 were immunocompromised. Oral or intravenous voriconazole was given as salvage therapy for 18 patients; 2 patients received voriconazole as first-line therapy. Median duration of voriconazole treatment was 83.5 days (range, 4-395 days). Global response at end of therapy was satisfactory in 11 (55%) of 20 patients, including complete responses in 4 patients and partial responses in 7 patients; there were no relapses of infection in the 4 patients with complete response to therapy with voriconazole. Treatment was generally well tolerated. CONCLUSIONS Long-term voriconazole treatment is a new therapeutic option for invasive aspergillosis with bone involvement.

Antiphospholipid syndrome during acute monocytic leukaemia

To the Editor: LUPUS anticoagulant and anticardiolipin antibodies are acquired antiphospholipid (aPL) antibodies. Their persistent presence is well-known in association with repeated thromboses, recurrent fetal loss and thrombocytopenia (1, 2). They have rarely been noted in association with non-leukaemic haematological malignancies (3), and only a few case reports have described their presence during the course of acute lymphoblastic leukaemia (ALL) (4). We report here a case of acute monocytic leukaemia (AML 5 , FAB classification) ( 5 ) associated with aPL antibodies which were responsible for multiple arterial thromboses. A 66-year-old woman was admitted to our unit in March, 1993, because of pancytopenia. She was treated for mild coronary artery disease with molsidomine and bepridil. Physical examination was normal. AML 5 was diagnosed, based on bone marrow smears. Laboratory test results showed: haemoglobin: 10 g/dl; platelets: 15 x 103/l; white blood cells; 1.7 x 103/1 (45% neutrophils, 12% monoblasts). Prothrombin time was normal and partial thromboplastin time was 15 seconds longer than the control, without correction by the addition of normal plasma. Coagulation factor levels were within the normal ranges. There was no sign of disseminated intravascular coagulation. The serum contained anticardiolipin antibodies, immunoglobulin G isotype 25 U GPL (ELISA normal range: 0 to 5 U GPL); IgG anti 2-glycoprotein I was negative. No antinuclear antibodies were detected and the serum complement level was normal. Forty-eight hours after admission, the patient developed incomplete right hemiplegia corresponding to a left frontotemporal infarction (CT scan) for which she received i.v. heparin (500 U/kg/d). Anticoagulant therapy was stopped 4 days later because of a haemorrhage in the infarcted part of the brain. Treatment with low-dose Ara-C (10 mg/d s.c.) (6) was started and stopped 12 d later because of aggravated pancytopenia. A bone marrow aspirate performed 1 month later showed complete remission. Consolidation chemotherapy with Ara-C (10 mg/d, s.c., 10 d per month) was started. The patient suffered a relapse 1 month later with 3.9 x lo3 circulating monoblasts/l. The platelet count was below 10 x 103/l. Concomitantly with the relapse, the patient developed bilateral ischaemia of the toes, with necrosis on the right side; doppler ultrasonography revealed thrombosis of the right tibia1 artery. The serum anticardiolipin antibody level (IgG) was 78 U GPL. Lupus anticoagulant was still present. She died of gastrointestinal bleeding a few days later. aPL antibodies are often found in patients with systemic lupus erythematosus or related autoirnmune diseases (1,2). They have also been noted in patients with solid tumours (7), infectious diseases (8), and haematological disorders including idiopathic thrombocytopenic purpura (9), monoclonal gammopathies and malignant lymphomas (3); and can also be induced by drugs (10). Among leukaemias, only a few cases presenting aPL antibodies during ALL have been reported to date. A relationship between AML and aPL seems probable in our patient. Indeed, she had not experienced arterial thrombosis before the diagnosis of AML and her two clinical episodes of leukaemic proliferation corresponded to arterial thromboses, despite profound thrombocytopenia. Furthermore, her serum anticardiolipin antibody level was increased at the time of relapse. In summary, thrombotic disorders may be observed during AML while not being directly caused by the leukaemic process itself. Therefore, appropriate immunological tests should be performed during the course of such diseases.