Patients with Ph-positive ALL have a poor prognosis, with a disease-free survival rate between 0 and 20% after standard chemotherapy.1 However, novel therapeutic approaches are being developed for these patients. The BCR-ABL tyrosine kinase inhibitor STI571 (imatinib, Glivec®, Novartis Pharma AG) has substantial activity in Ph-positive ALL.2 The increasing use of intensive chemotherapy and stem cell transplantation for the treatment of ALL results in prolonged and profound neutropenia and an increase in the frequency of invasive fungal infections. Approximately 36% of patients with acute leukaemia develop invasive fungal infections.3 We report the successful use of a combination of imatinib and FLAG regimen in patients with relapse of Ph-positive ALL and favorable response of refractory invasive pulmonary aspergillosis (IPA) on treatment with Caspofungin.
A 29-year-old man was hospitalized on February 27, 2003 with ALL. Cytogenetic study of the bone marrow showed 46, XY, t(9; 22) (q34; q11). The patient had a history of refractory lung tuberculosis (1993–1995 years) with cavitary lesion in the upper lobe of the right lung and was treated by partial pulmonary resection with thoracoplasty combined with antituberculosis chemotherapy. From March 3, 2003 he was treated by the BFMT 05/93 induction protocol. BM examination on day 29 revealed 81% blasts. Cytopenia persisted (WBC 0.2 × 109/l, platelets 30 × 109/l, haemoglobin 7 g/dl). The patient developed severe mucositis and enteropathy and prolonged parenteral nutrition was necessary. From April 8, 2003 he was treated with HAM protocol (Ara-C 3 g/m2 twice daily intravenously (i.v.) for 3 consecutive days (total six doses) and mitoxantrone 10 mg/m2/day i.v. for 3 consecutive days). Standard antifungal prophylaxis with fluconasole 150 mg/day was used. The patient developed severe neutropenia and high fever, severe enteropathy with gastrointestinal bleeding. Empirical treatment with broad-spectrum antibiotics produced an initial improvement, but later fever recurred. During the third week of neutropenia he developed pleuritic chest pain, and a chest radiograph revealed an infiltrate in the lower lobe of the left lung with massive pleural effusion and later in the lower lobe of the right lung. Repeated blood cultures and pleural fluid culture were negative. The bronchoalveolar lavage fluid culture was also negative. The fever persisted despite the use of imipenem 3 g/day and amphotericin B 1 mg/kg/day since April 30. Neutropenia resolved 8 days later and a BM examination on May 7 revealed normal cellularity and 1% blasts. After neutrophils recovering he improved clinically and a chest radiograph revealed the presence of several cavitated nodules with an air crescent sign in lungs. After 2 weeks, the patient developed spontaneous pneumothorax with massive collapse of the left lung. This complication was successfully treated by intercostal tube drainage, which was removed after 2 days. The post-drainage thoracic computed tomographic (CT) scan showed two cavitated nodular opacities with diameters 22 and 25 mm in the right lung (one of them under thoracoplasty) and three in the left lung (one with diameter 10 mm in the upper lobe; two with diameters 30 and 26 mm in the lower lobe subpleural).
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