Successful reintroduction of methotrexate after acute pneumonitis in a patient with acute lymphoblastic leukemia

Low-dose methotrexate (MTX) is used as disease-modifying therapy in severe rheumatoid arthritis and as maintenance treatment in patients with complete remission of acute lymphoblastic leukemia (ALL). It is generally well tolerated, but in 27% of patients acute pneumonitis leads to discontinuation of treatment. We describe a 56-year-old female patient with newly diagnosed pre-B-ALL. She was treated with induction chemotherapy in July 1999 which lead to complete remission. Maintenance treatment with low-dose MTX and 6-mercaptopurine (6-MP) was started in December 1999. In April 2000 she was hospitalized because of fever, cough, and rapidly progressive dyspnea. No pathogens could be cultured from blood or bronchoalveolar lavage fluid. Computed tomography of the lungs revealed interstitial infiltration and ground-glass opacities. Acute pneumonitis was diagnosed, and MTX was stopped. Prednisone therapy lead to rapid clinical amelioration of dyspnea and hypoxemia. Since for this patient there was no alternative leukemia therapy, MTX was successfully reintroduced in August 2000 without reappearance of any respiratory symptoms. We discuss risk profile, clinical and histological presentation, and therapy of MTX-induced pneumonitis. To our knowledge, this is the first patient with ALL in whom successful reintroduction of MTX after severe pneumonitis has been reported.