Secondary myelodysplastic syndrome after fludarabine therapy of a low-grade non-Hodgkin's lymphoma.

We diagnosed a probable fludarabine-induced secondary MDS approximately 18 months after treatment of a low grade non-Hodgkin's lymphoma. After diagnosis of a B-cell lymphoma composed of relatively small cells, fludarabine was administered between May and October, 1997, to a 64-year-old female patient. In December 1998, a mild bicytopenia was present with a leukocyte count of 3800/microl and platelets of 142000/microl. The white cell differential count was normal. The hemoglobin level was normal, but MCV was elevated. Bone marrow cytology revealed normal cellularity with dyserythropoiesis and dysmegakaryocytopoiesis. PAS staining showed scattered positivity in early erythroid cells. In 12 of 20 mitoses, the karyotype showed complex rearrangements, described as 46,XX,t(4;11)(q23?24;q13),del(5q),del(7)(q22),+mar[8]/45,-3. A diagnosis of treatment-related MDS was made. While there was no evidence of bone marrow infiltration by the lymphoma, CT scans demonstrated paraaortic lymph nodes up to 10 cm in diameter. After one course of CHOP chemotherapy, prolonged bone marrow aplasia and septic complications occurred. Chemotherapy was abandoned and Rituximab was administered. In July and November, 1999, bilateral pneumonia and urinary tract infection, respectively, were treated with antibiotics. NHL was in complete remission, but peripheral blood counts deteriorated markedly, and transfusions of packed red cells had to be started in November, 1999. The suspicion of leukemic transformation could not be confirmed because the patient declined further bone marrow biopsies. In December, 1999, the patient died from pneumonia.