Effect of 2-CDA on thrombocytopenia in myelofibrosis

Tefferi et al (1997 ) presented their results on the use of 2-chlorodeoxyadenosine (2-CDA) in nine patients with myelofibrosis. They reported that 2-CDA was an effective palliative treatment after splenectomy in non-cytopenic patients. Here, we provide data on two additional patients treated at our institution. In one patient a prolonged beneficial response occurred with 2-CDA despite pre-treatment thrombocytopenia. Patient 1 was 46 years old when initially referred for minimal thrombocytopenia and anaemia. Peripheral blood smear showed teardrops and a bone marrow aspirate and biopsy confirmed myelofibrosis. When her platelet count declined to 53 × 109/l she was treated unsuccessfully with danazol, after which she underwent a splenectomy with a brief response. For the next 4 years increases in her white cell count and the appearance of a low percentage of blasts resulted in a series of treatments, including hydroxyurea, busulphan, cyclophosphamide, interferon and cytosine arabinoside. Eight years after the original diagnosis an accelerated phase of her disease occurred characterized by leucocytosis (58 × 109/l) containing 25% blasts and continuing thrombocytopenia. As shown in 1, she received two courses of 2-CDA at 0.09 mg/kg/d, each for 7 d. With the first treatment, the number of blasts decreased and a significant improvement in the platelet count followed. When the platelet count fell again a second course of 2-CDA was initiated. Since the second treatment the platelet count has remained >100 × 109/l for most of the time, her leucocyte counts have been <10 × 109/l and blast counts remain at <10%. The peripheral smear still shows abnormalities consistent with myelofibrosis and post-splenectomy. Patient 2 was 47 years old when diagnosed with myelofibrosis. She received treatment with hydroxyurea and interferon as well as splenectomy. Ten years after the original diagnosis, blast crisis occurred with a white cell count of 131 × 109/l containing 30% blasts and a platelet count of 24 × 109/l. She declined standard acute leukaemia therapy. 2-CDA was given at 0.09 mg/kg/d for 7 d. On the tenth day after beginning treatment her white cell count fell to 20 × 109/l with only 3% blasts and her platelets were 15 × 109/l. One month after the therapy the blast crises reappeared. A second course was started but she died. These two patients provide additional clinical information to parallel those of Tefferi et al (1997 ) on the use of 2-CDA in myelofibrosis. In both instances the white cell count and blast count declined promptly. In the first patient the use of 2-CDA was prompted by increasing blasts in the peripheral blood coupled with thrombocytopenia. This patient had a sustained benefit with normal platelet counts after only two treatments; the number of blasts decreased considerably but they persisted in low numbers on peripheral smears. The second patient had far-advanced blast conversion when 2-CDA was started. She was also treated despite thrombocytopenia. Although the number of blasts quickly fell, her disease continued to progress and she died. In summary, 2-CDA was associated with a decrease in blasts in these two patients and a long-standing correction of thrombocytopenia occurred in one of them.