Effect of alkylating agents on hematopoiesis in myelofibrosis. 4 case report

Four patients presenting with myelofibrosis (2 primary myelofibrosis and 2 postpolycythemic myeloid metaplasia) were treated with alkylating agents. For three patients (one treated with busulfan and two treated with chlorambucil) the treatment was a success: the general condition improved, the splenomegaly decreased or disappeared, and the blood picture returned to normal. Moreover, for two cases, a trend towards polycythemia was observed under treatment. For the fourth patient, treated with chlorambucil, there was no improvement: a life-threatening, pancytopenic phase developed at the end of the treatment, but it disappeared after 2 months. For the three successfully treated cases, a redistribution of hematopoiesis from spleen to bone marrow was shown by ferrokinetics, 59Fe scans, and bone marrow biopsies. In addition, in the case treated with busulfan, a decrease in the bone marrow granulopoietic pool at the expense of the erythropoietic one was observed. No redistribution was seen in the patient for whom the treatment was a failure. In this case, the spleen remained the major site of active hematopoiesis. Studies on blood granulomonocytic-colony forming cells (GM-CFC's) helped to discriminate the successfully treated patients from the unsuccessfully treated one. In the successfully treated patients, the GM-CFC concentrations dropped to normal values and increased again within weeks following the treatment interruption; this increase involved mainly high density GM-CFC's (greater than 1.060). In the unsuccessfully treated patient, GM-CFC concentrations decreased only after 5 weeks of intensive treatment. The mean density of the GM-CFC's was 1.064 before treatment, shifted towards 1.060 during the neutropenic phase and returned to 1.064 during the recovery.