Multiple myeloma and Waldenstrom's macroglobulinemia terminating in acute leukemia. Review with emphasis on karyotypic and ultrastructural abnormalities

Patients with the syndrome of acute leukemia occurring as a terminal event in multiple myeloma and Waldenstrom's macroglobulinemia are analyzed. The syndrome often includes a preleukemic period characterized by several weeks to months of pancytopenia and/or dyserythropoiesis with or without the presence of ringed sideroblasts in the bone marrow. These changes may be related to previous chemotherapy, especially melphalan and cyclophosphamide. Radiation may also play a role. The syndrome of acute leukemia in multiple myeloma is also associated with a refractoriness to antileukemic chemotherapy and with a very short survival. There is a disproportionately high frequency of the myelomonocytic or monocytic variety of acute leukemia with an accompanying increase in serum and/or urinary lysozyme levels. Also typical of this syndrome is the occurrence of chromosomal aberrations, mostly hypodiploidy but also hyperdiploidy. A marker chromosome is often present, and the Philadelphia chromosome has been observed in at least two patients. Whether melphalan is the direct or indirect cause of the increased frequency of occurrence of acute leukemia in patients with multiple myeloma, approximately 1 to 7 percent in several series, and of Waldenstrom's macroglobulinemia too, or whether the prolonged survival induced by this and other drugs may have unmasked a hitherto unrecognized aspect of the natural history of myeloma cannot be answered with certainty. The evidence seems to favor the former.