Secondary acute myelocytic leukemia after adjuvant therapy for early-stage breast carcinoma. A new complication of cyclophosphamide, methotrexate, and 5-fluorouracil therapy.

The occurrence of treatment-related hematologic malignancies after adjuvant therapy with alkylating agents for gastrointestinal cancers, ovarian carcinoma, and breast cancer and after treatment for Hodgkin's disease, non-Hodgkin's lymphoma, germ-cell tumors, and multiple myeloma has been well documented. Adjuvant chemotherapy is frequently used for the treatment of early stage breast cancer, and to date there has been no increase in the incidence of secondary myelodysplastic syndromes or acute leukemia after cyclophosphamide-based regimens when compared with surgical controls. This report describes two patients who developed acute myelocytic leukemia only after exposure to cyclophosphamide, methotrexate, and 5-fluorouracil adjuvant therapy. These two cases of acute leukemia, which developed 3 years after diagnosis of breast cancer and initiation of chemotherapy, were characterized by trilineage dysplasia and pancytopenia, and had abnormalities of chromosomes 5 and 7: characteristics consistent with treatment-related leukemia. Many women are diagnosed with early stage breast cancer each year who are potential candidates for adjuvant therapy. Although certain subgroups of patients have been shown to benefit from adjuvant therapy, continued efforts must be directed at identifying responders so that others will not be exposed to the additional risks of chemotherapy.

Malignant large cell lymphoma of B-cell type with multilobated nuclei. Report of a case and review of the literature.

Malignant lymphomas with multilobated nuclei are rare, recently recognized neoplasms of the immune system initially thought to be of T-cell type. Reported is a case of large cell lymphoma with multilobated nuclei in which immunologic marker studies demonstrated that the neoplastic cells had characteristics of B-lymphocytes. The neoplastic cells possessed surface and cytoplasmic immunoglobulin of the IgG, lambda type, and stained diffusely with monoclonal antibodies to B1, Leu-10 and OKIaI antigens and focally with anti-B2. The lymphoma cells did not react with monoclonal antibodies directed against T-cells and monocytes/granulocytes. As documented here with multiple monoclonal antibody lymphocyte markers, the multilobated lymphoma can have a B-cell phenotype as well as the cell phenotype described previously. Thus, even the unique finding of multilobated nuclear morphologic features is unreliable in predicting the lymphocyte lineage.

Acquired immune deficiency syndrome and pancytopenia.

A patient with the acquired immune deficiency syndrome experienced pancytopenia during the course of his illness. At the time of maximum depression of the blood cell counts, the hematocrit value was 21%; the WBC count, 1,000/cu mm; and the platelet count, 27,000/cu mm. Lymphopenia was persistent but the number of juvenile neutrophilis was not diminished. Peripheral blood smears were noteworthy for the presence of atypical monocytes with phagocytic vacuoles. Histiocytic hemophagocytophagia was prominent in bone marrow aspirate specimens. Bone marrow biopsy specimens were usually hypocellular and contained collections of atypical lymphocytes and increased reticulin. These hematologic abnormalities are most likely the consequence of persistent viral infection in an immunocompromised host.

Induction of differentiation of the human promyelocytic leukemia cell line (HL-60) by retinoic acid.

The HL-60 cell line, derived from a patient with acute promyelocytic leukemia, proliferates continuously in suspension culture and consists predominantly (greater than 90%) of promyelocytes. These cells can be induced to differentiate to morphologically and functionally mature granulocytes by incubation with a wide variety of compounds, including butyrate and hypoxanthine and polar planar compounds such as dimethyl sulfoxide and hexamethylene bisacetamide. We have now found that retinoic acid (all-trans-retinoic acid) induces differentiation (as measured morphologically and by the ability to reduce nitroblue tetrazolium) of HL-60 at concentrations as low as 1 nM. Maximal differentiation (approximately 90%) occurs at 1 micro M, a concentration 1/500th to 1/160,000th the concentrations of butyrate (0.5 mM) and dimethyl sulfoxide (160 mM) that promote a similar increase in differentiation. Continuous exposure to retinoic acid is necessary for optimal differentiation, with the percentage of mature cells in the culture directly related to the length of time of exposure to retinoic acid. Retinoic acid and 13-cis-retinoic acid are equally effective in inducing differentiation of HL-60. Retinol (vitamin A), retinal, and retinyl acetate are approximately 1/1000th less potent. This study suggests that retinoids could provide a therapeutic tool in the treatment of acute myeloid leukemia, a disease that has been looked upon as primarily involving a block in myeloid differentiation, and indicates that retinoids, in addition to their well-characterized involvement in epithelial cell differentiation, may also be involved in the differentiation of certain hematopoietic cells.