The cytogenetic status of bone marrow stromal elements obtained from six patients with Ph1-positive chronic myelogenous leukemia (CML), two in blast crisis, was studied in vitro utilizing the potential of marrow to form surface-adherent colonies morphologically compatible with mesenchymal elements. We demonstrated the absence of both the marker chromosome and other chromosomal abnormalities in all the fibroblastic colonies studied, indicating that the progenitors of such colonies (plaque-forming units in culture, PFU-C) are not closely related to hematopoietic elements including macrophages. This supports previous reports suggesting that the stromal elements in myelofibrosis associated with CML are not derived from the primary Ph1-positive malignant clone but represent a stromal reactive component of benign or independent malignant potential.
Tritiated thymidine incorporation in a whole blood lymphocyte stimulation test (LST) and lymphocyte colony formation (CFU-L) from whole blood were measured following in vitro x-irradiation. Lymphocytes from patients with myelodysplastic disorders, acute nonlymphocytic leukemia, and patients at increased risk for leukemia because of their primary disease and/or cytotoxic therapy were found to be significantly more sensitive to in vitro x-irradiation than lymphocytes from clinically normal individuals. Cloning efficiencies and mitogenic responsiveness of patient lymphocytes were significantly depressed as compared to normal values. Using monoclonal antibodies to specific surface markers, quantitative abnormalities in lymphocytic subpopulations from myelodysplastic patients also were observed. These findings are suggestive of a defect at the T-cell level that may directly or indirectly affect hematopoiesis.
In vitro radiation survival of peripheral blood T lymphocytes was studied in 15 clinically normal adults and 4 patients with Fanconi's anemia. Tritiated thymidine incorporation in a whole blood lymphocyte stimulation test (LST) and a newly developed whole blood T-lymphocyte colony assay were used to measure lymphocyte blastogenesis and colony formation in response to phytohemagglutinin (PHA) or concanavalin-A (Con-A) stimulation. Lymphocyte colony formation was found to be consistently more sensitive than the LST for detection of low-level radiation effects using both normal cells and lymphocytes from Fanconi's anemia patients. Lymphocytes from patients with Fanconi's anemia were significantly more sensitive to in vitro x-irradiation than lymphocytes from clinically normal individuals as measured by their ability to divide when stimulated by PHA in the LST (patients, D37 = 198 R; normals, D37 = 309 R, p = 0.057) and colony formation assay (patients, D37 = 53 R; normals, D37 = 109 R, p = 0.016). No significant difference in the radiosensitivity of the Con-A response was observed between the two groups. The PHA-responsive T-lymphocyte subpopulation in Fanconi's anemia patients appears to be intrinsically defective. The nature of this defect, significance in the disease process, and relevancy of these findings to the establishment of radiation protection standards are discussed.
A patient with polycythemia rubra Vera developed marked thrombocytosis and hemorrhage after splenectomy. Plateletpheresis with a blood processor proved to be a safe, efficient, and rapid method for the mechanical removal of large quantities of platelets prior to adequate control with chemotherapy. Medicine
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