Blood
-
The effects on bone marrow (BM) cell proliferation and differentiation of recombinant human interleukin-3 (rhIL-3) and recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) administered after high-dose (7 g/m2/d) cyclophosphamide (HD-CTX) chemotherapy were studied in nine patients with malignancies without BM involvement and in three control patients. rhIL-3 at a dose of 1 to 5 micrograms/kg/day was administered for 14 to 18 days by continuous intravenous (i.v.) infusion and rhGM-CSF was administered at a dose of 5.5 micrograms/kg/day for 14 days. Changes induced by cytokine treatment were assessed by morphoimmunohistochemical analysis of BM biopsies. Comparison was made in the cytokine-treated groups and with control patients who received HD-CTX alone. ⋯ BM stroma changes observed in both treated groups included endothelial cell proliferation, increased BM macrophage concentration, and increase in BM fibroblasts as detected with an anti-nerve growth factor receptor antibody. In most rhIL-3-treated cases, BM fibrosis developed after treatment. The same effect was not observed in rhGM-CSF patients.
-
Regular red blood cell transfusions reduce the rate of recurrent cerebral infarction in sickle cell disease but lead to accumulation of excessive iron. We studied the effect on the prevention of recurrent stroke and the volume of blood transfused of a modified transfusion program in which the pretransfusion percentage of hemoglobin S (HbS) was maintained at 50%, rather than the conventional 30%. Fifteen patients with sickle cell disease and cerebral infarction who had been free of recurrent stroke for at least 4 years during which the pretransfusion HbS was maintained below 30% were assigned to a transfusion program in which the HbS was allowed to increase to 50%. ⋯ Manual or automated partial exchange transfusions and a target HbS level of 50% in eight patients reduced blood requirements by 33% to 99% (mean 67%) in comparison with simple transfusion and a target HbS level of 30% (P less than .001). This study offers evidence that a target pretransfusion HbS level of 50% affords a continuing high rate of protection against recurrent cerebral infarction in sickle cell disease after 4 years of a conventional transfusion program. Increasing the target HbS level from 30% to 50% provides a major reduction in blood requirements and lowers the rate of iron accumulation.
-
Cardiopulmonary bypass (CPB) has been demonstrated to activate platelets, producing an increased number of circulating platelets that have undergone alpha-granule release and express granule membrane protein-140 (GMP-140) on their surface. In vitro, GMP-140 mediates activated platelet adhesion to neutrophils (PMN) and monocytes, causing the formation of leukocyte-platelet conjugates. ⋯ We conclude that CPB, through increased platelet GMP-140 expression, causes formation of monocyte-platelet, and to a lesser extent, PMN-platelet conjugates. The activation of monocytes and PMN on CPB, as evidenced by CD11b expression, occurs with differing time courses.
-
To determine whether patients with acquired asplastic anemia (AA) exhibit clonal hematopoiesis, we used restriction fragment length polymorphisms of the X-linked genes phosphoglycerate kinase (PGK1) and hypoxanthine phosphoribosyltransferase (HPRT) and the X-linked probe M27 beta. Of the 19 female patients studied, 18 (95%) patients were informative for at least one marker. Of these, eight patients (42%) were heterozygous for PGK1, two (11%) for HPRT, and 16 (84%) for M27 beta. ⋯ Other potential markers to study clonality, including cytogenetic abnormalities or point mutations of the N-ras protooncogene, were not found in any of the patients. It is concluded that patients with AA may exhibit clonal hematopoiesis. The significance with respect to evolution to disorders with clonal hematopoiesis like paroxysmal nocturnal hemoglobinuria, myelodysplasia, and acute leukemia remains to be determined.
-
Recombinant human interleukin-2 (IL-2), administered to cancer patients by continuous intravenous (IV) infusion (3 x 10(6) U/m2/d), was found to induce the in vivo production of colony-stimulating factors (CSF). Plasma obtained from patients during IL-2 treatment stimulated in vitro colony formation of normal human bone marrow cells, depleted of mononuclear phagocytes and T lymphocytes. This colony-stimulating activity (CSA) was identified as IL-5, granulocyte-macrophage CSF (GM-CSF), and macrophage CSF (M-CSF), by the ability of specific antibodies against these factors to neutralize their effects. ⋯ Furthermore, no negative regulators of hematopoiesis, such as interferon gamma (IFN-gamma) or tumor necrosis factor-alpha (TNF-alpha), were found in plasma. These data illustrate that in vivo administration of high-dose IL-2 may result in a stimulatory effect on hematopoiesis. The induction of detectable levels of IL-5 and GM-CSF in the circulation may explain the eosinophilia and neutrophilia observed in these patients.