Paracentric inversion of chromosome 3 (q21q26) in a patient with chronic myelomonocytic leukemia and a normal platelet count.

Clonal chromosomal abnormalities occur in about one-third of patients with chronic myelomonocytic leukemia (CMMoL) and are usually those found in other myelodysplastic syndromes. Abnormalities of chromosome 3, which have been associated with abnormal thrombopoiesis, are relatively uncommon. A patient with CMMoL with inv(3)(q21q26) and normal thrombopoiesis is presented, and the cytogenetics of CMMoL are reviewed. The possible significance of chromosome 3 in thrombopoiesis is discussed.

Quantitative and functional studies of impaired natural killer (NK) cells in patients with myelofibrosis, essential thrombocythemia, and polycythemia vera. I. A potential role for platelet-derived growth factor in defective NK cytotoxicity.

In view of the possibility that immunological dysfunctions may be involved in initiating or contributing to the pathogenesis of myeloproliferative disease, we investigated quantitative and functional activity of natural killer (NK) cells in patients with polycythemia vera, essential thrombocythemia and myelofibrosis, and have demonstrated, especially in myelofibrosis, a measurable cytotoxic defect in the ability of their peripheral blood mononuclear cells to efficiently kill the standard NK target, K-562. Furthermore, highly purified, FACS-sorted CD16+ lymphoid cells from patients with myelofibrosis were consistently defective in their ability to lyse K-562 targets, and could not be augmented substantially with recombinant interleukin (IL)-2. Only patients with myelofibrosis had significantly lower percentages and absolute numbers of CD16+ cells as compared to patients with essential thrombocythemia and polycythemia vera. Further experiments demonstrated that patients with myelofibrosis, although having fewer CD16+ NK cells, had a significantly increased proportion of CD16+ cells with detectable platelet-derived growth factor (PDGF) on their surface. In contrast, surface PDGF was barely detectable on CD16+ cells from patients with polycythemia vera and essential thrombocythemia, as well as from normal controls. Having previously reported that physiologic quantities of PDGF significantly inhibit human NK cell cytotoxicity, and that patients with myelofibrosis and essential thrombocythemia have significantly elevated circulating levels of plasma PDGF, we now have demonstrated that pretreatment of normal NK cells with concentrated, PDGF-containing, platelet-poor plasma from patients with these diseases significantly inhibits NK cytotoxicity. This inhibitory effect was reversed by neutralization of plasma PDGF with anti-PDGF (coupled to Sepharose resin). Both the NK defects demonstrated in this study, and the abnormal plasma PDGF results reported earlier, are most striking in myelofibrosis and least abnormal in polycythemia vera, with an intermediate degree of abnormality in essential thrombocythemia. Our new findings suggest a causal correlation between abnormal platelet release, plasma accumulation of PDGF, and the observed NK immunodeficiency in these myeloproliferative patients.

Metabolic evidence of cobalamin deficiency in bone marrow cells harvested for transplantation from donors given nitrous oxide.

Nitrous oxide inactivates cobalamin, but clinically apparent sequelae ensue in nondeficient individuals only when exposure is prolonged. The gas is widely used in anesthesia, therefore, and is commonly given to donors during harvesting of their bone marrow cells for transplantation. The present study shows that nitrous oxide administered for only 75-120 minutes induced mild but unequivocal DNA synthetic abnormalities attributable to cobalamin deficiency in the harvested marrow cells of 4 out of 5 donors; the deoxyuridine suppression test in these 4 patients showed abnormal results more than 4 standard deviations above the reference mean. Metabolic evidence of cobalamin deficiency in cryopreserved cells diminished only slightly when they were thawed and retested 1 day later, but was no longer detectable in cells thawed and tested on the 3rd day. In contrast, cells harvested under nitrous oxide-free anesthesia in 4 subjects showed no evidence of cobalamin deficiency in the deoxyuridine suppression test. These results demonstrate that even relatively brief exposure to nitrous oxide induces cobalamin deficiency in harvested bone marrow cells, and that the cells remain metabolically impaired for more than 24 hours. Although clinical sequelae are not apparent at this time, the several potential implications of our findings indicate that the use of nitrous oxide in bone marrow transplantation needs to be evaluated further.

Peripheral blood stem cells harvested during marrow recovery from disease-specific chemotherapy shorten duration of neutropenia in patients undergoing autologous bone marrow transplantation.

A total of 41 patients who underwent autologous bone marrow transplantation without the use of granulocyte-macrophage colony-stimulating factor were retrospectively evaluated to determine whether the infusion of peripheral blood stem cells collected during the period of recovery of bone marrow from previous disease-specific chemotherapy could shorten the time to bone marrow engraftment after transplantation. Of the 41 patients, 24 patients received bone marrow only (group 1), 8 patients received bone marrow plus steady-state peripheral blood stem cells (group 2) and 9 patients received bone marrow plus rebound peripheral blood stem cells collected during the period of recovery from disease-specific chemotherapy (group 3). Infusion of rebound peripheral blood stem cells (group 3) accelerated recovery of white blood cells and neutrophils and resulted in a white blood cell count of > 10(9)/L by day 15 compared with day 25 in group 1 (P < 0.001), and a neutrophil count of > 0.5 x 10(9)/L by day 16 versus day 26 in group 1 (P = 0.0034). Addition of steady-state peripheral blood stem cells (group 2) did not hasten myeloid engraftment, and recovery of platelets was not improved in either group given peripheral blood stem cells. Compared with patients in group 1, patients in group 3 required 7 fewer days of parenteral antibiotics (25 days versus 18 days, respectively; P = 0.0072) and were discharged about 3 weeks earlier than patients in group 1 (day + 41 verus day +21; P = 0.0002).(ABSTRACT TRUNCATED AT 250 WORDS)

Iron-deficiency anemia: a medically treatable chronic anemia as a model for transfusion overuse.

PURPOSE: Transfusion practice in patients with iron deficiency was reviewed. PATIENTS AND METHODS: During the study period, records of 265 consecutive patients with an unsaturated iron-binding capacity of greater than 53.7 mumol/L were evaluated for possible iron-deficiency anemia. RESULTS: Two hundred sixty-three patients met the study criteria for iron deficiency. Of these patients, 50 received 1 or more units of red blood cells (RBCs). The transfusion therapy of 12 patients could not be justified; physicians used laboratory results rather than the clinical status of the patients to initiate transfusion therapy. As a result, units of RBCs were transfused to raise the hematocrit to an arbitrarily chosen level. Furthermore, iron therapy was not prescribed for 97 of the 263 iron-deficient patients, including 11 of the patients for whom transfusion was justifiable and 2 patients for whom transfusion could not be justified. Based on records reviewed, no work-up was initiated to identify the cause of iron deficiency in 13 patients, including 4 patients who received transfusions. CONCLUSION: These findings suggest that the evaluation and treatment of iron deficiency, including transfusion therapy for that condition, may be problematic. In view of the risks of blood transfusion therapy, improvement in transfusion practices for iron deficiency should be emphasized.

Hemolytic anemia in a cancer patient treated with recombinant interferon-gamma.

Currently, three classes of interferon are used in the treatment of malignancies. Interferon-gamma is the best studied. Bone marrow suppression as well as immune hemolytic anemia have been described. Heretofore, only bone marrow suppression has been attributed to interferon-gamma (IFN gamma). In this report, we describe a woman with lung cancer being treated with IFN gamma in whom acute hemolytic anemia occurred. Immune hemolysis did not appear to be the cause. We concluded that in addition to bone marrow suppression, hemolysis should be considered in a patient receiving IFN gamma in whom an unexplained drop in hematocrit occurs.

Autoimmune cytopenias in pernicious anemia: a report of four cases and review of the literature.

Pernicious anemia appears to be autoimmune in origin and is associated with immune disorders of several organ systems. We report 4 patients with pernicious anemia and immune cytopenias, an association that may sometimes pose diagnostic problems unless specifically considered. Pernicious anemia coexisted with or was closely followed by idiopathic thrombocytopenic purpura in 3 patients and by autoimmune hemolytic anemia in a 4th patient. In addition to cobalamin therapy, all patients required corticosteroids (2 also received danazol), while 1 also required splenectomy. All 4 patients were women. The 3 patients with idiopathic thrombocytopenic purpura were also blood group O and were iron-deficient. Autoimmune cytopenias may occur in patients with treated or untreated pernicious anemia and require specific therapy.