Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0039730 (thalassemia)
 10,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

T-cell-mediated inhibition of granulomonopoietic progenitors (CFU-GM) was studied in vitro in 27 patients with severe aplastic anaemia (AA). In nine out of 13 responders to anti-thymocyte globulin (ATG), cultured T-cells obtained prior to therapy, as well as their conditioned medium strongly suppressed both normal allogeneic and autologous CFU-GM (the latter obtained after marrow recovery). Addition of anti-interferon-gamma to the cultures abolished the suppressive effect on CFU-GM. After ATG therapy, no similar inhibitory effect was detected. Employing the panning method with monoclonal antibodies (CD4+ for inducer/helper and CD8+ for cytotoxic/suppressor T-cells) we were able to show that the cells responsible for in vitro CFU-GM inhibition were included in the cytotoxic/suppressor T-cell subpopulation. Cultured T-cells and their conditioned medium obtained from 14 non-responders to ATG did not show CFU-GM suppression. The mean interferon (IFN) levels in the T-cell conditioned media of ATG-responders was 625 +/- 125 mu/ml while in non-responders the level was 45 +/- 15 mu/ml (normal control levels 43 +/- 24 mu/ml). Freshly isolated peripheral blood lymphocytes from either group did not show any in vitro inhibitory effect. The response rate to ATG was statistically significant when the generation in culture of high versus low IFN production was compared (P = 0.0001). Experiments with T-cells obtained from heavily transfused thalassaemia major, and myelodysplastic syndrome patients, as well as normal volunteers, also did not demonstrate any suppression of CFU-GM. Our results indicate that the response rate to ATG is significantly higher in patients with AA who have an abnormal regulation of interferon-gamma (g-IFN) production.
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PMID:In vitro interferon-gamma production by cultured T-cells in severe aplastic anaemia: correlation with granulomonopoietic inhibition in patients who respond to anti-thymocyte globulin. 313 95

This study reviews results of fetal liver transplantation in hematologic disorders including aplastic anemia, leukemia and thalassemia. One hundred and twenty two patients received transplants for aplastic anemia; engraftment was reported in 4 patients; graft-versus-host disease (GvHD) did not occur. Complete and partial responses were reported in one-half of patients, the majority of whom had no evidence of engraftment. Thirty-nine patients received transplants for leukemia. Transient engraftment was reported in 40% and two developed GvHD; survival extended to more than 2 years. The higher rate of engraftment in patients with leukemia suggests a role of pretransplant immune suppression. The risk of GvHD appears to be low despite complete HLA-mismatching. These data suggest a possible role for fetal liver transplantation in man. Future studies should probably be based on preclinical data obtained in large animal models.
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PMID:Fetal liver transplantation in aplastic anemia and leukemia. 332 6

The major barriers to successful bone marrow transplantation (BMT) are graft-versus-host disease (GVHD), infection, rejection and relapse. The combination of methotrexate and cyclosporin is significantly better than either alone in controlling GVHD. Removal of T cells from donor marrow prior to BMT has also decreased GVHD significantly, but a 5-10% rejection rate occurs and an increased relapse risk is being reported by some centres. Cyclosporin is valuable in the treatment of both acute and chronic GVHD. Interstitial pneumonitis due to cytomegalovirus (CMV) is a major cause of mortality. Protection can be provided with CMV hyperimmune globulin and also by the avoidance of blood donors who are CMV antibody positive. Fractionated total body irradiation is associated with decreased toxicity compared to single dose. There is a 75% 4 year disease-free survival following BMT for acute non-lymphoblastic leukemia in first remission, a 50% survival for acute lymphoblastic leukemia in second remission and an 88% survival for chronic myeloid leukemia in chronic phase. BMT for beta-thalassaemia major in young patients without organ dysfunction cures 80% of patients and identical results are achieved for severe aplastic anaemia when BMT is undertaken prior to blood product transfusion.
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PMID:Recent advances in bone marrow transplantation. 332 11

A 5 year 9 month-old boy has received a bone marrow allograft for beta-thalassaemia major. Conditioning included busulfan: 16 mg/kg, cyclophosphamide 200 mg/kg and a (6 Gy) thoracoabdominal irradiation. After a 16 months follow-up, the child is currently in complete remission without treatment with all the markers of his donor. His 9 year-old sister has been allografted for beta-thalassaemia major, with the same conditioning regimen. After engraftment, rejection occurred at day 85 with severe aplastic anaemia. A second graft was performed with the same donor without engraftment and the patient died at day 18 of pneumonitis. A review of the literature is proposed and the ethical choices are discussed.
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PMID:[Major beta-thalassemia and bone marrow allograft. Two cases and a study of the literature]. 332 38

Bone marrow transplantation is increasingly used to treat a spectrum of diseases in man, including immune and genetic disorders, hematological diseases, and cancer. Approximately 11,000 transplants have been performed worldwide since 1970. About two-thirds of these transplants have involved donors, including related and unrelated individuals, and in the remaining third the patient's bone marrow has been used in the form of an autotransplant. In some disorders and under carefully defined circumstances, bone marrow transplantation appears to be the preferred therapy; these diseases include aplastic anemia, acute myelogenous leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia, and selected immune and genetic disorders. In other circumstances, the value of bone marrow transplantation is less well defined. Diseases in which bone marrow transplantation may be of benefit include Hodgkin's and non-Hodgkin's lymphoma, other cancers, thalassemia, hemoglobinopathies, genetic disorders, and possibly multiple myeloma. It has been difficult to precisely identify the role of bone marrow transplantation in many of these diseases. Prospective randomized controlled clinical trials have sometimes shown an advantage for bone marrow transplantation, but in most circumstances a benefit is as yet unproven. In the U.S. the annual incidence of individuals with diseases in which bone marrow transplantation is thought to be of proven benefit is approximately 5,400, and an additional 15,000 individuals annually have diseases in which bone marrow transplantation is thought to be of possible benefit. This study reviews data available from both controlled and uncontrolled clinical trials indicating the potential role of bone marrow transplantation in the treatment of human diseases.
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PMID:Clinical trials of bone marrow transplantation. 352 45

Toxicity to the bone marrow is a frequent limiting factor in the use of high doses of chemotherapeutic agents. Bone marrow transplantation overcomes the marrow toxicity problem, but it is not protective to other organs. Extensive animal studies have been carried out in the mouse, the rat, rhesus monkeys, and dogs to delineate the dose-limiting toxicity of cyclophosphamide (Cytoxan) (CY) therapy. Studies in the dog have shown 100 mg/kg of CY to be lethal with supportive care alone. Dogs given this dose followed by stored autologous marrow recovered after a period of profound pancytopenia and severe gastrointestinal toxicity. This dose of CY also permitted allogeneic engraftment in the dog. Monkeys given up to 200 mg/kg of CY have uneventful hematopoietic recovery, but doses of 240 mg/kg were generally fatal even when stored autologous marrow was infused. Cardiac toxicity was the limiting factor. CY 180 mg/kg was not lethal and permitted successful allogeneic marrow engraftment. CY is successfully used for conditioning leukemia or aplastic anemia patients for bone marrow transplantation. Patients with severe aplastic anemia are conditioned with CY 50 mg/kg on each of four days followed by allogeneic marrow transplantation. Patients undergoing transplantation before transfusion have a long-term survival rate of about 80%. Patients with genetic disorders of the marrow generally have a normocellular or hypercellular marrow, and the preparative regimen must include destruction of the abnormal marrow as well as immunosuppression sufficient to permit engraftment. Patients with thalassemia are treated with dimethylbusulfan 5 mg/kg or busulfan 14 mg/kg followed by CY 50 mg/kg on each of four days. Approximately 100 thalassemia patients have been treated, with a survival rate of approximately 75%. For patients with leukemia, radiotherapy is generally added to the CY conditioning regimen. In the early Seattle studies, 1,000 rad total body irradiation was combined with CY 60 mg/kg on each of two days. There were many early deaths, but some long-term survivors are alive and well 5 to 13 years later. Current regimens involve fractionated total body irradiation and various post-grafting immunosuppressive regimens designed to prevent graft-v-host disease. Complications and problems of current regimens are discussed, and future goals for marrow transplantation are presented.
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PMID:High-dose therapy and bone marrow transplantation. 390 18

Bone marrow transplantation is increasingly used to treat a broad spectrum of human diseases including aplastic anemia, leukemia, solid tumors, immune and genetic disorders. In certain circumstances the role of transplantation is reasonably well established, such as aplastic anemia and resistant leukemia. In other circumstances there is controversey as to the role of transplantation such as leukemia in remission. An increasing number of genetic disorders including severe combined immunodeficiency, Wiskott-Aldrich syndrome, osteopetrosis, and Thalassemia have been cured by transplantation. Despite substantial progress, with transplantation that remain to be solved including graft-vs.-host disease, interstitial pneumonia, immune deficiency, and the lack of suitable donors for most potential recipients. These problems and potential approaches are discussed in detail Future direction of research include the application of transplantation to other diseases as well as the use of this approach either as a prelude to solid-organ grafts or as a vehicle for the introduction of new genetic information.
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PMID:Bone marrow transplantation. 391 31

Monocyte ferritin (MF) content was measured in normal subjects and patients with a variety of disorders of iron storage. MF was above the normal range in 4 patients with idiopathic haemochromatosis (IHC). However, in 4 patients with transfusion siderosis (TS), secondary to aplastic anaemia, who had similar elevations in serum ferritin, MF was highly elevated. 10 patients with thalassaemia intermedia and thalassaemia major with no previous history of transfusions, but with elevated serum ferritin, also had significantly elevated MF. Disproportionately low MF in IHC could reflect defective ferritin metabolism in reticuloendothelial cells in this disorder. Finally, in 3 patients with acute rises in serum ferritin caused by acute hepatitis, MF was not increased. This suggests that MF is not directly affected by high circulating levels of serum ferritin raised acutely, but rather reflects iron storage status in conditions not associated with primary disorders of iron metabolism.
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PMID:Monocyte ferritin in idiopathic haemochromatosis, thalassaemia and liver disease. 395 67

Classification of platelet disorders has been based on the platelet count. Addition of a second variable, mean platelet volume (MPV), to the routine blood count allows classification of patients into 9 categories: high, low, or normal MPV, and high, low or normal platelet count. We studied 1,244 adult inpatients. 1,134 had both platelet values normal. 11 patients had high MPV and low platelet count: all had hyperdestructive causes. 15 patients had high MPV and normal platelet count: 12 had heterozygous thalassemia, and three had iron deficiency. Seven patients had high MPV and high platelet count: causes included myeloproliferative disorders, inflammation, iron deficiency, and splenectomy, 25 patients had high platelet counts and normal MPV: the causes were inflammation, infection, sickle cell anemia, iron deficiency, or chronic myelogenous leukemia. 52 patients had an MPV that was inappropriately low for the platelet count (high, normal, or low). All had sepsis, splenomegaly, aplastic anemia, chronic renal failure, or a disease being treated with myelosuppressive drugs. High MPV thus appears correlated with myeloproliferative disease or thalassemia; and low MPV, with cytotoxic drugs or marrow hypoplasia. Addition of MPV to the platelet count allows subtler disorders to be detected (when the platelet count is normal), and allows distinction of the cause of thrombocytopenia.
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PMID:Use of mean platelet volume improves detection of platelet disorders. 407 87

A 27 year old male with aplastic anemia developed a high fetal hemoglobin, a low hemoglobin A2, a decreased beta/alpha synthetic ratio, and an increased G gamma/A gamma synthetic ratio. This acquired hemoglobinopathy resembling delta beta-thalassemia was recognized at the onset of acute erythroleukemia. Certain features of this abnormal globin synthetic pattern resemble those of the normal fetus and thus appear to provide another example of gene expression by malignant cells resembling that of an earlier stage of the organism's development.
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PMID:Erythroleukemia manifesting delta beta-thalassemia. 618 18


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