Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002874 (aplastic anemia)
 5,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fourteen patients with aplastic anemia and one with the Wiskott-Aldrich syndrome who were specifically sensitized against their donors were successfully engrafted with bone marrow from those donors. Sensitivity was detected in antibody-independent and antibody-dependent cell-mediated lysis assays. In order to erase this immunity to non-MHR familial transplantation antigens, multiagent immunosuppression with cyclophosphamide, procarbazine, and whole rabbit antithymocyte serum (ATS) was used. The data suggest that ATS was largely responsible for abrogation of this sensitivity and indicate that immunity does not represent a barrier to successful transplantation.
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PMID:Successful bone marrow transplantation in sensitized recipients. 37 31

The lack of a simple, rapid, and quantitative test of the functional activity of the monocyte has hampered studies of the contribution of this cell type to host defense and human disease. This report describes an assay of antibody-dependent cellular cytotoxicity, which depends exclusively upon the monocyte as the effector cell and therefore provides a convenient test of monocyte function. In this system, mononuclear leukocytes (MNL) obtained by Ficoll-Hypaque separation of whole blood are cytotoxic for 51Cr-labeled human erythrocyte targets coated with anti-blood group antibody. Removal of phagocytic monocytes from the MNL by iron ingestion, followed by exposure to a magnetic field, completely abolishes all cytotoxic activity from the remaining MNL population. Similarly, in severely mono-cytopenic patients with aplastic anemia, cytotoxic effector activity is absent. In normals and less severely monocytopenic aplastic anemia patients, cytotoxicity correlates significantly (p less than 0.001) with monocyte number. Application of this monocyte-mediated antibody-dependent cellular cytotoxicity assay to the study of patients with the Wiskott-Aldrich syndrome has revealed defective monocyte cytotoxic activity in spite of normal monocyte numbers, suggesting that this test may be useful for the assessment of monocyte function in a variety of clinical situations.
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PMID:Monocyte-mediated antibody-dependent cellular cytotoxicity: a clinical test of monocyte function. 100 82

Growth of the patients with hematological malignancies, aplastic anemia, Fanconi's anemia, and Wiscott-Aldrich syndrome who had been treated with bone marrow transplantation (BMT) was studied. Fourteen out of 21 patients showed suppression of linear growth after BMT. Recovery of the growth velocity after 1-2 years tended to occur if BMT was performed at younger age. Six of eight patients with chronic graft-versus-host-disease (CGVHD) had impaired growth after BMT, whereas eight of 13 (61%) without CGVHD did. Provocative tests for growth hormone (GH) performed 5-72 months after BMT revealed three boys who showed poor response to more than two different stimuli. Two of these three boys had prolonged suppression of growth. Neither the age at BMT, difference in disease, nor presence of posttransplant growth retardation gave significant difference in the response of GH to provocative tests. It was concluded that approximately two-thirds of marrow-grafted children experienced transient decrease in growth velocity after BMT.
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PMID:Growth after bone marrow transplantation in children. 179 50

Clinicopathologic records and neuropathologic tissues of 109 patients who underwent necropsy after treatment with bone marrow transplantation (BMT) were examined. Underlying disorders included leukemia (70), aplastic anemia (25), solid tumors (7), lymphoma (5), Hodgkin's disease (1) and Wiskott-Aldrich syndrome (1). There were 34 females and 75 males, ranging in age from 2 to 56 years. Survival after transplantation averaged 3.6 months. The most common findings were cerebrovascular lesions (29), including hematomas, hemorrhagic necrosis, and infarcts. Central nervous system infections comprised the next most common finding, including 10 fungal and four bacterial infections. A recurrence of underlying malignancy for which transplant had been performed occurred in five patients. Leukoencephalopathy of varying severity was found in eight patients, half of whom had received intrathecal chemotherapy and/or cranial radiation. Patients with systemic graft-versus-host disease had a variety of nonspecific neuropathologic findings in the nervous system; however, nearly half (44%) showed no detectable changes. Other nonspecific alterations included hypoxic/ischemic changes, vascular siderocalcinosis, and neuroaxonal spheroids (associated with hemorrhage or necrosis). These findings provide a guide as to likely causes of a neurologic syndrome in a patient who has undergone BMT, and can be compared with neuropathologic findings in other forms of immunosuppression.
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PMID:Neuropathologic findings after bone marrow transplantation: an autopsy study. 219 Sep 10

Cryopreservation has been used extensively in autologous marrow transplantation (BMT), but there has been limited use in allogeneic BMT. We describe here 6 cases of successful engraftment following allogeneic BMT with cryopreserved marrow. Patients suffered from Wiscott-Aldrich syndrome, osteopetrosis, aplastic anemia, and acute lymphocytic, acute non-lymphocytic, and chronic myelogenous leukemia, and ranged in age from 5 mos to 35 yrs. Marrow was collected using standard techniques. In one case T-cells were removed to prevent graft-vs-host disease. Marrow was frozen for a variety of reasons. Buffy coat cells were frozen at controlled rate in 10% DMSO, and stored in liquid nitrogen for 6 to 49 d. Engraftment (WBC greater than 1000/uL x 3 d) occurred from 13 to 37 d post BMT. In 4 of 4 cases in which data are available, donor origin of engraftment was documented, 1 with cytogenetics, 2 with red cell typing, and 4 with restriction fragment length polymorphisms. 3 patients are alive and well 21, 21, and 42 months post BMT. These results suggest frozen marrow can be successfully used for allogeneic BMT.
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PMID:Successful allogeneic cryopreserved marrow transplantation. 264 97

Allogeneic bone marrow transplantation (BMT) was applied in 1968 to treat severe combined immunodeficiency disease (SCID). Almost simultaneously, marrow from an MHC-matched donor corrected the immunological deficiency of a patient with Wiscott-Aldrich Syndrome (WAS). In the first successful treatment of X-linked SCID the match was imperfect and, although SCID was cured, a graft vs. host reaction caused pancytopenia. A second BMT from the same donor successfully treated a complicating aplastic anemia. Subsequently, it has been possible to cure most patients with SCID who are in reasonably good condition at the time of BMT without other manipulation if a matched sibling donor is available. Successes are reported from Holland, France, Italy, England, Scandinavia, Japan, Germany, and from many centers in the United States. Similarly, BMT is used to correct SCID due to adenosine deaminase (ADA) deficiency or nucleoside phosphorylase (NP) deficiency, which underlie two forms of SCID. Bone marrow transplantation using HLA-matched sibling donors can now treat, successfully, at least eight genetically separable forms of SCID. Highly lethal defects of phagocytic function (including LFA-1, MO-1, CR-3 deficiencies, IL-2 and IL-1 receptor deficiencies), defects of killing after phagocytosis (as in chronic granulomatous disease, WAS, and Kostmann's Syndrome), and certain inborn errors of metabolism can be cured by BMT.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Bone marrow transplantation for immunodeficiency diseases. 330 7

Patients who undergo bone marrow transplantation are generally immunosuppressed with a dose of cyclophosphamide (CYA) which is usually calculated based on the patient's weight. At these high doses of CYA, serious cardiotoxicity may occur, but definitive risk factors for the development of such cardiotoxicity have not been described. Since chemotherapeutic agent toxicity generally correlates with dose per body surface area, we retrospectively calculated the dose of CYA in patients transplanted at our institution to determine whether the incidence of CYA cardiotoxicity correlated with the dose per body surface area. Eighty patients who were to receive CYA 50 mg/kg/d for four days as preparation for marrow grafting underwent a total of 84 transplants for aplastic anemia, Wiskott-Aldrich syndrome, or severe combined immunodeficiency syndrome. Fourteen of 84 (17%) patients had symptoms and signs consistent with CYA cardiotoxicity within ten days of receiving 1 to 4 doses of CYA. Six of the 14 patients died with congestive heart failure. The dose of CYA per body surface area was calculated for all patients and the patients were divided into two groups based on daily CYA dose: Group 1, CYA less than or equal to 1.55 g/m2/d; Group 2, CYA greater than 1.55 g/m2/d. Cardiotoxicity that was thought to be related to CYA occurred in 1/32 (3%) of patients in Group 1 and in 13/52 (25%) patients in Group 2 (P less than 0.025). Congestive heart failure caused or contributed to death in 0/32 patients in Group 1 v 6/52 (12%) of patients in Group 2 (P less than 0.25). There was no difference in the rate of engraftment of evaluable patients in the two groups (P greater than 0.5). We conclude that the CYA cardiotoxicity correlates with CYA dosage as calculated by body surface area, and that patients with aplastic anemia and immunodeficiencies can be effectively prepared for bone marrow grafting at a CYA dose of 1.55 g/m2/d for four days with a lower incidence of cardiotoxicity than patients whose CYA dosage is calculated based on weight. This study reaffirms the principle that drug toxicity correlates with dose per body surface area.
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PMID:Cyclophosphamide cardiotoxicity: an analysis of dosing as a risk factor. 353 79

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

Mepartricin, a new semisynthetic heptene, was given for systemic Candida infections to 11 immunocompromised patients. All patients were undergoing bone marrow transplantation or treatment with antilymphocytic globulin: 6 had acute leukemia, 4 aplastic anemia and 1 had Wiskott-Aldrich syndrome. In all patients systemic Candida infection was diagnosed on the basis of fungemia or positive cultures from at least three different sites, two of which were outside the gut. Mepartricin was given intravenously as a slow drip, at the dose of 100-700 U/kg/day for a total of 198 patient-days (range 9-36, mean +/- SD 18 +/- 8). Patients had to be premedicated with steroids and antihistamines to avoid reactions such as chills and fever. The treatment was well tolerated in all patients, and renal function tests were unchanged during therapy. There was a complete resolution of the fungal infection in 10 of the 11 patients.
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PMID:Mepartricin: a new antifungal agent for the treatment of disseminated Candida infections in the immunocompromised host. 613 15

Bone marrow transplantation in childhood is an established treatment modality for aplastic anemia, the acute and chronic leukemias, and severe combined immune deficiency. Recently, experience with this treatment has also been favorable with small numbers of children who have Wiskott-Aldrich syndrome, several types of inherited storage diseases, Fanconi's anemia, thalassemia, infantile malignant osteopetrosis, and selected cases of lymphoma and other solid tumors. The psychosocial impact and financial costs of bone marrow transplantation can be substantial. Multi-institutional, prospective, randomized trials that would compare transplantation and conventional therapy are necessary to establish the indications and precise timing for this procedure. Further development of monoclonal antibodies, a better understanding of the histocompatibility antigen systems, and improvement in pretransplantation conditioning regimens should increase the spectrum of effectiveness for bone marrow transplantation in the coming years.
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PMID:Bone marrow transplantation for diseases of childhood. 636 12


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