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)

During 1980-1988 bone marrow transplantation was performed in 14 patients with acquired severe aplastic anemia. Twelve of these patients had HLA identical and two patients incompatible family donors. Two patients died before marrow engraftment. Twelve patients engrafted 12-30 days after marrow transplantation with continued normal marrow function. The actuarial probability for long term survival was found to be 67% after HLA identical allogeneic sibling marrow transplantation. The longest time of observation was 9 years and the patient is still alive. All deaths occurred during the first six months posttransplant. It is concluded that the serious prognosis for patients with SAA has improved if the patients have the possibility for allogeneic HLA identical family donor transplantation.
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PMID:[Acquired severe aplastic anemia. Therapeutic effect and prognosis after allogeneic bone marrow transplantation]. 198 60

The current working hypothesis on the pathogenesis of autoimmune disease focuses on the interactions between susceptibility genes and environmental stimuli. In Graves' disease it is postulated that aberrant expression of HLA class II antigens on thyroid epithelial cells permits the presentation of specific thyroid antigen to activated lymphocytes. Evidence suggests that thyrocyte HLA-DR expression is secondary to the production of cytokines by presensitized T-lymphocytes. A 20-yr-old woman and her 18-yr-old brother presented with classical findings of Graves' disease with ophthalmopathy within a year of each other. Diagnosis was confirmed by demonstration of elevated serum levels of T4 and T3, strongly positive titers of TSH binding inhibitory immunoglobulins, and histological examination after subtotal thyroidectomy. Eight years previously, acute life-threatening aplastic anemia in the brother led to therapeutic transplantation of bone marrow from his sister. After the procedure, 100% of his peripheral leucocytes were genotype 46,XX. HLA typing performed before transplantation and 2 months after thyroidectomy in the female indicated complete identity with her brother's leukocytes for class I and class II antigens. Thyroid autoantibodies at this time were weakly positive. Although the concordance of thyroid disease in these patients could be due to chance, the patients were of different sexes, the family history was negative, and neither the probands nor the first degree relatives bore the HLA-DR3/B8 antigens. We propose that the male passively acquired a clone of programmed or activated lymphocytes from his sister and that his hyperthyroidism was not primarily dependent on exposure to specific thyroid-derived antigen.
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PMID:Concordant Graves' disease after bone marrow transplantation: implications for pathogenesis. 200 10

Thirty-five patients underwent allogeneic bone marrow transplantation (BMT) from unrelated donors (UD), in a pilot study of the Canadian Bone Marrow Transplant Group with techniques routinely used in BMT from HLA-identical related donors. Thirty-two of the patients had hematologic malignancies and 3 had aplastic anemia. Donors and patients were matched at all HLA loci tested serologically in 29 cases; 19 of these patients had mutually non-reactive mixed leukocyte cultures (MLC's). Six patients had some degree of serologic mismatch. Stable engraftment occurred in all but 3 evaluable patients. Acute graft-versus-host disease (GVHD) developed in greater than 80% and fatal BMT-related deaths occurred in a total of 55% of all patients. Conversely, only two relapses have occurred, and the 1-year actuarial event-free survival for all patients is 40% (95% confidence intervals [CI], 24-55%) with a follow-up of 0.8 to 2.7 years. All survivors are out of the hospital and all save 1 have a normal performance status. Our study has confirmed the utility of unrelated donors for allogeneic BMT. Although more complications are seen than with HLA-matched sibling donors, these patients did not have such donors available and virtually all were incurable without transplants. Further studies, especially those using new methods to prevent transplant-related complications, are needed.
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PMID:The use of unrelated donors (UD) for allogeneic bone marrow transplantation (BMT): a pilot study of the Canadian BMT Group. 204 87

A multiplicative model is described relating HLA typing information to disease incidence. A likelihood-based method for estimating parameters in this model is proposed for use with data sets in which HLA haplotype information is available on a series of cases and their parents. This approach is extended to incorporate information from a matched control series for the purpose of estimating HLA and environmental risk factor effects simultaneously. The method is applied to data from aplastic anemia patients treated by bone marrow transplantation and the results are compared to unmatched case-control analyses using the same case series and several different control series.
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PMID:On estimating HLA/disease association with application to a study of aplastic anemia. 204 13

Bone marrow transplantation (BMT) in patient affected by severe aplastic anemia (SAA), is successful in 70-80% of cases, when performed with HLA identical brother or syngeneic twin as donors, and in 11-45% of cases when performed from aploidentical-identical related or HLA identical unrelated donor. The different conditioning regimens (Cy alone or in combination with TBI) have shown similar results in the long term outcomes. Cyclosporin-A is very effective in avoiding rejection and controlling GVHD.
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PMID:[Bone marrow transplantation in the treatment of severe aplastic anemia]. 205 53

Intensive chemoradiotherapy conditioning regimens and acute graft-versus-host disease (GVHD) are both associated with significant morbidity and mortality after bone marrow transplantation. In this study, we investigated whether the conditioning regimen affected the development of acute GVHD. Thirty-four patients, four with severe aplastic anemia and 30 with a lymphohemopoietic malignancy, were prepared for transplantation either with cyclophosphamide (CY) alone, with CY combined with total body irradiation (TBI) or CY combined with etoposide and either TBI or busulfan. GVHD prophylaxis included methotrexate (MTX 10 mg/m2) given on days 1, 3 and 6, and daily cyclosporine (CSP) on days--1 through 180. The overall incidence of acute GVHD was 36% (15% for HLA identical, 87% for HLA non-identical recipients). However, when assessed by the severity of conditioning regimen-related toxicity, the incidence of GVHD grades II-IV (HLA identical; HLA non-identical) was 0% (0%; 0%), 37% (20%; 67%) and 50% (22%; 100%) for patients with mild, moderate and severe toxicity, respectively. Compliance with GVHD prophylaxis declined with increasing intensity and toxicity of the conditioning regimen. These data suggest that a regimen of three doses of MTX and daily CSP is as effective as four doses of MTX/CSP for GVHD prophylaxis in patients given HLA identical marrow grafts. However, GVHD regimen compliance and efficacy of GVHD prevention are inversely related to the intensity of the conditioning regimen.
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PMID:Conditioning-related toxicity and acute graft-versus-host disease in patients given methotrexate/cyclosporine prophylaxis. 205 56

A preparative regimen for allogeneic bone marrow transplantation, consisting of total lymphoid irradiation (TLI) with 750 cGy and cyclophosphamide (CY), was used in five girls with aplastic anemia. All patients received bone marrow from HLA matched/mixed lymphocyte culture negative siblings. In our regimen the "inverted Y" field to irradiate the pelvic nodes was modified, which did not include the whole pelvic cavity in an attempt to protect the ovaries from irradiation. Although some of the pelvic nodes was supported not to be irradiated in order to protect the ovaries, engraftment occurred in all five patients including four who had been transfused prior to transplantation. All five are alive from 47 days to 1378 days (median 285 days) after transplantation without transplantation-associated complications. The calculated dose to the ovaries was sixteen percent of the entire dose of the regimen. Both of the two evaluable patients that had received transplantation just before or during the puberty are developing normal sex maturity including menstruation. This study suggests that our preparative regimen is effective not only for engraftment of the donor marrow but also for protecting the ovaries from irradiation.
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PMID:[Bone marrow transplantation for girls with aplastic anemia utilizing modified field of total lymphoid irradiation and cyclophosphamide: with emphasis on the field of pelvic cavity]. 207 26

Bone marrow was harvested from a 3.95 kg premature 7-week-old female baby for donation to a 13 kg HLA-identical sister with severe aplastic anemia. Two hundred ml of donor bone marrow were aspirated, containing a calculated dose of 3 x 10(8)/kg nucleated bone marrow cells for the recipient. This was equivalent to two-thirds of the donor's calculated blood volume (320 ml). Peri-operative care included invasive monitoring of intravascular pressures, arterial blood gas analysis, careful temperature control and the infusion of 150 ml of packed red cells, 150 ml of colloid and 50 ml of crystalloid. Rapid engraftment occurred. There were no complications and both donor and recipient are healthy 12 months later.
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PMID:Anesthetic management of marrow harvesting from a 7-week-old premature baby. 209 14

At Huddinge Hospital 275 patients underwent allogeneic bone marrow transplantation. Among children in first remission of acute leukemia or chronic phase CML (early leukemia), with HLA-identical marrow the 8-year leukemia-free survival was 77%. This was better than 38% in children undergoing transplantation in second to fourth remission (p less than 0.0009). In adults with early leukemia, the 8-year leukemia-free survival was 47% compared to 21% for intermediate-risk adults (p = 0.007). Among 25 patients with severe aplastic anemia receiving marrow from HLA-identical siblings, the actuarial 10-year survival was 78%. In 14 patients with various metabolic disorders, of whom half received marrow from HLA-mismatched donors, the actuarial 7-year survival was 71%. Forty-three patients were given marrow from HLA-mismatched donors and had an increased incidence of acute graft-versus-host disease (GvHD) and death due to GvHD compared to recipients of HLA-identical bone marrow. The major causes of death among our patients were relapse of leukemia, death due to GvHD, cytomegalovirus (CMV) pneumonitis, bacterial infection and invasive fungal infections. By preventing GvHD with T-cell depletion or methotrexate (MTX) combined with cyclosporine (CsA) acute GvHD decreased, but the incidence of relapse increased compared to patients treated with MTX or CsA alone. This resulted in improved survival in patients older than 30 years, but a nonsignificant decrease in leukemia-free survival in younger patients. There was an association between herpes virus immunity in the recipient and GvHD. CMV pneumonitis increased following GvHD and decreased in patients treated with MTX combined with CsA. Invasive fungal infections may be treated or prevented using amphotericin B encapsulated in liposomes with few side effects.
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PMID:Allogeneic bone marrow transplantations at Huddinge Hospital and strategies to improve survival. 210 43

Use of allogeneic BMTs continues to increase. During the 33-year period between 1955 and 1987, more than 20,000 patients received allogeneic BMTs; more than 50% of these were performed in the 3 years, 1985 through 1987. Transplants are effective therapy for leukemia and other hematologic diseases. They are the treatment of choice for aplastic anemia and chronic myelogenous leukemia, those who fail conventional therapy for acute leukemia, and a variety of immune deficiency disorders. Successful application of BMT is limited by complications such as graft failure, GvHD and interstitial pneumonia, and, until recently, the requirement for an HLA-identical sibling donor. In the past few years, an increasing number of transplants was performed using HLA partially matched related or unrelated donors, with some success. The development of posttransplant complications can often be predicted by risk factor assessment. In this report, current data from the IBMTR are summarized and several risk factors affecting outcome identified.
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PMID:Current status of allogeneic bone marrow transplantation. 210 63


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