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)

A 26-year-old ABO-O positive patient with aplastic anemia received a bone marrow transplant from his genotypically HLA identical, but ABO-A positive, brother. Engraftment of myeloid and megakaryocytic lineages occurred within 4 weeks but pure red cell aplasia and transfusion dependent anemia persisted for 160 days. The authors postulated that the failure of erythropoiesis was due to a high titer of anti-A isohemagglutinins. They tested this hypothesis with clonal cell cultures and flow cytometric analysis of ABO antigen expression by colony forming cells in vitro. During the period of prolonged red cell aplasia, the patient had normal numbers (85 +/- 12 per 10(6) cells) of circulating donor derived, burst forming units-erythroid (BFU-E). Immunophenotypic analysis of erythroid burst colonies derived from culture of the patient's bone marrow cells showed that 91 +/- 5% of 274 nucleated red cells were A-antigen positive, confirming full donor engraftment. Autologous plasma and complement added on day 1 of culture did not affect the colony growth (82.5 +/- 15 per 10(6) cells). However, when the addition of complement was delayed until day 7 of culture, there was 90% inhibition of BFU-E (7.5 +/- 5 per 10(6) cells) compared to controls (p less than 0.0004). Based on this, the authors propose a model for expression of ABO antigens during erythropoiesis, in which BFU-E do not express ABO antigens but their progeny do. The data support the hypothesis that the mechanism of prolonged pure red cell aplasia after ABO-incompatible bone marrow transplantation is complement mediated immune destruction of erythroid progenitors past the stage of BFU-E in differentiation.
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PMID:Case report: isoimmune inhibition of erythropoiesis following ABO-incompatible bone marrow transplantation. 177 22

Between February 1988 and January 1990, 35 patients underwent allogeneic bone marrow transplantation (BMT) from unrelated donors using measures routinely employed for matched related donors. Median patient age was 34 years (range 2-49). Thirty-two patients had hematologic malignancies, including chronic myelogenous leukemia (CML) in 16; three patients had severe aplastic anemia. Donor-patient pairs were matched at the HLA loci tested serologically (HLA-A, -B, -DR) in 29 cases; mixed leukocyte culture results were variable but often reactive. Five patients died prior to day +28 without evidence of myeloid engraftment, and one patient developed fatal graft failure several months after initial engraftment. Acute graft-versus-host disease (GVHD) occurred in 77% (95% confidence interval [CI] 60-90%) of all patients, and GVHD contributed to the death of 10 patients. Fatal regimen-related toxicity occurred in four patients and another died due to neurologic complications of a process that resembled the hemolytic-uremic syndrome. Two acute leukemia patients relapsed, and a CML patient was found to have a localized non-Hodgkin's lymphoma at necropsy. As of 1 June 1991, 14 patients are alive and in remission at a median follow-up of 1.9 years (range 1.5-3.3); all except one have normal performance scores. The 2-year actuarial event-free survival for all patients is 40% (95% CI 24-56%). Proportional hazards analysis revealed favorable significance for female patient sex, less advanced disease status and shorter interval from diagnosis to BMT. While unrelated-donor transplants need not necessarily duplicate the results of related-donor transplants to be of benefit, the event-free survival in this series was roughly similar to that expected in the related-donor situation, with the high transplant-related mortality somewhat offset by a low recurrence rate. Further studies using unrelated donors, employing new methods of preventing transplant-related complications, are indicated.
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PMID:Allogeneic bone marrow transplantation using unrelated donors: a pilot study of the Canadian Bone Marrow Transplant Group. 179 Apr 28

In bone marrow transplantation (BMT) the main reason for early treatment failure is transplant-associated mortality (TAM) due to GvHD, interstitial pneumonia, veno-occlusive disease and infections. Since 1981, 84 consecutive HLA-identical BMT have been performed (13 aplastic anemia, 61 leukemia/lymphoma, 3 genetic diseases; mean age 28 [5-51] years) according to a standardized protocol designed to reduce TAM: fractionated, low dose rate irradiation; strict laminar air flow isolation plus complete intestinal decontamination; cyclosporine therapy for 4 months and CMV prophylaxis (hyperimmune plasma infusion, CMV-negative blood products). 11 patients (13%) died in TAM. Continuous complete remission was obtained in 78% of standard risk patients (n = 55) and 28% of high risk patients (n = 29). Mean observation time was 42 (3-116) months post transplantation. This result points to the necessity of a liberal indication for BMT early in the course of acute or chronic myelogenous leukemia, in the course of acute or chronic myelogenous leukemia, severe aplastic anemia and other eventually lethal hemato-oncological diseases.
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PMID:[Indications for allogeneic and autologous bone marrow transplantation]. 185 73

We report the case of a 6.5-year-old male who received an unrelated orthotopic liver transplant for hepatic failure and encephalopathy following non-A-non-B hepatitis and subsequently developed severe aplastic anemia. For treatment of his aplastic anemia, he received a successful marrow transplant from his 9-year-old genotypically HLA-identical sister following conditioning with cyclophosphamide 200 mg/kg and anti-thymocyte globulin 90 mg/kg. Significant veno-occlusive disease of the liver and graft-versus-host disease did not occur. The patient remains alive without clinical chronic active hepatitis or need for blood product therapy. His hematocrit is 36%, white blood cell count 9.7 x 10(3)/mm3, and platelet count 1.7 x 10(5)/mm3 almost 2 years after marrow transplantation.
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PMID:Successful allogeneic bone marrow transplantation in a 6.5-year-old male for severe aplastic anemia complicating orthotopic liver transplantation for fulminant non-A-non-B hepatitis. 190 74

The case survey of drug-induced hematologic disorders in Shikoku District (Ehime Prefecture) disclosed 21 patients. Cases were 12 rheumatoid arthritis patients, 2 brain tumor, one epilepsy, 2 liver cirrhosis, one neuralgia, one arthralgia, one hyperthyroidism, and one IBL-like T-lymphoma. Causative drugs for aplastic anemia were Metalcaptase, Shiosol, Voltaren and Emeside. Drug-induced aplastic anemia was so severe that 4 out of 5 patients had died of bone marrow dysfunction. Neutropenia was caused by drugs as Rimatil, Cefobit, Sepatren, Mercazole, Sulpyrin, Aleviatin, Cefamedin and Metalcaptase. The real causes of these drug-induced hematologic disorders have not been clear. Remarkably high incidence among rheumatoid arthritis patients is suggestive several reasons as unique reactivity associated with HLA, suppression on hematologic stem cells by abnormal metabolites, and immunologic dysfunction commonly seen in collagen diseases. Further studies of more accurate incidence of drug-induced hematologic disorders are needed in investigating real causes of unhappy side-effects.
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PMID:[Drug-induced hematologic disorders in Shikoku district]. 192 Aug 31

Since 1980, 107 consecutive patients (pts) underwent bone marrow transplantation (BMT) for nonconstitutional severe aplastic anemia (SAA) at our institution. All received conditioning with Cytoxan (150 mg/kg) and thoraco-abdominal irradiation (6 Gy) from an HLA-identical sibling donor. Mean age was 19 years (5 to 46 years). Forty-nine pts had less than 0.2 x 10(9)/L PMN and 53 failed to respond to previous immunosuppressive therapy before BMT. Graft-versus-host disease (GVHD) prophylaxis consisted of methotrexate (22 pts), cyclosporine (52 pts), or both (33 pts). With a median follow-up of 45 months (12 to 120 months), overall actuarial survival was 68% (confidence interval 95%:9.7). Of 16 factors tested, five were shown to adversely influence survival by multivariate analysis: grade greater than or equal to 2 acute GVHD (relative risk [RR]: 5.5), prior immunosuppressive therapy (RR: 3.5), female as donor (RR: 2.4), nonidiopathic SAA (RR: 2), and more than 0.2 x 10(9)/L PMN AA (RR: 2). Because acute GVHD was the most potent factor for survival, we analysed risk factors for acute GVHD. By multivariate analysis, 2 of 14 factors tested were independent: male as recipient (RR: 3) and previous alloimmunization of the donor (RR: 4.3). On long-term follow-up, chronic GVHD was observed in 49 pts of 89 surviving more than 100 days (55%). Multivariate analysis showed that infection before transplant (RR: 1.3) and previous history of acute GVHD (RR: 1.8) were associated with an increased risk of chronic GVHD.
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PMID:Bone marrow transplantation in 107 patients with severe aplastic anemia using cyclophosphamide and thoraco-abdominal irradiation for conditioning: long-term follow-up. 193 58

Allogeneic marrow transplantation from an HLA-identical sibling has proven to be an effective treatment for severe aplastic anemia with restoration of normal hematopoiesis and long-term survival in 70-80% of recipients. Results are related to patient age, with improved survival in younger patients. Marrow transplantation from HLA nonidentical family and unrelated donors has been less successful and is the focus of ongoing clinical research. Graft rejection and graft-versus-host disease (GVHD) remain major problems. A number of pre- and post-transplant immunosuppressive regimens to prevent these complications continue to be studied. The risk of graft rejection is increased in patients who have been transfused before transplant, whereas the risk is decreased with the infusion of larger numbers of transplanted marrow cells. The incidence of graft rejection is 10-32% when cyclophosphamide is used alone as the pretransplant conditioning regimen. The addition of donor buffy coat cells and whole body or limited field radiation have reduced the rate of graft rejection, but increased the incidence of complications such as chronic GVHD and secondary malignancies. GVHD is an immune disorder caused by incompatibility between donor and recipient for histocompatibility antigens. Approximately 18-40% of patients experience moderate to severe acute GVHD. Previous pregnancy in female donors and increasing age of the patient are factors predictive of its development. Methotrexate and cyclosporin have been used most frequently as prophylactic immunosuppressive agents; various combinations of these drugs and prednisone are being evaluated. Symptomatic chronic GVHD occurs in approximately 25% of recipients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Bone marrow transplantation for severe aplastic anemia. 193 61

Severe aplastic anemia is a rare disorder which is most often fatal when bone marrow transplantation or an immunosuppressive regimen is not applied. The cause of the disease in individual patients is not identifiable by laboratory investigations. The decision for a therapeutic modality is based on patient age and availability of an HLA-identical bone marrow donor. Early application of bone marrow transplantation may cure up to 80% of patients. Many patients may also be rescued with combined, intensive immunosuppression. Each of these treatment modalities, however, require early application, prior to the onset of typical complications such as infection and bleeding.
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PMID:[Severe aplastic anemia]. 194 45

During 1990 143 teams in 20 European countries performed a total of 4234 bone marrow transplants. Donor source was in 1802 cases an HLA-identical family donor, in 118 cases a non-identical family donor, in 36 cases a twin donor, in 181 an unrelated volunteer donor and in 2097 cases autologous bone marrow. Indications for the transplant were leukaemias in 2365 patients, lymphoproliferative disorders in 1104 patients, solid tumours in 382 patients, aplastic anaemia and thalassaemia in 281 patients, inborn errors in 58 patients and miscellaneous disorders in 44 patients. This survey of the European Group for Bone Marrow Transplantation on transplant activity clearly indicates that within the last decade bone marrow transplantation has become an established therapy in Europe. The results of this first complete survey provide a basis for planning therapeutic trials and health policy strategies.
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PMID:Bone marrow transplantation activity in Europe 1990. European Group for Bone Marrow Transplantation (EBMT) 151 Dec 60

It has been shown that human umbilical cord blood contains stem/progenitor cells comparable in number to that of adult bone marrow. We report here the first successful cases of transplantation of umbilical cord blood cells. The patients were suffering from Fanconi's anemia, complicated by severe aplastic anemia. During pregnancy, it was shown that the mother was carrying a sibling unaffected by the disease and with HLA identical to the patient. Cord blood was collected and frozen in liquid nitrogen at birth. After conditioning with low-dose cyclophosphamide (20 mg/kg) and thoraco-abdominal irradiation (5 grays), the patients received a cord blood transplant of thawed cells. Three patients have been transplanted without any immediate side-effect. One has not enough follow-up, but two patients are alive and well with complete donor hematologic reconstitution and no chronic graft versus host disease. Potential developments of this technique are an extension of applicability with regard to other diseases that might be transplanted and whether such transplants can be performed in adults. The relative immaturity of the lymphoid system at birth may be advantageous in decreasing the graft versus host reaction if these cells are used in a mismatched transplantation. Cord blood cell banks may be useful for transplants in patients lacking an HLA-identical donor.
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PMID:Transplantation of umbilical cord blood in Fanconi's anemia. 198 24


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