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 to O bone marrow transplantation was performed in a 25-year-old male affected with severe aplastic anaemia, the donor being an HLA compatible brother. Three plasma exchanges had to be performed with an Aminco separator to remove the original and recurring anti-A isohaemagglutinins. The dynamics of O to A blood group conversion were followed by means of differential agglutination. An early wave of marked dyserythropoiesis was observed in the engrafted marrow. Mild to moderate GvHD was treated successfully with MTX, bolus high dosage 6-methylprednisolone and, at relapse, with intravenous ALG.
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PMID:A to O bone marrow transplantation in severe aplastic anaemia: dynamics of blood group conversion and demonstration of early dyserythropoiesis in the engrafted marrow. 1 32

A total of 21 multiply transfused patients with severe aplastic anemia (SAA) were treated with bone marrow transplantation between March 1985 and September 1990: 20 allogeneic and one syngeneic transplants. A positive response in mixed lymphocyte culture (MLC) was also noted in 7 allogeneic recipients. Pregraft conditioning included high-dose cyclophosphamide (CY) 200 mg/kg over 4 consecutive days, followed by 300 cGy total-body irradiation the day before BMT. Seventeen patients older than 14 years received additional donor buffy-coat cells infusion for 5 days posttransplant. A combination of methotrexate and cyclosporine was used for prophylaxis of graft-versus-host disease. Seventeen patients were alive with a functional graft, and Kaplan-Meier product limit estimates showed a 80.95% probability of survival at 67.7 months. There were 4 deaths: two died of primary graft failure, one from secondary rejection, and the other from chronic GVHD-related complications. Acute GVHD, grade I was noted in only one patient (5.6%). In contrast, chronic GVHD was observed in 10 out of 18 (55.6%) evaluable patients. Venoocclusive liver disease and interstitial pneumonitis were not diagnosed. Our findings indicate that the combination of CY/TBI/BC is well tolerated and results in a low incidence of graft failure/rejection in multiply transfused Chinese patients who received transplants for SAA. The MTX/CsA combination was confirmed as being remarkable in reducing the incidence and severity of acute GVHD. For patients with SAA under the age of 40, with an HLA-identical sibling, we highly recommend BMT as the treatment of choice.
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PMID:Bone marrow transplantation for severe aplastic anemia--a study of twenty-one Chinese patients in Taiwan. 154 48

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

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

Survival of patients with aplastic anemia after immunosuppressive therapy with ATG/ALG ranges from 35% to 60%. However, long-term follow-up on these patients has indicated a high frequency of hematologic complications, including PNH, myelodysplasia, ANL, and recurrent aplasia. In contrast to immunosuppressive therapy, allogeneic marrow transplantation results in cure of aplasia. Problems initially limiting the success of HLA-matched allogeneic marrow transplants included graft rejection and complications associated with acute and chronic GVHD. Infusion of donor buffy coat cells along with marrow or alternatively more intensive immunosuppressive regimens containing irradiation have substantially decreased the risk of rejection. However, buffy coat infusion increases the incidence of chronic GVHD and irradiation treatment adds to toxicity of the conditioning regimen as well as producing long-term complications. The incidence and severity of acute GVHD have been significantly decreased by the use of MTX/CSP as GVHD prophylaxis; however, this regimen has had no impact on the incidence of chronic GVHD. Long-term survival in multiply transfused patients after HLA-identical marrow transplantation is on the order of 60% to 70%; survival in untransfused patients approximates 80%. Patients less than age 18 transplanted on protocols currently active in Seattle have greater than 90% survival. Further increases in survival must come from improvement in preventing and treating chronic GVHD. Patients diagnosed with aplastic anemia should have rapid HLA typing performed to identify possible marrow donors. Transfusions from prospective marrow donors should be avoided and the patient referred to a major treatment center. We continue to recommend allogeneic marrow transplantation for patients with severe aplastic anemia who are less than 40 years old and who have HLA-identical related donors. Immunosuppressive therapy should be tried first in patients without HLA-matched donors and for patients over the age of 40. HLA-mismatched marrow transplantation and use of unrelated marrow donors for severe aplastic anemia remain areas of active research.
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PMID:Treatment of aplastic anemia. 219 14

Forty-six patients with aplastic anaemia (median age 23 years) were given cyclophosphamide followed by infusion of marrow from an HLA-identical family member. To evaluate postgrafting prophylaxis for graft-versus-host disease (GVHD), the patients were entered into a randomized prospective trial comparing a combination of methotrexate and cyclosporin (n = 22) to methotrexate alone (n = 24). Methotrexate/cyclosporin significantly reduced the incidence and severity of acute GVHD and improved early survival. This report updates the results of the randomized trial with followup ranging from 3 to more than 6 years. The methotrexate/cyclosporin regimen did not interfere with sustained engraftment, and there were no significant differences in the incidence of early or late graft rejection among the two treatment groups (10% v 4%). The incidence of chronic GVHD was higher among methotrexate/cyclosporin-treated patients (58% v 36%; P = 0.18). Two patients in each treatment group still require treatment for chronic GVHD, while treatment is no longer needed in the other patients. Projected 4-year survival is 73% in patients given methotrexate/cyclosporin compared to 58% in patients given methotrexate alone (P = 0.16). Having achieved a reduction in the incidence of acute GVHD and associated early mortality without impairing engraftment, it is clear that future progress in marrow grafting for aplastic anaemia must come in the area of chronic GVHD.
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PMID:Graft-versus-host disease prevention by methotrexate combined with cyclosporin compared to methotrexate alone in patients given marrow grafts for severe aplastic anaemia: long-term follow-up of a controlled trial. 234 39

In Essen 142 bone marrow transplantations were carried out between December 1975 and February 1985. In 74 cases the indication was acute leukemia in relapse (n = 23) or in first or consecutive remission (n = 51). The conditioning regimen consisted of cyclophosphamide or the combination of cyclophosphamide and total body irradiation. All patients were treated under strict gnotobiotic care. To mitigate the risk of CMV infections, intravenous CMV-hyperimmune globulin and CMV-negative blood products have been applied routinely for 2 years. MTX was used as prophylaxis against GvHD. In the prognostically unfavorable group of acute leukemia in relapse, only one patient showed long-term survival. In this patient, leukemic relapse occurred 6 years after transplantation. The survival rate of AML patients grafted during the first remission is 55% (16/29) with a median observation time of 41 months. For patients grafted in first or consecutive remission of acute lymphoblastic leukemia, the survival rate is 50% (7/14) with a maximal observation time of 34 months. The overall incidence of GvHD in patients at risk was 28% in aplastic anemia, 26% in AML, 9% in ALL, and 63% in CML. In aplastic anemia, no patient developed an interstitial pneumonia. In leukemia, the risk of fatal interstitial pneumonia was 34%.
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PMID:Bone marrow transplantation in acute leukemia. 330 98

In Essen 121 bone marrow transplantations were carried out. The indications were severe aplastic anemia (n = 18), acute leukemia in relapse (n = 20), acute leukemia in remission (n = 46) or chronic myeloid leukemia (n = 37). The conditioning regimen consisted of cyclophosphamide or the combination of cyclophosphamide and total body irradiation. All patients were treated under strict gnotobiotic care. To mitigate the risk of CMV infections intravenous CMV-hyperimmunoglobulin and CMV-negative blood products have been applied routinely since two years. MTX was used as prophylaxis against GVH-disease. In case of severe aplastic anemia 13 patients (72%) are still alive with a median observation time of 24 months. In the prognostically unfavourable group of acute leukemia in relapse only one patient showed long term survival. In this patient leukemic relapse occurred six years after transplantation. The survival rate of AML patients grafted during the first remission is 55% (15/27) with a median observation time of 40 months. For patients grafted in first or consecutive remission of ALL the survival rate is 42% (5/12) with a maximal observation time of 29 months. Out of 37 patients grafted because of CML, eight were in an advanced stage of the disease. 13 patients are still alive, the maximal observation time is 37 months. The overall incidence of GVHD in patients at risk was 28% in aplastic anemia, 26% in AML, 9% in ALL and 63% in CML. In aplastic anemia no patient developed an interstitial pneumonia. In leukemia the risk of fatal interstitial pneumonia was 34%.
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PMID:Bone marrow transplantation in severe aplastic anemia and acute or chronic leukemia. 351 96

A new regimen for prevention of acute graft-versus-host disease (GvHD)--OKT3 (murine monoclonal anti-pan-T antibody), prednisone and methotrexate (OKT3-pred-MTX)--was compared with the Minnesota standard regimen--antithymocyte globulin, prednisone and methotrexate (ATG-pred-MTX)--for adverse effects, effect on incidence of acute GvHD, and survival at 1 year post-transplant. Twenty patients (aged 25 +/- 9 years) had bone-marrow transplantation (BMT) from their HLA-MLC identical sibling donors for treatment of aplastic anaemia (four), acute leukaemia in remission (13) or chronic myelogenous leukaemia (three). These 20 patients received (OKT3-pred-MTX) on days 8-22 post-transplant. Results of this group are compared to those of 19 concurrent patients (aged 26 +/- 12 years) who received ATG-pred-MTX on days 8-22 post-transplant. On the first day of treatment, 20/20 OKT3 patients and 18/19 ATG patients were febrile. Within 24 h of the first dose of OKT3, 6/20 patients experienced dyspnoea or chest pain and 3/20 patients developed diarrhoea. No further adverse effects were seen after the second dose of OKT3 and no late adverse effects were attributed to this drug. Time to engraftment (means 25 d) was not statistically significantly different in the two prophylactic groups. Acute GvHD was diagnosed in 14 of 20 patients who received OKT3-pred-MTX and in eight of 19 patients who received ATG-pred-MTX (P = 0.06). The incidence of hepatic or gastrointestinal GVHD (greater than or equal to grade 2) was similar in the two groups: 4/20 OKT3-pred-MTX, 6/19 ATG-pred-MTX. Characteristics of post-transplant infections were also similar for the two prophylactic groups. Survival at 1 year post-transplant was 65% for patients who received OKT3 and 44% for patients who received ATG (P = 0.13). The use of OKT3 with prednisone and methotrexate is relatively safe and is associated with a similar incidence of moderate-severe acute GvHD to that experienced in the use of ATG with prednisone and methotrexate.
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PMID:Graft-versus-host disease prophylaxis with anti-T-cell monoclonal antibody OKT3, prednisone and methotrexate in allogeneic bone-marrow transplantation. 389 Sep 26

Methotrexate has been used as the mainstay therapy to prevent or ameliorate graft-versus-host disease (GVHD) in allogeneic bone marrow transplantation. We began a nonrandomized study in which methotrexate was not given routinely. Fifty-five patients underwent transplant for acute leukemia (44 patients), aplastic anemia (6 patients), and other malignancies (5 patients). Methotrexate was given to 34 patients (MTX +) and was withheld in 21 patients (MTX -). Median (range) age of patients was 12 (0.8-43) years in the MTX + group, and 16 (3-45) years in the MTX- group. Mean days (+/- SEM) to engraftment (neutrophils greater than 500/microL, and platelets greater than 20,000/microL untransfused) occurred earlier in the MTX- patients (19.6 +/- 1.4 v 24.9 +/- 1.8 days for granulocytes, and 19.3 +/- 1.5 v 27.4 +/- 2.8 days for platelets, P less than .05). There were no statistically significant differences between the patient groups for the incidence or severity of GVHD (10/34 in the MTX + group had grade O-l GVHD compared to 9/21 in the MTX- group). The interstitial pneumonitis occurred at a significantly increased rate in patients who received methotrexate (15/34) compared to those patients who did not (3/21) (P = .02). However, there was also a significant relationship between the interstitial pneumonitis and the preparative regimen: if the preparative regimen contained 1,000 rad single fraction total body irradiation, 8/14 patients were affected compared to 5/22 patients affected when 1,200 rad fractionated total body irradiation was used (P = .03). Because methotrexate significantly retards hematopoietic reconstitution, randomized trials for GVHD prevention are recommended.
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PMID:Incidence of acute graft-versus-host disease with and without methotrexate prophylaxis in allogeneic bone marrow transplant patients. 637 59


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