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)

If ABO antigens/antibodies play any role in the pathogenesis of acute graft-versus-host disease (GVHD), one would expect the highest incidence of GVHD in recipients of minor ABO-mismatched grafts, followed by ABO-matched grafts, and the lowest incidence in major ABO-mismatched transplants. To test this hypothesis 174 patients receiving an HLA-identical allogeneic bone marrow transplant (BMT) for aplastic anemia (n = 32) or leukemia (n = 142) were analyzed for factors associated with acute GVHD. Variables analyzed included diagnosis, sex, age, blood group of donor and recipient, ABO compatibility, Rhesus compatibility, sex compatibility, number of bone marrow cells given at BMT, year of transplant, day of engraftment, and GVHD prophylaxis. We first carried out an exploratory contingency table analysis: minor ABO incompatibility was associated with a significantly higher risk of severe acute GVHD when compared with ABO-matched and major-ABO mismatched pairs (P = 0.003): 14/9, 57/67, and 5/22 patients developed, respectively, 0-I/II-IV acute GVHD in ABO major-mismatched, matched, and minor-mismatched pairs. Donors of group 0, (P = 0.06), older recipient's age (P = 0.08), fast engraftment (P = 0.03), and older donor's age (0.08) were also associated with a higher risk of GVHD. Recipient's ABO group, diagnosis, year of transplant, Rhesus group of donor or recipient, Rhesus compatibility, sex of donor or recipient, sex compatibility, and type of GVHD prophylaxis were not predictive of GVHD. A Cox multifactorial proportional hazards analysis confirmed that ABO matching was the single most significant factor associated with GVHD (P = 0.006). The cumulative incidence of GVHD grade II+ was 39%, 54%, and 82% for ABO major-mismatched, matched, and minor-mismatched pairs (P = 0.01). This study suggests that ABO antigens may play a role in the development of acute GVHD.
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PMID:ABO compatibility and acute graft-versus-host disease following allogeneic bone marrow transplantation. 328 50

A patient with aplastic anemia received an ABO incompatible bone marrow transplant (BMT) from an HLA identical sibling. Weekly HLA antibody screens were performed as part of the BMT protocol. At the time of transplant, a hemolytic anti-Le(a) was detected in the Le (a-b-) donor. The Le (a-b+) recipient had no red cell or LCT antibody. A hemolytic anti-Le(a) was detected in the recipient on day 8, but no LCT reactivity was noted at this time. On day 15, the LCT panel demonstrated reactivity with 9 of 50 panel cells without apparent HLA specificity. Graft vs. host disease (GVHD) was present on the skin at this time. The dose of cyclosporin A was increased, but by day 20 the GVHD worsened and the LCT titers increased to 8. This strong reactivity was noted only in the Le (a+) panel members (12/50) and was neutralized with commercial Lewis substance. On day 34 there was no evidence of GVHD, but the lymphocytotoxic anti-Lea continued to be present. The patient began experiencing renal and gastrointestinal difficulties by day 48, and expired on day 60. In renal transplants the kidneys retain their Lewis type and secrete Lewis substance in the urine. In our experience BMT patients retain their Lewis type regardless of the type of the donor. The Lewis system has been linked to renal allograft rejection, and Lewis antigens may function as transplantation antigens in BMT patients as well. In addition, lymphocytotoxic Lewis antibodies can mask other significant HLA antibodies and must be identified when screening patients in need of plateletpheresis products.
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PMID:A bone marrow transplant with an acquired anti-Le(a): a case study. 353 Nov 8

Bone marrow transplantation results in the infusion of 150 to 360 ml of erythrocytes. While this poses no problem to a recipient of marrow from an ABO-compatible donor, it clearly represents a serious risk of intravascular hemolysis for the recipient of an ABO-incompatible marrow. Thus, there is a need for removing incompatible erythrocytes from the marrow preparation. We removed erythrocytes from the marrow preparations by automated centrifugation. The erythrocyte-depleted marrow (EDM) contained a mean of 5 ml erythrocytes, representing an average reduction of 98%. The mean mononuclear cell recovery was 88%, resulting in a mean infusion of 0.6 X 10(8) cells/Kg of recipient's body weight in a final average volume of 155 ml. EDM was infused into 22 ABO-incompatible marrow recipients (21 patients with hematologic malignancies and one patient with aplastic anemia) without clinical evidence of hemolysis. The isohemagglutinin titers of recipients ranged from 4 to 4096 and were not lowered prior to infusion. Engraftment (i.e., recovery of peripheral leukocyte and platelet counts) and incidence of graft versus host disease were similar to those observed in recipients of ABO-compatible marrow transplantation. Erythrocyte engraftment was significantly delayed in only one patient who had a high isohemagglutinin titer. The post-transplantation red cell requirement was increased in EDM recipients: 9 units compared to 6 units in ABO-compatible bone marrow transplanted patients with neither hemolysis nor interference with successful engraftment.
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PMID:Erythrocyte depletion of ABO-incompatible bone marrow. 389 6

The regeneration of peripheral blood cells in six patients receiving ABO incompatible bone marrow transplants for severe aplastic anaemia has been studied. The results are compared with those of 18 similar aplastic patients treated with ABO compatible transplants. Reticulocyte recovery in the ABO incompatible cases was significantly delayed (P less than 0.01) and associated with greatly prolonged red cell transfusion requirements (P less than 0.001). Peripheral blood regeneration of neutrophils, lymphocytes and platelets was also significantly delayed (P less than 0.01). Platelet support was required for longer in the ABO incompatible cases (P less than 0.001) but there was no increase in the incidence or severity of infections in the post transplant period.
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PMID:Regeneration of peripheral blood cells following ABO incompatible allogeneic bone marrow transplantation for severe aplastic anaemia. 633 49

Red blood cell (RBC) and platelet (PLT) transfusion requirements during the first 13 weeks after HLA-identical marrow transplantation were studied in 82 patients with aplastic anemia. On the average, patients were given 9 units of RBCs (1-82) and 44 units of PLTS (6-468). The greatest need for support was during the first 4 weeks postgrafting. A multivariate statistical analysis of 22 variables showed that RBC and PLT requirements increased with age. In addition, RBC requirements increased if the patient had isohemagglutinins against the marrow donor's RBC, i.e., if the marrow transplant was across a major ABO barrier.
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PMID:Transfusion requirements after HLA-identical marrow transplantation in 82 patients with aplastic anemia. 634 24

It has been recommended that red blood cell transfusions to patients with hemoglobinopathy or aplastic anemia be matched for antigens other than ABO and Rho(D). We studied 1,010 patients with disorders that often lead to repetitive transfusion. The frequency of transfused patients with clinically important antibodies was not significantly different among the disease groups except for those with lymphocytic leukemia. The frequency of multiple red cell antibodies was about 3% overall. Most antibodies (71%) developed early in the transfusion course, before the 15th transfusion. From the standpoints of frequency of alloimmunization, multiplicity of antibodies, and time course of antibody development, patients with hemoglobinopathy and aplastic anemia were not significantly different from other transfused patients. Matching for antigens other than ABO or Rho(D) might increase costs in our hospital by 40,000-370,000 dollars per year for these patients. Because morbidity or mortality due to these antibodies is rare, antigen matching for other than ABO and Rho(D) is not cost-effective.
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PMID:Should chronic transfusions be matched for antigens other than ABO and Rho(D)? 643 96

We have studied the pattern of regeneration of peripheral blood cells following ABO compatible bone marrow transplantation for severe aplastic anaemia. 18 patients were treated with cyclosporin A and six with methotrexate for post graft immunosuppression. The number of days taken for the neutrophil count to reach 0.5 x 10(9)/l, the lymphocyte count to reach 1.0 x 10(9)/l, the platelet count to reach 100 x 10(9)/l and the reticulocytes to reach 1% was shorter in the CyA treated patients. This finding reached statistical significance for all types of cells except the platelets (neutrophils, P less than 0.001; lymphocytes, P less than 0.02; platelets, P greater than 0.05; reticulocytes, P less than 0.001). The more rapid regeneration of peripheral blood cells in patients treated with cyclosporin A has contributed to reducing the length of time patients are dependent on blood product support in the post transplant period.
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PMID:Regeneration of peripheral blood cells following allogeneic bone marrow transplantation for severe aplastic anaemia. 675 13

Human blood groups (ABO) are known to be determined by the terminal glycosyl residues attached to common carbohydrate chains of the red cell surface. N-acetylgalactosaminyltransferase (A-enzyme) in blood group A persons and galactosyltransferase (B-enzyme) in blood group B persons are responsible for producing A and B substances on the red cell surface, with both enzymes absent in blood group O persons. The plasma transferase (A - and B-) activity was assayed after the complete replacement of the bone marrow of patients with acute leukemia or aplastic anemia by transplantation bone marrow from donors with ABO blood group differing from the recipient. The patient's blood type completely changed from the recipient's type to the donor's type. However, the A- and B-enzyme activities of the patients changed only slightly after bone marrow transplantation. The results indicate that most of the A- and B-enzymes in the circulatory plasma is not derived from the bone marrow, lymphoid, or macrophage tissue. Other tissues must be the primary source of the enzymes in plasma.
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PMID:Plasma blood group glycosyltransferase activities after bone marrow transplantation. 676 57

An 11-yr, 9-mo-old girl with a 5-hr history of severe aplastic anemia unresponsive to androgen or steroid therapy was treated a bone marrow transplant from her 7-yr-old, HLA-MLC identical, APO incompatible, male sibling. Donor neutrophils were positive for the NA1 antigen. The patient's pretransplant serum contained a neutrophil specific antibody, anti-NA1, reactive against donor neutrophils, which was demonstrable by both granulocyte agglutination and granulocyte cytotoxicity assays. The transplant preparative regimen consisted of cyclophosphamide, 50 mg/kg/day for 4 days, and total lymphoid irradiation (750 rads, 26 rads/min by 4 meV linear accelerator). A two plasma volume exchange (4,800 ml) by continuous flow centrifugation with an Aminco cell separator was performed one day prior to transplant because of ABO incompatibility. Following plasma exchange, anti-NA1 cytotoxic titer, 1:8 preexchange, was no longer detectable; anti-NA1 agglutinating titer had only decreased from 1:64 to 1:32. She experienced no adverse reaction to transplantation of 4:8 X 10(8) nucleated cells/kg. Marrow engraftment was demonstrable by Day 14 by steadily increasing leukocyte and platelet counts, red cells of donor ABO group, and bone marrow chromosomes showing a normal male, 46 XY karyotype. This case of successful bone marrow engraftment without delayed neutrophil recovery in the presence of a neutrophil specific antibody NA1 suggest that neutrophil specific antigens are not functionally present on the pluripotent stem cell. Histoincompatibility for neutrophil specific determinants need not eliminate the possibility of bone marrow transplantation for aplastic anemia between siblings identical for the major histocompatibility loci.
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PMID:Successful engraftment of NA1 positive bone marrow in a patient with a neutrophil antibody, anti-NA1. 702 91

ABO incompatible allogeneic bone marrow transplants can be performed successfully to treat patients with leukemia or aplastic anemia. These transplants carry no great risk of rejection or graft-versus-host disease, however, some method must be used to avoid acute hemolysis at the time of infusion of ABO incompatible marrow. We have used successfully large volume plasma exchange to remove anti-A or anti-B antibodies prior to marrow infusion. More recently we have used immunoadsorbent columns containing synthetic A or B antigen specifically to remove anti-A or anti-B antibodies in lieu of plasma exchange. These columns are better tolerated than plasma exchange where allergic reactions are common.
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PMID:Plasma exchange and immunoadsorption for removal of antibodies prior to ABO incompatible bone marrow transplant. 703 Feb 80


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