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)

Serum IgE levels were followed longitudinally twice a week for up to 100 days in 60 children treated for leukemia, severe aplastic anemia or severe combined immunodeficiency: 52 underwent allogeneic bone-marrow transplantation and 8 immunosuppressive treatment. In 55 of 58 treatment periods which could be analyzed (95%), a transient sharp increase of serum IgE was detected, irrespective of the initial diagnosis and mode of treatment. A second IgE peak was recorded in 16% of evaluable treatment periods. In the transplanted leukemia and aplastic anemia patients, the rise of serum IgE levels occurred at the same time, i.e. at a mean of 14 days after transplantation; it occurred significantly later in children grafted for severe combined immunodeficiency. In children who received immunosuppression for the treatment of severe aplastic anemia, IgE elevations were always seen within 2 weeks after institution of therapy. No relation was found between either the occurrence of clinically acute graft-versus-host disease or infections after treatment, and the time of onset of IgE elevations. It is suggested that the phenomenon of IgE peaks in the population of patients investigated was due to disturbance of T-cell regulation, i.e. a temporary impairment of T-suppressor cell activity.
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PMID:Transient elevation of serum IgE after allogeneic bone-marrow transplantation. 330 75

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

Lymphoid cell engraftment was monitored for several years after bone marrow transplantation by Y-chromatin staining of T and B lymphocytes in the peripheral blood and/or by immunoglobulin allotyping in the serum of 20 of 52 pediatric patients grafted successively between October 1973 and October 1983. Data on 2 patients with severe combined immunodeficiency, grafted earlier in December 1968 and April 1971, are also included. These children received an allogeneic bone marrow graft for leukemia (n = 7), severe aplastic anemia (n = 11), or severe combined immunodeficiency (n = 4) and were informative for this study, because they differed from their donor by sex (n = 16) and/or by immunoglobulin phenotype (n = 13). Of 16 pairs in which the donor was of the opposite sex, 11 patients ultimately showed circulating T and B lymphocytes of donor origin after bone marrow transplantation; in the remaining 5, there was an incomplete chimerism of the circulating lymphoid cells. Of 13 pairs with a difference in immunoglobulin phenotype between donor and recipient, 8 patients exhibited donor allotypes 3 months or later after transplantation, in 3 of them together with recipient allotypes. In the remaining 5 patients, recipient allotypes were detected after transplantation, but the simultaneous presence of donor-type immunoglobulin production could not be excluded in 4. The persistence of either a split (T lineage of donor origin and B lineage of recipient origin) or mixed (T and/or B lineage of donor and recipient origin) chimerism was related to the type of disease. In 3 children circulating B cells of donor-origin did not fit with the recipient origin of the sessile immunoglobulin-secreting plasma cells. This implies that different immune compartments--e.g., bone marrow and peripheral lymphoid tissues--should be investigated following allogeneic bone marrow transplantation. A prolonged presence of recipient-type lymphoid cells increased the risk of leukemic relapse in the patients investigated.
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PMID:Lymphoid chimerism after allogeneic bone marrow transplantation. Y-chromatin staining of peripheral T and B lymphocytes and allotyping of serum immunoglobulins. 331 34

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

In this chapter, we have considered the theoretical and practical background of bone marrow transplantation. The immune response and its regulation by genes within the major histocompatibility complex, particularly of the I region of the mouse and of the HLA-D/DR region in man, is of central importance in both graft acceptance (rejection) and graft-versus-host disease. Methods which are available for typing alleles at the HLA-A, -C, -B, -DR and complotype (BF, C2, C4A, C4B) loci, have been considered in detail. The extent to which recombination affects specific alleles on haplotypes within families is discussed, as is the occurrence of linkage disequilibrium and extended haplotypes in populations of unrelated individuals. Because the HLA-DR and complotype region in man is thought to be critical for the success of bone marrow transplantation, methods for typing of HLA-D by both the HTC and PLT approaches have been examined. Although HLA-D/DR assignments are easily made in normal subjects, they are ambiguous in about 50 per cent of candidates for bone marrow transplantation, including, particularly, patients with aplastic anaemia, leukaemia, and severe combined immunodeficiency. In this setting, it is particularly important to obtain additional information by modification of HLA-D typing procedures and through complotype and GLO allele determinations in all family members. Finally, we can hope that there will be an increased possibility of using non-family donors through methods for removing cytotoxic T cells from donor marrow and through the identification, in the general population, of individuals who are genotypically similar or identical to the recipient. In this regard, the recognition that some 30 per cent of chromosome 6 in caucasians (50 per cent of individuals) bear extended haplotypes, which include a relatively fixed set of alleles particularly in the HLA-B, -DR, complotype and GLO regions, offers considerable promise.
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PMID:The MHC in human bone marrow allotransplantation. 622 38

Cell substitution in the form of "tailored haemotherapy " should be an essential part of medical oncology at the present time. In the conventional therapy of solid tumors patients do not enter into prolonged phases of severe haemopoietic insufficiency. Accordingly platelet and granulocyte transfusions will be exceptional. It is mainly the red cell transfusion which plays the most important role. The possible complication of cell substitution should always be kept in mind. Here the risk of alloimmunisation which makes a continuation of transfusion therapy or a subsequent bone marrow transplantation problematic, is just one of the examples. Modern cell separation techniques allow the production of highly concentrated cell preparations aiming at the reduction of the frequency of transfusions and minimizing the risk of sensitisation. If rich concentrated preparations have to be given to immunodeficient patients an irradiation should proceed their transfusion, otherwise the immunocompetent lymphocytes contained in the preparations could induce graft versus host reactions. Allogenic bone marrow transplantation is more becoming the treatment of choice for severe combined immunodeficiency, severe aplastic anemia, acute myeloid leukemia, and chronic myeloid leukemia. At the present time the place of allogeneic or autologous bone marrow transplantation as a treatment of lymphomas and solid tumors is still unsettled.
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PMID:[Substitution of blood components]. 637 39

Life-threatening medical conditions such as severe combined immunodeficiency disease, leukemia, severe aplastic anemia, radiation injury, burns, organ transplantation, and aggressive administration of chemotherapy often necessitate the isolation of the patient in a protected germ-free environment for weeks or months. This treatment milieu has the effect of extensive psychological and physical isolation from family and staff. A review of the literature was undertaken to investigate the psychological implications of such treatment and to question the possibility that this isolation therapy might produce a unique type of psychological stress. Most authors agree that patients are able to withstand the emotional stress of germ-free isolation and that behavioral changes relate more to the severity of the illness rather than to the isolation. However, there may be inherent stresses related to isolator therapy that can be alleviated by environmental manipulation. Case vignettes are included and patient management in such an environment is outlined.
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PMID:Psychological aspects of patients in germ-free isolation: a review of child, adult, and patient management literature. 670 May 41

A patient with severe combined immunodeficiency received three transplants of bone marrow from the HLA-B- and -D-identical mother. The first transplantation led to a severe graft-versus-host reaction followed by immunological reconstitution. A split chimerism was found with engraftment only of the maternal lymphocytes. Five months after the transplantation an autoimmune hemolytic anemia was observed which was due to rhesus incompatibility as well as polyspecific antibodies. At the same time agranulocytosis developed and 9 mth after the first transplantation the child suffered from aplastic anemia. Two further attempts failed to engraft the maternal hematopoiesis. The child died during the treatment with cyclophosphamide as conditioning for a third transplantation.
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PMID:Rhesus incompatibility and aplastic anemia as the consequence of split chimerism after bone-marrow transplantation for severe combined immunodeficiency. 677 9

Bone marrow transplantation is an established form of therapy for aplastic anemia and severe combined immunodeficiency. It is also a therapeutic option for acute leukemia in remission. Unfortunately, compatible donors are not available for most patients who could benefit from it. Further refinement of the techniques involved may make it suitable for more patients. Graft rejection, recurrent leukemia, graft-versus-host disease and interstitial pneumonia continue to be the main unsolved complications of bone marrow transplantation, but recent advances have decreased their frequency and severity. Most of the complications of allogeneic bone marrow transplantation may be eliminated with the use of autologous stem cells. For further refinement bone marrow transplantation should continue to be performed in large centres that combine treatment with research.
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PMID:Bone marrow transplantation in Canada. 699 51


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