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 patient with severe combined immunodeficiency received seven transplants of bone marrow from an HLA-B-compatible and HLA-D-compatible unrelated donor in an attempt to provide immunologic reconstitution. The first four transplants achieved restricted engraftment with evidence of rudimentary immunologic function. A fifth transplant, given after low-dose cyclophosphamide, produced reconstituion of cell-mediated immunity. Marrow aplasia developed after recontamination with a nonpathogenic microflora. Transplantation of marrow previously stored in liquid nitrogen was ineffective. A subsequent transplant, administered after high-dose cyclophosphamide, achieved durable engraftment, with complete hematopoietic and immunologic reconstitution. Seventeen months after transplantation, full functional engraftment persists. Graft-versus-host disease has been chronic and moderately severe, but limited to the skin and oral mucosa. Transplantation of marrow from unrelated histocompatible donors may provide a useful treatment for patients with severe combined immunodeficiency or aplastic anemia who lack a matched sibling or related donor.
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PMID:Reconstitution in severe combined immunodeficiency by transplantation of marrow from an unrelated donor. 2 51

Forty-four human long-term survivors after marrow transplantation for aplastic anemia or hematologic malignancy were studied for the presence of circulating nonspecific suppressor cells. Twenty-two of the patients were healthy and 22 had mild to moderately severe chronic graft-vs-host disease (GVHD). Patient mononuclear cells (of donor origin) were tested for their ability to suppress the responses of lymphocytes obtained from the respective marrow donors to alloantigens in mixed leukocyte culture (MLC) and/or to concanavalin A (Con A). Tests were carried out between 199 and 2393 (median 376) days after transplantation. Cells from only 1 of 22 patients without chronic GVHD showed suppression of donor cell blastogeneis responses. In contrast, cells from 11 of 22 patients with chronic GVHD showed more than 30% suppression of donor cell responses in MLC and/or to Con A. The finding of suppressor cells was not related to the time of testing after grafting nor to immmunosuppressive therapy. Nonspecific suppressor activity was abrogated by irradiation with 1600 rads in vitro in five of six cases tested. Nonspecific suppressor cells may be one explanation for the severe combined immunodeficiency and the recurrent infectious complications characteristic of patients with chronic GVHD.
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PMID:Nonspecific suppressor cells in patients with chronic graft-vs-host disease after marrow grafting. 3 62

Bone marrow transplantation is an experimental therapy, which has been used with success in patients with aplastic anemia, severe combined immunodeficiency and leukemia. We report here on the procedure of transplantation and the possible difficulties which can be encountered.
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PMID:[Bone marrow transplantation (author's transl)]. 32 Mar 76

Main indications for allogeneic bone marrow transplantation are severe aplastic anemia, severe combined immunodeficiency, acute leukemia and chronic myeloid leukemia. In standard risk situations survival rates are 50 to 80%. The probability of disease-free survival after bone marrow transplantation is depending on the stage of disease. If possible bone marrow transplantation should be performed early, not in advanced disease when conventional measures failed. Main problems are therapy-related organ toxicity, rejection, graft-versus-host disease and a long lasting risk of infection. Usually histocompatible relatives of the patients are selected as marrow donors. Bone marrow transplantation using unrelated donors is under investigation. Autologous transplantations with cryopreserved marrow are performed in acute leukemia, malignant lymphomas and some solid tumors, but prospective studies comparing transplantation and conventional therapeutic procedures are still missing.
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PMID:[Bone marrow transplantation. Overview and personal results]. 128 79

We have observed two patients who exhibited an exclusive increase of delta TCS1+ subset of gamma delta T cells in the peripheral blood after bone marrow transplantation (BMT). In one case with severe combined immunodeficiency (SCID) who received haploidentical BMT from his father, gamma delta T cells appeared only after thymus transplantation. However, his T cell-mediated immunity remained severely defective despite the generation of T cells of donor origin. In the other case with aplastic anemia, delta TCS1- gamma delta T cells began to increase in the peripheral blood later. This indicates that the thymus is necessary for the generation of gamma delta T cells and that the delta TCS1+ subset is dominant in the early stages of their ontogeny. delta TCS1+ T cell lines were established from both patients, and allo-reactivity was investigated. The cell line from the latter case reacted to recipient cells in a mixed lymphocyte reaction, but did not show cytotoxity to the allogeneic cells including recipient cells. The other cell line, from the former case, did not react to either donor or recipient cells. This indicates that an intact thymus is needed for gamma delta T cells to acquire allo-reactivity. Both cell lines showed MHC non-restricted cytotoxity against NK-sensitive target cells.
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PMID:Generation and function of gamma delta T cells after allogeneic bone marrow transplantation in humans: comparison in absence or presence of HLA-matched or mismatched thymus. 195 38

Of 25 HLA-identical, MLC negative transplants 10 patients had acute lymphoblastic leukaemia (ALL), 8 acute nonlymphoblastic leukaemia (ANLL), 3 severe aplastic anaemia, 2 malignant histiocytosis, 1 patients neuroblastoma and 1 Fanconi anaemia. 3 HLA nonidentical, MLC positive transplants were performed, two children had malignant infantile osteopetrosis and 1 child had a severe combined immunodeficiency disease. Patients with ALL and ANLL received cyclophosphamide and single dose total body irradiation. 3 patients received fractionated TBI. The results for the allogeneic group overall indicate that the actuarial disease free survival rate is 0.62. 16 of 25 patients are in continuous complete remission (CCR) periods of 3-78 months posttransplant. All three transplanted children with severe aplastic anaemia alive disease-free for periods of 21-81 months. 10 patients with ALL were transplanted (2 in first remission for high risk ALL, 8 in second remission). 7 of 10 patients are alive and disease-free (CCR rate 0.67). 8 patients underwent BMT for ANNL while in first remission in 7 patients and in third partial remission in 1 patient. 4 of 8 patients are alive and disease-free for periods of 25-56 months (CCR rate 0.50). 1 patient with neuroblastoma stage IV survives 24 months, 1 child with Fanconi anemia died on day +25 of GVHD and septicaemia. 1 of the 2 patients transplanted for malignant histiocytosis relapsed 3 months posttransplant, 1 patient is alive and disease-free 5 months posttransplant. In none of the HLA-nonidentical and MLC positive transplantations T-cell depleted marrow engrafted.
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PMID:Status of allogeneic bone marrow transplantation in childhood in the GDR. 248 Feb 79

In mammalian ontogeny, the liver constitutes the primary hematopoietic organ for some time. Fetal liver cells (FLC) are rich in hematopoietic stem cells with a high proliferative potential but contain few post-thymic T cells. In animal studies, FLC restored hematopoiesis without severe graft-versus-host disease. However, genetic disparity between donor and host frequently limited durable engraftment and prevented or protracted complete immune reconstitution in most fully allogeneic recipients. Some children with severe combined immunodeficiency have been cured by FLC infusion, whereas favorable effects in aplastic anemia, acute leukemia, and inborn errors of metabolism have been limited and badly understood. Fetal liver transplantation in animals may serve as a model for the analysis and management of complications associated with the transfer of purified hematopoietic stem cell grafts and aid in the development of future therapeutic strategies requiring rapidly proliferating stem cell populations.
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PMID:The fetal liver as an alternative stem cell source for hemolymphopoietic reconstitution. 287 17

Serum IgD levels were followed longitudinally twice a week for up to 100 days in 60 children undergoing allogeneic bone-marrow transplantation (n = 52) or immunosuppression (n = 8) for the treatment of leukaemia, severe aplastic anaemia or severe combined immunodeficiency. In 40 out of the 49 post-transplantation periods analysed (82%), a transient sharp increase of serum IgD was detected, irrespective of initial disease. A similar peak was found in one out of five children after immunosuppressive treatment. A second IgD peak was only recorded in grafted patients (14/49 post-transfusion periods). Peak levels of IgD ranged from 1.3 to 185.7 IU/ml (median 12.2 IU/ml), which represents a 2.6 to 22.4-fold increase over 'baseline' levels. In the transplanted leukaemia and aplastic anaemia patients, the rise of serum IgD occurred at the same time (geometric mean 16 days after transplantation) and was shown to represent heterogeneous polyclonal IgD in six of them. The onset of the serum IgD peak was significantly delayed in children suffering from severe combined immunodeficiency (P less than 0.05) and was demonstrated in one patient to consist of homogeneous IgD. No relation was found between either the occurrence of clinical acute graft-versus-host disease or infections after treatment, and the time of onset of IgD elevations. To detect transient serum IgD peaks as described here, frequent sampling of sera is necessary. The origin of the early IgD peaks seems to reside within the recipient's cells by an unknown mechanism. The late IgD peaks are most probably an expression of gradual reconstitution of the immune system following bone-marrow transplantation.
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PMID:Transient increase of serum IgD levels after allogeneic bone-marrow transplantation. 304 51

The "F1 hybrid transplantation law" states that F1 hybrids of two unrelated inbred strains of mice accept grafts from either parent strain while neither parent accept grafts from the F1 hybrid. However, there are two notable exceptions to this law. Indeed, parent grafts containing immunologically competent cells (spleen cells, bone marrow etc.) react against the F1 normal hosts in which they are placed. In the absence of a host-versus-graft reaction, the graft-versus-host reaction (GvH) may dominate the field and cause untoward reactions which not only negate any benefit derived from the graft, but also cause significant, and often fatal morbidity of the host, that is, a GvH Disease (GvHD). Furthermore, irradiated F1 mice are refractory to the grafting of parental bone marrow, lymphoma cells and normal lymphocytes because of a restriction by non-co-dominant, besides that of codominant MHC-H2 genes. These non-co-dominant genes have been designated Hh genes for Hybrid histocompatibility and the phenomenon itself, hybrid resistance. The cellular, humoral and genetic mechanisms involved in the GvH and hybrid resistance production are explained and discussed in the first, while in the second section of the present review, their equivalent in three human pathological situations are taken into consideration. We focus in detail on two principal immunologic aspects of human bone marrow transplantation: GvH and hematopoietic engraftment; each one of these immunologic aspects has considerable impact on the course and outcome of marrow transplantation in humans. The allograft implantation between HLA-genetically-identical siblings, HLA-aploidentical family members or HLA-phenotypically identical donor-recipient couples are herewith examined, while the autologous bone marrow rescue approach is not taken into consideration. The outcome of bone marrow transplantation depends not only on the degree of genetic disparity between the donor and the recipient, but also on the underlying disease. Bone marrow transplantation is the therapy of choice for patients with aplastic anemia, severe combined immunodeficiency (SCID) and other genetic and acquired immunodeficiency, some leukemias and a few other diseases, mainly if HLA-genetically-identical siblings are available. However, in many cases such siblings are not available. Therefore, the probability of acute or chronic GvHD or graft rejection increases significantly. The clinical and pathologic manifestations, the prognostic factors, and the treatment and prevention of acute and chronic GvHD are illustrated in detail.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Graft versus host reaction and hybrid resistance in experimental models and clinical practice]. 307 13

Human fetal liver (HFL) transplantations have been performed in infants with severe combined immunodeficiency and in patients with aplastic anemia, but the success rates have been extremely low, partly due to insufficient cell doses in grafts from a single donor. In order to explore the possible use of combining several HFL grafts from multiple donors, we studied immunological parameters as well as the in vitro responses of HFL cells from 20 fetuses, at 6 to 11 weeks of gestation, to allogeneic HFL cells and to adult lymphocytes in the mixed lymphocyte reaction (MLR), and the granulocyte-macrophage colony-forming cells (GM-CFC) assay. HFL cells of 6 to 11 weeks of gestation were found to lack populations of cells bearing surface markers of T- and B-lymphocytes and were capable of proliferating into lymphoid colonies. Virtually no MLR was found to allogeneic HFL cells or to adult lymphocytes [stimulation index (SI) 0.63 to 1.94], whereas adult lymphocytes responded normally to HFL cells (SI 3.9 to 62.0). Coculturing mixtures of allogeneic HFL cells in agar did not lead to suppression of the GM-CFC capacity of each liver. It appears that HFL at 6 to 11 weeks of gestation lack immunocompetent cells capable of provoking positive MLR in response to allogeneic HFL cells or to adult lymphocytes, and also capable of inactivating HFL-derived hematopoietic stem cells. This model may represent an in vitro counterpart for the in vivo pooling of HFL cells from multiple donors performed in order to increase graft cell dosage in man.
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PMID:Lymphoid cells and granulocyte progenitors in early human fetal livers: immunological parameters and in vitro cellular interactions. 315 1


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