Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thyroid function was evaluated in children surviving disease-free for 2 years or more following bone marrow transplantation (BMT) for severe aplastic anemia (27 patients), acute non-lymphoblastic leukemia (28 patients), and acute lymphoblastic leukemia (25 patients). Pre-BMT conditioning consisted of high dose chemotherapy and total lymphoid irradiation with 750 cGy for patients with severe aplastic anemia, and for patients with leukemia, high dose chemotherapy and single dose total body irradiation with 750-850 cGy (33 patients) or fractionated total body irradiation with 1320 cGy (20 patients). Compensated hypothyroidism (elevated thyroid stimulating hormone (TSH) with a normal thyroxine index) occurred in 20/80 patients with a median time of onset of 12.3 months post-BMT (range 4-30). No patients developed primary hypothyroidism (elevated thyroid stimulating hormone with low thyroxine index). In seven patients, compensated hypothyroidism was transient with TSH returning to normal at a median of 60 months post-BMT (range 11-75). Six patients with compensated hypothyroidism received thyroid hormone replacement therapy. Time to development of compensated hypothyroidism was associated (p = 0.03) with underlying disease and radiation (11 of 27 patients with severe aplastic anemia + total lymphoid irradiation versus nine of 53 patients with leukemia + total body irradiation). In aplastic anemia patients, but not patients with leukemia, the incidence of thyroid hypofunction 5 years post-transplant was significantly higher (p less than 0.001) in those receiving methotrexate alone (82%) as prophylaxis for graft-versus-host disease compared with those receiving a regimen of methotrexate, antithymocyte globulin and prednisone (16%).
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PMID:Thyroid dysfunction following bone marrow transplantation: long-term follow-up of 80 pediatric patients. 235 Jun 28

We describe the transfer of autoimmune thyroiditis by bone marrow transplantation. The male recipient developed compensated hypothyroidism 3 years after transplantation, and progressed to thyroid failure 1 year later. The female sibling had compensated hypothyroidism when screened 4 years after marrow donation. The donor, the recipient, and an older male sibling were HLA DR4, 5; the father was presumed homozygous for DR4 and the mother for DR5. Only the donor and recipient had abnormal thyroid function and positive antithyroid antimicrosomal antibodies. The most probable mechanism for the organ specific autoimmune dysfunction is the transfer of abnormal B and T cell clones from the donor. Radiation damage to the thyroid prior to transplantation, the mild graft-versus-host disease immediately following transplantation, and the general immune dysregulation seen in the first several years after marrow engraftment may have contributed to an acceleration of the autoimmune destruction of the recipient's thyroid.
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PMID:Autoimmune thyroiditis after bone marrow transplantation. 235 Jun 29

Pseudo-scleroderma should not be confused with true scleroderma, the prognosis of which is unpredictable and often serious. Progressive acrosclerosis must be differentiated from Raynaud's disease, congenital or hereditary disorders of unknown aetiology: Werner's syndrome, acrogeria and progeria; Rothmund-Thomson's syndrome, Steinert's disease, phenylketonuria, disorders of glycogen metabolism; metabolic disorders: mutilating acropathies, scleromyxoedema, porphyria cutanea tarda; occupational and iatrogenic disorders: acroosteolysis, toxic epidermic syndrome (Spain), scleroderma-like change induced by bleomycin, chronic graft-versus-host disease; and leprosy. Acute diffuse scleroderma should not be confused with Buschke's scleroedema, sclerema neonatorum, systemic amyloidosis and scleroderma-like changes in hypothyroidism. Linear pseudo-scleroderma is suggested by the following scleroderma-like conditions: facial hemiatrophy, acrodermatitis atrophicans, melorheostosis, pseudo-scleroderma after corticosteroid injection, and cutaneous lesions in carcinoid syndrome. Scleroderma in plaque must be differentiated from hypodermitis sclerotisans, panatrophy and localized lipoatrophies, hypodermitis after vitamin K injection, basal cell carcinoma, necrobiosis lipoidica, vitiligo, chronic radiodermatitis, cutaneous lymphatic invasion. Scleroderma-like changes after drug injection (vitamin B12, progestin), anetoderma barely resemble morphea guttata.
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PMID:[Pseudoscleroderma and sclerodermiform states]. 624 36

Thyroid function studies were followed serially in 27 long-term survivors (median 33 months) of bone marrow transplantation. There were 15 men and 12 women (median age 13 1/12 years, range 11/12 to 22 6/12 years). Aplastic anemia (14 patients) and acute nonlymphocytic leukemia (eight patients) were the major reasons for bone marrow transplantation. Pretransplant conditioning consisted of single-dose irradiation combined with high-dose, short-term chemotherapy in 23 patients, while four patients received a bone marrow transplantation without any radiation therapy. Thyroid dysfunction occurred in 10 of 23 (43 percent) irradiated patients; compensated hypothyroidism (elevated thyroid-stimulating hormone levels only) developed in eight subjects, and two patients had primary thyroid failure (elevated thyroid-stimulating hormone levels and low T4 index). The abnormal thyroid studies were detected a median of 13 months after bone marrow transplantation. The four subjects who underwent transplantation without radiation therapy have remained euthyroid (median follow-up two years). The only variable that appeared to correlate with the subsequent development of impaired thyroid function was the type of graft-versus-host disease prophylaxis employed; the irradiated subjects treated with methotrexate alone had a higher incidence of thyroid dysfunction compared to those treated with methotrexate combined with antithymocyte globulin and prednisone (eight of 12 versus two of 11, p less than 0.05). The high incidence and subtle nature of impaired thyroid function following single-dose irradiation for bone marrow transplantation are discussed.
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PMID:Thyroid dysfunction among long-term survivors of bone marrow transplantation. 675 76

Eighty-eight children 0.5 to 17 years of age (median, 9 years of age) received an unrelated donor marrow transplant for treatment of chronic myeloid leukemia (CML; n = 16), acute lymphoblastic leukemia (ALL) in first or second remission (n = 15) or more advanced stage (n = 28), acute myeloid leukemia (AML; n = 13), or other hematologic diseases (n = 16) between June 1985 and April 1993. All patients were conditioned with cyclophosphamide and total body irradiation and received a combination of methotrexate and cyclosporine as graft-versus-host disease (GVHD) prophylaxis. Fourty-six patients received transplants from HLA-identical donors and 42 patients received transplants from donors who were minor-mismatched at one HLA-A or B or D/DRB1 locus. The Kaplan-Meier estimates of disease-free survival and relapse were 75% and 0% for patients with CML, 47% and 20% for ALL in first or second remission, 10% and 60% for ALL in relapse or third remission, 46% and 46% for AML in first remission (n = 1) or more advanced disease (n = 12), and 29% and 69% for other diseases. HLA disparity was not significantly associated with lower disease-free survival, but the results suggest more relapses in HLA-matched recipients and there was significantly more transplant-related mortality in mismatched recipients (51% v 24%, P = .04). Most deaths were due to infections associated with acute or chronic GVHD and occurred within the first 2 years after transplantation. Granulocyte engraftment occurred in all evaluable patients. Sixty-three percent of HLA-matched and 57% of HLA-mismatched recipients were discharged home disease-free at a median of 98 and 103 days, respectively, after transplantation (P = not significant [NS]). The incidence of grades II-IV acute GVHD was 83% in HLA-matched and 98% in HLA-mismatched recipients (P = .009). The incidence of chronic GVHD was 60% in HLA-matched and 69% in HLA-mismatched recipients (P = NS). One or multiple late adverse events such as cataracts, osteonecrosis of the hip or knee, restrictive or obstructive pulmonary disease, and hypothyroidism have occurred in 11 of 33 (33%) surviving patients. Immunosuppression was discontinued in 58% of surviving patients, including all 12 patients surviving more than 3.2 years, all of whom have a Lansky or Karnofsky score of 100%. These data show that marrow transplantation from fully or partially HLA-matched unrelated donors can be effective therapy for children with hematologic disorders and that pretransplantation disease status and posttransplantation GVHD remain important factors affecting patient outcome.
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PMID:Unrelated donor marrow transplantation in children. 757 22

Since the number of children receiving a bone marrow transplantation (BMT) and becoming long-term survivors continues to increase, more attention has to be paid to detect long-term side effects in these unique patients. Follow-up studies to timely identify these untoward sequelae are a matter of particular concern for pediatricians due to the longer life expectancy of children cured by BMT. The more frequently recognized sequelae affecting lung, eyes, brain and the endocrine system have been analyzed in this review. The majority of long-term side effects could be related to the conditioning regimens employed to prepare children before marrow transplantation and radiotherapy has been indicated as the most important agent determining deleterious toxicities. Most children receiving BMT present a decreased growth velocity and this growth impairment is especially observed in patients receiving total body irradiation (TBI) and prophylactic cranial irradiation prior to marrow transplant. Growth hormone deficiency could be demonstrated in the majority of patients with a reduced growth rate, even though an impairment of liver somatomedin production or a direct radiation-induced skeletal dysplasia could not be excluded. Overt and compensated hypothyroidism have been reported after TBI and patients given single dose radiotherapy are at greater risk with an overall incidence of thyroid function abnormalities approaching 30-40%. Delayed puberty development was reported in boys and girls after a TBI-containing conditioning regimen, whereas patients given BMT for severe aplastic anaemia presented a normal puberty. The absence of pubertal growth spurt contributes to the growth impairment of prepubertal children. In post-pubertal patients amenorrhea, azoospermia and gonadal failure can be observed after radiotherapy and several patients can require hormonal substitutive therapy. Skin and mucosal abnormalities referred to teguments involvement by chronic graft-versus-host disease (GVHD). Moreover, alopecia or abnormal pigmentation of the skin are observed in patients given busulfan as part of their myeloablative therapy. Cataracts are a well recognized complication of children receiving ionizing radiations and chronic steroid therapy. Again, posterior subcapsular cataracts occur more frequently in patients given TB1 as single exposure. Decreased lacrimal gland function, with impairment of tear production is another late effect of irradiation to the eye. Lung function abnormalities are not rare after transplant and may cause late mortality and morbidity.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Late effects in children after bone marrow transplantation: a review. 831 62

Thyroid function abnormalities in 270 adult patients post-BMT are described. Various conditioning regimens were used and the effects of three TBI and one chemotherapy only based regimens are compared. The overall incidence of elevated TSH is 8.9; 3.8, 7.2 and 16.7% in those patients who received 300, 500 and 1200 cGy respectively and 11.7% in those who received BuCy conditioning. Three cases (1.1%) of clinial hypothyroidism were observed. Compensated hypothyroidism defined as an elevated TSH in the presence of normal T3, T4 levels and transient in some cases, was the most common finding. All but four cases occurred in the first 2 years after BMT. In the remaining four, three occurred in patients with chronic GVHD. The results reported here show a lower prevalence than observed in most other reviews, particularly for children. A trend was observed with increasing radiation doses. The results are not significantly different from those we observed in the BuCy regimen.
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PMID:Abnormal thyroid stimulating hormone (TSH) levels in adults following allogeneic bone marrow transplants. 916 46

A 28-year-old female patient underwent allogeneic PBSCT from her HLA-identical sister for AML in first CR. CD34+ cells were positively selected from PBPC using immunoaffinity columns. She received 8.0 x 10(6) CD34+ cells/kg and 1.74 x 10(6) CD3+ cells/kg body weight (BW). The patient developed acute GVHD III and mild limited chronic GVHD. Thirteen months after transplantation severe thyrotoxicosis requiring plasmapheresis occurred. Immune thyroiditis was confirmed cytologically by lymphocytic infiltration in a fine needle aspirate and by elevated thyroid-Ab-titers. The patient's donor had received thyroid hormone substitution for 10 years for hypothyroidism. The most probable cause of immune thyroiditis after allogeneic BMT is the transfer of antithyroid donor lymphocytes. These lymphocytes can also be transferred with a CD34+ selected peripheral stem cell graft. The transplantation of lymphocyte-depleted autologous bone marrow or PBPC grafts after myeloablative treatment is increasingly considered as potential treatment of severe autoimmune diseases. This case demonstrates that even low numbers of lymphocytes are capable of transferring autoimmune disorders.
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PMID:Immune thyroiditis after transplantation of allogeneic CD34+ selected peripheral blood cells. 938 36

The exact contribution of growth hormone (GH) deficiency to the adverse growth outcome, in those receiving cranial irradiation (18-24 Gy) or total-body irradiation for haematological malignancies in childhood, remains difficult to disentangle as nearly always the cause of the growth disturbance is multifactorial: chemotherapy, graft-versus-host disease, hypothyroidism, and skeletal dysplasia may all impact on growth. There are few published data from which one can assess the efficacy of GH replacement on final height in those children who received cranial irradiation (18-24 Gy) and/or total-body irradiation; there is no evidence, however, of an increased risk of leukaemic relapse. Endocrine reassessment in the teenagers, who received cranial irradiation (18-24 Gy) for acute lymphoblastic leukaemia many years earlier, revealed a significant incidence of GH deficiency with the additional suggestion that many had been GH deficient for several years. This raises a number of important questions: What is the best way to organize long-term endocrine follow-up? How often should GH status be reassessed? What are the specific benefits of GH replacement in adult life for such individuals? These and other questions require further study.
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PMID:Growth and growth hormone status following treatment for childhood leukaemia. 969 Dec 6

BMT can both transmit and eliminate autoimmune diseases, and hence it has been suggested as an optional treatment for severe autoimmune conditions. In this communication we deal with the question of whether chronic GVHD is an autoimmune disease in itself, review the literature reports of autoimmune diseases following BMT in humans, and describe the autoimmune nature of the post-BMT state. Chronic GVHD, which is a frequent complication post-BMT, has clinical and pathogenic characteristics similar to autoimmune diseases, such as scleroderma and Sjogren's syndrome. Although the pathogenesis of chronic GVHD is not yet clear, thymic damage induced by acute GVHD may contribute to both the immunodeficiency and autoimmunity characterising chronic GVHD. A similar phenomenon is syngeneic GVHD, which results from an imbalance between autoreactive and autoregulatory lymphocytes. Additionally, other autoimmune diseases have been reported in post-BMT patients, and among these the most common are hypothyroidism, hyperthyroidism, myasthenia gravis and immune cytopenias. Although these diseases also occur also outside the post-BMT setting, they are unique with respect to pathogenesis (no association between myasthenia gravis and thymic pathology), diagnosis (symptoms of hyperthyroidism may be inadvertently related to other conditions), and prognosis (post-BMT autoimmune cytopenias may be fatal and treatment non-responsive). Nevertheless, many other autoimmune diseases have been reported after BMT, and these are mainly presented as case reports. Regarding the mechanism of post-BMT autoimmunity, the minority of cases stem from donor-related transfer of pathogenic lymphocytes or their progenitors, while most of the cases (either chronic GVHD or specific diseases) can be attributed to the immunologic imbalances characterising the post-BMT setting. The factors that may expose an individual to autoimmunity development post-BMT include genetic predisposition, an environmental factor such as CMV, and the nature of the donor who may aid in creating microchimerism and subsequently chronic GVHD and its related autoimmune manifestations.
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PMID:Autoimmune diseases and autoimmunity post-bone marrow transplantation. 982 15


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