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)

We report a single center experience of 222 patients (pts) less than 18 years old transplanted from 1973 to 1987. The median age was 11 years (1-18). The donor was a monozygotic twin (9 pts), an HLA-id sibling (193 pts), an HLA-id, parent (9 pts), a mismatched related donor (9 pts) and a matched unrelated donor (1 pt). Ninety-six pts were transplanted for SAA. Conditioning varied with time but the majority (59 pts) received CY 150 mg/kg and 6 Gy TAI. The long term actuarial survival is 66% with a median follow-up of 3 years. The group who received CY 200 mg/kg and MTX had a 33% long term survival (LTS). GVH was the main complication with 40% acute and 37% chronic GVHD. Chronic GVHD tended to improve with time after 2 to 4 years of evolution. Ninety pts were transplanted for leukemia (35 AML, 45 ALL and 11 CGL), 20 pts were in relapse. Pts in CR had a LTS of 40%, in pts in relapse, it was 12%. The main causes of death were: interstitial pneumonitis (30%), relapse (27%), GVH (15%). Thirty-five pts were transplanted for constitutional disease: Fanconi anemia (FA) (26 pts), Dyskeratosis congenita (2 pts), Blackfan-Diamond erythroblastopenia (2 pts), Glanzmann thrombasthenia (1 pt), osteopetrosis (1 pt) and Gaucher's disease (1 pt). In FA, the LTS is 70% with a CY 20 mg/kg, 5 Gy TAI regimen. In all disease categories, we did not find any influence of donor's sex on GVH and survival.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pediatric bone marrow transplantation for leukemia and aplastic anemia. Report of 222 cases transplanted in a single center. 267 24

Seventy-three BMT procedures (42 allogeneic-BMT, 30 autologous-BMT, 1 syngeneic transplant) were undertaken at the Shariati Hospital in Tehran between March 1991 and November 1993. Allogeneic-BMT was performed for thalassaemia major (n = 23), AML in complete remission (n = 3), severe aplastic anaemia (n = 7), CML (n = 7), dyskeratosis congenita (n = 2) and Fanconi anaemia (n = 1). Conditioning regimens comprised busulphan (BU) plus cyclophosphamide (CY) or CY only. Thirty-two (78%) of the 43 patients remain alive 1-34 months after BMT. Twelve patients died: the causes of death were haemorrhagic cystitis (n = 1), CMV pneumonitis (n = 1), GVHD (n = 3), infection (n = 3), rejection (n = 1), VOD (n = 2) and hepatitis (n = 1). Autologous-BMT was performed for patients with AML in CR (n = 16), ALL in CR (n = 9), lymphoma in relapse (n = 3), Ewing sarcoma (n = 1) and multiple myeloma (n = 1). The median age was 18 years. Conditioning regimens were Ara C plus CY, etoposide plus CY and high-dose melphalan. Sixteen (54%) of the 30 patients survive, 14 in continuous complete remission. The causes of death were relapse (AML (n = 7), ALL (n = 4), lymphoma (n = 1)), VOD (n = 1) and infection (n = 1).
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PMID:Bone marrow transplantation in Iran. 792 Mar 8

A 12-year-old boy had striking reticulate hyperpigmentation of the neck and upper chest, dystrophic nails, patchy alopecia, and a white streak on the buccal mucosa. He was diagnosed as having chronic graft-versus-host disease (GVHD) based on clinical findings, skin biopsy findings, and his history of a bone marrow transplantation for aplastic anemia eight years earlier. Dyskeratosis congenita (DC) was not a diagnostic consideration, although the clinical findings and history of aplastic anemia made it a compelling possibility. This case highlights the clinical similarities between DC and chronic GVHD and the difficulty in arriving at an unequivocal diagnosis.
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PMID:Dyskeratosis congenita or chronic graft-versus-host disease? A diagnostic dilemma in a child eight years after bone marrow transplantation for aplastic anemia. 830 41

Eight patients with aplastic anaemia associated with dyskeratosis congenita received allogeneic marrow grafts from either HLA-identical siblings (six patients) or HLA-matched unrelated donors (two patients). Patients who received marrow from HLA-identical siblings were conditioned with cyclophosphamide (140-200 mg/kg), with or without antithymocyte globulin. Patients who received unrelated donor marrow were conditioned with cyclophosphamide (120 mg/kg) and total body irradiation (1200 cGy). The six patients who survived for >2 weeks following transplant all had haematological evidence of engraftment, and all three patients who survived for at least a year following transplant recovered normal haematological function. Three patients died with respiratory failure and pulmonary fibrosis at 70 d. 8 years and 20 years posttransplant; three patients died during the neutropenic period of invasive fungal infections; one patient died on day 44 of refractory acute graft-versus-host disease; and one patient remains alive 463 d following transplant. The surviving patient recently underwent surgical resection of a Dukes' stage C rectal carcinoma diagnosed 14 months posttransplant. The aplastic anaemia associated with dyskeratosis congenita can be successfully treated by allogeneic bone marrow transplantation; however, this approach does not reverse the other systemic manifestations of the syndrome. The pathogenesis of the intestinal lung disease observed in dyskeratosis congenita patients following marrow transplantation is not understood.
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PMID:Allogeneic marrow transplantation for aplastic anaemia associated with dyskeratosis congenita. 861 50

Chronic restrictive lung disease in a 9-year-old boy with dyskeratosis congenita (DC) 7 years after allogeneic bone marrow transplantation (BMT) is described. When he was 1 year and 10 months old, severe aplastic anemia developed. He received a marrow transplant from his HLA serologically identical, but HLA-DP mismatched brother. He developed grade II acute graft-versus-host disease (GVHD) and thereafter chronic GVHD of progressive type, and was treated with both prednisolone and azathioprine resulting in clinical improvement. Thereafter he complained of dyspnea, and bilateral noncircumscribed interstitial shadows on chest CT scan were present. His pulmonary function showed restrictive changes. Prednisolone was not effective and he died of respiratory failure. Post-mortem examination confirmed interstitial fibrosis, lymphocytic infiltration of the bronchioles and alveoli with luminal fibrosis. There was no evidence of chronic GVHD in the skin and the liver. These findings raise the possibility that this pulmonary complication was associated with DC itself.
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PMID:Fatal interstitial pulmonary disease in a patient with dyskeratosis congenita after allogeneic bone marrow transplantation. 905 Dec 51

Hematopoietic stem-cell transplantation (HSCT) is an effective mode of therapy in pediatrics for the treatment of both malignant and non-malignant disorders. We compared the course of children transplanted with unrelated umbilical cord blood (UCB) to those transplanted with allogeneic sibling bone marrow (BM) for bone marrow failure syndromes. Thirteen patients with a median age of 6.3 years were transplanted for the following diseases between April 1992 and November 1997: myelodysplastic syndromes, aplastic anemia, Diamond-Blackfan anemia, myelofibrosis, paroxysmal nocturnal hemoglobinuria, osteopetrosis and dyskeratosis congenita. The stem cell source was BM in ten patients and UCB in three. We retrospectively examined the conditioning regimens, stem cell source and dose, days to engraftment, survival and complication rate to see whether there was a significant advantage in using one source over the other. The median time to an absolute neutrophil count > 500 per microL was 25 days for UCB patients and 16 days for BM patients. The median time to a platelet count > 20,000 per microL was 55 days for UCB patients and 22 days for BM patients. The 100-day mortality was 66% in UCB patients and 20% in BM patients. The overall mortality rates were 66% and 40%, respectively. Three patients died prior to engraftment. Seven patients (54%) were still alive as of May 1999 with a median follow-up of 1574 days post-transplant. The patients transplanted with BM had faster engraftment and lower rates of graft-versus-host disease, 100-day mortality and overall mortality. HLA-matched sibling BM is preferred as a source but transplantation using unrelated UCB is still an option in treating pediatric bone marrow failure syndromes.
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PMID:Hematopoietic stem-cell transplantation using unrelated cord-blood versus matched sibling marrow in pediatric bone marrow failure syndrome: one center's experience. 1056 77

We describe the treatment of a 10-year-old girl with autosomal recessive Dyskeratosis congenita (DC), neutropenia, thrombocytopenia and combined immunodeficiency by nonmyeloablative hematopoietic stem cell transplantation. The conditioning regimen consisted of fludarabine 30 mg/m(2)/day (days -5, -4, -3) and 2 Gy TBI (0.07 Gy/min; day 0). For graft-versus-host disease (GVHD) prophylaxis a course of intravenous MMF and CSA was administered. At 2 years after transplantation of granulocyte colony-stimulating factor (G-CSF) mobilized peripheral blood stem cells from a healthy 11-year-old HLA-identical brother, peripheral blood counts and T- and B-cell functions have completely normalized and donor chimerism was 100% in all cell lineages. No GVHD occurred. Neurological examination and lung function remained normal. The current transplantation regimen appears suitable, safe and efficacious in patients with DC.
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PMID:Nonmyeloablative allogeneic hematopoietic stem cell transplantation for treatment of Dyskeratosis congenita. 1263 34

Dyskeratosis congenita (DC) is a rare inherited bone marrow failure syndrome characterized by the triad of reticular pigmentation of the skin, nail dystrophy, and mucosal leukoplakia. DC is often associated with severe pancytopenia, and bone marrow failure is the principal cause of early mortality. Malignant transformation of mucosal leukoplakias may also occur. Rarely, aplastic anemia precedes the other clinical manifestations of the disease. We present a case of a 13-year-old boy who was diagnosed at age four with idopathic aplastic anemia, was treated successfully with an allogeneic bone marrow transplant, then subsequently developed skin, nail, and tongue lesions. While the initial impression was chronic graft-versus-host disease, additional work-up confirmed the diagnosis of DC.
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PMID:Dyskeratosis congenita vs. chronic graft versus host disease: report of a case and a review of the literature. 1552 28

Dyskeratosis congenita (DC) is a rare inherited disorder characterized by the triad of nail dystrophy, mucosal leukoplakia, and reticular pigmentation. Bone marrow failure is the principal cause of early mortality, and stem cell transplantation is the only cure for these patients. However, the results of conventional hematopoietic stem cell transplantation (HSCT) for patients with DC are poor because of the high incidence of transplant-related complications. We describe the successful treatment of a 21-year-old male with DC by nonmyeloablative HSCT from a matched unrelated donor. The gene responsible for the X-linked form of DC was screened and hemizygosity for the mutation Gln31Lys was found, which is consistent with the diagnosis. The conditioning regimen consisted of only fludarabine and antithymocyte globulin. Additionally, a graft-versus-host disease (GVHD) prophylaxis was administered with cyclosporine A (CSA) and mycophenolate mofetil (MMF). The regimen was well tolerated, no severe posttransplantation complications were observed, and engraftment was rapid and complete (granulocytes on day +11 and platelets on day +13). Seven months after HSCT, the patient developed GVHD of the liver after tapering CSA which was successfully treated with prednisolone, CSA, and MMF. At the time of reporting, 3 years after HSCT, the patient remained in good clinical condition with minimal signs of chronic GVHD of the oral mucosa. Thus, we conclude that a low-intensity conditioning regimen might be sufficient to induce permanent engraftment by using matched unrelated donor HSCT in DC patients and may avoid severe organ toxicity. Although allogeneic HSCT in patients with DC will not cure the underlying genetic defect it may significantly prolong survival through effective therapy for hematologic complications.
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PMID:Reduced-intensity conditioning using fludarabine and antithymocyte globulin alone allows stable engraftment in a patient with dyskeratosis congenita. 2104 11

The recent recognition of genetic defects in telomeres and telomere repair in multiple human diseases has practical implications for hematologists and oncologists and their patients; consequences for future clinical research in hematology and other subspecialties; and even importance in the interpretation of animal experiments involving cell propagation. Telomere diseases include constitutional marrow failure as dyskeratosis congenita, some apparently acquired aplastic anemia, myelodysplasia and acute myeloid leukemia; pulmonary fibrosis; and hepatic nodular regenerative hyperplasia and cirrhosis. Accelerated telomere attrition is a likely pathophysiology of cancer arising from chronic inflammation. Telomerase can be modulated by sex hormones, which may explain the activity of androgens in marrow failure. Measurement of telomere length of peripheral blood leukocytes is a simple screening clinical assay. Detection of a mutation in a patient has implications for therapy, prognosis, monitoring, and genetic counseling. For research in hematology and oncology, telomere biology could be assessed as a risk for secondary malignancies and in graft-versus-host disease, for progression in a variety of blood cancers, and as potentially modifiable by hormone replacement strategies.
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PMID:Telomere biology and telomere diseases: implications for practice and research. 2123 67


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