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)

The efficacy and safety of mycophenolate mofetil (MMF) in combination with CsA and prednisolone for the treatment of acute and chronic GVHD (aGVHD and cGVHD, respectively) after BMT and PBSCT from HLA-mismatched and -matched donors was evaluated in an open single center trial. Twenty-four patients, 17-48 years of age, with acute (n = 17) and chronic GVHD (n = 7) were treated with 2 g MMF daily in addition to CsA and prednisolone. Overall grade improvement of aGVHD was found in 11 of 17 (65%) patients treated with MMF. MMF therapy in the treatment of cGVHD led to moderate improvement in three of six patients with limited cGVHD. The most common adverse hematologic events of MMF were leukopenia (n = 6), anemia (n = 4) and thrombocytopenia (n = 3). Hematological adverse events were not severe and did not require the discontinuation of MMF. In this preliminary study, we have shown that MMF can be used safely for the treatment of aGVHD. In addition, the MMF therapy resulted in significant dose reduction of prednisolone for the treatment of GVHD.
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PMID:Mycophenolate mofetil for the treatment of acute and chronic GVHD in bone marrow transplant patients. 1122 81

An immunosuppressive but not myeloablative regimen followed by HLA-matched donor mobilized haemopoietic stem cell transplantation was employed in two high-risk patients. The first patient had refractory anaemia with excess blasts (RAEB) and cytogenetic evidence of translocation 1;3(p36;q21). The second patient had Philadelphia-negative but p190 BCR-ABL chimaeric gene positive chronic myelogenous leukaemia in accelerated phase (AP-CML). The conditioning regimen consisted of fludarabine (30 mg/m2/d, days 1-3) with cyclophosphamide (300 mg/m2/d, days 1-3). Cyclosporine and methotrexate were employed for acute graft-versus-host disease (aGVHD) prophylaxis. In both cases the engraftment of donor cells was demonstrated by cytogenetics and short tandem repeat polymorphisms via PCR. Both patients are alive with normal cytogenetic (RAEB) and molecular (AP-CML) remissions, 100 and 150 d after allografting, respectively. In particular, in the AP-CML patient, the BCR-ABL became undetectable and the BCR-ABL/ABL ratio was <0.0001.
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PMID:Evidence of cytogenetic and molecular remission by allogeneic cells after immunosuppressive therapy alone. 982 37

Murine graft-versus-host (GVH) disease takes two forms depending upon the parental/F1 strain combination employed. Anemia, lymphopenia, hypogammaglobulinemia, profound anti-F1 cytotoxicity, and the loss of cytotoxic potential against third party alloantigen is seen in acute lethal GVH disease. In contrast to this, in chronic GVH disease there is polyclonal B cell activation, auto-antibody production, no anti-F1 cytotoxicity, and retained cytotoxicity against allotargets. We have previously reported that this marked disparity in disease expression results from a radiosensitive host veto cell which protects the F1 mouse from parental anti-F1 cytotoxicity in mice undergoing CGVH disease. This cell could be induced in vitro or in vivo in CGVH disease. Using an in vitro system, we now demonstrate that a CD4(+), radiation-sensitive, T cell does emerge in acute lethal GVH disease which is capable of down-regulating cytotoxicity. The cell does not appear to be a veto cell in that it attenuates cytotoxicity directed against nonself alloantigen. The function of this cell does not appear to be influenced by minor lymphocyte stimulatory gene products. We further report that, in ALGVH disease, regulation by this cell is not readily apparent due to the emergence of a CD8(+) T cell of parental (B6) origin, which opposes its action.
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PMID:CD8(+), radiosensitive T cells of parental origin, oppose cells capable of down-regulating cytotoxicity in murine acute lethal graft-versus-host disease. 983 96

Since 1988, 34 pediatric patients with severe sickle cell disease have received bone marrow transplantation (BMT) from HLA-identical siblings in France. After 1992, documentation of the favorable effect of hydroxyurea therapy on the frequency of vasoocclusive crisis (VOC) left a history of stroke (n = 16) as the main indication for BMT. Among patients treated by genoidentical BMT, 85% were cured and 9% died. All deaths were due to severe graft-versus-host disease. The rejection rate fell from 25% to 5% after addition of ATG to the conditioning regimen. BMT reversed some sickle cell disease-related abnormalities: splenic function improved and some cases of osteonecrosis showed a favorable course. Fifteen of 16 patients with a history of stroke showed no stroke recurrence after BMT, and arterial stenoses improved. BMT should be offered to sickle cell anemia patients with a history of stroke if a genoidentical donor is available. To prevent stroke-related residual impairment and transfusion-related complications, BMT should be considered early in patients with Doppler or MRI evidence of silent stroke associated with cognitive function impairment, failure to respond to hydroxyurea therapy (frequent VOCs, severe anemia and thrombocytosis, multifocal osteonecrosis), or polyerythroalloimmunization. Storage of frozen of cord blood samples from siblings should be considered.
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PMID:[Results and current indications of bone marrow allograft in sickle cell disease]. 1008 81

As advances in cancer therapy improve the prognosis of patients with childhood malignancies, awareness of the consequences of treatment methods assumes increasing importance. All cancer treatment modalities are associated with toxic effects, and the spectrum of therapy-induced complications involves all organ systems. Radiologists have a pivotal role in detecting these sequelae, which can be categorized by the affected organ system and by whether they occur (a) at diagnosis or during initial therapy or (b) after the completion of treatment. The first group consists of oncologic emergencies, infectious complications, and irritant effects. Oncologic emergencies can be further categorized as space-occupying lesions (e.g., superior vena cava syndrome or spinal cord compression), vascular abnormalities (e.g., hyperleukocytosis, anemia, coagulopathy), and metabolic emergencies (e.g., tumor lysis syndrome). Common complications developing after completion of treatment include leukoencephalopathy and neurocognitive defects; cataract formation; cardiomyopathy and congestive heart failure; hepatic dysfunction, fibrosis, and cirrhosis; radiation enteritis; renal dysfunction or failure; scoliosis and short stature; hypothyroidism; gonadal dysfunction; graft-versus-host disease; and development of secondary malignancies. Physician awareness of these complications will permit more effective patient surveillance, which may afford patients the opportunity for earlier intervention in these situations and improved quality of life.
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PMID:Complications of cancer therapy in children: a radiologist's guide. 1019 80

We described the successful allogeneic matched sibling bone marrow transplantation (BMT) in a 5-year-old Thai boy in whom osteopetrosis was diagnosed on the basis of anemia, thrombocytopenia, leukoerythroblastosis, sclerotic bone, hepatosplenomegaly, and visual deficit from an encroachment of cranial nerve foramina. The preparative regimen included 4 days of busulfan 4 mg/kg/day, and 4 days of cyclophosphamide 50 mg/kg/day. Complete hematopoietic engraftment and no evidence of graft versus host disease were shown after BMT. Complete hematologic findings were corrected. His hematopoietic chimerism was changed to that of his donor. Post BMT, he has no hepatosplenomegaly. His bone radiographic findings revealed normal after BMT. Bone marrow biopsy showed normalized bone and bone marrow matrix. However, his vision remained impaired. We believe that this is the first case of successful bone marrow transplantation in an osteopetrosis patient in Thailand.
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PMID:Allogeneic bone marrow transplantation in an osteopetrosis patient: first report in Thailand. 1021 1

The problems of immunologic adaptation during the transitional period from intra- to extrauterine life are responsible for the physiologic immaturity of the immune function in newborn infants. In preterm neonates the immunodeficiency is more severe and prolonged and is associated with a higher incidence of infections and sepsis. Furthermore, due to immaturity of the hematologic system, anemia, thrombocytopenia, and neutropenia are frequently observed in very low birth weight infants. The dysregulation of cytokine and hematopoietic growth factor synthesis is an important contributory factor to the complex deficiency of immunologic and hematologic function in the neonate and may explain the reduced incidence of acute graft-versus-host disease observed after cord blood transplantation in children. Human milk is a rich source of most of the cytokines that are reduced in the neonate. Granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, and erythropoietin are currently under evaluation in newborn infants with septic neutropenia or anemia of prematurity.
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PMID:Hematopoietic growth factor levels in term and preterm infants. 1022 41

Fanconi anemia (FA), a rare autosomal recessive disease, frequently evolves to bone marrow failure and acute myeloid leukemia, and BMT is the treatment of choice for patients with FA. However, their exquisite hypersensitivity to DNA cross-linking agents is associated with severe complications and several investigators have been looking for the ideal preparatory regimen. We have been involved in a program of progressively decreasing doses of cyclophosphamide (CY) as conditioning therapy, in an attempt to identify the lowest dose of CY capable of maintaining the graft with minimum complications. Here, we describe our experience of allogeneic BMT offered to 16 patients with FA and an HLA-compatible sibling donor, conditioned with 100 mg/kg of CY. The actuarial survival is 88% at approximately 37 months. Mucositis >/= grade II was the most common complication (94%), followed by bacteremias (38%). Veno-occlusive disease and hemorrhagic cystitis did not occur. Sustained engraftment was obtained in 94% of patients, and acute and chronic GVHD was diagnosed in 13% and 7%, respectively. The lowest dose of CY for transplant in FA patients is yet to be determined, but further reductions seem possible.
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PMID:Bone marrow transplantation for patients with Fanconi anemia: reduced doses of cyclophosphamide without irradiation as conditioning. 1087 42

Allogeneic stem cell transplantation is the only treatment that can restore a normal hematopoiesis in Fanconi anemia (FA). In this retrospective multicenter study, we analyzed the results of this approach using HLA-matched unrelated bone marrow donors, and tried to identify covariates predicting the outcome of the transplant. From January 1985 to June 1998, 69 FA patients were transplanted with unrelated HLA-matched donors. Patients' characteristics before and after transplant were provided by the European group blood and marrow transplant registry and were analyzed in collaboration with the European Fanconi Anemia Registry. The 3-year probability of survival was 33%. Extensive malformations, a positive recipient cytomegalovirus serology, the use of androgens before transplant, and female donors were associated with a worse outcome. Primary graft failures were observed more frequently when female donors were used, mainly because the grafts contained lower nucleated cell doses per kilogram of recipient body weight compared with grafts coming from male donors. The probability of grade III-IV acute graft-versus-host disease (GVHD) was 34%. Elevated serum alanine/aspartate transaminases before transplantation; limb, urogenital tract, or nephrologic malformations; and non-T-cell-depleted grafts were predictors of severe acute GVHD. This study shows the dramatic impact of preexisting congenital malformations on the outcome of FA patients transplanted with HLA-matched unrelated donors. If the use of T-cell depletion has led to a dramatic reduction of acute GVHD incidence, no significant outcome improvement was observed with this approach, mainly because of an increased risk of graft failure. (Blood. 2000;95:422-429)
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PMID:Outcome of 69 allogeneic stem cell transplantations for Fanconi anemia using HLA-matched unrelated donors: a study on behalf of the European Group for Blood and Marrow Transplantation. 1062 45

Allogeneic haematopoietic cell transplantation (HCT) is the only therapeutic modality capable of correcting the haematologic manifestations of Fanconi anaemia (FA). However, HCT from alternative donors has been associated with poor survival. Between June 1993 and July 1998, 29 FA patients (median age 12.1 years; range 3.7-48.5 years) were enrolled in a prospective phase I-II dose escalation study. All patients were treated with cyclophosphamide 40 mg/kg, total body irradiation (TBI) 450 cGy or 600 cGy and antithymocyte globulin (ATG), followed by HCT from an alternative donor. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporin A for 6 months, short course methylprednisolone (2 mg/kg/day) between days +5 and +19 and marrow T-cell depletion by counterflow elutriation. The probability of developing grade III-IV toxicity was 17% (95% CI 3-31%). For the 25 marrow recipients, the probability of neutrophil engraftment (ANC 0.5 x 109/l by day 45) was 63% (95% CI 42-82%). Probabilities of grade II-IV acute GVHD and chronic GVHD were 32% (95%CI 10-54%) and 0% respectively. With a median follow-up of 18 months, the probability of survival for the entire cohort at 1 year was 34% (95% CI 17-51%). The presence of lymphocyte somatic mosaicism [i.e. the presence of diepoxybutane (DEB)-insensitive cells] was associated with a significantly increased risk of graft failure. Disappointingly, the use of higher dose TBI and post-transplant ATG did not improve engraftment. More effective peritransplant immunosuppression, especially in FA patients with somatic mosaicism, was required to overcome the barrier of graft rejection. New conditioning regimens adapted to each individual's alkylator sensitivity are needed to improve the outcome of alternative donor HCT for FA.
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PMID:Haematopoietic cell transplantation in patients with Fanconi anaemia using alternate donors: results of a total body irradiation dose escalation trial. 1084 91


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