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)

A 38-year-old woman with agnogenic myeloid metaplasia complicated by the poor prognostic factors of severe osteosclerosis, prominent hepatosplenomegaly, and profound anemia was treated with FLAG chemotherapy to decrease her organomegaly before undergoing a nonmyeloablative allogeneic stem cell transplant from a matched-sibling donor. The patient's pre- and post transplant course were complicated by an autoimmune disorder and her post transplant course was complicated by severe hepatic and gastrointestinal GVHD. A technetium-99m sulfur colloid scan 4 months post transplant and bone marrow studies 8 months post transplant demonstrated intramedullary hematopoiesis, complete resolution of marrow fibrosis, and partial resolution of osteosclerosis.
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PMID:FLAG chemotherapy followed by allogeneic stem cell transplant using nonmyeloablative conditioning induces regression of myelofibrosis with myeloid metaplasia. 1295 30

Allogeneic haemopoietic stem cell transplantation (SCT) is the only curative option for severe bone marrow (BM) failure in patients with Fanconi anaemia (FA). We have developed a non total body irradiation (TBI) conditioning protocol consisting of fludarabine (120-150 mg/m(2)), low dose of cyclophosphamide (40 mg/kg) and antilymphocyte globulin (45 mg/kg). Graft-versus-host disease (GVHD) prophylaxis was with cyclosporin alone for sibling allografts but also included Campath-1 H (days 1-5 post SCT) for the unrelated allografts. We have performed two sibling and two unrelated BM transplants with a follow-up of 11-51 months. All patients experienced minimal toxicity and were discharged from hospital 28-32 days post SCT. Neutrophil and platelet engraftment occurred from days 11 to 19 and 15 to 34, respectively. All patients achieved stable full donor haemopoiesis with normalisation of the peripheral blood count despite one of them having myelodysplasia (MDS) with 8% blasts prior to the SCT. The only site of acute GVHD was in the skin (grade I-II) and only one patient progressed to limited chronic GVHD. This protocol is associated with reduced toxicity and prompt engraftment in FA patients with AA and/or MDS undergoing SCT using sibling or unrelated donors.
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PMID:Non-TBI stem cell transplantation protocol for Fanconi anaemia using HLA-compatible sibling and unrelated donors. 1313 Mar 11

The only proven cure for Fanconi anemia (FA)-associated bone marrow failure is successful allogeneic hematopoietic stem cell transplantation (HSCT). However, HSCT with donors other than HLA-identical siblings is associated with high morbidity and poor survival. Therefore, we used preimplantation genetic diagnosis (PGD) to select an embryo produced by in vitro fertilization (IVF) that was unaffected by FA and was HLA-identical to the proband. The patient was a 6-year-old girl with FA and myelodysplasia previously treated with oxymetholone and prednisone. After her parents underwent 5 cycles of IVF with intrauterine transfer of 7 embryos over a span of 4 years, successful pregnancy ensued. Twenty-eight days after delivery, the patient underwent transplantation with her newborn sibling donor's HLA-identical umbilical cord blood hematopoietic stem cells (HSCs). Neutrophil recovery occurred on day 17 without subsequent acute or chronic graft-versus-host disease. Currently, 2.5 years after transplantation, the patient is well and hematopoiesis is normal. In summary, we have described the first successful transplantation, using IVF and PGD, of HSCs from a donor selected on the basis of specific, desirable disease and HLA characteristics. The medical, legal, and ethical issues involved with this approach are discussed.
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PMID:Successful hematopoietic stem cell transplantation for Fanconi anemia from an unaffected HLA-genotype-identical sibling selected using preimplantation genetic diagnosis. 1450 2

The dramatic advances that have taken place in recent years in the care of sick and premature infants also have been matched by a similar increase in the use of blood transfusion therapy. Haematological features indicate that a newborn has a blood volume of 85-125 ml/kg the foetal haemoglobin is 60-85% and average Hb in full term infant is 18 gm/dl. By 2-3 months it falls to 11-12 g/dl the main cause of anemia are iron poor diet, weaning diets recurrent or chronic infections and hemolytic episodes in malarious areas. The red cells transfusions are usually top up transfusions, exchange transfusions, partial exchange transfusions. Top up- are for investigational losses and correction of mild degrees of anemias, upto to 5-15 ml/kg. They comprise 90% of all neonatal transfusions and are used in low birth babies in special care units for a maximum of 9-10 episodes. The walk in donor programs once popular are not much in vogue. The threshold for transfusion is 8-10 g/dl Hb for upto 5 weeks. Exchange transfusions are done for correction of anemia, removal of bilirubin, removal of antibodies and replacement of red cells. Ideally plasma reduced red cells that are not older than 5 days are used. It is prepared by removal of 120 ml of standard whole blood donation. The advantage of fresh cells is that hyperkalemia is avoided and good post transfusion survival acceptable red cell oxygen affinity. However it has to be screened for sickle cell disease and G6PD deficiency. Indications for exchange transfusion are kernicterus, neonatal hemolysis, G6PD deficiency, ARDS, neonatal sepsis, DIC and neonatal isoimmune thrombocytopaenia. Complications include over transfusion, perforation of major vessels, hypocalcaemia, citrate toxicity, hypothermia, hypoglycaemia, thrombocytopenia, necrotizing enterocolitis, GVHD, bacterial, viral infections. Partial exchange transfusions are done for symptomatic anemia, where Hb<10 g/dl, it is indicated in polycythemia and hyperviscosity syndromes. Exchange volume = Blood volume x (observed Hct-Desired HCt) divided observed Hct. Points to consider-there is weak expression of ABO antigens so particular care while grouping. Transfusing volumes should be 2-5 ml/kg/hour in paediatric bags of 50-100 ml with infusion devices. Platelet transfusion are indicated in neonatal throbocytopaenia, thrombocytopaenia due to sepsis, DIC, bacterial pathogens, CMV, TORCHS, Obstetric conditions such as pre eclampsia, intrauterine death abruption placenta birth injury hypoxia schock neonatal iso immune thrombocytopaenia and maternal ITP. Administration 1 RDE/pack per 2.5 kg single dose of fresh platelets less than 24hrs which contains 55 x 10(9) cells. This also contributes fresh plasma so is useful for coagulation defects also, though there is a risk of CMV and GVHD due to leucocyte contamination. Granulocyte concentrate; Gravity leucopheresis-1:8 ratio of 60 ml of 6% HES made to stand for 1hr.
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PMID:Component therapy. 1451 88

Anemia is common after liver transplantation, with the incidence ranging from 4.3% to 28.2% depending on the criteria used to define anemia. The cause of anemia is unidentified in the majority of patients, and it is likely to be multifactorial. Immunosuppressive-medication-induced bone marrow suppression is perhaps the most common cause of unexplained anemia. Chronic blood loss, iron deficiency, hemolysis, and renal insufficiency are other potential causes of chronic anemia. Rare causes, somewhat unique to transplantation, include aplastic anemia, graft-versus-host disease (GVHD), and lymphoproliferative disease. Anemia due to immunosuppressive medication is challenging, since almost all drugs currently used for this purpose cause anemia, but the renal-sparing property of sirolimus may benefit the subgroup in which renal insufficiency is contributing to anemia. Aplastic anemia is seen in young patients transplanted for non-A, non-B, non-C, fulminant hepatic failure. It is thought to be immunologically mediated, secondary to an unknown viral infection, and is associated with a grave prognosis. GVHD is another infrequent (approximately 1% of transplant recipients) but serious cause of severe anemia that carries a dismal prognosis. Lymphoproliferative disorder, too may rarely rare cause anemia and it may respond to reduction of immunosuppression. Recipients of solid-organ transplants do not mount a significant increase in erythropoietin in response to anemia. In conclusion, though there are no data on the response of anemia to erythropoietin in liver transplant recipients, it appears to benefit other solid-organ-transplant recipients with anemia.
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PMID:Post-liver-transplant anemia: etiology and management. 1476 52

Recent studies on animal and human autoimmune hemolytic anaemia (AIHA) suggest that the loss of immunological tolerance vs. erythrocyte (Er) self antigens (Ag) may be primed by different mechanisms: ignorance of Er self Ag, molecular mimicry between self and non-self Ag, polyclonal T and/or B cells activation, errors in central or peripheral tolerance, immunoregulatory disturbances including the alteration of cytokines network. In vitro stimulation by synthetic Rh peptides indicates that ignorant T and/or B cells from patients with AIHA may recognize criptic Er self Ag. The AIHA associated with bacterial or viral infections seems to be produced by polyclonal T and/or B cell activation against foreign Ag that mimics protein or carbohydrate epitopes on Er. Polyclonal activation of host B cell clones by donor T cells causes the AIHA in chronic graft-versus-host disease. Mouse lines expressing a transgene with autoantibody (autoAb) activity against murine Er have shown that non-deleted peripheral B cell clones may produce Er autoAb. In human a genetic defect of Fas/FasL autoreactive lymphocyte apoptosis may be associated with AIHA. Th1/Th2 cytokines or IL10/IL12 imbalance may induce AIHA: in NZB mice and in human AIHA there is an increased production of Th2 cytokines such as IL4 and IL10 but INF-gamma and IL12 reduced production. Particularly, IL10 seems to act as critical mediator for the Er autoAb production.
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PMID:Immunological tolerance loss vs. erythrocyte self antigens and cytokine network disregulation in autoimmune hemolytic anaemia. 1500 88

Allogeneic hematopoietic stem cell transplantation (SCT) from unaffected donors remains the only modality for the correction of hematological abnormalities in Fanconi anemia (FA) patients. We performed four HLA-matched related donor SCT using a novel irradiation and cyclophosphamide-free conditioning regimen. The protocol included fludarabine 150 mg/m(2), busulfan 4 mg/kg, and antithymocyte globulin 90 mg/kg. Graft-versus-host disease (GVHD) prophylaxis was cyclosporin A, MTX, and daclizumab. The engraftment and occurrence of full stable donor hemopoiesis was rapid in all cases with minimal short-term toxic complications. There were no infections or febrile episodes during the inpatient phase. Three patients developed acute GVHD grade I-II involving gut and skin and one patient progressed to extensive chronic GVHD. The preparative conditioning regimen is safe and associated with low organ toxicity and effective immunosupression for the stable engraftment in FA patients undergoing SCT with matched related donors.
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PMID:Fludarabine, low-dose busulfan and antithymocyte globulin as conditioning for Fanconi anemia patients receiving bone marrow transplantation from HLA-compatible related donors. 1519 80

Neurological complications may occur in BMT recipients (11-59%), frequently contributing to morbidity or mortality. They are the main causes of death in 10-15%. Life-threatening neurological complications were seen in 11 out of 113 (9.7%) children who underwent BMT from HLA-matched family (n=7) or mismatched donors (n=4) at our institution. Diagnoses of patients with neurological complications were acute myeloblastic leukemia (AML) (five), thalassemia major (two), Fanconi anemia (two), Omenn syndrome (one) and leukodystrophy (one), and the neurological events were seen between days +13 and +85 after transplantation. Minor symptoms including reversible, nonrepetitive seizures were excluded. Cyclosporine A toxicity was diagnosed in six children. The rest of the complications were brain abscess/meningoencephalitis (two), severe hypomagnesemia (one), busulfan toxicity (one), sustained hypertension (three), and intracranial hemorrhage (three). Six patients with neurological complications suffered from >grade II graft-versus-host disease (GvHD), and all were high risk for transplant-related complications. In this study, risk status of the underlying disease, mismatched transplantation, a diagnosis of AML (advanced stage), older age and >grade II GvHD were important adverse factors for the development of severe life-threatening neurological complications.
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PMID:Life-threatening neurological complications after bone marrow transplantation in children. 1553 98

In all, 22 patients with confirmed Fanconi anemia (FA) underwent stem cell transplantation (SCT) from HLA-matched, related donors at KFSHRC. Median age at SCT was 7.6 years (range, 2.5-14.6 years). Conditioning regimen consisted of cyclophosphamide (CY) 15 mg/kg/day intravenously (i.v.) for 4 consecutive days, in addition to equine antithymocyte globulins (ATG) given i.v. at 40 mg/kg/day for four doses pre-SCT. No radiation therapy was given. For graft-versus-host disease prophylaxis, we used cyclosporin at the standard doses; ATG was added at 20 mg/kg/dose i.v. on days 2, 4, 6, 8, 10, and 12 post-SCT (total of six doses). All patients engrafted and are alive and transfusion independent with a median follow-up time of 20.2 months (range, 3.3-59 months). One patient however developed a decrease in her WBC and platelet count. Her work-up revealed slightly hypocellular bone marrow, and a series of chimerism studies over 1 year confirmed that she has stable mixed chimerism; she remains transfusion independent. We conclude that low-dose CY without radiation therapy can be used satisfactorily in the conditioning of patients with FA undergoing related SCT.
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PMID:Stem cell transplantation for patients with Fanconi anemia with low-dose cyclophosphamide and antithymocyte globulins without the use of radiation therapy. 1565 54

Allogeneic haematopoietic cell transplantation (HCT) is effective therapy for Fanconi anaemia (FA). FA patients do not tolerate conditioning with 200 mg/kg of cyclophosphamide (Cy), typically used in aplastic anaemia. We previously published results of studies in which Cy doses were gradually reduced from 200 to 100 mg/kg. Here we update results of the initial studies and report data on 30 new patients conditioned with Cy either at 80 mg/kg (n = 7) or at 60 mg/kg (n = 23), given over 4 days before HCT from human leucocyte antigen-matched related donors. Methotrexate and cyclosporine were given for graft-versus-host disease (GVHD) prophylaxis. All seven patients given Cy at 80 mg/kg and 21 of 23 given Cy at 60 mg/kg had sustained engraftment, while two patients, both with clonal cytogenetics abnormalities, experienced graft failure. Grades 2-3 acute GVHD rates were 57% and 14% for patients given the higher and lower Cy doses, respectively (P = 0.001). Four patients given Cy at 80 mg/kg and 22 given Cy at 60 mg/kg were alive at a median of 47 (44-58) months and 16 (3-52) months, respectively. Cy at 60 mg/kg has acceptable toxicities, low rates of GVHD, and is sufficient for engraftment of related grafts in most FA patients.
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PMID:Low-dose cyclophosphamide conditioning for haematopoietic cell transplantation from HLA-matched related donors in patients with Fanconi anaemia. 1598 51


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