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

Thrombotic microangiopathy (TMA) is a well-recognised disorder which may occur in up to 6% of patients following bone marrow transplantation (BMT). Reported cases of post-BMT TMA vary widely in their reported clinical features, severity and response to therapy. Several factors are important in the aetiology, including cyclosporin A (CsA), graft-versus-host disease, irradiation, intensive conditioning chemotherapy and infection. A unifying pathogenetic mechanism is suggested, wherein these factors may interact to produce post-BMT TMA. On the basis of differences in clinical features and prognosis, we propose the classification of post-BMT TMA into four distinctive although overlapping subtypes: multifactorial fulminant TMA, conditioning-associated haemolytic-uraemic syndrome, CsA-associated nephrotoxicity with microangiopathic haemolytic anaemia (MAHA) and CsA-associated neurotoxicity with MAHA. Treatment of post-BMT TMA, especially of the poor-prognosis multifactorial fulminant subtype, is currently unsatisfactory, although occasional cases may respond to plasma exchange.
 ...
PMID:Thrombotic microangiopathy following bone marrow transplantation. 873 19

Thrombotic microangiopathy (TMA) is an infrequent but serious complication of allogeneic transplantation. The success rate of plasma exchange (PE) reported in the treatment of this entity is a controversial subject. We report the outcome of 10 patients with TMA post-allogeneic transplantation after treatment with PE. Two out of the 10 patients have not responded, five had a partial response, but died of acute GVHD or interstitial pneumonitis, and three have responded and recovered. Our study suggests that there are different degrees of TMA severity. Only mild multifactorial cases with no severe hemolysis (LDH activity <1000 U/l) may be fully resolved with PE.
 ...
PMID:Management of thrombotic microangiopathy following allogeneic transplantation: what is the role of plasma exchange? 928 45

Growth factor administration to donors prior to bone marrow (BM) harvesting results in an enrichment of the graft for myeloid precursors. In animals, growth factor-primed BM has a higher repopulating ability than untreated BM. Ten patients received an HLA-identical sibling, allogeneic transplant using granulocyte colony-stimulating factor (G-CSF)-stimulated BM. Stimulation consisted of G-CSF at 10 microg/kg/day for 2 days prior to harvest. Patients were transplanted for various benign and malignant hematological conditions. The GVHD prophylaxis consisted of cyclosporine, methotrexate and/or prednisone. Compared to untreated historical control BM, stimulated BM infusions contained similar number of nucleated cells (mean +/- s.d.: 3.5 +/- 1.5 vs 4.0 +/- 0.9 x 10(8)/kg), CD34+ cells (mean +/- s.d.: 7.5 +/- 3.0 vs 9.4 +/- 6.7 x 10(6)/kg), and CD3+ cells (mean +/- s.d.: 129 +/- 30 vs 190 +/- 59 x 10(6)/kg) but higher numbers of granulocyte-macrophage colony-forming units (mean +/- s.d.: 20 +/- 12 vs 96 +/- 34 x 10(4)/kg). Patients receiving stimulated BM had prompt and stable engraftment of white cells and platelets. On average they attained an ANC of > or = 1 x 10(9)/l 9 days earlier and a platelet count of > or = 20 x 10(9)/l 6 days earlier than historical controls receiving unstimulated HLA-identical sibling BM. Hospitalization was shortened by a mean of 10 days and transfusion requirements were modest. None of the patients developed severe GVHD or disease relapse. Two patients died of severe VOD post-BMT and thus were unevaluable for platelet engraftment. A third patient died of TTP on day 76 post-BMT. Seven patients are alive and well 49-585 days post-BMT. Stimulated BM may provide a valuable alternative to allogeneic BM and PBSC transplants. Ideal stimulation regimens need to be investigated.
 ...
PMID:A pilot study of allogeneic bone marrow transplantation using related donors stimulated with G-CSF. 946 75

Thrombotic microangiopathy (TM), manifesting clinically as thrombotic thrombocytopenic purpura or hemolytic uremic syndrome, is an uncommon complication after bone marrow transplantation (BMT). A retrospective analysis of potential risk factors for TM following allogeneic BMT was performed. Clinical data were analyzed from seven patients diagnosed with severe TM and 409 patients who underwent BMT during the same time period and who survived for at least 100 days afterwards. Six of the seven patients with TM received intensive GVHD prophylaxis consisting of cyclosporine, methotrexate and glucocorticoids, whereas only 66 of the 409 patients without TM received this regimen (P < 0.001, Fisher's exact test). This regimen was administered to patients older than 40 years, or recipients of a mismatched or unrelated allograft. Univariate analysis also revealed an increased risk of TM associated with the use of an unrelated bone marrow donor (P = 0.02), but no significant association with patient age or gender, diagnosis, amount of prior chemotherapy, transplant conditioning regimen or severity of GVHD. A multivariate exact logistic regression analysis revealed that only the type of GVHD prophylaxis had a significant impact on the risk for TM. The combined use of cyclosporine, methotrexate and glucocorticoids as GVHD prophylaxis may predispose to the development of TM following BMT.
 ...
PMID:Thrombotic microangiopathy following allogeneic bone marrow transplantation is associated with intensive graft-versus-host disease prophylaxis. 972 70

Thrombotic microangiopathy (TM) is a potentially fatal complication of allogeneic bone marrow transplantation (BMT). The underlying pathophysiology is thought to be generalized endothelial cell damage caused by several factors including conditioning treatment, cyclosporin A (CsA), or graft versus host disease (GVHD). In the present retrospective study, 6 patients suffering from Grade 2 BMT-TM at a mean of 62 days post BMT were treated by 3-15 daily sessions of therapeutic plasma exchange (TPE). In most sessions, cryosupernatant (CSN) of plasma, in some fresh frozen plasma (FFP) was used as the substitution fluid. All patients suffered from acute graft versus host disease (aGVHD) of the skin, which was treated by CsA. CsA was withdrawn in all patients. TPE caused a response in 4 of 6 patients evidenced by a decrease to Grade 0 (n = 3) or 1 (n = 1) BMT-TM. Only 1 patient had mild renal insufficiency which did not improve during TPE. While all patients were dependent on platelet transfusions at baseline, the platelet counts improved in 2 of 6 patients after the TPE course. One patient did not show any response to TPE with FFP, and his disease improved only after CSN was introduced as substitution fluid (Grade 0). Four patients were still alive 175-495 days post BMT, and 2 patients died about 2-3 weeks after the end of the TPE course, 1 from cachexia and 1 from systemic aspergillosis. In summary, in this pilot study, TPE positively influenced BMT-TM, especially if CSN was used as the substitution fluid.
 ...
PMID:Therapeutic plasma exchange in patients suffering from thrombotic microangiopathy after allogeneic bone marrow transplantation. 1042 24

Thrombotic microangiopathy is one of the complications of bone marrow transplantation and is related to other complications such as graft-versus-host disease, veno-occlusive disease, diffuse alveolar hemorrhage, and cytomegalovirus infection. Thrombotic microangiopathy occurred in three out of 12 patients who underwent allogeneic bone marrow transplantation over the past 1 year at our department. We compared the changes in cytokines and other molecules between patients with and without microangiopathy from before conditioning to the early post-transplantation period. All three patients with microangiopathy showed a significant increase of interleukin-12 at the time of leukocyte recovery after transplantation (two-way layout analysis of variance; P < 0.05), while none of the patients without microangiopathy showed an increase of interleukin-12. No significant differences were found between the two groups with respect to the other cytokines and molecules that were tested. These findings suggested that thrombotic microangiopathy might be predicted at an early stage after bone marrow transplantation by detecting an increase of interleukin-12 at the time of leukocyte recovery. The possibility that thrombotic microangiopathy is related to inflammation or autoimmunity was also suggested.
 ...
PMID:Thrombotic microangiopathy following allogeneic bone marrow transplantation. 1045 70

Thrombotic microangiopathy (TMA) is a serious complication of BMT. Several factors are important in the etiology of TMA, such as cyclosporin A, GVHD, irradiation, intensive conditioning chemotherapy and infection, which cause damage to vascular endothelial cells leading to activation of these cells. We describe two young children with TMA following high-dose chemotherapy with autologous BMT. Development of TMA was accompanied by reactivation of HHV-6, which was identified by both an increase in the copy number of HHV-6 DNA in the peripheral blood and a significant increase in antibody titers to HHV-6. Thus, it was suggested that reactivation of HHV-6 together with high-dose chemotherapy played an important role in the pathogenesis of TMA in these patients. Since HHV-6 is known to infect vascular endothelial cells, and CMV which is virologically closely related to HHV-6, has been reported to be a pathogen that causes TMA, infection with HHV-6 of vascular endothelial cells may induce TMA via damage and activation of these cells.
 ...
PMID:Thrombotic microangiopathy associated with reactivation of human herpesvirus-6 following high-dose chemotherapy with autologous bone marrow transplantation in young children. 1051 6

Although allogeneic transplantation can be curative for patients with sickle cell disease, the toxicity of conditioning regimens has precluded its use in adults with significant end-organ damage. Newer conditioning regimens have been developed that are less toxic and that may broaden the applicability of allogeneic transplantation in this disorder. We report two adults with end-stage sickle cell disease, who underwent allogeneic transplantation from an HLA-identical sibling donor after conditioning with fludarabine/melphalan and ATG. Both patients had been extensively transfused and one had multiple RBC antibodies. One of the patients also had end-stage renal disease, and was dialysis dependent. Engraftment occurred promptly in both patients. Both achieved 100% donor chimerism and both were free of pain crises after transplant. The first patient died of a respiratory failure related to chronic graft-versus-host disease (GVHD) on day 335 after transplantation. The second patient developed severe gastro-intestinal GVHD and TTP and died on day 147 after transplantation. Conditioning with fludarabine/melphalan and ATG followed by allogeneic stem cell transplantation resulted in prompt and reliable engraftment in adults with end-stage sickle cell disease. The incidence of severe GVHD was unacceptably high and may be related to the ethnicity of the patients or to the inflammatory state associated with pre-existing sickle cell disease.
 ...
PMID:Fludarabine-based conditioning for allogeneic transplantation in adults with sickle cell disease. 1098 93

Thrombotic microangiopathy is a severe microvascular disorder which may occur in up to 70% of patients undergoing bone marrow transplant. Clinically the term thrombotic microangiopathy encompasses a wide spectrum of syndromes, most importantly the thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS). Thrombotic microangiopathy is characterized by the presence of thrombocytopenia, microangiopathic hemolytic anemia, renal impairment, neurological disturbances and multiorgan failure. Several causative agents have been advocated as triggering factors for bone marrow transplant associated thrombotic microangiopathy, including cyclosporine, FK506, the use of total body irradiation, infections and the presence of severe graft-versus-host disease. Plasma exchange represents the standard treatment for patients who develop TTP/HUS after bone marrow transplant, however, the mortality rate still remains high despite aggressive therapy.
 ...
PMID:BMT: Bone Marrow Transplant Associated Thrombotic Microangiopathy. 1139 2

Candidemia is a serious complication in patients following allogeneic blood, marrow, and organ transplantation. Fourteen patients developed nosocomial fungemia among 204 allogeneic marrow transplants performed during 1997-1999. Incidence of hematogenous candidiasis was 6.8 per 100 allogeneic BMT. All 14 had an indwelling central venous catheter (CVC) and fluconazole (100-200 mg daily) was given prophylactically. In 11 (78.5%) neutropenic patients, duration between agranulocytosis and diagnosis of fungemia was (median, +/- s.d.) 10 +/- 8 days. Candida glabrata (53.3%) was the most common yeast species, followed by C. krusei (33.3%), and C. parapsilosis (13.3%). Candida albicans was conspicuously absent. Ten patients (71.4%) had primary transplant-related complication (>2 days) including hemolytic uremic syndrome/thrombotic thrombocytopenic purpura (HUS/TTP) (n = 5), severe hemorrhagic cystitis (n = 3), and bacteremia (n = 2). Seven (50.0%) patients expired and in three (21.4%) deaths were attributed to fungemia. The impact of a primary transplant-related complication on short-term survival in this setting was not significant (P = 0.07) (HUS/TTP (P > 0.5); neutropenia (P > 0.5); GVHD (P = 0.35)). Removal of CVC did not alter outcome in our group (P > or = 0.5) although in patients with persistent fungemia (>72 h), and those with preceding bacteremia, mortality was significantly higher (P = 0.002). Conventional prognosticators of poor outcome did not adversely effect short-term survival in our transplant recipients with hematogenous candidiasis. The predominance of C. glabrata and C. krusei breakthrough infections was similar to what is seen with high-dose fluconazole (400 mg) prophylaxis, and no adverse effects of low-dose fluconazole in terms of increased incidence of non-susceptible Candida species was seen.
 ...
PMID:Candida glabrata and Candida krusei fungemia after high-risk allogeneic marrow transplantation: no adverse effect of low-dose fluconazole prophylaxis on incidence and outcome. 1178 48


1 2 3 Next >>