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 full potential of a graft-versus-myeloma effect after allogeneic hematopoietic cell transplantation (HCT) for patients with multiple myeloma (MM) has not been realized because of excessive early transplantation-related mortality (TRM) with conventional HCT. Autologous HCTs have been characterized by almost universal disease recurrences. The current trial combined autologous HCT with subsequent nonmyeloablative allogeneic HCT to maintain the benefits of both approaches with acceptable toxicity. Fifty-four patients, 52 years of age (median; range, 29-71 years), with previously treated stage II or III MM (52% refractory or relapsed disease) were given melphalan 200 mg/m2 and autologous HC transplants. Regimen-related toxicities after autologous HCT were moderate with a median of 6 days of neutropenia, 7 days of hospitalization, and 1 death from infection. Forty to 229 days later (median, 62 days), 52 patients received a single fraction dose of 2 Gy total body irradiation and HC transplants from HLA-identical siblings with postgrafting immunosuppression with mycophenolate mofetil (MMF) and cyclosporine (CSP). Patients experienced medians of 0 days of hospitalization, neutropenia, and thrombocytopenia. Sustained engraftment was uniform. With a median follow-up of 552 days after allografting, overall survival is 78%. One patient (2%) died before day 100 from disease progression. Thirty-eight percent of patients developed acute graft-versus-host disease (GVHD; grade II in all but 4 cases) and 46% chronic GVHD requiring therapy. Tumor responses occurred slowly. Thus far, 57% of patients have achieved complete remissions and 26% have achieved partial remissions for an overall response of 83%. Despite being evaluated in elderly patients with MM, this 2-step approach has reduced the acute toxicities of allogeneic HCT while achieving potent antitumor activities.
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PMID:Allografting with nonmyeloablative conditioning following cytoreductive autografts for the treatment of patients with multiple myeloma. 1285 72

Thrombocytopenia is well known to be one of the clinical manifestations of chronic graft-versus-host disease (cGVHD). However, there exist cases in which the cause of thrombocytopenia has been unexplained. Recently, thrombopoietin (TPO) from bone marrow (BM) stromal cells and transforming growth factor (TGF)-beta from platelets and megakaryocytes have been identified as strong positive and negative regulators of megakaryopoiesis in vivo. We hypothesized that the decreased TPO production from BM could be one of the causes of thrombocytopenia in the patients with cGVHD. In the present study, therefore, TPO and TGF-beta concentrations in peripheral blood (PB) and BM were measured serially in two patients with acute leukemia who had received fully matched stem cell transplantation from relatives and subsequently developed extensive cGVHD with thrombocytopenia. The results showed that platelet numbers correlated well with the TPO concentrations, which were consistently higher in BM than in PB. The difference in TPO concentrations between BM and PB was decreased when the platelet levels were low, indicating that the amount of TPO production from BM decreased throughout the duration of thrombocytopenia. TGF-beta concentrations were normal during all periods in which measurements were carried out. Thus, our results suggest that one mechanism of thrombocytopenia in patients with cGVHD is low TPO production by BM cells.
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PMID:Thrombopoietin concentrations in peripheral blood correlated with platelet numbers in two patients with thrombocytopenia by chronic graft-versus-host disease. 1287 35

Five lymphoma patients relapsed from allogeneic hematopoietic stem cell transplantation (HSCT). Three patients who received myeloablative conditioning had full donor chimerism at relapse, whereas two who received nonmyeloablative conditioning had partially or completely lost the graft. All received mini-BEAM [carmustine (BCNU), etoposide, cytarabine (AraC), melphalan], followed by infusion of HSC (four peripheral blood, one marrow) from the initial donor. Neutropenia and thrombocytopenia were brief, and full donor chimerism was established in all cases. There were four complete and one partial remissions. Graft-versus-host disease occurred in three cases, all with full donor chimerism at relapse. Two patients died subsequently of disease relapse or progression. Another two patients died from fungal infection, one of whom was still in remission at death. One patient had remained in remission 47 months after treatment. Mini-BEAM/HSC is an effective treatment for lymphoma relapses after allogeneic HSCT, but optimal strategies of remission consolidation and prevention of treatment-related complications are needed to improve outcome.
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PMID:Treatment of lymphoma relapses after allogeneic hematopoietic stem cell transplantation with intensive chemotherapy followed by infusion of hematopoietic stem cell from the original donor. 1450 11

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

Allogeneic haemopoietic stem cell transplantation was initially considered as a means of delivering supralethal doses of chemotherapy with or without total body irradiation for the treatment of malignancy. However, it has become clear that this mode of therapy does not eradicate the malignancy in many patients and its benefit is largely due to the immune mediated graft versus malignancy effect. This has led to development of alternative strategy to utilize a less intensive preparative regimen pre-transplantation that provides sufficient immunosuppression to achieve engraftment of an allogeneic stem cell graft, thus allowing the evolution of a graft versus malignancy effect post-transplantation. Since September 1999, we had carried out 10 cases of allogeneic peripheral blood stem cell transplantation: one case of aplastic anaemia, four cases of acute myeloid leukemia (AML) in first remission, and five cases of chronic myeloid leukemia (CML) in chronic phase. The preparative regimen was non-myeloablative comprising Fludarabine with Cyclophosphamide or Busulphan. Recovery from transplantation was rapid with no or brief period of neutropenia or thrombocytopenia. Engraftment was established by determining donor's short tandem repeats in the recipient's bone marrow at day 30, 60 and 100 post-transplantation. Seven cases (70%) show partial or complete donor's chimerism by day 30 indicating successful engraftment. No treatment mortality was noted at day 100. Graft versus host disease was generally limited. Up to the date of reporting, two patients with CML had graft failure, one was successfully re-transplanted later. Two patients with AML had since relapsed and passed away. The others remain alive and well. The cost of transplantation on average was estimated to be about a quarter of that using a myeloablative regimen. It appears that this treatment strategy is a promising approach for the management of blood disorders.
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PMID:Allogeneic haemopoietic stem cell transplantation using non-myeloablative conditioning--a local experience. 1456 43

Good prognosis after imatinib mesylate treatment has been reported if cytogenetic clonal evolution (CE) is the only criterion of accelerated phase (AP) chronic myelogenous leukemia (CML). To evaluate the impact of CE upon imatinib treatment in post-transplant settings, responses and toxicities in the relapsed AP-CE were analyzed in comparison with those in the relapsed chronic phase (CP). Both CP (n=7) and AP-CE patients (n=6) received imatinib mesylate in an oral dose of 400 mg/day. Complete cytogenetic responses were obtained in six patients of each group, CP (86%) and AC-CE (100%), while molecular remission was seen in 43 and 50%, respectively. Granulocytopenia or thrombocytopenia of grade III or more occurred in four (57%) and two (33%) patients with CP and AP-CE, respectively. Nonhematological adverse events were mild and tolerable in both groups and only one (7%) of the 13 patients experienced recurrent graft-versus-host disease after imatinib treatment. Although this is a relatively small group of patients, we suggest that imatinib mesylate should be considered as a front-line treatment for relapsed CML as it showed the high response rate and low toxicity. We also suggest that CE alone is not an important factor in the induction of cytogenetic and molecular remissions in post-transplant relapse.
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PMID:Cytogenetic clonal evolution alone in CML relapse post-transplantation does not adversely affect response to imatinib mesylate treatment. 1462 81

Patients who had suffered chronic GVHD after an allogeneic PBSCT were evaluated using a new chronic GVHD grading system. The study included 36 consecutive adult patients with hematological diseases, who survived at least until day 90 following allogeneic PBSCT and who could be evaluated for chronic GVHD. Extensive skin involvement was observed in five patients, thrombocytopenia in 14, and progressive-type onset in 10, while grade 1 chronic GVHD appeared in 21 patients, grade 2 in 10, and grade 3 in five. There was a significant difference in the probability of relapse between the groups with grade 1 and 2+3 chronic GVHD (55.3 vs 16.4%, P=0.0211). The difference was particularly marked in patients with high-risk hematological malignancies (grade 1 vs grade 2+3, 75 vs 0%, P=0.0115). With a median follow-up of 12 months (range, 4-52 months), 22 (66.1%) patients were still alive. The estimated 2-year survival rate for the whole population was 57.6%, while that for the group with chronic GVHD grade 1 and grade 2+3 was 53.5 and 56.3%, respectively (P=0.4387). Accordingly, there was a significant difference in the probability of relapse between the groups with grade 1 and grade 2+3 chronic GVHD.
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PMID:Transplantation outcome in allogeneic PBSCT patients according to a new chronic GVHD grading system, including extensive skin involvement, thrombocytopenia, and progressive-type onset. 1513 86

We describe a patient who had received reduced-intensity stem cell transplantation (RIST) for metastatic renal cell carcinoma (RCC). A 37-year-old man developed rapid progression of RCC during steroid therapy for immune-mediated thrombocytopenia and graft-versus-host disease (GVHD). After discontinuation of corticosteroid, RCC achieved long stable disease with the presence of chronic GVHD, despite low dose of prednisolone. This case suggests the impact of immunosuppression on progression of metastatic RCC after RIST.
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PMID:Balance between acute graft-versus-host disease and graft-versus-tumor effect after reduced-intensity transplantation for metastatic renal cell carcinoma. 1516 16

A 50-year-old man was admitted to our hospital because of thrombocytopenia during a follow up study of diffuse large B-cell lymphoma in second complete remission. He was diagnosed as having therapy-related acute myelgenous leukemia (t-AML) on the basis of the bone marrow findings and his chemotherapeutic agent history including alkylating agents. Complete remission was achieved by induction chemotherapy. Although allogeneic stem cell transplantation was thought to be needed, the patient was thought to be ineligible for any myeloablative conditioning regimen because of his age and the history of long term chemoradiotherapy. A non-myeloblative regimen was thus selected. After preconditioning with fludarabine, cyclophosphamide and cytarabine, the patient underwent peripheral blood stem cell transplantation from an HLA identical sibling donor. Complete donor chimeras were obtained on day 28 after transplantation. Regimen related toxicities over grade 2 were not observed. Although he suffered from mild chronic graft-versus-host disease(GVHD), he is in good condition without any signs of relapse during a follow-up period of 33 months. It is suggested that non-myeloablative transplantation is feasible and benefical for patients with t-AML who are often ineligible for myeloablative transplants because of their histories of long term chemoradiotherapies.
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PMID:[Non-myeloablative stem cell transplantation from an HLA identical sibling donor in a case of treatment-related acute myelogenous leukemia]. 1516 47

A 34-year-old woman was admitted for chronic graft-versus-host disease ten months after an unrelated bone marrow transplantation. Cytomegalovirus (CMV) antigenemia on day 5 of hospitalization was negative. Thrombocytopenia occurred on day 9. Laboratory findings revealed severe liver dysfunction on day 13. On day 14, the patient developed interstitial pneumonia and disseminated intravascular coagulation, and died from progressive respiratory failure. Multinucleated giant cells were found in the lung, liver, spleen, esophagus, pancreas and intestine obtained at autopsy. Varicella-zoster virus (VZV) was detected in the blood using the polymerase chain reaction (PCR) technique. CMV, herpes virus type 6 and Epstein-Barr virus were detected in the liver and lung with the PCR technique. We concluded visceral VZV infection was the main cause of her death because of her aggressive clinical course and the histology at autopsy. In this case, chronic GVHD and its immunosuppressive treatment resulted in her fatal VZV reactivation.
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PMID:[Fatal acute visceral disseminated varicella-zoster virus infection in a patient with chronic graft-versus-host disease]. 1551 Aug 35


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