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)

BMT has become an important therapy for many hematologic disorders. Following BMT, the recipient may develop GVHD when it appears that immunocompetent donor lymphocytes react to host antigens. Acute and chronic GVHD represent two distinct syndromes. Acute GVHD has not been associated with primary neurologic involvement. Polymyositis has been reported in 12 patients with chronic GVHD, with the most common underlying illness being aplastic anemia. The clinical, serologic, and muscle biopsy features of the myositis in GVHD have been similar to those observed in idiopathic polymyositis. Weakness was moderate to severe and responded to prednisone, sometimes with the addition of azathioprine. Prognosis depended upon the underlying disease and not on the severity of the myositis. MG occurs rarely in chronic GVHD. Most patients with MG and GVHD have had aplastic anemia; those with aplastic anemia are more likely to have anti-AchR prior to BMT. The clinical manifestations of GVHD MG have not differed from classic autoimmune MG; each patient had elevated antiacetylcholine receptor antibodies titers. All patients have responded well to cholinesterase inhibitors but have received other immunosuppressants. These observations suggest that aplastic anemia is an important host factor in the development of the autoimmune disorders seen with chronic GVHD, certainly of myositis and MG. Herpes zoster peripheral nerve infections have occurred in patients with chronic GVHD. One patient had mononeuritis multiplex. In both acute and chronic GVHD, CNS impairment is usually caused by metabolic encephalopathy or infection. Primary CNS involvement has not been recognized.
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PMID:Neurologic complications of graft-versus-host disease. 304 48

BMT is a well-established treatment for children with ALL in second remission, ANLL in first and second remission and children with JCML and CML. Improvements in transplantation technology and supportive care have resulted in significant increases in the percentage of long-term survivors of allogeneic marrow transplantation. Newer strategies, such as partially matched donor, unrelated matched donor, and autologous transplants, are bineg pursued to overcome the histocompatability barrier. The development of more effective antileukemic cytoreductive chemotherapy and radiation therapy regimens and better methods of preventing GVHD are areas in which further improvements are necessary. Newer methods of marrow purging, such as the use of monoclonal antibodies linked to immunotoxins, already are being tested. In addition, the recent development of molecularly cloned hematopoietic growth factors, such as CSFGM, may make it possible to improve marrow recovery and hasten return of normal immunologic function, thereby increasing the overall safety of the transplant procedure. It is hoped that these innovations eventually will increase the overall applicability of BMT and its role in the treatment of leukemia.
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PMID:Bone marrow transplantation for treatment of leukemia in children. 304 59

This article has outlined the special problems associated with evaluation of bone marrow before and after BMT. Marrow grafting has become a major form of therapy in oncology and hematology whose potential is only beginning to be fully realized. The transplantation of healthy hematopoietic and lymphoid cells has made possible the use of otherwise superlethal doses of radiation and chemotherapy in preparing the patient for engraftment. In the case of tumors, this allows massive doses of tumorocidal therapy prior to rescue with a BMT. In the case of aplastic anemia, it allows massive immunosuppression and ablation of the residual host marrow in preparation for replacement by the healthy donor marrow. The complications of this procedure include the toxicity of chemotherapy and irradiation upon the liver, lung, and gut as well as less serious toxicity to skin and other organs. The double barrier associated with marrow transplantation consists of rejection and GVHD. Marrow graft failure occurs by two distinct mechanisms, graft resistance and graft rejection. The former is marked by a total failure of any evidence of engraftment and the latter by engraftment followed by disappearance of the graft. GVHD is the immunologic attack upon host tissues by donor lymphoid cells (predominantly mature T cells). In the acute phase, it attacks liver, skin, and gut, with the latter producing the most life-threatening syndrome. Chronic GVHD resembles scleroderma. Treatment of GVHD includes the use of prednisone, cyclosporin A, ATG, and monoclonal antilymphoid antibodies. Prevention includes the attempt to remove T cells from the donor marrow with monoclonal antibodies using complement-mediated cytolysis and other approaches such as conjugation of antibodies to ricin and other toxins. GVHD also produces severe immunosuppression in and of itself added to that produced by chemoirradiation therapy. As a result, the marrow transplant recipient is extremely susceptible to infections. During the early period, the patient is granulocytopenic and susceptible to bacterial and fungal infections, which are dealt with by antibiotics and isolation procedures. Later, viral infections become very important, particularly CMV and other herpes viruses. The relative success in dealing with bacterial and, to some extent, viral infections has brought fungal infections to the fore as major causes of death, especially in higher risk categories of patients. Hemorrhage is a frequent complication owing to delayed megakaryocyte engraftment and thrombocytopenia during the early period and is a serious problem in patients with GVHD of the gut.
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PMID:Pathology of bone marrow in transplant recipients. 306 26

Complete microbial decontamination (laminar air flow room, sterile nursing and oral administration of cefamandole, gentamicin and nystatin) was carried out in 65 consecutive patients prior to allogeneic BMT for leukaemia (n = 58) or aplastic anaemia (n = 7). Very few microorganisms persisted during the post-transplant treatment period, and the gut became sterile in all except for Candida in 11 patients. Six uncomplicated septicaemias, all with persistent organisms simultaneously present in the mouth (Pseudomonas 3, Serratia 1, Candida 2) occurred during a total of 1,360 days with granulocyte counts less than 0.5 X 10(9)/l. Post-transplant fever occurred in 52 patients, exceeding 40 degrees C in 25. Guided by the surveillance cultures only 46% of 43 unexplained febrile reactions were treated with systemic antimicrobials. Significant acute graft versus host disease (AGVHD) occurred in 14 (27%) of 52 patients receiving standard prophylaxis and HLA-matched grafts; immunosuppressive treatment was needed in 8 cases (16%). Thus, the additional costs of total microbial decontamination appear partially regained by a decreased morbidity and a reduced need for antimicrobial and immunosuppressive treatment, although neither fever nor AGVHD could be prevented.
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PMID:Strict protective isolation in allogenic bone marrow transplantation: effect on infectious complications, fever and graft versus host disease. 310 49

Using T-depleted BM from HLA-identical sibling donors we have performed 36 BMTs since 5/83 in first remission (CR1) of acute leukaemia (AL). Standard conditioning for BMT consisted of Cy 60 mg/kg X 2 and 7.5 Gy single fraction TBI (n = 27). Six patients received Ara-C 3 g/m2 X 6, Cy 45 mg/kg X 2 and 7.5 Gy, while 3 received Cy 60 mg/kg X 2 and 8 Gy radiation. T lymphocytes were depleted in vitro with 2 murine McAbs (MBG6 + RFT8, n = 17; or RFT8 + RFT12, n = 13; or RFT2, RFT8 + RFT12, n = 6) plus rabbit C'-mediated lysis. No immunosuppressive therapy was given in the absence of graft-versus-host disease (GvHD). Of 34 patients evaluable for a GvHD, 4 had grade I, 2 grade II and 1 grade III. Chronic GvHD occurred in 3 of 22 evaluable patients (greater than 150 days). There have been 13 deaths but only 1 from leukaemic relapse (CNS). The mean KS of surviving patients is 86% and actuarial disease-free survival is 53% at 40 months or 65% in those having 'standard conditioning'. The previous major problems of GvHD and leukaemic relapse appear to have been largely overcome. The major risk factor now is infection, particularly pneumonitis, and this problem is surmountable.
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PMID:Bone marrow transplantation in acute or chronic leukaemia. 312 47

100 Ph+ CML patients submitted to BMT were studied cytogenetically before grafting and serially after transplantation. The 12 European institutions participating in the study, including transplant units and laboratories of cytogenetics, collected a total of 520 studies. The Ph chromosome was observed after BMT in 22 patients who did not enter relapse during the observation time (10-1400 days--median 420 d) following initial detection of the chromosome. This abnormality was observed in 1 to 30% of the cells analyzed. In 10 patients, abnormal cells were detected only within the first 90 d after BMT, in 5 patients both before and after 90 d and in 7 patients only after 90 d. 44% of these 22 patients had a moderate-to-severe cGVHD. Future studies are needed in order to better evaluate the real incidence of persistent disease and the correlations with the GVHD.
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PMID:Cytogenetic follow-up of 100 patients submitted to bone marrow transplantation for Philadelphia chromosome-positive chronic myeloid leukemia. Cooperative Study Group on Chromosomes in Transplanted Patients. 327 55

In February 1986 we transplanted a 10-year-old girl with AML in second remission with the bone marrow of an unrelated donor. HLA-types were different for one A- and one B-antigen between patient and donor. Conditioning regimen consisted of 14 Gy total body irradiation with lung shielding, 8 X 3 g/m2 cytosin arabinoside and 90 mg/kg cyclophosphamide. GVHD-prophylaxis was performed with cyclosporin A, methotrexate and prednisolone. Only mild GVHD I of the skin could be observed after rapid engraftment. 100 days after transplantation the patient was in good clinical condition and GVHD-prophylaxis was discontinued without any reactivation of acute or chronic GVHD. Engraftment was documented by sex chromosome and blood group typing. 120 days after transplantation leukemic blasts were detected in the peripheral blood and the child died 130 days after BMT from relapse of the leukemia. Despite the negative outcome, this was the first successful bone marrow transplantation from a unrelated donor in Germany.
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PMID:Successful bone marrow transplantation from an unrelated donor in a child with AML in second remission. 331 Dec 27

Fever after bone marrow transplantation may indicate the onset of bacterial or opportunistic infection, or acute graft-versus-host disease (GVHD). In an attempt to differentiate between infection and GVHD, we prospectively studied 41 bone marrow transplants in 38 patients (24 allogeneic, 17 autologous). Elevation of C-reactive protein (CRP) proved to be a good indicator of disseminated infections. In 40 episodes of documented (11) or presumed (29) sepsis, CRP rose above 5 mg/dl in 38 episodes (95%), and above 10 mg/dl in 32 episodes (80%). The CRP concentration paralleled the clinical course of the infectious episodes. Elevated CRP values were not observed in the 15 episodes of acute GVHD without concurrent infection. High peak values of serum total IgE, ranging from 4-fold to over 4000-fold baseline, were observed posttransplant in 18/22 allogeneic BMT recipients, temporally associated with activation of acute GVHD. IgE was elevated neither in episodes of sepsis without concurrent GVHD, nor in viral or focal bacterial infections. In general, septic infections were characterized by high CRP but low IgE levels. Acute GVHD without concurrent infection was characterized by high IgE but low CRP. We conclude that CRP and serum total IgE utilized together in serial fashion are helpful in distinguishing sepsis from acute GVHD.
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PMID:Differentiation of presumed sepsis from acute graft-versus-host disease by C-reactive protein and serum total IgE in bone marrow transplant recipients. 331 43

Current results show that 50% of young patients with ANLL who undergo allogeneic BMT experience prolonged DFS and may be cured. Encouraging results with high-dose chemo/radiotherapy and autologous BMT are likewise being reported. In addition, some studies using intensive postremission treatment without BMT have shown results comparable to many transplant series. As better ways of preventing GVHD are found, the morbidity and mortality of allogeneic BMT should be reduced and the benefits of transplantation for curing patients with ANLL should be increased. However, the applicability of allogeneic BMT will remain limited due to the availability of compatible donors whether related or unrelated. Further studies are needed in the use of postremission intensive therapy with and without autologous bone marrow support. However, results to date should engender the same degree of enthusiastic optimism that followed the early reports of improved outcome with allogeneic BMT when applied to first remission patients.
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PMID:Allogeneic and autologous bone marrow transplantation for acute nonlymphocytic leukemia. 332 45

After conventional bone marrow transplantation serum IgG, IgM and IgA levels fall from pre-transplant levels and may not return to normal for 3-12 months. In contrast IgE may rise to supranormal levels, an event that may be associated with graft-versus-host disease. We have investigated the recovery of immunoglobulin isotypes in the recipients of allogeneic marrows depleted of T-cells to prevent graft-versus-host disease. We find that pre-transplant IgG, IgM and IgA levels are maintained throughout the post-transplant period but that there is a short-lived rise in IgE about 3 weeks after transplantation: this rise occurs in the absence of clinically detectable graft-versus-host disease. We conclude that specific T-cell depletion does not impair and may actually enhance the functional recovery of B cells after allogeneic BMT.
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PMID:Recovery of immunoglobulin isotypes following T-cell depleted allogeneic bone marrow transplantation. 353 Mar 13


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