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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)

Infections are an almost inevitable complication of human bone marrow transplantation and account for the majority of deaths in transplant recipients. Even prior to the initiation of the transplantation procedure, patients may present with infections complicating previously unsuccessful chemotherapy for hematological malignancy or aplastic anemia. Nevertheless, these pre-transplantation infections should not exclude the possibility of bone marrow transplantation if they can be successfully controlled with specific antimicrobial therapy and necessary adjunctive measures. The immediate post-transplantation period prior to engraftment is characterized by severe marrow aplasia that results from high-dose chemotherapy and total-body irradiation. Infections are primarily septicemias and localized processes caused by bacteria and fungi and their incidence increases as the intensity of immunosuppression is escalated. The high mortality associated with bacterial septicemia makes early, empirical antibacterial therapy mandatory. However, the reduction in mortality from bacterial infection resulting from such an aggressive approach may be offset by a higher mortality from invasive fungal infection, especially in patients with prior fungal colonization and undergoing prolonged conditioning therapy. Thus, until more specific and sensitive tests for the diagnosis of invasive fungal infection become available, empirical intravenous amphotericin should be considered in patients who are persistently febrile and deteriorate clinically in the face of appropriate antibacterial therapy. Interstitial pneumonia associated with severe GVHD is the major infectious complication after successful marrow engraftment and is the most significant barrier to long-term survival. Trimethoprim-sulfamethoxazole is effective prophylaxis against interstitial pneumonia due to Pneumocystis carinii, but one half of the patients still develop a pneumonitis either associated with CMV or of unknown etiology. Mortality from interstitial pneumonia is related to prior radiation therapy while survival is associated with a four-fold rise in CMV CF antibody titer. The latter observation supports the need to investigate passive immunization with CMV antibody as a means of preventing some interstitial pneumonias. Despite the progress made in many areas of human bone marrow transplantation, the majority of graft recipients still die of infectious complications. Thus, new approaches to the management of infections in transplant recipients are urgently needed. Better-tolerated oral nonabsorbable antibiotics, laminar-air-flow rooms, granulocyte transfusions, and chemotherapy and immunotherapy for CMV are among the prophylactic and therapeutic measures that must be critically evaluated in well-controlled, prospective studies. Continued assessment of the infectious complications of bone marrow transplantation is a critical aspect of any ongoing transplant program, not just a research goal...
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PMID:Infectious complications of human bone marrow transplantation. 36 7

Gastrointestinal tract disease (GIT) is relatively common following bone marrow transplantation (BMT). Infections, particularly with viral agents, are similar to those affecting any immunosuppressed transplant recipient. However, two unique aspects of BMT are (a) cytotoxic damage caused by the chemotherapy and irradiation used to eradicate the patient's native marrow and (b) gastrointestinal involvement with graft-versus-host disease (GVHD). GVHD may affect any portion of the GIT; therefore, both upper and lower GIT biopsies may provide diagnostic information not evident in biopsy from a single site. The upper GI tract has a higher yield of positive biopsy specimens, but it is more difficult to biopsy. The basic histopathological feature of acute GIT GVHD, which occurs in the first 100 days posttransplant, is necrosis of individual cells in the regenerating compartment of the mucosa. Severe disease may lead to loss of crypts and eventual sloughing of the mucosa. The histology of acute GVHD may be simulated by cytoreductive agents and viral infections, particularly with cytomegalovirus (CMV). Therefore, an absolute biopsy diagnosis of acute GVHD cannot be made in the first 21 days posttransplant or in any mucosa containing CMV inclusions. The GIT is less often involved in chronic than in acute GVHD. The basic pathology of chronic GIT GVHD is fibrosis of the submucosa and subserosa. Therefore, mucosal biopsy is of limited usefulness in the diagnosis of chronic GVHD.
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PMID:Graft-versus-host disease of the gastrointestinal tract. 218 40

Infections continue to be common complications of bone marrow transplantation, but recent advances have improved their outcome. Oral chemoprophylaxis with the fluoroquinolones has reduced gram-negative infections during periods of granulocytopenia, while new triazole drugs show promise for improving antifungal prophylaxis. Similarly, recombinant hematopoietic growth factors may reduce infections by shortening the period of post-transplant granulocytopenia. The efficacy of double beta-lactam antibiotic therapy or monotherapy with imipenem has obviated the need to use aminoglycosides in the empiric treatment of febrile patients receiving cyclosporine or other nephrotoxic agents. Treatment of post-transplant interstitial pneumonia associated with cytomegalovirus (CMV) remains problematic, but recent results using the combination of ganciclovir plus intravenous immune globulin have been favorable. In CMV-seronegative patients, CMV infections and pneumonia can be prevented or modified by using CMV-seronegative blood products and intravenous immune globulin. Intravenous immune globulin also has the additional benefits of modifying graft versus host disease and preventing late bacterial infections after marrow engraftment. In CMV-seropositive patients, prophylactic ganciclovir may prevent CMV reactivation and pneumonia and is the subject of an ongoing controlled clinical trial.
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PMID:Current approaches to management of infections in bone marrow transplants. 269 7

The effects of ex-vivo depletion of T lymphocytes from donor bone marrow using a monoclonal anti-T-cell antibody (CT-2) and complement on the outcome of allogeneic bone marrow transplantation was evaluated in a prospective, randomized, double-blind study of 40 patients with leukemia. Patients receiving T-cell-depleted bone marrow had a lower incidence of acute graft-versus-host disease than control patients (3 of 20 compared with 13 of 20; p = 0.004), and mortality due to acute graft-versus-host disease was reduced. Five patients in the T-cell-depletion group developed graft failure; all control patients had sustained engraftment (p less than 0.05). Clinically apparent relapse of leukemia occurred in 7 patients from the T-cell-depletion group and in 2 controls (p, not significant). Cytogenetic evidence of residual leukemia was also detected in the 5 patients with graft failure without overt relapse. Infections and overall survival were similar in the two groups. The effects of T-cell depletion on engraftment and recurrence of leukemia require further evaluation.
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PMID:Treatment of donor bone marrow with monoclonal anti-T-cell antibody and complement for the prevention of graft-versus-host disease. A prospective, randomized, double-blind trial. 352 27

Infections occurring 6 mo or later after bone marrow transplantation for severe aplastic anemia or hematologic malignancy were analyzed in 98 long-term survivors. Varicella-zoster (VZ) infections were analyzed separately from all other infections. The factor predisposing most strongly to late VZ infection was genotypic nonidentity for HLA between marrow donor and recipient. There was a suggestion that chronic graft-versus-host disease (GVHD) associated with the presence of nonspecific suppressor cells also predisposed to late VZ infection, while age less than 10 yr was protective against such infections. Chronic GVHD predisposed to late non-VZ infections, but this was not increased by the presence of nonspecific suppressor cells. HLA nonidentify between patient and marrow donor further increased the risk of late non-VZ infections over and above that due to the presence of chronic GVHD. Receipt of a syngeneic transplant appeared protective for late non-VZ infections. These findings suggest that full genotypic identity for HLA between donor and recipient may be required for optimal immune reconstitution after marrow transplantation and may denote a possible biologic role for nonspecific suppressor T cells in humans.
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PMID:Analysis of late infections after human bone marrow transplantation: role of genotypic nonidentity between marrow donor and recipient and of nonspecific suppressor cells in patients with chronic graft-versus-host disease. 621 76

Twenty-eight consecutive recipients of HLA-identical sibling marrow grafts received prophylaxis for GVHD with high-dose cyclosporine (CsA) and corticosteroids. CsA 5 mg/kg/day (2.5 mg/kg infused over 4 h twice daily) was started on day -1 and continued until patients could take oral CsA (15 mg/kg/day). CsA doses were adjusted to maintain concentrations between 200-800 ng/ml (whole-blood HPLC) until the tapering period (days 268-361). Methylprednisolone 0.5 mg/kg/day was started on day 7, increased to 1 mg/kg/day during days 15-28, and tapered thereafter until discontinuance on day 194. Low CsA trough levels occurred in 15 patients (54%) during the i.v. administration period. Ten patients (36%) developed grade I and 3 patients (11%) developed grade II acute GVHD; there were no cases of grade III or IV disease. The actuarial incidence of chronic GVHD was 29% at 1 year but 57% at 2 years due to development of chronic GVHD after discontinuation of immunosuppressive agents. High blood CsA concentrations in stable outpatients led to dose-limiting nephrotoxicity. Infections occurred throughout the period of extended immunosuppression (from 6 to 12 months) but were not life-threatening. The actuarial incidence of leukemic relapse was 18% at 1 year and 25% at 2 years. Actuarial survival at 1 and 2 years was 68 and 51%, respectively. Despite the frequent occurrence of low CsA trough levels, this regimen appeared to be effective in preventing acute GVHD. Immunosuppressive prophylaxis beyond 1 year may be required to reduce late-onset chronic GVHD.
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PMID:High-dose cyclosporine and corticosteroids for prophylaxis of acute and chronic graft-versus-host disease. 758 Nov 15

Infections and graft-versus-host disease are the major causes of morbidity and mortality in bone marrow transplantation (BMT). Bacterial infections can nowadays be treated effectively in most instances. The prophylactic and therapeutic armamentarium for viral infections is improving. Fungal infections on the contrary remain a major obstacle for successful outcome in the transplant situation. Invasive fungal infections are mainly caused by Candida and Aspergillus spp. and more seldom by Mucor, Trichosporon and Fusarium. Invasive fungal infections are notoriously difficult to diagnose early and effective non-toxic treatments are still out of reach. Prophylaxis for Candida albicans has become more effective with new triazoles but for species other than albicans and for Aspergillus spp. prophylaxis still remains a major problem. Better treatment modalities, more effective prophylaxis and better knowledge of risk factors are urgently needed. The recently created Invasive Fungal Infections Cooperative Group of the EORTC chaired by Professor F. Meunier runs different surveys to investigate the incidence and nature of invasive fungal infections in cancer patients and in BMT. The group runs different clinical trials on the prophylaxis and treatment of invasive fungal infections.
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PMID:Epidemiology of invasive fungal infections in bone marrow transplantation. EORTC Invasive Fungal Infections Cooperative Group. 770 24

We have reviewed the causes and risk factors for early death in a group of 295 children who underwent any form of first bone marrow transplantation (BMT) between 1978 and 1992. The commonest indications for transplantation were acute lymphoblastic leukaemia 80 (27.1%), neuroblastoma 69 (23.3%), immune deficiency 57 (19.3%) and myeloid leukaemias/myelodysplasia 50 (16.9%). There were 120 (40.6%) allogeneic BMTs, 118 (40%) autologous BMTs, while 51 (17.2%) children usually with severe combine immune deficiency received BMT from a non-HLA-identical parent, sibling or other relative (FBMT). Two were from identical twins and four from matched unrelated donors (MUD). Thirty-three children (11.2%) died in the first 100 days; the main causes of death being infection (n = 5), relapse (n = 7), graft failure (n = 4), GVHD (n = 7) and organ failure with or without infection (n = 6). There was no significant change in the incidence of early deaths in the three successive 5 year periods (1978-82, 1983-87, 1988-92) although there was some shift in the causes. Infections were the commonest cause during the first 5 year period, relapses followed by GVHD in the second period and single organ failure followed by GVHD and infections in the third period. The main causes of early death were relapse after high-dose chemo/radiotherapy and autologous BMT (7 of 9 deaths) and GVHD and infection after allogeneic BMT (9 of 13 deaths). In the group of 51 children undergoing FBMT there were five deaths from infection, three from graft failure, one from organ failure and one from GVHD.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Early deaths in children undergoing marrow ablative therapy and bone marrow transplantation. 771 76

One hundred forty-seven patients with hematologic diseases and treated by allogeneic marrow transplants received graft-versus-host disease (GVHD) prevention with methotrexate and cyclosporine. In addition, 73 of the 147 patients were randomized to receive methylprednisolone during the first 35 days after transplant to improve GVHD prevention, whereas 74 patients were randomized not to receive methylprednisolone. The randomized trial enabled us to examine whether methylprednisolone increased the risk of infection after marrow grafting. Charts of study patients were analyzed retrospectively for infection events including bacteremia, septicemia, and fungemia. The randomization was stratified by diagnosis, patient age, genotypic HLA identity, and assignment to laminar airflow room isolation. All patients were given a short course of methotrexate (no longer than 11 days) and cyclosporine for no longer than 180 days after marrow transplantation. Methylprednisolone was begun on the day of marrow grafting at a dose of 1 mg/kg body weight intravenously in divided AM and PM doses through day 22. Methylprednisolone was administered at a dose of 0.5 mg/kg in divided doses from days 22 through 35, and then discontinued. Infections were analyzed for the time interval ending on day 65 after transplantation, which included the period of methylprednisolone administration and 1 month thereafter. Seventy-one episodes of first infection events were observed in patients receiving methylprednisolone compared with 47 episodes in patients not receiving the drug. Predominant infections were bacteremias, followed in descending order by fungemias and septicemias. The most prevalent organisms cultured were gram-positive bacteria, especially coagulase-negative Staphylococcus and Streptococcus species. Pseudomonas species were the most common gram negative bacteria, and the most prevalent fungus was Candida albicans. Multivariable Cox regression analysis showed that patients receiving methylprednisolone had a 1.5 times higher risk of infection (P = .03), with acute GVHD being another independent risk factor for infections (P = .005). Methylprednisolone, when added to GVHD prevention by methotrexate and cyclosporine, increases the risk of infection during the early posttransplantation period.
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PMID:Increased risk of infection in marrow transplant patients receiving methylprednisolone for graft-versus-host disease prevention. 804 48

The pathological complications of bone marrow transplantation are complex and may affect any organ in the body. The causes are often multifactorial and include the effects of chemotherapy, the conditioning regimen, drugs used in the post-transplant period such as immunosuppressants and antibiotics, graft-versus-host disease (GvHD) and the effects of the primary disease itself. Infections are common and result from the immunosuppressive effects of cytotoxic drugs and irradiation, GvHD and marrow failure. Haemorrhage is not infrequent. Graft-versus-host disease remains a significant problem and can be difficult to diagnose. Some of its histological features simulate the effects of chemoradiation and the diagnostic lesions may not be present early in the disease, when treatment is most effective. Evidence has accumulated that inflammatory cytokines have a key role in the pathogenesis of GvHD. It can be prevented by eliminating T-cells from the donor marrow but this procedure adversely affects marrow engraftment, increases the changes of rejection and results in a higher incidence of leukaemic relapse. Immunohistochemical staining for various cytokine-inducible molecules has led to some improvement in early diagnosis.
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PMID:The pathology of bone marrow transplantation. 849 53


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