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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)

Patients who received bone marrow transplantation (= BMT) for the treatment of severe combined immunodeficiency (= SCID), and who were reported in the medical literature from 1968 to 1977, were collected and analysed. Eighteen of these 80 children are still alive, 10 months to 9 years after transplantation. It is thus the first successful form of therapy for this otherwise invariably fatal disease. Fifteen of the 18 survivors received bone marrow cells from HLA and MLC compatible donors; the remaining 3 survivors received grafts from MLC-compatible but HLA-incompatible donors. Bone marrow transplantation is the treatment of choice for SCID when recipient and donor are HLA- and MLC-identical. All patients who received MLC-incompatible grafts died, and bone marrow transplantation for SCID from MLC-incompatible donors should be abandoned. Milt-to-severe graft-versus-host disease (= GVHD) occurred in spite of HLA- and/or MLC-compatibility, with some correlation to the number of cells transplanted. This should preferably be kept below 50 million cells per kilo body weight. Infection was the chief cause of death in all groups. Strict reverse isolation, bowel decontamination and routine pre- and post-transplant Pneumocystis carinii prophylactic treatment are recommended. The clinical picture and laboratory findings of these 80 children before BMT did not differ from non-transplanted SCID patients. Three of the 18 survivors are adenosinedeaminase deficient.
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PMID:Bone marrow transplantation for severe combined immunodeficiency disease. Reported from 1968 to 1977. 3 63

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

Infection and acute graft versus host disease (GVHD) are the most common complications of allogeneic bone marrow transplantation, which compromise this therapeutical method for hematologic diseases. Beside the appreciation of customary preventive measures and the treatment of infections, it is necessary for every bone marrow transplantation center to analyze the development of bacterial, fungal and viral infections in the patients and to generate the most efficient and most rational program for their prevention and treatment. At the Hematology Department in Novi Sad seven allogenic bone marrow transplantations were performed in patients with malignant hematologic diseases and severe form of aplastic anemia. Prevention of the infection by isolation of the patient in a sterile unit, selective decontamination of the digestive tract with sterile food, skin and mucus hygiene and prophylactic drug administration proved rather beneficial and adequate for patients with the graft accepted, hematopoiesis recovered and immunity reconstructed. Risks of infections were increased by permanent vein catheter, acute GVHD and rejection of the bone marrow graft. Prompt isolation and identification of bacteria and fungi, especially in blood, the establishment of a minimal suppressing and bactericide antibiotic concentration, along with the assessment of their synergism, as well as early diagnosis of cytomegalovirus and administration of specific drugs, can significantly contribute to the more successful treatment of infections in transplanted patients.
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PMID:[Prophylaxis and therapy of infections in allogenic bone marrow transplantation in patients with hematologic diseases]. 134 65

To determine the outcome and prognostic factors associated with bone marrow transplantation (BMT), we reviewed the clinical course of 35 adult recipients of such a transplant who were admitted to our intensive-care unit (ICU). This constituted 24% of patients who underwent BMT for treatment of hematologic disorders during the study period. The reasons for admission to the ICU were postsurgical care in 5, respiratory failure in 25, shock in 4, and renal failure in 1. The in-hospital mortality was 20% for the postsurgical patients and 87% for the others. None of the postsurgical patients required mechanical ventilation, whereas 90% of the others did, and the associated mortality was 93%. Infection was the cause of the respiratory failure in all but 3 of the 25 patients and was associated with 95% mortality. Complications that involved multiple organs increased the mortality to 100%. No significant differences were found in age, sex, type of BMT, serologic tests for cytomegalovirus, history of graft-versus-host disease, conditioning regimen for BMT, and duration of stay in the ICU and the hospital between survivors and nonsurvivors. The APACHE II (acute physiology and chronic health evaluation) prognostic scoring system underestimated mortality and had no correlation with the duration of stay in the ICU or the hospital. Vasopressors, total parenteral nutrition, and transfusion of blood components in the ICU had no influence on the outcome. Open-lung biopsy was helpful in making specific diagnoses, and pulmonary artery catheters were used in most patients to guide therapy but did not improve survival.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Outcome of recipients of bone marrow transplants who require intensive-care unit support. 154 82

The value of C-reactive protein (CRP) determinations in the analysis of fever after allogeneic bone marrow transplantation (BMT) was studied prospectively by serial measurements of serum CRP levels during 30 BMT episodes in 28 children and adolescents. The treatments and procedures accompanying BMT did not elicit a significant CRP response. Forty-three febrile episodes were registered and analyzed, without previous knowledge of the results of CRP determinations. The incidence of bacterial infection and acute graft-versus-host disease (GvHD) was low, 8/30 and 5/30, respectively. Raised CRP levels occurred only once in association with GvHD. A CRP level higher than 50 mg/l was not sensitive as an indicator of bacterial infection (4/8). A CRP level below 50 mg/l in the presence of fever, however, excluded bacterial infection with a specificity of 86% and a negative predictive value of 88%. When timed properly and interpreted together with clinical and microbiological findings, CRP measurements can be a valuable aid in the management of fever after BMT, especially as a negative predictor.
Infection
PMID:C-reactive protein in the management of children with fever after allogeneic bone marrow transplantation. 205 Apr 27

Thirty-four patients received bone marrow transplants from unrelated donors. Donors and recipients were phenotypically matched for 6 of 6 HLA-A, B, and DR antigens in 27 cases and at 5 of 6 antigens in 7 cases. Twenty-three patients had leukemia, six had myelodysplasia, and five had aplastic anemia. Twenty-four patients had durable engraftment. Five died of sepsis prior to engraftment. Five patients failed to engraft; 2 of these patients had autologous bone marrow recovery. Seventeen patients developed grade greater than or equal to II acute graft-versus-host disease for an actuarial probability of 67 +/- 20%. The severity of acute graft-versus-host disease and its mortality appeared increased for recipients matched for 5 of 6 HLA-A, B, and DR antigens. Of the 34 patients, 13 (38%) are alive; actuarial survival beyond 6 months is 44 +/- 17%. None of the 25 leukemia and myelodysplasia patients achieving engraftment have relapsed. For leukemia and myelodysplasia recipients of 6 of 6 HLA-matched grafts, actuarial survival at 6 months was 55 +/- 21% compared with 14 +/- 26% for recipients matched for 5 of 6 HLA loci (P = 0.19). Infection and acute graft-versus-host disease were the primary causes of death in the engrafted patients. Survival for aplastic anemia patients was 20%. Late deaths due to pneumonia and bronchiolitis obliterans occurred after one year in 2 patients. Closely matched unrelated donor bone marrow transplants are associated with a higher incidence of graft failure and graft-versus-host disease than typically reported for transplants from HLA-identical siblings, but these preliminary data suggest a lower rate of relapse.
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PMID:Bone marrow transplantation using unrelated donors for patients with advanced leukemia or bone marrow failure. 214 25

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

The infectious complications during different time intervals after allogeneic bone marrow transplantation (BMT) (day 0 to day 30, 31 to 100, 101 to 365, 366 to 730) were reviewed in 67 adult patients, 27 of whom received transplants without T-cell depletion (TCD) using methotrexate or cyclosporin A for prophylaxis of graft-versus-host disease (GvHD) and 40 of whom received donor marrow with TCD using the monoclonal anti-lymphocyte antibody campath-1 and human complement. The use of TCD reduced the incidence and severity of GvHD significantly (p less than 0.01), but was associated with an increased rate of graft rejections. During all time intervals patients with TCD had a similar, lower or statistically significantly lower number of bacterial, fungal or viral infections and a statistically significantly lower number of lethal infections (p = 0.05) as compared with patients without TCD. This finding might be explained by the fact that with TCD immunological reconstitution can take place unimpaired by GvHD or its prophylaxis or treatment, resulting in a decreased incidence of infections.
Infection
PMID:Infectious complications after allogeneic bone marrow transplantation with and without T-cell depletion of donor marrow. 266 37

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

Acute murine cytomegalovirus (MCMV) infection enhances the ability of parental spleen cells to induce graft-vs.-host immunodeficiency (GVHID) in F1 hybrid mice when the two processes occur simultaneously in the recipient. The present study assessed GVHID as the ability of spleen cells to generate in vitro cytotoxic T lymphocyte responses to trinitrophenyl-modified syngeneic cells. The results indicate that MCMV infection not only reduces the number of parental spleen cells required to induce GVHID, but accelerates the onset of GVHID, which occurs as early as 3 days after cell and virus challenge. To determine whether MCMV infection exerts this synergistic effect primarily through the donor or the host component, we examined the effect of MCMV infection of either donor mice or recipient mice at 3, 10, and 17 days prior to spleen cell transfer. Two weeks after cell transfer, splenocytes were tested for their ability to generate CTL. When donor mice were infected with MCMV three days prior to cell transfer, the ability of donor cells to induce GVHID was reduced. In contrast, MCMV infection of the recipients three days prior to cell transfer increased their susceptibility to GVHID induction. Infection of either donor or host mice 10 days or 17 days prior to parental spleen cell transfer had little effect on the ability to induce or resist GVHID when compared with sham-infected mice. Thus, acute MCMV infection can modulate the severity of GVHID depending on whether it is the donor or the host that is infected. The ability of acute MCMV to alter the course and severity of GVHID may be relevant for human bone marrow transplants in which preceding CMV infection has been associated with chronic GVH. In this setting, CMV may lower the threshold necessary to induce a GVH reaction.
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PMID:Altered threshold for the induction of graft-versus-host immunodeficiency following murine cytomegalovirus infection. Host and donor contributions. 284 80


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