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)

Twenty-one patients (median age = 34, range = 10-49; F:M = 7:14) received a preparative regimen consisting of busulfan 4 mg/kg/day x 4, cytosine arabinoside 2 g/m2/12 h x 4 and cyclophosphamide 60 mg/kg/day x 2 ('BAC' regimen) for allogeneic bone marrow transplantation. Out of 12 patients with acute myeloid leukemia (AML), two were in first remission, six were in second remission and four had resistant, relapsed disease or prolonged marrow aplasia after induction chemotherapy. Five of the 12 patients with AML had secondary AML. Four patients had transfusion-dependent myelodysplastic syndrome. Three patients with chronic myeloid leukemia were in the accelerated phase and two were in the blastic phase. Organ toxicities related to the preparative regimen were graded. Liver toxicity occurred in 11 patients, two of these were fatal veno-occlusive disease (VOD) (10%). Nineteen of the 21 patients had grade 2 or less diarrhea, and 13 also had mucositis. One patient developed grade 3 cardiac toxicity, and one other patient had grade 1 skin toxicity. Four patients had gross hematuria related to treatment (19%). No renal, pulmonary or CNS toxicities were encountered. Ten patients have died, two from regimen-related hepatic VOD. Of the remaining eight deaths, four were from respiratory failure in four patients (one case each of Pneumocystis pneumonia, CMV pneumonia, bronchiolitis obliterans associated with chronic graft-versus-host disease, and interstitial pneumonitis complicated pulmonary emboli), and one patient each from GI bleeding, cardiac arrhythmia, sepsis and CNS bleeding. Thus far, only one patient transplanted for secondary AML in second remission relapsed at day 230.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Allogeneic bone marrow transplantation in high-risk myeloid disorders using busulfan, cytosine arabinoside and cyclophosphamide (BAC). 154 49

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

Since 1973, over 3,000 newborns have been treated worldwide for respiratory failure with extracorporeal membrane oxygenation (ECMO). ECMO requires transfusion of numerous blood products including platelets and packed red blood cells. Transfusion-associated graft-versus-host disease (GVHD) developed in one of the authors' patients following treatment with ECMO. ECMO exposes newborn infants to a large number of blood components. Although a rare complication, GVHD can be prevented by irradiating blood products prior to transfusion. We now irradiate all blood products prior to use during ECMO and recommend that other institutions do the same.
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PMID:Graft-versus-host disease following ECMO. 203 Apr 78

We prospectively followed a well characterized cohort of patients post-bone marrow transplantation for changes in pulmonary function. Thirty-four recipients without respiratory symptoms were available for follow up with a mean of two years. Spirometry and other measures of lung volume were well preserved following bone marrow transplantation. A progressive 11.9 percent decline in percent predicted diffusing capacity per year occurred. Age, cigarette smoking, type of cytoreductive therapy, type of GVHD prophylaxis, and the occurrence of AGVHD did not affect longitudinal changes in pulmonary function. Patients receiving transplants for CML developed a highly significant fall in diffusing capacity. Asymptomatic patients with CGVHD developed evidence of progressive obstructive ventilatory impairment. This suggests a subclinical spectrum of patients who may progress to the development of bronchiolitis obliterans and respiratory failure post-bone marrow transplantation.
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PMID:Longitudinal changes in pulmonary function following bone marrow transplantation. 266 44

Patients with bone marrow transplant may present with acute, life-threatening complications which frequently (40% of our cases) require intensive care unit treatment and result in an increased mortality (76% in this series). In an attempt to reach a more objective prognostic assessment, we have analyzed those factors related to the worst outcome in the 25 patients with bone marrow transplant admitted into our intensive care unit. Respiratory failure was the most frequent complication (72%), with an 83% mortality. Graft-versus-host disease and neutropenia led to a greater number of infectious complications with a poor outcome. Failure of more than three organ systems, septic shock and mechanical ventilation were statistically associated with mortality (p less than 0.05), and all patients who required mechanical ventilation for more than seven days or needed intensive therapy for more than 10 days died. The presence of septic shock, multisystem failure and severe neutropenia on admission should be considered as initial indicators of a poor prognosis. More than 7 days of mechanical ventilation and an intensive care unit stay of more than 10 days could be critical points in the reassessment of the intensity and prolongation of treatment.
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PMID:Prognostic assessment of the acute complications of bone marrow transplantation requiring intensive therapy. 304 27

We report the cases of 3 patients with marked dyspnea and an obstructive ventilation disorder associated with chronic graft-versus-host disease after allogeneic bone marrow transplantation. This disorder was characterized by recurrent pulmonary infections and colonization of the lower respiratory tract by Pseudomonas aeruginosa. Two patients have shown rapidly progressive deterioration with death following due to respiratory failure. Intensive therapy with antibiotics, bronchodilators, high-dose steroids, and azathioprine was not effective in arresting the malignant course of this disorder.
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PMID:Obstructive lung disease after allogeneic bone marrow transplantation. 636 98

Cryptogenic organizing pneumonia (COP), also known as bronchiolitis obliterans organizing pneumonia (BOOP), is an uncommon lung disease characterized by the presence of granulation tissue within the alveolar ducts and alveoli. Because of the limited published literature on this topic and limited information on outcome we reviewed our own experience over an 8-year period and also critically evaluated the literature. We reviewed all cases of COP diagnosed from 1985 through 1992 at Vancouver General Hospital: 25 patients (14 male, 11 female) aged 20-77 years (mean, 49 yr, SD +/- 17 yr). Nine patients had myeloproliferative disorder, including 6 who had allogenic bone marrow transplants; 2 patients had connective tissue disease; and 14 patients had no underlying disease (idiopathic). Data retrieved retrospectively from clinical records included demographics, risk factors, symptoms, chest radiographs, computerized tomograms, lung function tests, therapy prescribed, and response to therapy. Symptoms included dyspnea and cough (n = 15) (60%), cough only (n = 10) (40%), and fever (n = 15) (60%). Twenty-two patients were diagnosed by open lung biopsy and 3 by transbronchial biopsy. Lung imaging showed bilateral patchy airspace consolidation or nodular opacities as the main finding in 22 patients. Pulmonary function tests showed a combined restrictive and obstructive pattern. All patients received prednisone therapy except 1 patient whose idiopathic findings resolved completely with minimal treatment. Eight patients died, including 4 of the 9 patients with myeloproliferative disorder--2 from a combination of respiratory failure due to COP and graft-versus-host disease. One of 2 patients with connective tissue disease died, and 3 of 14 patients with idiopathic COP died. COP is an uncommon condition but should be considered in patients with bilateral airspace disease, especially those who fail to respond to antibiotics for presumed pneumonia. Although pulmonary function tests and CT scan findings in conjunction with the clinical features usually suggest the diagnosis, definite confirmation usually requires either open lung biopsy or transbronchial biopsy. Histologic confirmation of the diagnosis is particularly warranted as therapy with corticosteroids is usually needed for a number of months. The prognosis is excellent with idiopathic cases but more guarded especially when COP is associated with lymphoproliferative or connective tissue disease.
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PMID:Cryptogenic organizing pneumonia. A report of 25 cases and a review of the literature. 762 55

Infusions of large numbers (> 10(8)/kg) of donor leukocytes can induce remissions in patients with chronic myeloid leukemia (CML) who relapse after marrow transplantation. We wanted to determine if substantially lower numbers of donor leukocytes could induce remissions and, if so, whether this would reduce the 90% incidence of graft-versus-host disease (GVHD) associated with this therapy. Twenty-two patients with relapsed CML were studied: 2 in molecular relapse, 6 in cytogenetic relapse, 10 in chronic phase, and 4 in accelerated phase. Each patient received escalating doses of donor leukocytes at 4- to 33-week intervals. Leukocyte doses were calculated as T cells per kilogram of recipient weight. There were 8 dose levels between 1 x 10(5) and 5 x 10(8). Lineage-specific chimerism and residual leukemia detection were assessed using sensitive polymerase chain reaction (PCR) methodologies. Nineteen of the 22 patients achieved remission. Remissions were achieved at the following T-cell doses: 1 x 10(7) (n = 8), 5 x 10(7) (n = 4), 1 x 10(8) (n = 3), and 5 x 10(8) (n = 4). To date, 15 of the 17 evaluable patients have become BCR-ABL negative by PCR. The incidence of GVHD was correlated with the dose of T cells administered. Only 1 of the 8 patients who achieved remission at a T-cell dose of 1 x 10(7)/kg developed GVHD, whereas this complication developed in 8 of the 11 responders who received a T-cell dose of > or = 5 x 10(7)/kg. Three patients died in remission, 1 secondary to marrow aplasia, 1 of respiratory failure and 1 of complications of chronic GVHD. Sixteen patients who were mixed T-cell chimeras before treatment became full donor T-cell chimeras at the time of remission. Donor leukocytes with a T-cell content as low as 1 x 10(7)/kg can result in complete donor chimerism together with a potent graft-versus-leukemia (GVL) effect. The dose of donor leukocytes or T cells used may be important in determining both the GVL response and the incidence of GVHD. In many patients, this potent GVL effect can occur in the absence of clinical GVHD.
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PMID:Adoptive immunotherapy evaluating escalating doses of donor leukocytes for relapse of chronic myeloid leukemia after bone marrow transplantation: separation of graft-versus-leukemia responses from graft-versus-host disease. 763 30

To determine whether pulmonary function test (PFT) results after marrow transplantation were predictive of nonrelapse mortality, a review was made of prospective, nonrandomized PFT results for association with nonrelapse mortality by log-rank test and Cox proportional hazards modeling. The setting was a tertiary referral center. The patients were all marrow recipients who performed PFT between Days 60 and 120 after marrow transplantation between July 1, 1983 and December 31, 1990 (n = 906). At 3 mo after transplantation, the mean values for total lung capacity (TLC) and diffusing capacity decreased, and restrictive ventilatory defects (TLC < 80% of predicted) were noted in 34% of the cohort. Airflow rates (FEV1/FVC) were unchanged. A restrictive lung defect at 3 mo after transplant or a significant decline (> or = 15%) in TLC from baseline despite remaining within the normal range was associated with a twofold increased risk of nonrelapse mortality. Neither airflow obstruction nor impairment in diffusing capacity was associated with an increased risk. Abnormalities of the TLC at 3 mo after transplant were associated with death with respiratory failure, but not with an increased risk of chronic graft-versus-host disease (GVHD). There is an increase in the nonrelapse mortality rate associated with either the presence of a restrictive defect 3 mo after marrow transplantation or a significant decline in lung volume compared with baseline. This effect is most pronounced more than 1 yr after marrow transplant and appears to be a result of an increase in the rate of death with respiratory failure, not chronic GVHD.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Abnormalities of pulmonary function tests after marrow transplantation predict nonrelapse mortality. 763 27

Acute graft-versus-host disease (GVHD) has recently been associated with endothelial cell injury. The potential clinical significance was explored here in an autopsy review. Thirty-seven allogeneic bone marrow recipients were identified in the autopsy files at The Johns Hopkins Hospital with no evidence of systemic infection. Forty-one percent (15/37) of these patients were found to have extensive recent pulmonary hemorrhage at autopsy which was thought to have led to terminal respiratory failure and death. The 37 patients were divided into 2 groups: those with significant acute GVHD (stage 2 or greater) and those without GVHD (stage 0 or 1). Fifty-nine percent (10/17) of the patients with significant acute GVHD died of acute respiratory failure due to recent pulmonary hemorrhage as opposed to 25% (5/20) of those without acute GVHD (P = 0.032, Fisher's exact test). Terminal pulmonary hemorrhage was also associated with preparation for BMT, with 67% (12/18) of those prepared with total body irradiation (TBI) having pulmonary hemorrhage as opposed to 15% (3/19) of those prepared with chemotherapy using Busulphan (P = 0.002). There was no significant difference in posttransplant survival, engraftment, or final platelet count between the patients stratified by GVHD or preparative protocol. The data support a strong association between significant acute GVHD and terminal hemorrhage, as well a possible association between TBI and pulmonary hemorrhage. Analysis of variance demonstrates that GVHD and TBI are independently associated with increased pulmonary hemorrhage (P < 0.01 for GVHD, P < 0.001 for TBI). We propose that GVHD contributes to terminal pulmonary hemorrhage by injuring the endothelium. However, this association could also be a secondary effect, i.e., toxicity from therapy for GVHD, or an abnormality in cytokines or growth factors. The pathogenic relationship between significant GVHD and terminal hemorrhage is discussed briefly.
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PMID:Pulmonary hemorrhage as a cause of death in allogeneic bone marrow recipients with severe acute graft-versus-host disease. 829 Nov 20


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