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)

Of the first 14 patients with acute or chronic leukemia to undergo bone marrow transplantation at our hospital, 9 (64%), all good-risk, are still alive in remission at 18 to 42 months of follow-up (mean, 29 months) with their Karnofsky performance status between 80% and 100%. The conditioning regimen of fractionated-dose irradiation and high-dose chemotherapy eradicated their disease; only two patients relapsed after transplantation. Toxicity was acceptable. Acute graft-versus-host disease developed in six patients (43%) (grade I or II in four, grade IV in two) and progressed to chronic graft-versus-host disease in four. Viral pneumonitis developed in three patients (21%), but none had idiopathic interstitial pneumonitis. The mean hospital charge was $54,355. These preliminary results suggest that good-risk patients with acute or chronic leukemia can be treated with bone marrow transplantation in a university affiliated hospital with appropriate staff and support facilities and achieve results comparable to those in research institutions at a competitive cost.
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PMID:Bone marrow transplantation for good-risk patients with leukemia in a university affiliated hospital. 352 2

This report deals with 81 pulmonary episodes occurring in 130 consecutive patients who underwent allogeneic bone marrow transplantation for hematologic malignancy in the same unit over a 5-year period. These episodes observed in 69/130 patients (53%) were mostly of infectious origin, and were investigated by bronchoalveolar lavage (BAL). The main causes of pneumonia were: cytomegalovirus (CMV) (n = 25), bacterial pneumonia (n = 17), invasive aspergillosis (n = 11) and pulmonary hemorrhage (n = 9). The overall mortality due to or associated with pneumonia was 26/130 (20%). Graft-versus-host disease clearly increased the incidence of infectious pneumonia and the mortality due to or associated with pneumonia. Granulocyte transfusions did not influence the incidence of CMV pneumonitis. The main causes and risk factors for pneumonia are discussed. The role of BAL as a noninvasive procedure is stressed.
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PMID:Pulmonary complications occurring after allogeneic bone marrow transplantation. A study of 130 consecutive transplanted patients. 352 98

We investigated if high dose melphalan and total body irradiation could be administered to adult patients with acceptable toxicity. Nineteen adult patients with relapsed disease, 15 of them having hematologic malignancies, were treated with high-dose melphalan (100 mg/m2-140 mg/m2) divided over 2 consecutive days followed by a rest period of 4 days before receiving total body irradiation, 850 rad administered in five fractionated doses over 3 days. Subsequently 11 patients received autologous, seven allogeneic and one syngeneic, bone marrow transplantation. All patients had severe myelosuppression and the major extramedullary toxicity was mucositis. There were three early deaths, two related to septicemia and one to graft-versus-host disease with associated cytomegalovirus pneumonitis. All patients were heavily pretreated, and 16 were demonstrating progressive disease on alternative salvage therapies at the time of bone marrow transplantation. Two of the 16 evaluable patients (12.5%) achieved complete remissions, and 10 (63%) achieved partial remissions for a total response rate of 75%. One patient is a long-term disease-free survivor (over 1 yr). An occasional patient may be cured by this approach. The combination of melphalan, an alternative alkylating agent to cyclophosphamide and total body irradiation are associated with moderate gastrointestinal toxicity in heavily pretreated adult patients. The combination warrants further investigation in a less heavily pretreated population to determine more accurately the complete response rate.
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PMID:High-dose melphalan and total body irradiation with bone marrow transplantation for refractory malignancies. 352 15

The case histories of 72 subsequently treated patients - 44 with acute leukemia, 10 with chronic myeloid leukemia, 16 with severe aplastic anemia and 2 with neuroblastoma - were analyzed after bone marrow transplantation (BMT) with respect to pulmonary diseases. Thirty-eight patients suffered from a total of 51 pulmonary complications, which led to death in 20. Of 13 patients, 3 died of bacterial pneumonia, all of them during granulocytopenia; 2 of 6 patients died of fungal pneumonia and 2 out of 3 of a mixed bacterial-mycotic infection. Adult respiratory distress syndrome (ARDS) led to death in 2 patients. A granulocyte count under 500/microliter correlated significantly (P less than 0.002) with the fatal outcome of bacterial, fungal and ARDS pneumonia as well as with bronchitis. Viral pneumonia led to death in 8 of 9 patients; in each there was a significant correlation (P less than 0.05) with graft-versus-host disease (GvHD). Patients with repeated episodes of pulmonary illness had significantly more chronic GvHD (P less than 0.05); several of these patients displayed a reduction in helper T cells and an increase in suppressor T cells in the peripheral blood. The natural killer (NK) cells were reduced and the percentage of activated NK cell level lay between 6% and 69%. B-cells were absent or deficient. These findings explain in part the absence of specific antibody reactivity. Five of these patients also contracted GvHD-associated obstructive bronchiolitis, which did not respond to therapy. Pulmonary infiltrates of unknown origin (including idiopathic interstitial pneumonia) occurred in 8 of the patients (11.1%), with a fatal outcome in 3 patients. Significant changes (P less than 0.05) in lung function after BMT appeared in the form of reduced vital capacity (VC) increased residual volume (RV) and an increase in RV expressed as the percentage of total lung capacity. Pulmonary diseases were the most common complication and cause of death in our patients after BMT.
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PMID:Lung diseases after bone marrow transplantation. Results of a clinical, radiological, histological, immunological and lung function study. 352 53

Inadequate leukemic ablative therapy ending in leukemic relapse is the source of most failures following bone marrow transplantation. Attempting to improve pretransplant leukemic ablative therapy, we report on a pilot regimen that includes teniposide, the principal chemotherapy, and total-body irradiation. Ten patients with acute lymphoblastic leukemia in relapse underwent allogeneic bone marrow transplantation. All patients engrafted. Toxicity, primarily mucositis, was manageable. Two patients have survived for 1547 and 1988 days in continued remission. Eight patients have died: three from sepsis in the immediate posttransplant period, four with recurrent leukemia, and one with chronic graft-versus-host disease and pneumonia. We believe that these results support further trials with teniposide in pretransplant leukemic ablative therapies.
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PMID:Total-body irradiation and high-dose teniposide: a pilot study in bone marrow transplantation for patients with relapsed acute lymphoblastic leukemia. 355 90

An experimental model has been developed for the study of combined effects of partial body irradiation (PBI) and graft-versus-host disease (GVHD) in which irradiation is delivered to the thorax 24 hr prior to induction of GVHD in hybrid mice by the injection of parental lymphoid cells. In mice irradiated to 1000 cGy or exposed to low doses of allogeneic lymphoid cells (20 X 10(6)), survival was 100% at 250 days. In contrast, combination of the two treatments, GVHD and PBI, resulted in a mortality of 83% and a mean survival time of 29 days, indicating synergy between GVHD and PBI. From histological studies of the lung it appeared that about 40% of the deaths occurring after combined GVHD/PBR treatment might be attributable to pneumonia. The cause of death in the remaining mice receiving combined treatment is not known. Mice receiving combined PBI/lymphoid cell treatment develop a characteristic skin lesion that is not seen in nonirradiated mice and is confined to the irradiated area. The effect of preinduction PBR on the timing and severity of GVHD is similar to that which would be produced by an increase in the number of effector cells.
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PMID:Amplification of the graft-versus-host reaction by partial body irradiation. 371 65

High dose whole body irradiation is commonly included in conditioning regimens for bone marrow transplantation for treatment of patients with hematological malignancies. Interstitial pneumonitis is a major complication after BMT. About one-fourth of all BMT patients die from IP. In about half of these cases, an infectious agent, particularly cytomegalovirus, is involved. When no infectious cause is found, it is classified as idiopathic IP (IIP). Total body irradiation is often associated with the induction of IIP; however, extrapolation of animal data from the experiments presented indicates that this is not the only factor contributing to IIP in man. Brown Norway (BN/Bi) rats were bilaterally irradiated to the lungs with 300 kV X rays at a high dose rate (HDR; 0.8 Gy/min) and at a low dose rate (LDR; 0.05 Gy/min). The dose-response curves found were very steep. In the LDR group, lung function studies were performed. There was a strong correlation between the increase in ventilation rate and the death pattern. The LD50 at 180 days was 13.3 Gy for HDR and 22.7 Gy for LDR. The ratios of LD50/180 at 0.05 Gy/min to that at 0.8 Gy/min is 1.7, which indicates a great repair capacity of the lungs. Extrapolation of animal data to patient data leads to an estimated dose of about 15-16 Gy at a 50% radiation pneumonitis induction for low dose rate TBI. As the absorbed dose in the lungs of BMT patients rarely exceeds 10 Gy, additional factors such as remission-induction chemotherapy, cyclophosphamide, methotrexate, cyclosporin A, graft-versus-host disease, etc., might be involved in the high incidence of IIP in man after BMT.
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PMID:Lung damage following bone marrow transplantation: I. The contribution of irradiation. 388 9

A 23-year-old woman gravely ill with Pseudomonas septicemia secondary to presumed drug-induced bone marrow aplasia received marrow transplantation from two male HL-A identical sibling donors. She had a successful engraftment with excellent but temporary clinical improvement. Subsequently she succumbed to graft-versus-host disease manifested by Pseudomonas and Candida albicans septicemia, cytomegalovirus pneumonitis, three phases of dermatitis, nausea, vomiting, dysphagia, diarrhea, fever, edema and bone pain, with gradual but complete graft suppression by the 74th day after the transplantation. A second marrow transplant on the 70th day was unsuccessful.
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PMID:Bone marrow transplantation in a patient with drug-induced aplastic anemia. 440 93

Marrow grafts were carried out between 16 canine sibling donor-recipient pairs. The pairs were matched by serological histocompatibility testing and were nonreactive in a one-way mixed leukocyte culture. Recipients were prepared for transplantation by 1500-1580 R of total body irradiation. Donor marrow was infused within 4 hr of irradiation. Recipients were not given immunosuppressive drug therapy after grafting. All 16 recipients showed evidence of prompt and sustained allogeneic marrow engraftment. Six died between 30 and 128 days after grafting with graft-versus-host disease, and three died between days 72 and 230 with pneumonia but no evidence of graft-versus-host disease with the exception of lymphoid atrophy. Seven recipients survived without graft-versus-host disease and are in excellent health between 200 and 684 after grafting. In summary, fatal graft-versus-host disease was observed in a number of canine recipients despite matching with their sibling donor by serological histocompatibility testing and by mixed leukocyte culture in a manner similar to that employed to define human HL-A matched sibling pairs. The graft-versus-host disease in these matched siblings developed more slowly than that observed in mismatched dogs, but the ultimate death of approximately half of the matched recipients emphasizes the need for posttransplantation immunosuppression even in this "compatible" situation.
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PMID:Marrow grafts between canine siblings matched by serotyping and mixed leukocyte culture. 493 Oct 83

Interstitial pneumonia, especially that due to cytomegalovirus (CMV), is a frequent and serious complication of allogeneic bone marrow transplantation (BMT). The influence of allogeneic BMT on the development of CMV pneumonia was investigated in comparison with that of autologous BMT. Data on 37 patients (23 allotransplants and 14 autotransplants) who survived for longer than one month were reviewed. All were conditioned for the transplant with marrow-lethal cytoreductive therapy. Interstitial pneumonia occurred in 15 allotransplant patients (65%) and in five autotransplant patients (36%), and was fatal in 10 allotransplant patients (67%) and in two autotransplant patients (40%), with no statistically significant difference between the two groups of patients. However, the high incidence of CMV pneumonia in allotransplant patients presented a striking contrast to that in autotransplant patients (13 of 23 versus one of 14, p less than 0.01). CMV pneumonia was closely associated with the occurrence of graft-versus-host disease (GVHD). Moreover, the data inferred that both delayed posttransplant immunologic recovery and numerous transfusions of blood products from multiple random donors predispose allotransplant patients to CMV pneumonia. Though combination therapy with acyclovir, interferon-alpha (IFN) and prednisolone seemed to be somewhat effective further studies are needed to verify its benefit considering that all the patients (five allotransplants and one autotransplant) who survived CMV pneumonia showed a significant seroconversion to CMV. On the other hand, neither IFN nor nonspecific gamma-globulin proved to be effective in preventing CMV pneumonia. It is thus suggested that special attention be focused not only on the development of better methods to prevent GVHD and improve posttransplant immunologic recovery but also on reduced exposure to exogenous CMV.
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PMID:Interstitial pneumonia after allogeneic and autologous bone marrow transplantation. 609 10


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