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)

Thirty patients undergoing allogeneic bone marrow transplantation (BMT) for hematologic malignancies received ciclosporin A (CS-A) as prophylaxis of graft-versus-host disease (GVHD). CS-A trough levels were determined in whole blood by radioimmunoassay (RIA); results were not used to adjust the CS-A dosage. Neither the dose of CS-A administered nor the CS-A concentration and fluctuation of blood levels during the first 15 days after BMT correlated with acute GVHD. Conversely in the 13 patients with acute GVHD, CS-A concentrations in the 10 days prior to the onset of the disease were increasingly lower with increasing severity of GVHD. Moreover, patients without GVHD had higher CS-A concentrations in a matched period of time. Upon withdrawal of CS-A treatment, 7 patients developed GVHD. There was no possibility to predict who would do so, but the analysis of CS-A disappearance profiles indicates that effective CS-A concentrations might be lower during long-term treatment than the concentrations required early after transplant. Despite these relationships, CS-A concentration is of little predictive value in the individual patient because of the considerable overlap among patients.
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PMID:Ciclosporin A: correlation of blood levels with acute graft-versus-host disease after bone marrow transplantation. 311 13

Graft-versus-host disease prevention was attempted in 35 consecutive patients with hematological malignancy who received bone marrow from an HLA match sibling donor who was depleted of T cells ex vivo. Five of the first 8 patients who received cyclophosphamide 60 mg/kg on 2 consecutive days followed by fractionated total body irradiation (TBI) (6 x 2 Gy) had graft failure. The subsequent 27 patients had received an extra fraction of TBI (7 x 2 Gy), and only one failed to have stable engraftment. There were no differences in nucleated cell dose, granulocyte-macrophage colony-forming units, or T cell numbers given to the two groups. Neutrophil but not platelet regeneration of those patients who successfully grafted was slower than in a group of historical controls receiving unmanipulated marrow. Significant graft-versus-host disease was prevented with no increase in relapse rate. We suggest that engraftment can be reliably achieved by augmenting the TBI conditioning in recipients of T cell-depleted matched allogeneic bone marrow.
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PMID:Prevention of graft-versus-host disease by ex vivo T cell depletion: reduction in graft failure with augmented total body irradiation. 328 16

We treated 73 patients with hematologic malignancies in first complete remission (acute lymphoblastic leukemia = 23 patients; acute non-lymphoblastic leukemia = 25 patients; chronic myelogenous leukemia in first chronic phase = 20 patients, and high grade lymphoma = five patients) with a uniform preparative regimen consisting of fractionated total body irradiation (1,320 cGy) and high dose cyclophosphamide (100 mg/kg), followed by allogeneic bone marrow transplantation. By radiation dosimetry we demonstrated that the calculated doses were delivered accurately and reproducibly. Actuarial survival rates (+/- SEM) in complete remission were as follows: Acute lymphoblastic leukemia = 74 +/- 9%; acute nonlymphoblastic leukemia = 50 +/- 11%; and chronic myelogenous leukemia = 55 +/- 11%. Actuarial relapse rates for these three diagnoses were 19 +/- 9%, 17 +/- 11%, and 0% respectively. Three of the five lymphoma patients are alive in complete remission at 22+, 28+, and 54+ months. Overall probability of survival for the 73 patients was 59 +/- 7%. Interstitial pneumonia, usually associated with cytomegalovirus infection and graft-versus-host disease, and relapse of the underlying malignancy were the major causes of death.
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PMID:Fractionated total body irradiation and high dose cyclophosphamide: a preparative regimen for bone marrow transplantation for patients with hematologic malignancies in first complete remission. 329 91

Sixteen patients with hematological malignancy received cyclophosphamide (120 mg/kg), fractionated total body irradiation (12 Gy), oral cyclosporin, and an HLA-identical sibling marrow transplant depleted of T cells by incubation with the monoclonal antibody anti-HuLy-m1 (CD2) and rabbit complement with (five patients) or without (11 patients) anti-HuLy-m8). These 16 patients were compared historically to 84 patients with hematological malignancy receiving cyclophosphamide (120 mg/kg), fractionated total body irradiation (12 or 14 Gy), oral cyclosporin, and unmanipulated HLA-identical sibling marrow, for parameters of engraftment and graft-versus-host disease (GVHD). Graft failure occurred in one of the 16 T-cell depleted recipients and in one of the 84 nondepleted recipients. Engraftment was slightly but significantly slower in the T-cell depleted group and bacterial infections significantly more frequent and severe than in the unmanipulated group. There was a suggestion that the severity of acute GVHD was reduced in those receiving T depleted marrow. Randomized trials will be necessary to determine if marrow T-cell depletion results in superior long-term leukemia-free survival.
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PMID:A comparative study of T-cell depleted and non-depleted marrow transplantation for hematological malignancy. 330 40

Nine patients with haematological malignancy relapsed 3-32 months after receiving cyclophosphamide 120 mg/kg, 12-14 Gy fractionated total body irradiation and an HLA-identical sibling bone marrow transplant. They were reconditioned with melphalan 180-220 mg/m2 and retransplanted using the same donor and the same cyclosporin regimen as prophylaxis for graft-versus-host disease (GVHD). Three of the nine remain alive greater than 81, greater than 33, and greater than 36 months after second transplant. While the rate of marrow engraftment, the incidence of acute GVHD and the incidence of interstitial pneumonitis were similar after first and second transplants, the use of melphalan before second transplant was associated with increased nephrotoxicity and oropharyngeal mucositis. The present study shows that second narrow transplants are feasible, can produce prolonged remission of haematological malignancies and should be considered in appropriate patients who relapse after first marrow transplant.
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PMID:Second marrow transplants for recurrence of haematological malignancy. 333 30

Cyclosporin, the first truly selective immunosuppressive agent, has a useful role in HLA-identical sibling bone marrow transplantation for haematological malignancy and severe aplastic anaemia. Specifically, it has been shown to minimise graft-versus-host disease, particularly when used in combination with methotrexate, and to reduce the risk of marrow graft rejection. Its mode of action, pharmacology, clinical utility and toxicology in the marrow transplant setting are described.
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PMID:Cyclosporin in bone marrow transplantation. 333 37

Sixteen patients with haematological malignancy received high-dose chemotherapy or chemotherapy and total body irradiation followed by an HLA-identical sibling marrow transplant from which the T lymphocytes had been depleted prior to infusion by incubation with an anti-CD2 anti-T cell antibody with (seven patients) or without (nine patients) an anti-CD8 anti-T cell antibody together with rabbit complement. Additionally, all patients received cyclosporin. The number of T cells present in the donor marrow was determined by limiting dilution analysis, and was found to correlate with the subsequent incidence and severity of acute graft-versus-host disease (GVHD). The number of T cells infused into patients with no acute GVHD or with minimal acute GVHD of the skin (skin rash present for 14 days or less) was 1.3 +/- 1.0 x 10(5)/kg, while the number infused into those with moderate acute GVHD or with skin acute GVHD present for 15 days or more was 12.3 +/- 11.5 x 10(5)/kg (p less than 0.001). Thus a dose of 10(5) (or less) T cells/kg was associated with minimal or no acute GVHD, while 10(6) T cells/kg (or more) caused significant disease.
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PMID:Human marrow T cell dose correlates with severity of subsequent acute graft-versus-host disease. 333 57

One-hundred-and-forty-three patients with haematological malignancy or severe aplastic anaemia received HLA-identical sibling bone marrow transplants. In 111 of these patients who had haematological malignancy and who were prepared for transplant with cyclophosphamide 120 mg/kg and fractionated total body irradiation 12-14 Gy, the incidence of haemorrhagic cystitis and hepatic veno-occlusive disease was 13% and 3%, respectively. In contrast, the incidence in 15 leukaemic patients prepared for transplant with chemotherapy regimens containing high-dose busulphan was 47% and 20%, respectively (p less than 0.001). Two patients in this latter group who developed fatal veno-occlusive disease had chronic myeloid leukaemia and had received long-term low-dose busulphan pre-transplant. Neither complication occurred in 26 patients prepared by cyclophosphamide alone (20 patients with severe aplastic anaemia) or with cyclophosphamide and melphalan (six patients with leukaemia). The regimen of busulphan 16 mg/kg in combination with cyclophosphamide 120 mg/kg was associated with a short duration of total leucopenia with a significantly higher leucocyte count on the day of marrow transplant compared to other regimens. Furthermore, oro-pharyngeal mucositis was not severe even when methotrexate was utilised as post-transplant prophylaxis for graft-versus-host disease. Thus, while the busulphan-cyclophosphamide regimen appeared useful, we suggest that (1) high-dose busulphan should not be used as a preparative regimen for patients previously exposed to busulphan, and (2) bladder irrigation (as well as intravenous hydration) is necessary to minimise haemorrhagic cystitis in patients given regimens that incorporate high-dose busulphan.
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PMID:Preparative regimens for marrow transplantation containing busulphan are associated with haemorrhagic cystitis and hepatic veno-occlusive disease but a short duration of leucopenia and little oro-pharyngeal mucositis. 333 86

Of 50 patients surviving 2 years or longer after HLA-identical sibling bone marrow transplantation for haematological malignancy or severe aplastic anaemia, five developed avascular necrosis of the femoral head. All had previously received corticosteroid therapy post-transplant for graft-versus-host disease. Median day of onset of symptoms was 545 days post-transplant (range 249-731). Clinical, radiological and radionuclide findings were typical of osteonecrosis. One patient has had bilateral hemiarthroplasties and one total hip replacements performed, both with excellent results. Bilateral arthroplasties are planned for a third patient but, interestingly, the disease process in the other two patients has been relatively mild with no progression over a period of greater than 256 and greater than 825 days, respectively. Since one patient had as little as 14 days treatment with prednisone, this complication should be borne in mind when designing prophylactic regimens for minimisation of GVHD that include corticosteroids.
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PMID:Avascular necrosis of the femoral head secondary to corticosteroid therapy for graft-versus-host disease after marrow transplantation: effective therapy with hip arthroplasty. 333 89

Ultraviolet irradiation is known to diminish the functional capacity of cells of the immune system. We have used ultraviolet A irradiation in combination with psoralen (PUVA) to treat three patients with drug-resistant graft-versus-host disease (GVHD) of the skin or mouth. Each of the three patients had received an HLA-identical sibling bone marrow transplant for haematological malignancy or severe aplastic anaemia. One patient developed acute GVHD of skin and mouth and two patients developed chronic GVHD of the mouth, which did not respond to conventional immunosuppressive drugs including cyclosporin and methyl prednisolone (all three patients) and anti-thymocyte globulin (two patients). PUVA irradiation to the skin was given at a dose of 0.75-1.25 J (joules) daily for four days per week and that to the mouth at 0.75 J daily four days per week. Before each treatment, 8-methoxypsoralen (0.6 mg/kg) was given orally as a photosensitizer. Each patient improved considerably and in each case the dosage of conventional immunosuppression was reduced. No flare was noted in the two patients with chronic GVHD of the mouth at 1 month after the end of treatment. PUVA irradiation is a useful therapeutic adjunct in GVHD affecting skin and mouth and appears to confer a steroid or cyclosporin sparing effect.
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PMID:PUVA therapy for drug-resistant graft-versus-host disease. 350 81


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