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)

To determine whether 6 months of cyclosporine therapy is associated with chronic renal dysfunction, we evaluated serum creatinine concentrations 1 year post-transplant in 82 marrow transplant recipients randomized to receive either cyclosporine (n = 40) or methotrexate (n = 42) as graft-versus-host disease (GVHD) prophylaxis. Nine patients in the methotrexate group were later given cyclosporine as treatment for acute or chronic GVHD (methotrexate----cyclosporine). Cyclosporine prophylaxis was started on the day before marrow infusion, given at full doses until day 50, then gradually tapered and discontinued by day 180. Methotrexate prophylaxis was started on day 1 and given intermittently until day 102. Patients in the cyclosporine and methotrexate----cyclosporine groups had significantly higher mean serum creatinine values during the first 100 days post-transplant than methotrexate-treated patients, but by 1 year mean serum creatinine values were not significantly different between the three groups. Serum creatinine values at 1 year were also not significantly different from baseline values in each of the groups. None of the patients who had their cyclosporine discontinued by day 180 developed chronic renal dysfunction, defined as a doubling of the baseline serum creatinine at 1 year. We conclude that chronic renal dysfunction occurs rarely in marrow transplant recipients treated with 6 months of cyclosporine and when it does occur, it appears to have minimal clinical significance.
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PMID:Minimal risk of chronic renal dysfunction in marrow transplant recipients treated with cyclosporine for 6 months. 268 9

Patients with haematological malignancies with HLA-identical marrow donors were randomized to treatment with cyclosporin (CSA) or methotrexate (MTX). Two of the 29 patients randomized to MTX died before engraftment compared with none of the 30 treated with CSA. Engraftment by leucocytes (P less than 0.0001), granulocytes (P less than 0.02), and reticulocytes (P less than 0.01) was faster among the CSA patients. There were no significant differences between the two groups regarding transfusions, hospitalization and incidence of early septicaemia. Granulocyte transfusions were required in seven of 29 MTX and two of 30 CSA patients (not significant: NS). Overall (grade I-IV) acute graft-versus-host disease (GVHD) was more common (P = 0.001) in the CSA patients. Grade II-IV acute GVHD was seen in 40% of the CSA patients compared with 22% in the MTX patients (NS). In the adult patients grade II-IV GVHD was slightly more common (P less than 0.05) in those treated with CSA compared with MTX. Chronic GVHD appeared in 30 and 39% in the two groups respectively. Actuarial 3-year survival was 58% for the CSA patients and 69% for the MTX patients. There were no significant differences regarding the incidence of interstitial pneumonitis or relapses between the two groups. The side-effects of CSA treatment includes nephrotoxicity (83%), hepatotoxicity (20%), hirsutism (43%), hypertension (23%), tremor (27%) and gingival hyperplasia (27%). Serum creatinine values were increased at 3 and 6 months in the CSA group but were within the normal range after 6 months. A blind study on oral side-effects revealed that CSA patients more often had a normal mucosa (P = 0.025) and less frequently had mucositis (P = 0.01) compared with the MTX group.
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PMID:A randomized trial comparing use of cyclosporin and methotrexate for graft-versus-host disease prophylaxis in bone marrow transplant recipients with haematological malignancies. 333 19

Twenty consecutive patients with diabetes who were dependent upon insulin underwent simultaneous pancreatic-duodenal and renal transplantation at our center between March 1984 and August 1985. Eighteen patients are alive, 17 have functioning renal allografts and 13 have normal fasting blood sugar levels and are free of insulin use. Pancreatic graft loss was secondary to venous thrombosis in four instances and inadequate perfusion in one. Graft versus host disease occurred in three patients with composite pancreatic and splenic grafts, which led to a policy of not including the spleen as part of the graft. Serum creatinine levels were a more sensitive indicator of rejection than blood sugar levels which represent a distinct advantage of the simultaneous pancreatic and renal procedure, as compared with pancreatic transplantation after renal transplantation. Duodenal intestinal anastomosis appeared to be a satisfactory way of establishing exocrine pancreatic drainage. As results of pancreatic transplantation continue to improve, this procedure should no longer be considered as experimental.
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PMID:Surgical treatment of diabetic nephropathy with simultaneous pancreatic duodenal and renal transplantation. 352 Sep 3

We retrospectively analyzed the relationship of serum cyclosporine concentration to renal dysfunction in 63 marrow transplant recipients who received cyclosporine for prophylaxis of acute graft-versus-host disease. Patients were divided into three groups according to their mean trough cyclosporine concentration for the first 28 days of therapy: less than 150, 150-250, and greater than 250 ng/ml. Baseline renal function and exposure to nephrotoxic antibiotics was comparable in the three groups. Renal dysfunction was defined as doubling of baseline serum creatinine. The likelihood of developing renal dysfunction was analyzed with Kaplan-Meier product limit estimates. The log-rank test was used to compare the three groups. Fifty-four (86%) of the patients developed renal dysfunction. The incidence of renal dysfunction was 73%, 95%, and 100%, and it developed at a median of 46, 29, and 20 days in patients with a mean trough concentration of less than 150, 150-250, and greater than 250 ng/ml, respectively (P less than 0.001). Eight of the nine patients who did not develop renal dysfunction had a mean trough concentration of less than 150 ng/ml. These data indicate that the incidence and the rate of development of renal dysfunction are related to serum cyclosporine concentration.
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PMID:Correlation of serum cyclosporine concentration with renal dysfunction in marrow transplant recipients. 389 89

Cyclosporin A(CyA) is a valuable post graft immunosuppressive agent in allogeneic bone marrow transplantation. The use of CyA is associated with a reduction in severity of graft versus host disease and improved marrow engraftment. A major side effect of CyA is nephrotoxicity. In 33 patients studied during the first 4 weeks of therapy there is a close correlation between trough (12 h) serum cyclosporin A concentrations and plasma creatinine (r = 0.93, P less than 0.001) and urea (r = 0.88, P less than 0.001). Trough CyA serum concentrations of greater than 500 ng/ml are potentially nephrotoxic. Other risk factors for early nephrotoxicity in cyclosporin therapy are the concurrent use of aminoglycoside antibiotics (P = 0.01) and hyperbilirubinaemia (P = 0.01). Early nephrotoxicity can be prevented by maintaining trough CyA levels in the range 100-400 ng/ml. During prolonged CyA therapy, cumulative renal impairment can occur and nephrotoxic episodes associated with microangiopathic peripheral blood changes and hypertension are seen in a minority of patients.
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PMID:Nephrotoxicity in bone marrow transplant recipients treated with cyclosporin A. 634 56

23 patients undergoing marrow transplantation for leukemia or aplastic anemia were given cyclosporin A (CyA) for graft-versus-host disease (GvHD) prophylaxis. A radioimmunoassay was used to monitor CyA serum levels in 13 patients and whole blood levels in 10. Serum creatinine levels were recorded daily until day 30 and then weekly. The severity of acute GvHD was recorded daily for a total of 1,738 patient days. CyA dose was then correlated with CyA serum or blood levels, serum creatinine levels and severity of acute GvHD. The daily dose of administered CyA correlated with serum CyA levels (p = 0.001) but not with whole-blood CyA levels. The cumulative CyA dose correlated with serum creatinine. There was an inverse correlation between the daily CyA dose and the severity of acute GvHD (p = 0.05). On the other hand the total amount of CyA given within 10 days after bone marrow transplantation had no influence on the severity of acute GvHD developing after day 10. Serum and whole-blood levels did not correlate with severity of GvHD nor with creatinine levels. The results of this study point out the nephrotoxicity of CyA, and a low GvHD score with high doses of administered CyA, at least on a daily basis. Serum but not blood levels reflect the dose of CyA given, but are not correlated with nephrotoxicity or GvHD.
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PMID:Cyclosporin A serum and blood levels in marrow graft recipients: correlation with administered dose, serum creatinine and graft-versus-host disease. 643 79

By serially measuring serum levels of alpha-1 microglobulin and beta-2 microglobulin following allogeneic bone marrow transplantation (BMT), we tried to define their relationship to renal dysfunction, acute graft-versus-host disease (GVHD) and infection as complications of the transplantation. The study involved a total of 25 patients with leukemia, myelodysplastic syndrome and aplastic anemia who received BMT in this department; one patient received re-transplantation, thus bringing the total number of transplants to 26. Twenty-four patients received BMT from HLA-identical siblings while two others received BMT from unrelated donors. Alpha-1 microglobulin was within normal limits in all patients before BMT; among various complications such as nephrotoxicity, acute GVHD and infection which took place after transplantation, a raised alpha-1 microglobulin level was found only in nephrotoxicity; however, the increase was not significant compared with the pre-transplantation level. The pre-transplantation beta-2 microglobulin level was higher than normal in some patients; it was significantly increased in all of the above complications compared with the pretransplantation level (1.57 +/- 0.57 mg/l). A significant correlation was found between the serum creatinine level and the beta-2 microglobulin level (r = 0.849) in patients with renal dysfunction. In some patients, however, the beta-2 microglobulin level increased earlier than the serum creatinine level, and this finding was considered useful for the early diagnosis of renal dysfunction following allogeneic BMT.
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PMID:Change of serum alpha-1 microglobulin and beta-2 microglobulin following allogeneic bone marrow transplantation. 753 65

Despite the use of conventional chemoprophylaxis regimens, patients receiving unrelated-donor BMT are at high risk of developing severe acute GVHD. We evaluated a prophylactic regimen combining CsA, MTX and anti-CD5-ricin A chain immunotoxin (H65-RTA) in 31 patients; pentoxifylline was also given to reduce the anticipated nephrotoxicity of CsA. In most cases, planned doses of CsA, MTX and H65-RTA were given (i.e. to 77%, 77% and 93% of patients, respectively). Although fluid retention requiring diuretic therapy was frequent, only 1 patient had a > 10% unexplained increase in body weight during the first 21 days post-BMT. Also, while significant increase of the baseline serum creatinine was noted in 7 patients, none required dialysis. One patient suffered a reversible allergic reaction to the immunotoxin; no other side effects attributable to this regimen were observed. All but 2 patients engrafted (1 died of fungemia on d + 19 and the other had persistent leukemia) and no late graft failures were observed. Seventeen patients developed acute GVHD grade > or = II (probability, 58% [95% CI 41-76%]); 7 had grade > or = III (probability, 24% [95% CI 12-43%]). In the 27 patients who achieved stable engraftment and have survived beyond d + 100, the 3-year probability of developing chronic GVHD was 66% (95% CI 48-84%). As of the last follow-up prior to 01 May 1994, 13 patients are alive in CR and one in relapse; 9 of these patients are off all immunosuppressives and well. Four other patients relapsed and died, and 13 died of other transplant-related causes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prophylaxis for acute graft-versus-host disease following unrelated donor bone marrow transplantation. 753 67

Patients with haematological malignancies undergoing allogeneic BMT were randomised to treatment with recombinant human erythropoietin (rHuEPO) (n = 25) or placebo (n = 25). rHuEPO was given at 200 U/kg daily for 4 weeks and 200 U/kg twice weekly for a further 4 weeks. The groups were similar regarding several prognostic factors. There were no differences between the two groups regarding time to engraftment, fever, hospitalisation, GVHD, infections, haemorrhages, transplant-related mortality, relapse and survival. However, more patients in the control group had a raised serum creatinine (43% vs 14%; p = 0.04). Red blood cell (RBC) transfusion requirements for the first 2 months after BMT were significantly lower in the rHuEPO group compared with the control group (5 units vs 10; p = 0.04). Time to unsupported Hb > 70 g/l was less in patients treated with rHuEPO (14 days vs 24; p = 0.03). No effect was seen on platelet engraftment or the number of transfused platelet units. Two patients in the control group compared with none in the rHuEPO group became refractory to platelet transfusions. According to the protocol the study drug was reduced (Hb > 100) or discontinued (Hb > 120) for a mean of 3.6 weeks among 11 rHuEPO patients compared with 1.9 weeks among 7 controls (p = 0.02). Seven of the treated patients compared with none of the controls reached Hb > 120 during the study period (p = 0.004). Among the rHuEPO treated patients, EPO-levels were significantly higher than in the controls.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Reduced blood transfusions requirements after allogeneic bone marrow transplantation: results of a randomised, double-blind study with high-dose erythropoietin. 801 63

A prospective randomized study was conducted comparing two conditioning regimens for the treatment of patients with chronic myeloid leukemia in chronic phase by marrow transplantation from HLA identical siblings. Sixty-nine patients received 60 mg/kg of cyclophosphamide on each of 2 successive days followed by 6 fractions of total body irradiation each of 2.0 Gy (CY-TBI), and 73 patients received 16 mg/kg of busulfan delivered over 4 days followed by 60 mg/kg CY on each of 2 successive days (BU-CY). There was no significant difference between the CY-TBI and the BU-CY groups in the 3-year probabilities of survival (0.80 for both), relapse (0.13 for both), or event-free survival (CY-TBI, 0.68; BU-CY, 0.71) or in speed of engraftment or incidence of venocclusive disease of the liver. The 4-year probabilities of survival and event-free survival for patients transplanted within 1 year of diagnosis were 0.86 and 0.72, respectively, for each group. Significantly more patients in the CY-TBI group experienced major creatinine elevations. There was significantly more acute graft-versus-host disease in the CY-TBI group. Fever days, positive blood cultures, hospitalizations, and inpatient hospital days were significantly more common in the CY-TBI group than in the BU-CY group. In conclusion, the BU-CY regimen was better tolerated than, and associated with survival and relapse probabilities that compare favorably with, the CY-TBI regimen.
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PMID:Marrow transplantation for chronic myeloid leukemia: a randomized study comparing cyclophosphamide and total body irradiation with busulfan and cyclophosphamide. 1139 26


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