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)

We compared fractionated total body irradiation (12 Gy)/cyclophosphamide (120 mg/kg) with busulfan (16 mg/kg)/cyclophosphamide (120 mg/kg) as preparative therapy in unrelated donor stem cell transplantation of CML patients. Fifty patients with CML (1.CP = 46; aP = 4) and a median age of 36 years (range 16-52) were enrolled in this sequential trial between 1994 and 1999. In both groups patients were well balanced with respect to age, disease status, stem cell source and CMV status. All patients received standard doses of cyclosporin A, methotrexate and anti-thymocyte globulin (ATG) as GVHD prophylaxis. No graft failures occurred in either group. The median day of leukocyte engraftment was earlier in the Bu/Cy than in the TBI/Cy group (day 15 vs 17; P = 0.006). The incidence of grade II-IV GVHD was 40% in the TBI/Cy and 36% in the Bu/Cy group, whereas severe grade III/IV GVHD was only observed in 12% of patients in both groups. The incidence of chronic GVHD (limited and extensive) at 1 year was higher in the Bu/Cy arm (65% vs 30%; P = 0.02). More toxicity grade I/II of the liver (88% vs 44%; P = 0.002) and more hemorrhagic cystitis (32% vs 8%; P = 0.02) were observed in the Bu/Cy regimen. Seven relapses in the TBI and no relapse in the Bu/Cy group were observed after a median follow-up of 44 and 15 months, respectively. The estimated 3 year OS and DFS was 72% (95% CI: 55-98%) and 58% (95% CI: 39-77%) in the TBI and 70% (95% CI: 51-89%) for DFS and OS in the Bu/Cy group. We conclude that the anti-leukemic effect of the Bu/Cy regimen seems to be at least as effective as the TBI/Cy combination in unrelated stem cell transplantation of CML patients, with no graft failures, but that it correlates with a higher incidence of liver toxicity, hemorrhagic cystitis and chronic GVHD. Longer follow-up is necessary to determine the late relapse rate and late toxicity.
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PMID:Comparison of total body irradiation vs busulfan in combination with cyclophosphamide as conditioning for unrelated stem cell transplantation in CML patients. 1131 63

Polyoma BK virus (BKV) is frequently identified in the urine of bone marrow transplantation (BMT) patients with hemorrhagic cystitis (HC). However, viruria is common even in asymptomatic patients, making a direct causative role of BKV difficult to establish. This study prospectively quantified BK viruria and viremia in 50 BMT patients to define the quantitative relationship of BKV reactivation with HC. Adenovirus (ADV) was similarly quantified as a control. More than 800 patient samples were quantified for BKV VP1 gene with a real-time quantitative polymerase chain reaction. Twenty patients (40%) developed HC, 6 with gross hematuria (HC grade 2 or higher) and 14 with microscopic hematuria (HC grade 1). When compared with asymptomatic patients, patients with HC had significantly higher peak BK viruria (6 x 10(12) versus 5.7 x 10(7) genome copies/d, P <.001) and larger total amounts of BKV excreted during BMT (4.9 x 10(13) versus 7.7 x 10(8) genome copies, P <.001). There was no detectable increase in BK viremia. Binary logistic regression analysis showed that BK viruria was the only risk factor, with HC not related to age, conditioning regimen, type of BMT, and graft-versus-host disease. Furthermore, the levels of ADV viruria in patients with or without HC were similar and comparable with those of BK viruria in patients without HC, suggesting that the significant increase in BK viruria in HC patients was not due to background viral reactivation or damage to the urothelium. BK viruria was quantitatively related to the occurrence of HC after BMT.
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PMID:Quantification of polyoma BK viruria in hemorrhagic cystitis complicating bone marrow transplantation. 1153 37

Candidemia is a serious complication in patients following allogeneic blood, marrow, and organ transplantation. Fourteen patients developed nosocomial fungemia among 204 allogeneic marrow transplants performed during 1997-1999. Incidence of hematogenous candidiasis was 6.8 per 100 allogeneic BMT. All 14 had an indwelling central venous catheter (CVC) and fluconazole (100-200 mg daily) was given prophylactically. In 11 (78.5%) neutropenic patients, duration between agranulocytosis and diagnosis of fungemia was (median, +/- s.d.) 10 +/- 8 days. Candida glabrata (53.3%) was the most common yeast species, followed by C. krusei (33.3%), and C. parapsilosis (13.3%). Candida albicans was conspicuously absent. Ten patients (71.4%) had primary transplant-related complication (>2 days) including hemolytic uremic syndrome/thrombotic thrombocytopenic purpura (HUS/TTP) (n = 5), severe hemorrhagic cystitis (n = 3), and bacteremia (n = 2). Seven (50.0%) patients expired and in three (21.4%) deaths were attributed to fungemia. The impact of a primary transplant-related complication on short-term survival in this setting was not significant (P = 0.07) (HUS/TTP (P > 0.5); neutropenia (P > 0.5); GVHD (P = 0.35)). Removal of CVC did not alter outcome in our group (P > or = 0.5) although in patients with persistent fungemia (>72 h), and those with preceding bacteremia, mortality was significantly higher (P = 0.002). Conventional prognosticators of poor outcome did not adversely effect short-term survival in our transplant recipients with hematogenous candidiasis. The predominance of C. glabrata and C. krusei breakthrough infections was similar to what is seen with high-dose fluconazole (400 mg) prophylaxis, and no adverse effects of low-dose fluconazole in terms of increased incidence of non-susceptible Candida species was seen.
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PMID:Candida glabrata and Candida krusei fungemia after high-risk allogeneic marrow transplantation: no adverse effect of low-dose fluconazole prophylaxis on incidence and outcome. 1178 48

KL-6, a mucinous high-molecular weight glycoprotein expressed on type 2 pneumocytes, has been shown to be elevated in the serum and bronchoalveolar lavage fluid of patients with interstitial pneumonitis (IP). We measured the serum levels of KL-6 in patients after they had undergone allogeneic bone marrow transplantation (BMT) to determine whether KL-6 could be a clinically useful indicator for the development of IP. The serum concentrations of KL-6 were determined by a sandwich-type enzyme-linked immunosorbent assay using an anti-KL-6 monoclonal antibody. A total of 1028 samples were tested from 76 patients (78 transplantations) who received BMTs. The KL-6 values were markedly elevated in patients with pulmonary complications, but not in those with acute and chronic graft-versus-host disease, hemorrhagic cystitis, herpes encephalitis, sepsis, and veno-occlusive disease. The serum levels of KL-6 from patients with pulmonary complications were significantly higher than from those without pulmonary complications (P < .001) and those with other complications (P < .001). Of the 12 patients with pulmonary complications, 6 had idiopathic IP (IIP). The levels were not high at the onset of IIP. Four of 6 IIP patients showed marked elevations of KL-6 levels in parallel with the severity of IP and died of respiratory failure without response to treatment. Assessment of serum KL-6 levels might not be useful for the early diagnosis of IP, but may be a useful indicator for monitoring the severity of IP after BMT.
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PMID:Serum KL-6 levels in patients with pulmonary complications after allogeneic bone marrow transplantation. 1179 6

A six-year-old boy was diagnosed with beta-thalassaemia major during infancy. Since then, he required monthly blood transfusion and irregular iron chelation therapy. He had hepatosplenomegaly and elevated liver enzymes; the serum ferritin was up to 3800 ng/mL. An echocardiogram showed left-ventricular enlargement. His one-antigen-mismatched mother was chosen as a bone marrow donor. He was pretreated with intensive red blood cell transfusion and hydroxyurea for 6 weeks prior to conditioning. The conditioning included total body irradiation (300 cGy), busulfan (14 mg/kg), cyclophosphamide (160 mg/kg) and anti-thymocyte globulin (rabbit; 90 mg/kg). Marrow cell dose was 5.4 x 108/kg. Graft versus host disease (GVHD) prophylaxis included cyclosporine A (CSA) and methylprednisolone. Neutrophil engraftment occurred on day 23. Grade II acute GVHD occurred on day 45. The patient developed complications including septicaemia, haemorrhagic cystitis, intracranial haemorrhage and heart failure. He subsequently recovered from the complications without sequelae. The patient remained transfusion-independent at a follow-up examination after 18 months. This case suggested that a mismatched family member may be considered as a bone marrow donor for beta-thalassaemia major. In places where conventional treatment is not feasible, for example, in China, this approach may be an alternative option. A more intensive immunosuppressive regimen and a higher marrow cell dose may be important for successful engraftment. High-dose anti-thymocyte globulin may also prevent severe GVHD.
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PMID:Bone marrow transplantation for beta-thalassaemia major by an HLA-mismatched parent. 1204 3

The availability of an i.v. form of busulfan (Bu) has prompted investigation of administration schedules other than the 4-times-daily dosage commonly used with oral Bu. We have studied an allogeneic stem cell transplantation (SCT) preparative regimen comprising fludarabine (FLU) 50 mg/m2 on days -6 to -2 plus i.v. Bu 3.2 mg/kg daily in a 3-hour infusion on days -5 to -2. The regimen was given to 70 patients aged 15 to 64 years (median, 41 years) with hematologic malignancy. Thirty-six patients (51%) had high-risk malignancy, 28 (40%) had unrelated or genotypically mismatched related donors (alternate donors [AD]) and 29 (41%) received bone marrow rather than blood as stem cell source. Acute GVHD prevention comprised antithymocyte globulin 4.5 mg/kg over 3 days pretransplantation, cyclosporin A, and short-course methotrexate with folinic acid. Hepatic toxicity was transient and there was no clinically diagnosed veno-occlusive disease. Grade II stomatitis occurred in 49 patients (70%) and hemorrhagic cystitis in 9 patients (13%). One patient with subtherapeutic phenytoin levels had a convulsion 8 hours after the third i.v. Bu dose, but no other neurotoxicity was apparent. Incidence of acute GVHD grades II to IV was 8% and incidence of grade III-IV was 3%, with no deaths from this cause. Actuarial incidence of chronic GVHD at 2 years is 38%. There were 2 cases of graft failure in unrelated donor BMT recipients, 1 of which was reversed by asecond transplantation. With a median follow-up of 16 months (range, 6-27 months), transplantation-related mortality at 100 days and 2 years was 2% and 5% for matched related donor (MRD) SCT and 8% and 19% for AD SCT, respectively (P = not significant). Relapse rates were 21% for 34 patients with acute myeloid leukemia (AML) in complete remission or chronic myeloid leukemia in chronic phase (low-risk), 66% for 19 patients with high-risk AML, and 18% for 17 patients with other active malignancy. Projected disease-free and overall survival rates at 2 years were 74% and 88% for low-risk disease, 26% and 37% for advanced AML, and 65% and 71% for other high-risk disease, respectively. Pharmacokinetic studies were done using 11 samples with the first and fourth doses of Bu. Kinetics were linear, and for the first and fourth doses, the half-lives were 2.60 +/- 0.44 and 2.57 +/- 0.36 hours, respectively. Clearances were 106.77 +/- 16.68 and 106.86 +/- 21.57 mL/min per m2, peak concentrations (Cmax) were 3.92 +/- 0.31 and 3.96 +/- 0.28 mcg/mL, and Bu areas under the plasma concentration versus time curve (AUC) were 4866.51 +/- 771.42 and 4980 +/- 882.80 microM x min, respectively. Bu was completely cleared within 24 hours and the day 4 pharmacokinetic values were very similar to those on day 1 for every patient. The cumulative AUC was comparable to the target range established for p.o. Bu. This regimen incorporating once-daily i.v. Bu is convenient to give, is relatively well tolerated, gives predictable blood levels, and deserves further study in circumstances in which cytoreduction as well as immune suppression is needed.
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PMID:Once-daily intravenous busulfan given with fludarabine as conditioning for allogeneic stem cell transplantation: study of pharmacokinetics and early clinical outcomes. 1237 50

Adenovirus (AdV) infections have been increasingly recognized as significant pathogens that may cause severe morbidity and mortality among stem cell transplant (SCT) recipients. AdV can cause localized infections such as hemorrhagic cystitis (HC), pneumonia, hepatitis and also disseminated disease that can lead to death. We report a case of severe hemorrhagic cystitis in a SCT recipient who died 83 days after transplant. In this patient, AdV recovery was not constantly detected. In fact, fluctuations of the AdV detection in leukocytes and urine were observed by culture and PCR. When analyzing this viral cyclic recovery with different signs or symptoms in the patient, we observed an inverse association with the presence of acute graft-versus-host disease (GVHD). Whether these fluctuations represent donor-derived reactivity, indirectly manifested by the presence of GVHD, requires further study. This is the first case describing a dynamic pattern of AdV replication in leukocytes and urine samples from a patient with severe HC and the temporal correlation with GVHD.
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PMID:Cyclic recovery of adenovirus in a stem cell transplant recipient: an inverse association with graft-versus-host disease. 1262 67

Busulfan (Bu) is an important component of some myeloablative regimens prior to stem cell transplantation (SCT). Over the last few years it has been shown that other drugs administered concomitantly can influence Bu pharmacokinetics. In the present study, we compared Bu concentrations (trough levels) in three groups of patients. Group A (n=5) received metronidazole as graft-versus-host disease prophylaxis during Bu treatment. Group B (n=9) received Bu only for 2 days followed by 2 days of Bu and metronidazole. Group C (n=10) was a control group that received Bu without metronidazole. The mean Bu levels for Group A receiving metronidazole during conditioning was significantly (P<0.001) higher (948+/-280 ng/ml), compared to those observed in the control group (507+/-75 ng/ml). In Group B, the administration of metronidazole resulted in a significant (P<0.001) increase in Bu levels (807+/-90 ng/ml) during the last 2 days, compared to 452+/-68 ng/ml during the first 2 days. In Group A, one patient died with multiorgan failure, three experienced veno-occlusive disease (VOD) and one developed hemorrhagic cystitis. Elevated liver transaminases (AST, ALT) and bilirubin were detected in all Group A patients. In Group B, six patients had elevated liver function tests but no VOD was observed. We conclude that metronidazole should not be administered simultaneously with Bu to avoid the high plasma levels of Bu, which may lead to severe toxicity and/or treatment related mortality.
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PMID:The effect of metronidazole on busulfan pharmacokinetics in patients undergoing hematopoietic stem cell transplantation. 1266 36

We conducted a retrospective study to investigate the incidence, risk factors, and clinical features of hemorrhagic cystitis (HC) following allogeneic hematopoietic cell transplantation (allo-HCT). Adult patients who developed HC after allo-HCT were identified from the HCT database of the Asan Medical Center and their medical records were reviewed. From December 1993 to August 2001, a total of 210 adult patients underwent allo-HCT. Fifty-one patients developed HC with a cumulative incidence of 25.7%. The median onset of HC was post-transplant day 24 (range, -2 to 474), and the median duration was 31 days (range, 8 to 369). Significant risk factors for HC by univariate analysis included diagnosis of chronic myelogenous leukemia (p=0.028), unrelated HCT (p=0.029), grade III-IV acute graft-versus-host disease (GVHD) (p<0.001), extensive chronic GVHD (p=0.001), and positive cytomegalovirus antigenemia between post transplant days 31 and 60 (p=0.031). Multivariate analysis showed that grade III-IV acute GVHD was the most important risk factor for the occurrence of HC after allo-HCT (odds ratio, 3.38; 95% CI, 1.36-8.39). Late-onset HC, which occurred beyond 3 weeks after allo-HCT, was more frequently associated with GVHD than early-onset HC (p=0.007). Our data suggest that a portion of late-onset HC might be a manifestation of GVHD.
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PMID:Hemorrhagic cystitis following allogeneic hematopoietic cell transplantation. 1269 15

A 35-year-old male with chronic myeloid leukemia in the accelerated phase received a peripheral blood stem cell transplant from his HLA-DR-mismatched mother. Graft-versus-host disease (GVHD) prophylaxis was with short-term methotrexate and tacrolimus. After transplantation, grade II skin acute GVHD occurred and was unsuccessfully treated with bolus methylprednisolone administration. The acute GVHD progressed to grade III of the skin, gut and liver, and mycophenolate mofetil (MMF) was accordingly administered at a daily dose of 2 g. This treatment resulted in a dramatic improvement in the clinical features of the acute GVHD. The patient suffered from hemorrhagic cystitis and several episodes of cytomegalovirus antigenemia. MMF may be useful for steroid-resistant acute GVHD despite an increasing risk of viral infections.
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PMID:[Successful treatment of refractory acute GVHD with mycophenolate mofetil after peripheral blood stem cell transplantation from the patient's one locus-mismatched mother]. 1457 20


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