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)

The aim of this study was to understand the impact of chronic graft-versus-host disease (cGVHD) on the overall health status of hematopoietic cell transplantation (HCT) survivors. Subjects included 584 individuals who had undergone allogeneic HCT between 1976 and 1999, survived 2 or more years, and completed a 255-item health questionnaire. Global assessment of health status was facilitated by measurement of 6 health status domains: general health, mental health, functional impairment, activity limitation, pain, and anxiety/fear. Information regarding diagnosis of cGVHD was abstracted from medical records, and presence of active cGVHD in the preceding 12 months was self-reported. The incidence of cGVHD in participants was 54%, of whom 46% reported active cGVHD. In multivariable analyses, subjects with active cGVHD were more likely to report adverse general health, mental health, functional impairments, activity limitation, and pain than were those with no history of cGVHD. However, health status did not differ between those with resolved cGVHD and those who never had cGVHD. We conclude that active cGVHD has a significant impact on many aspects of the overall health status of HCT survivors and that, most importantly, those successfully treated for cGVHD do not appear to have long-term impairments.
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PMID:Impact of chronic graft-versus-host disease on the health status of hematopoietic cell transplantation survivors: a report from the Bone Marrow Transplant Survivor Study. 1678

Fasciitis, one of the presentations of chronic skin graft-versus-host disease (GVHD), is characterized by symmetrical inflammatory swelling of extremities with or without eosinophilia, but it is rarely reported. This article describes a patient with the clinical and histologic features of fasciitis, as the only form of chronic GVHD that developed 20 months after HLA-matched allogeneic peripheral hematopoietic stem cell transplantation (HSCT) for chronic myelogenous leukemia (CML). She reported tightness of the skin and pain in both wrists and elbows on motion, with edema of the limbs. A deep cutaneous biopsy showed thickening of the subcutaneous fascia with inflammatory infiltrates. The patient was treated with cyclosporine and prednisone, which resulted in much improvement of her symptoms and signs related to the fasciitis. The authors recommend that clinicians maintain a high index of suspicion for fasciitis because fasciitis is a distinct entity among the chronic GVHD that may lead to a functional disability.
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PMID:Fasciitis after allogeneic peripheral blood stem cell transplantation in a patient with chronic myelogenous leukemia. 1704 14

Mucositis occurs in < or = 98% of patients undergoing stem cell transplant for haematological malignancies and is associated with significant morbidity and mortality. Patients with severe mucositis have more pain, more difficulty with daily activities such as talking and eating, and are more likely to have bacteraemia. Palifermin is a keratinocyte growth factor that has been shown to decrease severity and duration of mucositis with a concurrent decrease in patient-reported symptoms and use of narcotics and total parenteral nutrition. Research is ongoing into palifermin's potential ability to decrease graft-versus-host disease and improve reconstitution of functional T lymphocytes after allogeneic stem cell transplant, to hasten wound healing and to reduce mucositis following external beam radiation therapy in solid tumour patients.
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PMID:Palifermin: a keratinocyte growth factor that reduces oral mucositis after stem cell transplant for haematological malignancies. 1705 84

A 42-year-old woman was referred to us for the treatment of relapsed Philadelphia-positive acute lymphoblastic leukemia (Ph+ALL), which had been maintained in complete remission for seven years after an allogeneic bone marrow transplantation (allo-BMT) from an unrelated donor. She received remission-reinduction chemotherapy combined with imatinib mesylate. After the documentation of the molecular remission of Ph+ALL, she underwent the second allo-BMT from another unrelated donor. GVHD prophylaxis consisted of tacrolimus (TAC) and short-term methotrexate. On day 21, she suddenly suffered from an intermittent severe, cramp-like pain in the right lower limb. The typical pain profile and exclusion of other causative diseases suggested calcineurin-inhibitor induced pain syndrome (CIPS) as a possible cause of pain. The pain was gradually relieved after discontinuation of TAC and administration of several analgesic drugs. CIPS is rarely seen following allogeneic stem cell transplantation (allo-SCT); only three cases have been so far reported to our knowledge. Thus, physicians should be alert to this complication in patients receiving allo-SCT.
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PMID:[Acute lymphoblastic leukemia presenting with calcineurin-inhibitor induced pain syndrome after a second allogeneic bone marrow transplantation]. 1709 76

Oral chronic graft versus host disease (cGVHD) is common and a major cause of morbidity and loss of quality of life in long term survivors. Cyclosporine with prednisone remains the first line therapy for oral manifestations of cGVHD. However, even with routine administration of systemic agents, many patients with oral manifestations of cGVHD do not have resolution of their disease and may benefit from incorporation of local therapy. Budesonide is a highly potent steroid which has minimal systemic side effects and being used for oral cGVHD. We designed a retrospective study to compare treatment results of patients with oral cGVHD who received topical budesonide in addition to systemic therapy that consists of combined prednisone and cyclosporine (Group A, n = 12), with the treatment results of patients who were administered the same systemic therapy alone (Group B, n = 11) to determine whether budesonide mouthwash had any advantage on response rates. Three mg topical budesonide/10 ml saline was used 3-4 times a day for up to 6 months in group A. Diagnosis, clinical staging, and treatment response scoring for cGVHD were performed according to National Institutes of Health (NIH) consensus criteria. At the baseline examination, there were no statistically significant differences in terms of median oral cGVHD examination scores between two groups. After treatment, there was statistically significant decrease in median oral cGVHD examination scores compared to baseline (P < 0.001 and 0.021), and significant differences were found between two groups (P < 0.032). Overall response rate was 83% and 36% for group A and B, respectively (P = 0.036). However, no statistically significant differences were found between median pain scores of two groups before and after treatment (P = 0.740 and P = 0.091). No major systemic side effects and oral candidiasis were observed in two groups of patients. We concluded that topical budesonide might be added to systemic therapy to obtain better response rates in patients with oral cGHVD.
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PMID:The effect of budesonide mouthwash on oral chronic graft versus host disease. 1710 90

The use of high-dose corticosteroids for graft-versus-host disease (GVHD) treatment represents a major risk factor for long-term invasive fungal infections. The aim of this study was to investigate the safety and tolerance of weekly prophylactic administration of once-weekly high-dose (7.5 mg/kg) of liposomal amphotericin B (L-AmB) therapy in 21 adult patients receiving high-dose prednisone (2 mg/kg/day) for acute GVHD therapy after reduced intensity conditioning (RIC) allogeneic stem cell transplantation (allo-SCT). Patients received a median of 4 (range, 1-8) infusions of L-AmB. Seven patients (33%; 95% confidence intervals (CI), 13-53%) discontinued taking the study drug owing to study drug-related adverse events, including elevated serum creatinine (>1.5 times from baseline values; n=5), hypotension and pain (n=1), and violent chest pain and arrhythmia (n=1). The overall frequency of infusion-related reactions was 29% (n=6; 95% CI, 10-48%), but these reactions were always transient and relieved by stopping the infusion. This safety data provide support for an efficacy study of this prophylaxis strategy, because this may help further improving the outcome of RIC or nonmyeloablative allo-SCT.
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PMID:High-dose weekly liposomal amphotericin B antifungal prophylaxis following reduced-intensity conditioning allogeneic stem cell transplantation. 1726 59

Graft versus host disease (GVHD) occurs after a hematopoietic stem cell transplantation (HSCT) when the donor's immune system rejects the recipient's body, leading to significant morbidity and mortality. Increased numbers of chronic GVHD (c-GVHD) patients are likely to be seen by dental professionals because of the advances made in transplantation. The oral cavity may be the primary or the only site of c-GVHD and may have persistent lesions after resolution has occurred in other areas. Approximately 80% of patients with extensive c-GVHD present some type of oral involvement, including xerostomia, oral pain and lesions. Dental and oral care can be challenging for these patients. This paper discusses the manifestations and treatment of oral c-GVHD and presents the case history of a 15-month-old girl who developed severe oral GVHD with an unusual periodontal presentation and early loss of primary teeth.
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PMID:Severe gingival recession and early loss of teeth in a child with chronic graft versus host disease: a case report. 1753 21

A patient with extensive cutaneous chronic graft-versus-host disease (cGVHD) affecting 100% of the body surface, with painful ulcerations that involved 20% of it, was treated unsuccessfully during 9 months with steroids, cyclosporine-A (CSa), sirolimus, tacrolimus, mychophenolate mofetil (MMF), infliximab, and rituximab. Twenty-one months after the allograft the patient was started on alemtuzumab, 10 mg/day subcutaneously, for 6 consecutive days every 4 weeks. Seven months after starting the treatment, 100% of the ulcers had disappeared, as had the pain. To our knowledge, there are no reports of the use of alemtuzumab in the treatment of extensive, ulcerated, refractory cutaneous cGVHD. The data presented here suggest that this agent may be useful in some patients with refractory forms of cGVHD.
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PMID:Alemtuzumab-induced resolution of refractory cutaneous chronic graft-versus-host disease. 1815 55

Oral chronic graft-versus-host disease (cGVHD) is a significant and serious complication following allogeneic hematopoietic stem cell transplantation (HSCT). The purpose of this study was to characterize the distribution, type, and extent of lesions and their correlation with patient-reported symptoms such as pain and discomfort. The effect of time since transplantation on these measures was also assessed. Consecutive patients with oral cGVHD referred to the Center for Oral Disease at Brigham and Women's Hospital, Boston, MA, were evaluated over a 2-year period. Subjective data included the responses to 4 targeted symptom questions (yes/no) and a visual analog scale pain score (0-10). Objective data included the location and extent of reticulation, erythema, and ulcerations using a previously published scoring system as well as time since HSCT. Multiple linear regression analyses were performed using SAS. We evaluated 27 patients, for a total of 79 clinic visits (median 2, range: 1-8). The median time since HSCT was 18 months (range: 5-157 months). The buccal and labial mucosa and tongue were the sites of 93% of all ulcerations, 72% of all erythematous lesions, and 76% of all reticular lesions, and were the most frequently affected sites. The gingiva, floor of mouth, and hard and soft palate were infrequently affected. Although uncommon, ulceration of the soft palate was the objective finding most highly correlated with increased pain (P < .0001), and there was a generalized significant trend for increased pain scores with increased extent of ulceration. Overall, 95% of pain scores were <or=5 (scale from 0-10, range: 0-7), with 40% reporting a score of zero. However, 80% admitted to avoiding certain foods because of mouth pain. After controlling for the presence and extent of ulcerations, we found that time since HSCT was inversely related to the pain score (P < .04). There was a statistically significant inverse relationship between the overall presence of ulceration and time since HSCT. We found that oral cGVHD most frequently affects the buccal and labial mucosa and the tongue. The functional impact was significant, as most patients had to restrict oral intake because of discomfort. Both the signs and symptoms associated with oral cGVHD tend to decrease over time. The association between ulceration of the soft palate and patient-reported pain highlights the significance of the location of involvement and the need for targeted approaches to therapy. Our findings, in large part, support the recently introduced National Institutes of Health response criteria for oral cGVHD, which is critical for the conduct of effective and meaningful research in this field; however, prospective application in clinical and investigative settings is necessary for evaluating its utility and efficacy in practice.
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PMID:Clinical evaluation of oral chronic graft-versus-host disease. 1815 67

Thalidomide, in development by Celgene, inhibits the effects of elevated TNFalpha and may consequently be of use in a range of diseases including cachexia, bacterial meningitis, rheumatoid arthritis, septic shock, AIDS, tuberculosis, multiple sclerosis, ulcerative colitis, graft-versus-host disease and systemic lupus erythematosus. In July 1998, Celgene received clearance from the US FDA to market and sell Thalomid (thalidomide) for the treatment of erythema nodosum leprosum (a severe and debilitating condition associated with leprosy) [291919], following a recommendation for approval by the FDA advisory committee in September 1997 [261846,263970]. In that same month, Celgene filed an IND for the treatment of the chronic autoimmune disorders Behcet's disease, and aphthosis [264366]. The trial will be conducted by investigators at the Mayo Clinic and Bowman Gray School of Medicine. It will be divided into two phases, the first phase lasting 4 weeks in which patients will receive 100 mg thalidomide or placebo, and a second open-label phase which will call back all patients to receive the same dose of thalidomide over a 24-week period. It will be determined whether the drug significantly reduces existing ulcerations and inhibits the formation of new lesions. Positive results of a National Institute of Allergy and Infectious Diseases trial for aphthous ulceration of the mouth in HIV-infected patients prompted Celgene to commence a pivotal trial for the same indication. A total of 84 patients will be randomized to 100 mg, 200 mg or 400 mg thalidomide/day for 4 weeks. Patients achieving a full response after 4 weeks will be re-randomized on 100 mg thalidomide or placebo for up to another year [248356]. The company has also completed the pivotal phase III trial for AIDS-related cachexia [225437]. Results from a pivotal phase II/III trial showed that the drug significantly increased body weight in AIDS patients, but also increased viral load initially. A total of 99 patients, who had lost more than 10% of their body weight due to HIV infection, received either 100 or 200 mg/day of thalidomide or placebo orally for 8 weeks. Although there was a significant increase in body weight associated with the 100 mg dose (p = 0.025), there was no difference in body weight changes between patients treated with 200 mg doses and those on placebo. There was a 55% dropout rate at the higher dose due to side-effects such as somnolence, rash, neutropenia, neuropathy and dizziness. Viral load was significantly increased after 4 weeks of treatment. However, there was no further increase in viral load at 8 weeks, and patients were not receiving triple combination antiviral therapy [243943]. In April 1996, Celgene initiated a phase II trial of thalidomide in London for the treatment of chronic intractable diarrhea in HIV positive patients. The double-blind, placebo-controlled trial will involve up to 120 patients, aged 18 to 65 inclusive, at three centers for 28 days of therapy; those on drugs will be orally dosed with 100 mg of thalidomide daily at bedtime. The primary endpoint is reduction in the occurrence of diarrhea [205006,206218]. The trial will be conducted in the US, the UK and Mexico [210069]. The company expanded its clinical trial program in June 1996, for use of thalidomide in graft versus host disease and AIDS complications, such as debilitating ulcers of the digestive system [212461]. A phase II trial for the treatment of cachexia in cancer patients was carried out at St George's Hospital, London. Ten patients received thalidomide (100 mg) orally for 8 weeks and ten received placebo. The study was structured to determine the ability of thalidomide to reduce or stabilize the symptoms of cachexia. Quality of life and levels of disease markers will also be assessed. Results showed that after a 3-week treatment period, patients who received thalidomide gained an average 4.5% in overall body weight versus 0.9% with placebo [190161]. Results from a 65 patient multicenter phase II/III trial for cachexia are still awaited [221227]. Celgene is also conducting a double-blind, placebo-controlled pivotal trial for the treatment of rheumatoid arthritis at New York University's Hospital of Joint Diseases. Levels of TNFalpha are increased in patients with rheumatoid arthritis. Indicators for the trial will be joint swelling and pain and levels of serological markers [177618]. A separate study is being conducted by the US National Institute for Allergy and Infectious Diseases, of thalidomide in combination with Chiron's IL-2 for the treatment of HIV infection [192218]. In vitro evidence suggests that thalidomide can inhibit the replication of HIV type 1 [169245]. In addition to the associated patent, WO-09214455, which discloses the use of thalidomide in TNF-related diseases, another Celgene patent, US-05463063, discloses a scaleable process to make high purity thalidomide [194937].
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PMID:Thalidomide Celgene Corp. 1846 84


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