Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 48-year-old Japanese man was admitted to our hospital because of general fatigue, nasal bleeding, and petechiae on his extremities. He was diagnosed with acute myelomonocytic leukemia with trilineage myelodysplasia (T-MDS). Chromosomal analysis of bone marrow cells revealed t(7;11)(p15;p15), which has been rarely reported but known to be characteristic of Japanese patients. Although t(7;11)(p15;p15) has been reported mainly in acute myelogenous leukemia (AML), it can be occasionally found in so-called stem cell diseases such as chronic myelogenous leukemia or chronic myeloproliferative disorders. Therefore, t(7;11)(p15;p15) might affect trilineage progenitors or stem cells as well as myeloid lineage cells, subsequently resulting in AML with T-MDS, as in our case reported here.
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PMID:t(7;11) and trilineage myelodysplasia in acute myelomonocytic leukemia. 861 92

Ilmofosine, an ether lipid derivative of lysophosphatidylcholine has antineoplastic activity in vitro and in vivo. Maximum efficacy in preclinical models is associated with prolonged exposure to the drug. In a Phase I trial of a weekly 2 hour infusion schedule of ilmofosine, a syndrome of lethargy, diminished performance status, and mild hepatotoxicity was dose-limiting at 550 mg/m2. To avoid the higher drug concentrations associated with a brief infusion, a Phase I study of a weekly 24 hour infusional schedule was undertaken in an attempt to maximize dose-intensity. Doses were escalated from 550 to 800 mg/m2. Toxicities included nausea, anorexia, fatigue, and minor elevations of liver function tests. The dose limiting toxicity at 800 mg/m2 was a syndrome of severe abdominal pain. No neutropenia or thrombocytopenia was observed except in one patient who was found to have a myelodysplastic syndrome, thought not to be related to drug therapy. The more prolonged infusion schedule of ilmofosine did not result in a substantial increase in the tolerable dose.
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PMID:Phase I trial of ilmofosine as a 24 hour infusion weekly. 872 47

The aminothiol, amifostine (Ethyol; U.S. Bioscience, West Conshohocken, PA), is a cytoprotective agent that ameliorates the toxicities of anticancer therapy. In vitro, amifostine promotes the formation and survival of primitive hematopoietic progenitors derived from myelodysplastic bone marrow (BM) specimens. To evaluate the hematological effects of amifostine, 18 patients with myelodysplastic syndrome (MDS) and one or more refractory cytopenias received treatment with amifostine in a Phase I/II study. Four cohorts received intravenous treatment with 100, 200, or 400 mg/m2 amifostine three times a week, or 740 mg/m2 weekly for three consecutive weeks followed by 2 weeks observation. Nonresponding patients received a second course of therapy at the next higher dose level depending upon drug tolerance. Bone marrow (BM) progenitor growth was assessed before treatment and after day 21. Diagnoses included refractory anemia (7), refractory anemia with ringed sideroblasts (5), refractory anemia with excess blasts (RAEB) (4), and RAEB-in transformation (RAEB-t) (2). Single- or multi-lineage hematologic responses occurred in 15 patients (83%) treated with the three-times-a-week dose schedule. Fourteen patients had a 50% or greater increase in absolute neutrophil count with amifostine treatment (range, 426 to 11,348/microL). Platelet count increased in 6 (43%) of 14 patients with thrombocytopenia (absolute increase, 16, 000 to 110,000/microL), and 5 of 15 red blood cell transfusion-dependent patients had a 50% of greater reduction in transfusion needs. Assayable hematopoietic progenitors increased in 13 of 15 evaluable patients; including CFU-GEMM (12), BFU-E (8), and CFU-GM (6). Amifostine doses less than or equal to 200 mg/m2 were well tolerated, whereas grade II nausea, vomiting, and fatigue was limiting at higher doses. Three patients with excess blasts before enrollment experienced an increase in BM blast percentage and two patients had evolution to acute leukemia that persisted after treatment withdrawal. We conclude that amifostine administered at doses </=200 mg/m2 three times a week is well tolerated and has hematologic activity in patients with MDS.
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PMID:Stimulation of hematopoiesis by amifostine in patients with myelodysplastic syndrome. 1153 40

Therapy-related leukemia and myelodysplastic syndrome (TRL/MDS) in Japan were analysed in a multi-institution study to assess clinical, cytogenetic aspects, and prognostic factor. From 1985 to 1994, 405 cases of adult TRL/MDS were diagnosed and overall percentage of TRL/MDS in leukemia and MDS was 1.9%. Median age was 61 years old. The median latency from primary malignancies was 53.4 months, which latency was significantly shorter in the patients treated with chemotherapy. Primary malignancies were hematologic in 39%. Common symptoms were fatigue/ weakness and anemia. Chromosome 7,5, and 11 were frequently involved. MLL gene rearrangement were detected in 12 of 64 analysed cases. Overall median survival was 10.0 months. Body weight loss, neurologic abnormality, hypoproteinemia, hypofibrinogenemia, proteinuria, lack of Auer rods, and 5q-were prognostic factors in TRL/MDS. This large population study documented some datas useful for the prevention of TRL/MDS.
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PMID:[Therapy-related leukemia and myelodysplastic syndrome: a multi-institution study in Japan]. 946 95

Health-related quality of life (QOL) is a dynamic, subjective, multidimensional concept. In chronic illnesses such as myelodysplastic syndromes (MDS), management typically focuses on control of the disease and its symptoms. Yet an equally important consideration is maintaining the patient's QOL. Much research remains to be done on the subject of QOL in the MDS population. MDS patients have unique problems that can affect QOL: they tend to be elderly and to have comorbid conditions; they develop complications resulting from cytopenias such as infection and bleeding; they experience fatigue; they run the risk of converting to a form of acute leukemia typically resistant to therapy; and they face uncertainty. This paper will address the above problems using a conceptual approach to QOL that has been useful for patients with cancer and various chronic illnesses. The approach, based on the work of Ferrell and Cella, concentrates on five areas of the patient's life: the physical, functional, emotional, social, and spiritual. Actual testing of this conceptual framework in the MDS patient population has begun. Here methods of systematically testing and assessing QOL are discussed in order to help clinicians meet the primary purpose of therapy in the setting of chronic illness: improving or preserving the individual's QOL.
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PMID:Quality of life and psychosocial adjustment in patients with myelodysplastic syndromes. 973 99

Topotecan, a water-soluble analogue of camptothecin, is a newly available cytotoxic agent which acts as an inhibitor of topoisomerase I, an enzyme necessary for DNA replication. Topotecan is a semisynthetic product derived from camptothecin, which was discovered during a National Cancer Institute cytotoxic drug screening program almost 30 years ago. It acts by forming a stable covalent complex with the DNA/topoisomerase I aggregate, the so-called 'cleavable complex'. This process leads to breaks in the DNA strand resulting in apoptosis and cell death. Topotecan possesses a serum half-life of approximately 3 h, a high volume of distribution with high tissue uptake and a low protein binding. The chemical structure is based on a lactone ring. Topotecan undergoes reversible hydrolysis from its biologically active lactone form to the open ring inactive carboxylate form. It is also able to penetrate the intact blood-brain barrier. Since most of the agent is excreted by the kidneys, dose adjustment is necessary when renal function is impaired. In contrast, pharmacokinetic behavior is unchanged in patients with limited hepatic function. The principal toxicity of topotecan when administered at standard doses is neutropenia, but thrombocytopenia and anemia occur as well, while the nonhematological toxicities are usually mild. Alopecia is frequently observed and some patients may suffer from pronounced fatigue. Most clinical data available are based on the following schedule: 1.5 mg/m2 topotecan given as a 30-min infusion, days 1-5. There are currently only minimal data available regarding a dose-antitumor activity relationship. Other topotecan administration schedules are currently being investigated. Preclinical data suggest that continuous-infusion schedules may be a better application form in terms of both, toxicity and antitumor activity. However, clinical trials could not confirm these results to date. Results of phase II studies suggest considerable antitumor activity of single agent topotecan in small cell lung cancer and ovarian cancer patients. A randomized phase III trial of topotecan versus paclitaxel in ovarian cancer patients pretreated with cisplatin/cyclophosphamide has demonstrated that topotecan is as effective as paclitaxel in the second-line treatment of these patients. Activity of topotecan was also observed in non-small-cell lung cancer, refractory leukemias/myelodysplastic syndromes and in childhood sarcomas. Due to its unique mechanism of action and lack of cross-resistance, cisplatin, etoposide, cytarabine and paclitaxel are potential interacting partners for combination chemotherapy regimens. However, the best combination regimen as well as the optimal combination schedule have yet to be conclusively determined. The potential of topotecan in a variety of solid tumors, as well as its use in combination regimens for ovarian and small cell lung cancer is currently being investigated.
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PMID:Topotecan - A novel topoisomerase I inhibitor: pharmacology and clinical experience. 988 71

In this pilot trial of interleukin (IL)-2-treated autologous bone marrow (BM) and peripheral stem cell (PSC)-supported high-dose chemoradiotherapy, we report 36 patients with poor-prognosis leukemia and lymphoma who received BM and/or granulocyte colony-stimulating factor (G-CSF)-mobilized autologous PSCs that had been exposed to IL-2 for 24 hours ex vivo. Patients then received IL-2 by low-dose continuous intravenous (i.v.) infusion until hematologic reconstitution and then by intermediate-dose continuous i.v. infusion for six 2-week maintenance cycles given at 1-month intervals. The median Day to neutrophils over 500/microL was 22 with BM and 10 with PSCs (p = 0.01). The median Day to platelets >20,000/microL was 50 for BM and 25 for PSCs, and to platelets >50,000/microL was 138 for BM and 34 for PSCs (p not significant). After the first three patients received IL-2 at 2 mIU x m(-2) x day(-1) and had slow reconstitution, four patients were treated without IL-2 until the maintenance phase following reconstitution. The remaining 29 patients received the initial "post-infusion" IL-2 at 1 mIU x m(-2) x day(-1). Toxicities associated with the infusion of IL-2-activated cells consisted of chills and fever in about one-half of the patients and transient hypotension in 12%. Low-dose IL-2 by continuous i.v. infusion in the early posttransplant period was associated with exacerbation of fever, diarrhea, and altered mental status in a minority of patients. The major dose-limiting toxicities of maintenance IL-2 were fever, fatigue, gastrointestinal symptoms, skin rash, and dyspnea. Among 24 lymphoma patients, nine are in continuous complete remission (CCR) from 18-48 months, and 15 have died (12 due to relapse and three of therapy-related toxicities). Of 12 acute leukemia patients, two with acute lymphoblastic leukemia (ALL) are in CCR at 38 and 43 months, and one patient who was in cytogenetic but not molecular remission of Philadelphia chromosome-positive ALL died of progressive leukemia at Day 108. Three of nine with myeloid leukemia are in CCR at 21, 46, and 53 months; one is in hematologic and cytogenetic remission of acute promyelocytic leukemia at 55 months with multiple new cytogenetic abnormalities; one is alive at 54 months with pancytopenia after incomplete hematologic recovery followed by multiple new cytogenetic abnormalities (myelodysplasia); and one had an unrelated donor transplant after relapsing 4 months following protocol therapy. One myeloid leukemia patient remains without evidence of relapse, but is transfusion-dependent at 15 months following transplant.
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PMID:Interleukin-2-activated autologous bone marrow and peripheral blood stem cells in the treatment of acute leukemia and lymphoma. 1023 39

A rare case of Behcet's disease associated with myelodysplastic syndrome (MDS) is described. A 50-year-old Korean female suffering recurrent oral ulcer, genital ulcer, fatigue, arthralgia in both knees and fever was diagnosed as Behcet's disease. The findings of bone marrow aspirates were consistent with refractory anemia, a subtype of myelodysplastic syndrome. Chromosomal analysis of bone marrow cells revealed 46,XX,-8,-20,+der(8)t(8;20)(p23;p10),+der(8) t(8;20)(p23;q10)[30]. The chromosomal changes found in this patient were different from those of previous reports, which mostly revealed trisomy 8. If anemia, low reticulocyte count and dyspoietic cells are sustained in Behcet's disease, physicians should be alert to the possibility of MDS with aberration in chromosome 8 and perform a bone marrow study for the proper diagnosis and treatment of the disease. We presented a case of Behcet's disease associated with MDS, which is the first Korean case.
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PMID:Behcet's disease associated with myelodysplastic syndrome: a case report. 1064 51

A 44-year-old woman suffered from recurrent fever, edema and fatigue. Laboratory data revealed renal dysfunction, low proteinemia, disseminated intravascular coagulation (DIC) and myelodysplasia. A renal and lymph node biopsy showed a marked angiogenesis. Serum levels of vascular endothelial growth factor (VEGF), and interleukin (IL)-6 were markedly increased, suggesting a pathogenesis related to VEGF-induced angiogenesis. The symptoms were remitted after treatment with cyclosporin A. No evidence of solid tumors, malignant lymphoma, Castleman's disease or POEMS (polyneuropathy, organomegaly, endocrine disorder, M-proteinemia and skin change) syndrome, reported to induce a high serum VEGF level, was obtained. This case may have involved an unknown mechanism which induced an overexpression of VEGF and IL-6.
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PMID:High fever, renal failure, disseminated intravascular coagulation and myelodysplasia accompanied with enhanced angiogenesis possibly due to overexpression of vascular endothelial growth factor. 1088 5

In addition to immunomodulatory and cytokine-modulatory properties, thalidomide has antiangiogenic activity. It has been investigated in a number of cancers including multiple myeloma, myelodysplastic syndromes, gliomas, Kaposi's sarcoma, renal cell carcinoma, advanced breast cancer, and colon cancer. Its role has been best explored in myeloma, where, at daily doses of 100 to 800 mg, it is remarkably active, causing clinically meaningful responses in one-third of extensively pretreated patients and in over half of patients treated early in the course of the disease. It also acts synergistically with corticosteroids and chemotherapy in myeloma. Thalidomide produces improvement of cytopenias characteristic of myelodysplastic syndrome, resulting in the reduction or elimination of transfusion dependence in some patients. Responses have also been seen in one-third of patients with Kaposi's sarcoma, in a small proportion of patients with renal cell carcinoma and high grade glioma and, in combination with irinotecan, in some patients with colon cancer. Thalidomide is being investigated currently in a number of clinical trials for cancer. Drowsiness, constipation and fatigue are common adverse effects seen in 75% of patients. Symptoms of peripheral neuropathy and skin rash are seen in 30%. A minority of patients experience bradycardia and thrombotic phenomena. Despite the high frequency of adverse effects, those severe enough to necessitate cessation of therapy are seen in only 10 to 15% of patients. A therapeutic trial of thalidomide should be considered in all patients with myeloma who are unresponsive to or relapse after standard therapy. In other malignant diseases, the most appropriate way to use the drug is in the setting of well designed clinical trials. In the absence of access to such studies, thalidomide could be considered singly or in combination with standard therapy in patients with no meaningful therapeutic options.
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PMID:Thalidomide in cancer: potential uses and limitations. 1143 82


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