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 single rising dose tolerance trial of rDNA interferon-alpha 2 (IFN-alpha 2) was conducted in eight patients with the diagnoses of non-Hodgkin's lymphoma (NHL), multiple myeloma, and chronic lymphocytic leukemia (CLL). Patients received a total of six i.m. doses at weekly intervals as follows: 1, 3, 10, 30, 60, and 100 x 10(6) IU. Patients were monitored at each dose level for serum IFN activity, anti-IFN antibodies, immunomodulation, clinical toxicity, and response. All patients exhibited clinical toxicity, including fever, chills, fatigue, headache, anorexia, mild-to-moderate leukopenia, nausea, and vomiting. Toxicity was dose-related, with significant side effects occurring in all patients at levels of 10 x 10(6) IU and above and some evidence of tachyphylaxis at higher doses. All side effects, including leukopenia and thrombocytopenia, were of short duration and were resolved within 3-5 days. Fevers, rigors, myalgias, and fatigue were partially alleviated by premedication with acetaminophen or hydrocortisone. Pharmacokinetic data indicated mean peak serum IFN titers greater than 90 at a dose of 10 x 10(6) IU and greater than or equal to 200 at doses greater than or equal to 30 x 10(6) IU 8 h after injection. No anti-IFN antibodies were detected. However, the serum levels achieved at higher doses were not linear, possibly indicating in vivo degradation. Total T cells, B cells, monocytes, and T subsets monitored by flow cytometry with monoclonal antibodies remained essentially constant throughout the trial. Although some patients demonstrated minor augmentations of antibody-dependent cellular cytotoxicity (ADCC) and natural killing (NK) activity at the lowest IFN-alpha 2 doses, the majority of patients demonstrated decreases in NK activity after higher IFN doses. No correlation between immunomodulation and clinical response to IFN was observed. At higher dose levels, the predominant immunomodulatory effect of IFN-alpha 2 was suppression of NK, ADCC, and blastogenic responses to T-cell mitogens and recall antigens. B-cell functional deficits as well as radioresistant T-helper and radiosensitive T-suppressor function assessed in a pokeweed mitogen-driven immunoglobulin secretion assay appeared unaffected by IFN administration. One myeloma patient showed progression and was discontinued after 60 x 10(6) IU. There were four patients (3 NHL, 1 myeloma) who achieved partial remission (greater than or equal to 50% tumor reduction) and three (1 CLL, 2 NHL) who showed objective tumor responses of less than 50%. These data suggest that rDNA IFN-alpha 2 is well-tolerated and may have significant antitumor activity against lymphoproliferative malignancies. Clin
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PMID:Immunomodulation by recombinant interferon-alpha 2 in a phase I trial in patients with lymphoproliferative malignancies. 660 23

Eighty-one patients with a variety of refractory disseminated malignant neoplasms have been treated in the first multiple fixed-dose phase I trial of recombinant leukocyte A interferon (IFL-rA). Each patient received IFL-rA by intramuscular injection, three times weekly for 28 days. Dosages were escalated in different patients from 1 to 136 x 10(6) units per injection. The toxic reactions seen with IFL-rA resembled those of nonrecombinant leukocyte interferon and included fever, chills, fatigue, anorexia, myalgia, headache, occasional nausea and vomiting, and dose-dependent reversible leukopenia and hepatic transaminase elevations. The pharmacokinetics of IFL-rA were also comparable with nonrecombinant leukocyte interferon. Objective evidence of antitumor activity was seen in non-Hodgkin's lymphoma, chronic lymphocytic leukemia, Hodgkin's disease, breast cancer, and melanoma, indicating that IFL-rA, the first genetically engineered biological response modifier available for testing in cancer patients, is biologically active in vivo.
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PMID:A multiple-dose phase I trial of recombinant leukocyte A interferon in cancer patients. 675 47

A 63-year-old man developed a mild hemorrhagic diathesis which led to the diagnosis of chronic lymphatic leukemia. Treatment with prednisone and chlorambucil was initiated. During the first 10 day-cycle (10 mg chlorambucil and 100 mg prednisone) no side effects were noted. On the 8th day of second cycle (10 mg chlorambucil and 25 mg prednisone) the patient noticed fever, tiredness, myalgia, pruritus and erythema on the skin. The third cycle (10 mg chlorambucil alone) hat to be stopped on the second day due to the development of myalgia, generalized erythroderma with exfoliation and edema of the face and arms. In the patch-test with chlorambucil, a strongly positive (histologically verified) allergic reaction was noted. A lymphocyte stimulation test (detecting in vitro lymphocytes sensitized to chlorambucil) was also positive. These findings, together with the marked clinical reaction to chlorambucil alone, led to the diagnosis of a delayed hypersensitivity reaction to chlorambucil. Such well documented allergic reactions to chlorambucil are very rarely described in the literature. Up to now only 1 case of immune hemolytic anemia, 1 case of Lyell-syndrome, 2 cases of delayed hypersensitivity reactions and a few cases of less well documented type I reactions have been described. In all these cases no crossreactivity with other alkylating agents occurred, and hence all patients could be successfully treated with cyclophosphamide.
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PMID:[Delayed allergic reaction to Chlorambucil (Leukeran). Case report and literature review]. 748 46

In Taiwan, as in other areas of Asia, the incidence of chronic lymphocytic leukemia (CLL) is low. A retrospective analysis was conducted to elucidate the clinicopathologic features of CLL patients in Taiwan. Of the 47 cases of CLL enrolled in this study, 45 were immunophenotyped as B-CLL; the other 2 were T-CLL. It was found that the lower the Binet and Rai stages of the B-CLL, the longer patients survive (p = 0.0131 and 0.0142, respectively). Univariate analysis showed that fatigue, splenomegaly, hepatomegaly and anemia are associated with poor survival with p values of 0.0203, 0.0184, 0.0001 and 0.171, respectively. By multivariate analysis with Cox's proportional hazard model, hepatomegaly and decrease in body weight were the two most significant predictors of survival. However, molecular parameters of kappa or lambda immunoglobulin (Ig) gene rearrangement or double allele rearrangement of Ig gene did not significantly increase the predictability of the prognosis.
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PMID:Genotypic characterization and multivariate survival analysis of chronic lymphocytic leukemia in Taiwan. 915 61

Interleukin 4 (IL-4) is a pleiotropic type II cytokine which has been shown to have a direct killing effect on lymphoma and B-cell chronic lymphocytic leukaemia (B-CLL) cells in vitro. The clinical effects and toxicity of IL-4 treatment in patients with B-CLL were evaluated. Fourteen patients with B-CLL who were in partial remission after chemotherapy received one, two or three 8-week cycles of escalating doses (2, 4 or 6 microg/kg/d s.c.) of IL-4 for 3 d/week. Clinical response was analysed after each treatment cycle and toxicity was monitored continuously. Ten patients (71%) had progressive disease (PD) during IL-4 treatment. This was mainly attributable to an increase (two- to fourfold) of the blood lymphocyte count during IL-4 therapy. After cessation of IL-4 treatment, the lymphocytosis decreased spontaneously in 8 out of 12 evaluable patients. Splenomegaly remained unchanged in 7/7 patients, whereas enlarged lymph nodes were reduced by > 50% in 1/13 patients and by 25-50% in 4/13 patients. None of the patients achieved an objective tumour regression (complete or partial remission). A temporary increase (16-60%) of the platelet count was observed during IL-4 treatment. The platelet count decreased in 8/11 patients after the end of IL-4 therapy. World Health Organization (WHO) grade I/II fever, arthralgia and fatigue was observed in one-third of the patients and was more commonly seen with the highest dose (6 microg/kg/d). One patient developed pulmonary oedema and WHO grade III neutropenia was recorded in three patients. IL-4 was well tolerated by most patients in an outpatient setting. The anti-tumour activity observed in previous in vitro studies was not verified by the present in vivo trial which showed that IL-4 may instead increase the number of CLL cells in blood, indicating that IL-4 may have induced a stimulatory or antiapoptotic effect on the CLL cells in blood. These results may have important implications for the development of immunotherapy of CLL. In addition, the potential platelet-stimulatory effect of IL-4 warrants further studies.
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PMID:Interleukin 4 therapy for patients with chronic lymphocytic leukaemia: a phase I/II study. 1116 96

Anemia is a common complication in patients with hematologic malignancies, and is caused by a variety of mechanisms, including neoplastic cell infiltration into the bone marrow, hemolysis, nutritional deficiencies, and defects in erythropoiesis as a result of the disease itself or cytotoxic therapy. The anemia associated with multiple myeloma is caused by inadequate erythropoietin levels consequent to renal impairment and the effect of inflammatory cytokines. The degree of anemia can have prognostic importance, as is the case with multiple myeloma, or be a significant indicator of disease stage, as noted with chronic lymphocytic leukemia. Anemia results in fatigue, exhaustion, dizziness, headache, dyspnea, and decreased motivation, seriously affecting a patient's quality of life. Since anemia is so prevalent in hematologic malignancy patients, its treatment must be an integral part of disease management, to improve quality of life and to possibly increase potential survival. Clinical studies have shown that effectively treating anemia and increasing hemoglobin levels using recombinant human erythropoietin (rHuEPO, epoetin alfa) has a significant effect on transfusion requirements and quality of life.
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PMID:The effects of anemia in hematologic malignancies: more than a symptom. 1208 53

Twenty-three adult patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or prolymphocytic leukemia (PLL) were treated for up to 12 weeks with the anti-CD52 monoclonal antibody alemtuzumab. Patients were a median of six years from diagnosis and had been treated with a median of four chemotherapy regimens (median of 24 total cycles) prior to enrollment. Fourteen patients (61%) had received prior monoclonal antibody therapy with rituximab. Adverse symptoms were primarily mild to moderate fever, rigor/chills, nausea/vomiting, or fatigue/malaise in up to 86% of patients. Patients with low blood counts at the initiation of alemtuzumab tolerated therapy well. A total of 17 patients were evaluable for disease response. Nine patients (53%) responded with complete remissions in the peripheral blood. Of these nine, five were evaluated by bone marrow biopsy with four complete responses (CR) and one partial response. Six of the nine presented with nodal disease at the start of alemtuzumab therapy with three CRs and three partial responses. Alemtuzumab is a monoclonal antibody that offers effective treatment for chemotherapy refractory CLL and PLL and is generally well tolerated in the outpatient setting.
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PMID:Alemtuzumab in relapsed or refractory chronic lymphocytic leukemia and prolymphocytic leukemia. 1214 79

Anemia is prevalent among cancer patients with hematologic malignancies, with fatigue and weakness, major symptoms of anemia, contributing to diminished quality of life (QOL). Data from several randomized, placebo-controlled clinical trials and three large community-based studies in patients with hematologic malignancies indicate that recombinant human erythropoietin (r-HuEPO, epoetin alfa) can correct anemia, reduce transfusion requirements, and improve QOL. Moreover, a positive relationship has been found between increased hemoglobin (Hb) levels and improvements in QOL assessments, regardless of disease state, with the greatest incremental improvement occurring when Hb increases from 11 g/dL to 12 g/dL (range, 11 to 13 g/dL). This suggests that patients with mild-to-moderate anemia may achieve the greatest QOL benefit from epoetin alfa therapy. Evidence from community-based studies suggests that epoetin alfa administered once weekly has a similar safety and efficacy profile as three-times-weekly administration. Further research is ongoing with less frequent dosing regimens. The beneficial effects of epoetin alfa therapy have been reported in studies involving patients with chronic lymphocytic leukemia (CLL), multiple myeloma, and lymphomas. Evidence also exists that epoetin alfa can benefit patients with myelodysplastic syndromes (MDS), although these results have not been as impressive. Combining epoetin alfa with other cytokine growth factors may confer some additional benefit in these patients, but more rigorous investigation is required.
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PMID:Epoetin alfa as a supportive measure in hematologic malignancies. 1244 49

Anemia is a frequent clinical feature with adverse prognostic effects in patients with chronic lymphocytic leukemia (CLL). It may complicate CLL at any time during the course of the disease. Different factors concur to the occurrence of anemia in CLL, as in other lymphoproliferative diseases: leukemic bone marrow infiltration, the myelosuppressive effect of chemotherapy and inhibiting cytokines, autoimmune phenomena, hypersplenism, a poor nutritional status that leads to folic acid, vitamin B12 and iron deficiency. In addition, a defective endogenous erythropoietin (EPO) production has also been described in patients with lymphoproliferative diseases. The severity of anemia, which may be worsened by an impaired cardiopulmonary function, may profoundly compromise the patients' quality of life and, indirectly, the outcome of cancer bearing patients. Several Authors have reported the clinical activity of recombinant human (rHu)EPO in anemic patients with lymphoproliferative diseases, including CLL. Low serum EPO levels at baseline and EPO levels inappropriately low for the degree of anemia help to identify patients who are likely to respond to EPO. A clear dose-dependent response to EPO has been reported by different Authors and it has been suggested that 5,000 IU should be considered as an appropriate initial dose for the majority of patients. rHuEPO represents a potentially effective and safe therapy for the management of anemia associated with lymphoproliferative diseases. The reduction of red blood cell transfusion requirement, the improvement of quality of life through the remission of fatigue-related anemia are two important results that should be considered in the management of patients with CLL. In prospect, the availability of new rHuEPO molecules with a more prolonged half-life may open new therapeutic avenues.
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PMID:Erythropoietin and chronic lymphocytic leukemia. 1273 12

We report a case of a 52-year-old male who developed classical Hodgkin's lymphoma (HL) four years after diagnosis of stage Rai II (Binet B) chronic lymphocytic leukemia (CLL). The patient was treated with fludarabine and cyclophosphamide with partial response. Subsequently, he presented with a 6-month history of weight loss and fatigue, and 6 weeks of fever, a progressively enlarged liver and elevated serum LDH level. An inguinal lymph node biopsy revealed both classical Hodgkin's lymphoma, nodular sclerosing type grade 2 and CLL. A bone marrow biopsy showed no Reed-Steinberg cells and an infiltrate composed of only scattered small lymphocytes consistent with CLL. Immuno-histochemical studies of the lymph node were consistent with both CLL and HL phenotypes. A cytogenic examination of the bone marrow revealed an abnormal karyotype (Y-) in 15% of the cell population. Treatment with MOPP/ABVD was started and fever subsided within 3 days. Our case is one of the very few descriptions of a rare Richter's variant of CLL with progression to HL in a CLL patient treated with fludarabine. Since fludarabine has become standard therapy in CLL such Richter's variant could be the result of therapy, an induced prolonged and severe immunosuppression. Clinicians should be aware of such association, which could become more frequent among CLL patients treated with purine analogs.
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PMID:Variant Richter's syndrome: a rare case of classical Hodgkin's lymphoma developing in a patient with chronic lymphocytic leukemia treated with fludarabine. 1495 63


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