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)

Waldenstrom's macroglobulinemia, (WM) first described in 1944, is an uncommon disease caused by the abnormal production of immunoglobulin M monoclonal macroglobulin. Presenting signs and symptoms most frequently include fatigue or generalized weakness; tendency to bleed from mucosal surfaces; characteristic retinal lesions, including dilated and tortuous retinal veins, retinal hemorrhages, and exudates; lymphadenopathy; hepatosplenomegaly; sensory motor peripheral neuropathy; worsening normochromic anemia; increased sedimentation rate; and extremely high serum viscosity. Hearing loss is an unusual presenting symptom of WM; only 6 cases are reported in literature. The etiology of hearing loss is unclear; however, hyperviscosity and thrombus formations are the most likely causes. We present a patient diagnosed with WM whose initial presenting symptoms were hearing loss and progressive sensory peripheral neuropathy with subsequent development of lymphadenopathy and hyperviscosity syndrome. Treatment with Fludarabine lead to improvement of her hearing and neurological deficits, as well as resolution of her other hyperviscosity-related symptoms.
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PMID:Waldenstrom's macroglobulinemia and sensorineural hearing loss. 1156 87

Randomized trials suggest improved disease-free survival in low-grade non-Hodgkin's lymphoma (LGNHL) when interferon is combined with multiagent chemotherapy. This phase II trial was conducted to investigate the feasibility of combining fludarabine monophosphate (fludarabine) and IFN in a regimen for treatment of LGNHL. Twenty-one patients were evaluable. Median age was 55 years, and patients had been treated with an average of 1.7 chemotherapy regimens before enrollment. Patients received 25 mg/m2 of fludarabine intravenously on days 1 through 5 followed by 2 x 10(6) U/m2 of interferon-alpha-2a subcutaneously on days 22 through 26. Cycles were repeated every 4 weeks with delays and dose modifications for significant cytopenias. Patients were restaged after cycles 4 and 8, and those with at least a partial response to therapy were given maintenance therapy consisting of 2 x 10(6) U/m2 interferon-alpha-2a subcutaneously three times per week for 6 months. The overall response rate was 76% with a 25% complete response (CR) rate. Overall response rates were 75% (3/4 with 2 CR's) for chemotherapy-naive patients and 76% (13/17 with 3 CR's) for previously treated patients. Median time to progression was 12 months, and currently two patients are without evidence of progression at a median follow-up of 55 months. Grade III or greater toxicities included neutropenia (39%), anemia (17%), thrombocytopenia (5%), fevers/chills (5%), and fatigue (5%). Fludarabine and interferon can be effectively and safely combined in a regimen with significant activity against LGNHL. A modification of this regimen may be suitable for further study.
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PMID:Phase II study of fludarabine combined with interferon-alpha-2a followed by maintenance therapy with interferon-alpha-2a in patients with low-grade non-hodgkin's lymphoma. 1215 72

The purpose of this literature review was to identify and summarize published studies describing the epidemiology and management of chronic lymphocytic leukaemia (CLL). Chronic lymphocytic leukaemia represents 22-30% of all leukaemia cases with a worldwide incidence projected to be between < 1 and 5.5 per 100,000 people. Australia, the USA, Ireland and Italy have the highest CLL incidence rates. Chronic lymphocytic leukaemia presents in adults, at higher rates in males than in females and in whites than in blacks. Median age at diagnosis is 64-70 years. Five-year survival rate in the USA is 83% for those < 65 years old and 68% for those 65 + years old. Hereditary and genetic links have been noted. Persons with close relatives who have CLL have an increased risk of developing it themselves. No single environmental risk factor has been found to be predictive for CLL. Patients are usually diagnosed at routine health care visits because of elevated lymphocyte counts. The most common presenting symptom of CLL is lymphadenopathy, while difficulty exercising and fatigue are common complaints. Most patients do not receive treatment after initial diagnosis unless presenting with clear pathologic conditions. Pharmacological therapy may consist of monotherapy or combination therapy involving glucocorticoids, alkylating agents, and purine analogs. Fludarabine may be the most effective single drug treatment currently available. Combination therapy protocols have not been shown to be more effective than fludarabine alone. As no cure is yet available, a strong unmet medical need exists for innovative new therapies. Experimental treatments under development include allogeneic stem cell transplant, mini-allogeneic transplants, and monoclonal antibodies (e.g. alemtuzumab against CD52; rituximab against CD20).
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PMID:The clinical and epidemiological burden of chronic lymphocytic leukaemia. 1519 32