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)

Acute lymphoblastic leukemia accounts for 80% of leukemia in children. The exact cause is unknown, but some genetic, immunologic, viral, and environmental factors have been implicated. Symptoms at the time of diagnosis frequently include fever, bleeding, fatigue, and irritability. Initial white blood cell count and patient age at diagnosis are the most reliable indicators of prognosis. Acute lymphoblastic leukemia is a heterogenous disease. Lymphoblast morphology, immunologic markers, enzyme abnormalities, cytogenetic findings, and staining characteristics in conjunction with clinical characteristics allow classification into risk groups. Appropriate therapy for each risk group is based on these parameters. Combination chemotherapy administered alone or with additional chemotherapy or radiotherapy to sanctuary sites is the principal modality for treatment of ALL. Optimal therapy for relapse has not yet been determined, but for patients with appropriate donors, allogeneic bone marrow transplant is promising. Common complications of chemotherapy include tumor lysis syndrome, myelosuppression, and other problems such as gastrointestinal toxicity, neurotoxicity and cardiac toxicity. Significant late effects of chemotherapy include neurological impairment ranging from learning problems to leukoencephalopathy and a possible increased risk of second malignancy. Complete remission is achieved in 95% of children with acute lymphoblastic leukemia, and more than 55% will continue to be in complete remission at five years. Optimal CNS prophylaxis, effective treatment of relapse, and adjustment of therapy to minimize acute and late adverse effects are a continuing challenge. With improved understanding of biologic factors, and development of more specific therapy for each subgroup, children with acute lymphoblastic leukemia should enjoy a better long term outcome.
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PMID:Childhood acute lymphoblastic leukemia. 328 Nov 3

Acute tumor lysis syndrome (ATLS), a condition which results from a rapid destruction of tumor cells with massive release of cellular breakdown products, has been well described following the treatment of various malignancies. However, only a handful of cases of spontaneous ATLS have been reported in the literature. We describe the first reported case of spontaneous ATLS in acute myeloid leukemia (AML). A previously healthy 63 year old woman presented with a two month history of fatigue and a one week history of easy bruising. On admission she had oliguric acute renal failure, with marked elevation in serum uric acid and phosphate. A bone marrow biopsy showed AML M7 with fibrosis. The renal failure resolved with supportive care and institution of allopurinol therapy. Following this, AML induction chemotherapy resulted in complete remission. Her biochemical and clinical course were very similar to the classical ATLS seen in patients after chemotherapy. Therefore, this case represents a rare instance of acute renal failure from spontaneous ATLS, and in our opinion the first reported occurrence of spontaneous ATLS associated with AML.
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PMID:Spontaneous acute tumor lysis syndrome in acute myeloid leukemia? A single case report with discussion of the literature. 964 77

Care of patients with cancer can be enhanced by continued involvement of the primary care physician. The physician's role may include informing the patient of the diagnosis, helping with decisions about treatment, providing psychological support, treating intercurrent disease, continuing patient-appropriate preventive care, and recognizing and managing or comanaging complications of cancer and cancer therapies. Adverse effects of therapy and cancer-related symptoms include nausea, febrile neutropenia, pain, fatigue, depression, and emotional distress. 5-Hydroxytryptamine antagonists are effective in controlling acute nausea associated with chemotherapy. Febrile neutropenia requires systematic evaluation and early empiric antibiotics while awaiting culture results. Cancer-related pain, depression, and fatigue often are underdiagnosed and undertreated. Use of brief screening tools for assessing fatigue and emotional distress can improve management of these symptoms. Exercise prescription, activity management, and psychosocial interventions are useful in treating cancer-related fatigue. The physician must be alert for signs and symptoms of cancer-related emergencies like spinal cord compression, hypercalcemia, tumor lysis syndrome, pericardial tamponade, and superior vena cava syndrome.
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PMID:Primary care of the patient with cancer. 1747 4

An 83-year-old woman had been suffering from palpitations and fatigue for a month. An annual screening test revealed an increased WBC count so she was referred to our hospital. CBC showed extremely elevated WBC count (186,300/microl), in which the population of blastic eosinophils was over 90%. The eosinophils expressed CD7/13/33/34/DR, and the karyotype demonstrated 47,XX,+8. The fusion gene of FIP1-LP/PDGFRalpha in peripheral blood was negative. As plural effusion due to the underlying disease progressively worsened, she was given prednisolone and hydroxyurea, but the effect was limited. Steroid pulse therapy and imatinib (100 mg/day) were administrated. As a result, a prompt response was observed. The WBC count rapidly decreased, but tumor lysis syndrome led to acute renal failure and disseminated intravasucular coagulation appeared. Supportive therapies such as artificial dialysis and transfusions were conducted, but unfortunately she died because of alveolar hemorrhage.
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PMID:[Acute-onset eosinophilic leukemia associated with tumor lysis syndrome after imatinib and steroid pulse therapy]. 2053 53

Lenalidomide is an immunomodulatory drug that has shown preliminary activity in the treatment of chronic lymphocytic leukemia (CLL). Much is known about the safety profile of lenalidomide from experience in other hematologic malignancies, such as myelodysplastic syndromes and multiple myeloma. In addition to the known adverse effects associated with lenalidomide (e.g., myelosuppression, rash, fatigue), some unique effects (e.g., tumor flare reactions, tumor lysis syndrome) have arisen during clinical studies of CLL. Typical signs of tumor flare reactions include early onset of painful enlargement of the lymph nodes or spleen, with or without low-grade fever, rash, and bone pain. Management may require nonsteroidal anti-inflammatory drugs or a short course of corticosteroids. Dose delays or reductions usually are not required for tumor flare reactions. Signs of tumor lysis syndrome may include shortness of breath, peripheral edema, generalized weakness, sweating, fever, and tachycardia. Untreated tumor lysis syndrome can result in renal impairment and congestive heart failure. Careful monitoring and appropriate management of treatment-related side effects can help ensure that patients with CLL achieve maximum therapeutic benefit from lenalidomide therapy.
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PMID:Management of patients with chronic lymphocytic leukemia treated with lenalidomide. 2068 5

The aim of this Phase II study was to determine the efficacy and safety of combined bortezomib and thalidomide (VT) regime as initial treatment for newly diagnosed patients with multiple myeloma (MM) in China. Thirty-four patients have been enrolled in this study and were planned to receive VT regime up to eight 21-day cycles. Bortezomib (1.3 mg/m(2) ) was given intravenously on days 1, 4, 8, and 11, while oral thalidomide (100 mg/day) was given on days 1 to 21. The primary end point was clinical response; the secondary end point was safety. Among 34 patients enrolled, 26 patients were able to complete the planned eight cycles of therapy. After eight cycles, the overall response rate was 100% (complete response 31%; near-complete response 23%; partial response 42%; minimal response 4%). The best response occurred within the first four cycles in 96% of patients. Adverse events included hematologic (53%), peripheral neuropathy (38%), fatigue (35%), gastrointestinal (45%), and fever (32%). Grade 3 nonhematologic adverse events included four patients (12%) with renal failure associated with tumor lysis syndrome, one patient (3%) with peripheral sensory and motor neuropathy that improved with VT dose reduction, and one patient (3%) with hypotension. One patient (3%) experienced Grade 4 thrombocytopenia. No patient experienced deep venous thrombosis, while 1 patient (3%) died due to acute renal failure. In conclusion, Bortezomib in combination with thalidomide is a very effective regimen for newly diagnosed MM patients and the toxicities are manageable.
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PMID:Bortezomib plus thalidomide for newly diagnosed multiple myeloma in China. 2073 18

Leukemia is a clonal proliferation of hematopoietic stem cells in the bone marrow. The four broad subtypes most likely to be encountered by primary care physicians are acute lymphoblastic, acute myelogenous, chronic lymphocytic, and chronic myelogenous. Acute lymphoblastic leukemia occurs more often in children, whereas the other subtypes are more common in adults. Risk factors include a genetic predisposition as well as environmental factors, such as exposure to ionizing radiation. Symptoms are nonspecific and include fever, fatigue, weight loss, bone pain, bruising, or bleeding. A complete blood count usually reveals leukocytosis and other abnormally elevated or depressed cell lines. Patients with suspected leukemia should be referred promptly to a hematologist-oncologist. The diagnosis is confirmed by further examination of the bone marrow or peripheral blood. Treatment may include chemotherapy, radiation, monoclonal antibodies, or hematopoietic stem cell transplantation. Complications of treatment include tumor lysis syndrome and serious infections from immunosuppression. Leukemia survivors should be monitored closely for secondary malignancies, cardiac complications, and endocrine disturbances such as metabolic syndrome, hypothyroidism, and hypogonadism. Five-year survival rates are highest in younger patients and in patients with chronic myelogenous leukemia or chronic lymphocytic leukemia.
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PMID:Leukemia: an overview for primary care. 2478 36

Lenalidomide is an oral immunomodulatory agent approved in relapsed multiple myeloma with dexamethasone, for transfusion-dependent anemia in myelodysplastic syndrome associated with deletion 5q, and in relapsed/progressive mantle cell lymphoma following bortezomib. In recent clinical trials, lenalidomide has shown promising activity in hematologic malignancies, including chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL). Starting doses and dosing schedules vary by malignancy, with lenalidomide started at a lower dose for CLL than for NHL or multiple myeloma. Certain adverse events (AEs) are common across tumor types (e.g., neutropenia, thrombocytopenia, fatigue), whereas others are more often associated with CLL patients (e.g., tumor lysis syndrome and tumor flare reaction). Effective management requires awareness of these differences as well as appropriate prophylaxis, monitoring, and treatment of AEs. This article reviews the efficacy and safety of lenalidomide in CLL and NHL, focusing on approaches for the advanced practitioner to improve patient quality of life through optimal management of side effects. With these steps, lenalidomide can be administered safely, at the best starting doses and with minimal dose interruptions or reductions across hematologic malignancies.
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PMID:Approaches to Managing Safety With Lenalidomide in Hematologic Malignancies. 2611 71

B-cell receptor pathway inhibitors (BCRis) have transformed treatment of chronic lymphocytic leukemia (CLL); however, the efficacy of therapies for patients whose disease is refractory to/relapses after (R/R) BCRis is unknown. Venetoclax is a selective, orally bioavailable BCL-2 inhibitor with activity in patients with CLL, including those who are heavily pretreated or have 17p deletion. This phase 2 study prospectively evaluated venetoclax in patients with R/R CLL after ibrutinib or idelalisib; here we report on patients who received idelalisib as the last BCRi before enrollment. Venetoclax was initiated at 20 mg daily, followed by intrapatient ramp-up to 400 mg daily. Primary objectives included efficacy (objective response rate [ORR]) and safety of venetoclax. The study enrolled 36 patients who previously received idelalisib (ORR, 67% [24/36]); 2 patients achieved complete remission, and 1 had complete remission with incomplete bone marrow recovery. Median progression-free survival (PFS) has not yet been reached; estimated 12-month PFS was 79%. The most common adverse events (AEs; all grades) were neutropenia (56%), diarrhea (42%), upper respiratory tract infection (39%), thrombocytopenia (36%), nausea (31%), fatigue (28%), cough (22%), rash (22%), and anemia (22%). Grade 3 or 4 AEs were primarily hematologic (neutropenia [50%], thrombocytopenia [25%], and anemia [17%]). No patients experienced tumor lysis syndrome. Venetoclax demonstrated promising clinical activity and favorable tolerability in patients with CLL whose disease progressed during or after idelalisib therapy. This trial was registered at www.clinicaltrials.gov as #NCT02141282.
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PMID:Venetoclax for patients with chronic lymphocytic leukemia who progressed during or after idelalisib therapy. 2965 Jul 29

Older patients with acute myeloid leukemia (AML) respond poorly to standard induction therapy. B-cell lymphoma 2 (BCL-2) overexpression is implicated in survival of AML cells and treatment resistance. We report safety and efficacy of venetoclax with decitabine or azacitidine from a large, multicenter, phase 1b dose-escalation and expansion study. Patients (N = 145) were at least 65 years old with treatment-naive AML and were ineligible for intensive chemotherapy. During dose escalation, oral venetoclax was administered at 400, 800, or 1200 mg daily in combination with either decitabine (20 mg/m2, days 1-5, intravenously [IV]) or azacitidine (75 mg/m2, days 1-7, IV or subcutaneously). In the expansion, 400 or 800 mg venetoclax with either hypomethylating agent (HMA) was given. Median age was 74 years, with poor-risk cytogenetics in 49% of patients. Common adverse events (>30%) included nausea, diarrhea, constipation, febrile neutropenia, fatigue, hypokalemia, decreased appetite, and decreased white blood cell count. No tumor lysis syndrome was observed. With a median time on study of 8.9 months, 67% of patients (all doses) achieved complete remission (CR) + CR with incomplete count recovery (CRi), with a CR + CRi rate of 73% in the venetoclax 400 mg + HMA cohort. Patients with poor-risk cytogenetics and those at least 75 years old had CR + CRi rates of 60% and 65%, respectively. The median duration of CR + CRi (all patients) was 11.3 months, and median overall survival (mOS) was 17.5 months; mOS has not been reached for the 400-mg venetoclax cohort. The novel combination of venetoclax with decitabine or azacitidine was effective and well tolerated in elderly patients with AML (This trial was registered at www.clinicaltrials.gov as #NCT02203773).
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PMID:Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia. 3060 7


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