Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 59 years old woman, born in Fukuoka Prefecture, was admitted to our hospital in Aug, 1988 because of diarrhea, fever and skin eruption. Physical examination revealed systemic lymphadenopathy and hepatosplenomegaly. The white blood cell count was 11,200/microliters with 28% atypical lymphocytes with convoluted nuclei. Mild anemia, thrombocytopenia and hypercalcemia were also observed. Antibody against the adult T-cell leukemia (ATL) associated antigen in serum was positive. OKT 4/8 ratio was high. A diagnosis of ATL was made. Because of the complications of pneumonia and herpes simplex, systemic chemotherapy was not given, and interferon (IFN)-alpha-2b was intramuscularly injected daily from Oct, 1988, resulting in the disappearance of atypical lymphocytes and improvement of skin lesions. The effect of IFN therapy lasted for three months, followed by increase of atypical lymphocytes. Although the patient became refractory to systemic IFN therapy, local injection of IFN into a buccal tumor infiltrated with atypical lymphocytes resulted in its regression of size. In spite of continued administration of IFN, the patient died of pneumonia in Jan, 1989.
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PMID:[Successful treatment of adult T-cell leukemia with interferon-alpha-2b by systemic and local administration]. 224 35

Phase II study of YNK01 (1-beta-D-arabinofuranosylcytosine-5'-stearylphosphate), a derivative of cytosine arabinoside, on hematological malignancies was conducted by multi-institutional cooperative group. YNK01 was administered orally at dose of 100-300 mg/body/day for more than 2 weeks. The number of registered and evaluated patients were 211 and 156, respectively. Of 23 patients with acute myelogeneous leukemia (AML), 2 complete response (CR), one partial response (PR) were observed (CR + PR: 13.0%). Hypoplastic leukemia (1/4: 25%), acute unclassified leukemia (1/1: 100%). Of 45 patients with MDS, 2CRs, 6 good response (GR) and 5PRs were observed (CR + PR: 28.9%). AML developing after a prior history of MDS (5/17: 29.4%), CML-BC (2/9: 22.2%). Of 19 patients with CML, 9 achieved CR, 3 achieved PR (63.2%). Of 11 patients with polycythemia vera, 4 achieved CR, 5 achieved PR (81.8%). Of 6 patients with essential thrombocytosis, 2 achieved CR, one achieved PR (50%). The major adverse effects included gastrointestinal toxicities such as nausea, vomiting, anorexia, diarrhea, and elevation of GOT and GPT which were tolerable and reversible. This study indicates that YNK01 is a useful agent against acute leukemia and MDS, especially RAEB, RAEB in T, CMMoL.
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PMID:[Phase II study of YNK01 (1-beta-D-arabinofuranosylcytosine-5'-stearylphosphate) on hematological malignancies]. 226 Aug 76

Spontaneous remission without any anti-cancer therapy in a 57-year-old woman with adult T-cell leukemia (ATL) is reported. The patient was referred to our department because of persistent cough and appearance of abnormal lymphocytes in the peripheral blood, and she was diagnosed as having chronic ATL. Eight months later, she was re-admitted because of cystitis, watery diarrhea and worsening of respiratory symptoms with an increase of ATL cells (WBC 31 x 10(9)/l with 56% ATL cells). Acute exacerbation of ATL was diagnosed. Interestingly, antibiotic therapy for the pulmonary and urinary tract infections brought about spontaneous reduction of the ATL cell count. Spontaneous remission of ATL continued for one year without chemotherapy. The role of infection as a trigger of acute exacerbation and spontaneous remission of ATL is discussed.
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PMID:Spontaneous remission from acute exacerbation of chronic adult T-cell leukemia. 229 81

Neutropenic enterocolitis is a recognized complication of immunosuppression or chemotherapy for leukemia. It presents as severe abdominal pain and tenderness, fever, and diarrhea associated with granulocytopenia. Gastrointestinal symptoms associated with chemotherapy for head and neck neoplasms include nausea and emesis, but not acute abdominal distress. We present, to our knowledge, the first case of neutropenic enterocolitis in a patient receiving cisplatin and fluorouracil chemotherapy for metastatic head and neck cancer.
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PMID:Neutropenic enterocolitis. A new complication of head and neck cancer chemotherapy. 229 18

Diaziquone (AZQ) and etoposide (VP-16) were administered as simultaneous 5-day continuous infusions to 27 patients with acute leukemia (22 with acute myeloid leukemia (AML), three with chronic myeloid leukemia in blast crisis (CML-B), and two with acute lymphocytic leukemia) at four different doses in a phase I trial. Gastrointestinal toxicity, primarily stomatitis, was dose limiting, occurring in six of 10 patients at the highest dose level. Diarrhea was the only other grade 3 toxicity noted (three of 10 at the highest dose level). The duration of bone marrow aplasia was excessive at the highest dose (median 48 days to granulocytes greater than 500/mm3, range 33-67) but acceptable (31 days) at the maximum tolerated dose: AZQ 28 mg/m2/day x 5 days, VP-16 150 mg/m2/day x 5 days. Complete remissions were seen in seven patients (six AML, one CML-B) and a partial remission in one patient with AML. The median duration of unmaintained complete remission was 3 months (range 1.5-26+).
Leukemia 1990 Mar
PMID:Continuous infusion diaziquone and etoposide: a phase I study in adult patients with acute leukemia. 231 18

In a clinical phase II study the combination of high dose cytosine arabinoside and mitoxantrone (HAM) was applied to 24 patients with refractory acute lymphoblastic leukemia (ALL). All patients had received a standardized first line treatment and were considered refractory against conventional chemotherapy as defined by nonresponse to induction treatment (n = 8), nonresponse to an alternative salvage regimen at first relapse (n = 9), second and third relapses (n = 5) and relapse after bone marrow transplantation (n = 2). Therapy consisted of HD-araC 3 g/m2 q 12 hr days 1-4 and mitoxantrone 10 mg/m2/d days 2-5 or 2-6. Twelve of the 24 patients (50%) achieved a complete remission (CR), one patient had a partial remission, and five patients were nonresponders. Five patients died in aplasia due to infections, one additional patient succumbed to HD-araC related CNS toxicity. Nonhematologic side effects consisted predominantly in infection, nausea and vomiting, mucositis and diarrhea. Recovery of blood counts occurred at a median of 28 days from the onset of treatment; the median time to CR was 33 days. Three of the 12 responders underwent subsequent bone marrow transplantations and one is alive disease free at 40+ months. The median remission duration for the remaining nine patients is 3.5 months, with one case in ongoing CCR at 36+ months; the median survival time is 5 months. Considering the selection of a highly unfavorable group of patients, these data demonstrate a significant antileukemic activity of HAM in refractory ALL and support its application as consolidation treatment during first line ALL therapy.
Leukemia 1990 Sep
PMID:Treatment of refractory acute lymphoblastic leukemia in adults with high dose cytosine arabinoside and mitoxantrone (HAM). 239 83

The acute reaction in the course of a total body irradiation (TBI) appears in an organ-specific damage of the stem cells. Moreover, there are unspecified central-nervous stress reactions. Clinical reactions are obtained by the study and symptomatic therapy is proposed. 90 patients with different forms of leukaemia were observed. We documented the course in a specific "protocol system". Reactions like an increase of body temperature, changes of pulse and blood pressure were registered. The occurrence of gastro-intestinal reactions is a typical symptom of the acute radiation syndrome e.g. vomiting and diarrhoea are demonstrated in dependence of the applicated dose of irradiation. Further symptoms of TBI appeared in the later period. Mucositis, parotitis, a decreased function of the salivary glands and diarrhoea as well as vomiting are characterized by different intensity and temporary termination. A difference between allogeneic and autologous transplantation is caused by a medicamental additional treatment. During the late period these symptoms will disappear completely. Moreover, after TBI and BMT late effects are a cataract and some changes in the hormonal system demanding a specific correction or substitution respectively.
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PMID:Acute and late effects in the course of and after total body irradiation with following bone marrow transplantation in patients with different forms of leukaemia. 248 Feb 95

Severe progressive immunodeficiency syndrome can be induced experimentally with a molecularly cloned isolate of feline leukemia virus (FeLV-FAIDS). The resultant disease syndrome is characterized by persistent viremia, lymphopenia, progressive weight loss, persistent diarrhea, enteropathy, and opportunistic infections. The onset of clinical immunodeficiency disease is prefigured by the replication of the FeLV-FAIDS variant virus in bone marrow and other tissues. The FeLV-FAIDS system can be used to evaluate antiviral agents which act on steps in the replication cycle which are conserved among retroviruses (e.g. reverse transcriptase, protease, assembly). The persistence and magnitude of viremia serves as a useful parameter in antiviral studies because it can be easily measured, presages the eventual development of immunodeficiency, and provides a convenient indicator of therapeutic efficacy either in preventing de novo FeLV infection or in reversing or ameliorating established infection. We describe here the evaluation of 2',3'-dideoxycytidine (ddC) against FeLV-FAIDS infection - both in vitro in cell culture assay systems and in vivo in cats administered ddC either via intravenous bolus dosage or via controlled release subcutaneous implants. We found that, although controlled release delivery of ddC inhibited de novo FeLV-FAIDS replication and delayed onset of viremia when therapy was discontinued (after 3 weeks), an equivalent incidence and level of viremia were established rapidly in both ddC-treated and control cats. The FeLV model, therefore, can be used to assess rapidly experimental single agent or combined antiviral therapies for persistent retrovirus infection and disease.
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PMID:Feline leukemia virus-induced immunodeficiency syndrome in cats as a model for evaluation of antiretroviral therapy. 254 Jan 9

Taxol, a novel antimicrotubule agent that enhances tubulin polymerization and microtubule stability, was administered to adults with refractory leukemias as a 24-h i.v. infusion in a Phase I study. The primary objectives were to determine the maximum tolerated dose of taxol administered on this schedule to patients with acute leukemias and describe the nonhematological toxicities which became dose limiting. The starting dose, 200 mg/m2, was based on the maximum tolerated dose in solid tumor trials, in which myelosuppression precluded dose escalation. Seventeen patients received 28 evaluable courses at 200, 250, 315, and 390 mg/m2. Severe mucositis limited further dose escalation. Other nonhematological effects included peripheral neuropathy, alopecia, myalgias, arthralgias, nausea, vomiting, diarrhea, and an acute pulmonary reaction that was presumptively due to taxol's Cremophor vehicle. Mean peak taxol plasma concentrations at all dose levels were in the range of concentrations that were previously demonstrated to induce microtubule bundles, a morphological effect associated with cytotoxicity, in leukemia cells in vitro. Pretreatment blasts from 12 patients were incubated with taxol ex vivo. Taxol-induced microtubule bundles were apparent in the blasts of eight patients who also had cytoreduction of tumor, and sensitivity to bundle formation was related to the magnitude of antitumor activity. In contrast, taxol did not induce microtubule bundles ex vivo in the blasts of the other four total nonresponders. Based on this study, the maximum tolerated doses and recommended Phase II doses for taxol, limited by nonhematological toxicity and administered as a 24-h i.v. infusion to patients with refractory leukemias, are 390 and 315 mg/m2. Phase II trials at these myelosuppressive doses are required to determine taxol's activity in the treatment of leukemias. In addition, further evaluation of microtubule bundle formation ex vivo in Phase II studies is necessary to determine the ultimate utility of this assay in assessing tumor sensitivity to taxol.
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PMID:Phase I and pharmacodynamic study of taxol in refractory acute leukemias. 256 75

The purposes of this work are to: review the biological activities of Interleukin-2 (IL-2); evaluate the reported therapeutic benefits and toxicity of IL-2/lymphokine activated killer (LAK) cells; and project the role of IL-2/LAK cells in cancer therapy. Interleukin-2 is a glycoprotein lymphokine (mw 15,000) produced naturally by mitogen or antigen stimulated T-lymphocytes. The activities of IL-2 include: enhancement of IL-2 receptor positive T-lymphocytes and a variety of other in vitro and in vivo alterations of T cell function. The IL-2 gene has been cloned from the Jurkat leukemia cell line and expressed by recombinant biotechnology in an E. coli vector. In vitro incubation of IL-2 with selected T-lymphocytes results in the formation of lymphocyte activated killer (LAK) cells. Rosenberg and colleagues, in 1983, demonstrated that both exogenous IL-2 and LAK cells were needed in order to get maximum tumor regression in a murine model and later humans. Patients selected for IL-2/LAK cell therapy have clinical metastases or advanced unresectable cancers. Almost all patients treated demonstrate some toxic effects, including chills, fever, nausea, vomiting, diarrhea and hepatic dysfunction. Approximately 75 percent of the patients have profound hypotension and require intensive nursing care. A review of the literature indicates that tumor responsiveness will range from negligible (adenocarcinoma of the lung with metastases) to a 30+ percent response in renal cell carcinoma when complete and partial responders are totalled. Interleukin-2/LAK cell therapy has promise for some wide spread tumors for which no other therapy is available.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interleukin-2 and lymphokine activated killer cells: promises and cautions. 264 90


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