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

Twelve children ages 3-15 years with relapsed acute lymphocyte leukemia (ALL) were treated over 25 days by intravenous or intramuscular administration of interferon-alpha n1 (IFN-alpha n1). Single doses ranged from 2.5 to 15 MU/m2, total doses from 60 to 200 MU/m2. Serum pharmacokinetics were determined following administration of two different doses. Calculation of area under serum concentration curve (AUC) values showed increased AUC with increased dose. Mean AUC (h x U/ml) ranged from 735 to 3986 at doses of 2.5 and 15 MU/m2, respectively, when given intramuscularly. AUC for i.v. and i.m. administration were similar. Side effects reported most commonly were fever and chills in 11 of 12 patients, nausea/vomiting in 7, mild lethargy in 3, and injection site pain in 4 of 9 treated i.m. Reversible hepatotoxicity occurred in the 3 patients receiving the highest doses, 10 then 15 MU/m2. Three patients had clinically significant bleeding associated with mildly increased coagulation studies and an additional three patients had increased coagulation parameters without bleeding. Four patients were considered to have stable disease; one treated at the highest dose level had clearance of peripheral blasts but remained in bone marrow relapse. IFN-alpha n1 as used in this study produced detectable blood levels with associated side effects. A Phase II intramuscular trial is recommended.
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PMID:Interferon-alpha n1 in children with recurrent acute lymphocytic leukemia: a phase I study of pharmacokinetics and tolerance. 316 26

Thirty-one patients with hairy-cell leukemia were treated with 2'-deoxycoformycin (DCF) in a National Cancer Institute of Canada multicenter trial. The DCF was administered in a cycle (4 mg/m2 iv weekly X 3), which was repeated every 8 weeks. Following a complete remission, consolidation was done with two further cycles of DCF. Of 28 patients evaluable for response, 25 obtained a complete remission; 3 had a partial response. To date there has been only one relapse; the median time with no therapy was 429.5 days (range 99-743 days). Toxicity was moderate and included nausea and vomiting, lethargy, and skin rash; with the first cycle of treatment, neutropenia and an increased incidence of fever or infection were also observed. We conclude that low-dose DCF is highly effective in treating hairy-cell leukemia.
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PMID:Efficacy of 2'-deoxycoformycin in hairy-cell leukemia: a study of the National Cancer Institute of Canada Clinical Trials Group. 329 Apr 98

Eight patients with hairy-cell leukaemia (HCL) complicated by pancytopenia were treated with low dose regimens of the adenosine deaminase (ADA) inhibitor 2'-deoxycoformycin (DCF). All patients had significant haematological and clinical improvement. One patient who had been splenectomized and five patients with mild to moderate splenomegaly achieved normal blood counts within 2 months, which have been maintained for up to 18 months. Complete remissions occurred in two patients and four patients had 50-95% marrow clearance of hairy cells. The initial DCF treatments produced a 1-3 g/dl fall in the haemoglobin levels and one patient had a temporary reduction in granulocyte and platelet counts. Five patients had nausea/vomiting, and/or lethargy following DCF, but there was no correlation between the plasma levels of deoxyadenosine and adenosine and the incidence or severity of these side effects. An increased incidence of infection and drug hypersensitivity may reflect the effects of DCF on the immune system. Low dose DCF is a highly effective agent in HCL.
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PMID:The treatment of hairy-cell leukaemia with 2'-deoxycoformycin. 348 71

Meningitis should be suspected in a patient who presents with fever, meningism, or severe headache. A careful physical examination should be performed of perimeningeal foci, with emphasis on the sinuses, ears, throat, neck, and lungs. A history of exposure to tuberculosis, viral disease, rodents, or suspicious dairy products or farm animals may give clues to the source of the meningitis. Immunosuppression through the use of corticosteroids or chemotherapy for such conditions as Hodgkin's disease, lymphoma, leukemia, malnutrition, or acquired immunodeficiency syndrome (AIDS) should also be noted and alert the clinician to the possible presence of an unusual pathogen. Meningitis associated with leukemia or most of the non-T-cell lymphomas is likely to be from a common bacterial agent (often Listeria), unless the patient is being treated with a steroid or is receiving other chemotherapy. Patients with Hodgkin's disease or AIDS or who have been treated with a steroid are more likely to have cryptococcal or tuberculous meningitis. Neonates and the very elderly may present with only irritability or lethargy and fever, without any of the other common symptoms. In neonates up to one week of age, group B streptococcal infection should be suspected. Gram-negative organisms should be suspected in elderly patients and those who have had neurosurgery. In patients with CSF shunts, infection with coagulase-negative Staphylococcus should be assumed and these patients are treated empirically until results of cultures are received. Several noninfectious conditions may mimic infectious meningitis, as may some unusual causes of infectious meningitis (eg, syphilis and schistosomiasis), which have not been discussed in this article.
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PMID:The many causes of meningitis. 361 11

Peripheral lymph node enlargement was found in 14 of a series of 132 feline lymph node biopsy specimens. Six of nine cats tested had antibodies for feline leukemia virus (FeLV). Half of the cats were clinically normal while the remainder had fever, lethargy, anorexia, and hepatosplenomegaly. There was severe distortion of lymph nodal architecture with variable loss of discernible follicles and sinuses. Histiocytes, lymphocytes, immunoblasts, and plasma cells were present in expanded paracortical regions which encroached on, and occasionally effaced, lymphoid follicles. Postcapillary venules were numerous and prominent throughout the paracortex. The lymphadenopathy was most commonly transient (86% of cases) with subsequent development of lymphoma in one cat. Lymph nodes from seven kittens with experimental FeLV infection were compared with spontaneously enlarged lymph nodes; four of seven had B and T lymphocyte hyperplasia with normal nodal architecture. Three had partial loss of nodal architecture as a result of expanded paracortical regions populated largely by histiocytes and lymphocytes. Proliferation of postcapillary venules was not prominent in nodes from FeLV-infected cats. The cause of spontaneous lymph node hyperplasia of young cats was not determined. However, the similarity of lesions to those of kittens with experimental FeLV infection and the association with FeLV by serologic tests in six of nine cats suggest that this retrovirus may be involved in the pathogenesis of the lesion.
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PMID:Distinctive peripheral lymph node hyperplasia of young cats. 375 Jul 32

A transient cerebral disturbance characterized by somnolence of varying degree is described in children after cranial irradiation given as part of central nervous system (C.N.S.) prophylaxis for acute lymphoblastic leukaemia in remission.Out of 28 such children receiving cranial irradiation as part of the Medical Research Council protocol for C.N.S. prophylaxis 11 (39%) developed pronounced symptoms of somnolence, anorexia, and lethargy some six weeks after the completion of cranial irradiation, and a further 11 (39%) developed these features in mild form. In all cases the symptoms were transient, no focal neurological abnormality was detected, and all children made a spontaneous and complete recovery. E.E.G. studies on five somnolent children showed similar abnormal activity of diffuse and patchy distribution over both hemispheres. Indirect evidence is presented to support the concept that this syndrome represents a transient radiation encephalopathy, analogous to acute transient radiation myelopathy, caused by temporary disturbance of myelin synthesis.
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PMID:Somnolence after prophylactic cranial irradiation in children with acute lymphoblastic leukaemia. 451 11

Six marrow transplant recipients receiving acyclovir at various dosages for herpesvirus infections developed neurologic symptoms during treatment. Three were receiving concomitant human alpha interferon, and all six had received previous intrathecal methotrexate. Symptoms developed a median of 8 days (range, 2 to 18 days) after initiation of therapy and consisted of lethargy or agitation in five patients, tremor in five, and disorientation or transient hemiparesthesias in one patient each. The only consistent laboratory finding was an abnormal electroencephalogram. Five patients had an increased myelin basic protein level in cerebrospinal fluid. Improvement or resolution of symptoms occurred a median of 13 days (range, 4 to 15 days) after cessation of acyclovir therapy. Acyclovir used at a wide range of dosages may be associated with reversible neurologic symptoms in patients after marrow transplantation. The contribution of previous prophylaxis for central nervous system leukemia, herpesvirus infections, marrow transplantation, or the concomitant use of interferon is unknown.
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PMID:Neurologic symptoms associated with parenteral acyclovir treatment after marrow transplantation. 630 45

Eleven academic institutions were selected to study mitoxantrone administered on a schedule of 10 mg/m2/d for five days initially and later at 12 mg/m2/d for five days, each given as a 30 minute intravenous (IV) infusion each day. Patients with acute or chronic leukemia were stratified by leukemic type and clinical status and included one group of patients considered to be in relapse after complete remission from previous chemotherapy and another group of patients considered refractory to standard induction and/or salvage chemotherapy. During the initial treatment schedule, complete remissions were obtained in two of seven patients with acute nonlymphoblastic leukemia, in one of three patients with acute lymphoblastic leukemia, but in none of the patients with chronic granulocytic leukemia in blast crisis. The durations of remission for these three patients were 22, 57, and 78 days, respectively. An increase in mitoxantrone dose to 12 mg/m2/d produced complete remissions in 8 of 19 evaluable patients with acute nonlymphoblastic leukemia, in one of ten patients with refractory acute nonlymphoblastic leukemia, and in one of four patients with chronic granulocytic leukemia in blast crisis. Each of these patients required only a single course of mitoxantrone to achieve remission; the median time to remission was 37 days (range 18 to 64 days). Remission duration ranged from 35 days (chronic granulocytic leukemia) to 186 days, with the median duration for those patients with acute nonlymphoblastic leukemia achieving remission being 135 days. Of the six patients with acute lymphoblastic leukemia, none achieved remission at the higher dose level. Drug-related gastrointestinal toxicity included mucositis (25%), diarrhea (21%), and nausea and vomiting (61%). Systemic infection (nonfatal) was experienced by 21% of patients and alopecia by 17%. Other side effects that occurred occasionally were hepatic dysfunction, decreased renal function, confusion, lethargy, anxiety, and fever. Possible drug-related phlebitis developed in one patient, and a single episode of minor epistaxis was reported in another. Cardiovascular toxicity was low. At a mitoxantrone dose of 10 mg/m2/d for five days, one patient developed hypotension, and one episode of congestive heart failure was reported in another. At the higher dose of 12 mg/m2/d, no drug-related hypotension, congestive heart failure, tachycardia, or chest pain were reported. These data indicate that mitoxantrone is a promising single drug for the treatment of acute nonlymphoblastic leukemia and possibly for acute lymphoblastic leukemia.
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PMID:Mitoxantrone in the treatment of relapsed and refractory acute leukemia. 638 65

The effects of thymidine (TdR) on the toxicity and antitumor activity of ftorafur (FT), a 5-FU analog, were determined. The LD10 of FT was 130, 430, and 680 mg/kg, respectively, when FT was administered ip in the following treatment schedules: (a) daily for 9 days, (b) every 4th day for three treatments, and (c) 1 day only. When FT was administered simultaneously with 250 mg/kg of TdR, the LD10 was 13, 62, and 630 mg/kg in the respective treatment schedules. Lethargy was observed in mice when the daily dose of FT was greater than or equal to 150 mg/kg. FT alone was active (% treated/control [T/C] = 153) against ascites P388 murine leukemia only at high, single doses. Simultaneous administration of FT and 250 mg/kg of TdR at or below the LD10 dose of FT resulted in an increase in the antitumor activity to a % T/C of 217 (daily, Days 1-9) and 188 (daily, Days 1, 5, and 9). The activity of FT administered simultaneously with TdR on Day 1 only (%T/C = 142) was lower than that for FT alone. Using a treatment schedule of Days 1, 5, and 9, a TdR/FT mol ratio of greater than or equal to 2.0 seems necessary to achieve an increase in therapeutic value against P388 murine leukemia. This may explain the lack of increase in activity against P388 when 250 mg/kg of TdR was coadministered with FT on Day 1 only. FT alone or coadministered with 250 mg/kg of TdR was equally active against L1210 ascites tumor at doses up to the LD10 with daily treatments on Days 1, 5, and 9 and on Days 1-9; the doses of FT, however, were below those which cause lethargy.
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PMID:Effect of thymidine on the toxicity and antitumor activity of ftorafur. 679 8

The inducers of microsomal drug-metabolizing enzymes phenobarbital (PB) and 20-methylcholanthrene (MC) inhibited the lethargic effect of high doses of ftorafur in C57BL/6j mice, but stimulated the animal mortality at days 4-8 after the drug administration. The opposite effect has been obtained by the combination of ftorafur with the inhibitor of the microsomal enzymes SKF 525A. Animal pretreatment with PB or with PB + MC markedly enhanced the antineoplastic activity of ftorafur in Rauscher leukemia-, leukemia La-, or hemangiopericytoma-bearing mice but seemed unlikely to afford any therapeutic advantage over this drug because the lethal toxicity of ftorafur was increased.
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PMID:Changes in toxic and antitumor properties of ftorafur by induction or inhibition of the microsomal enzymes activity. 679 84


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