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)

Methotrexate (MTX) and 6-mercaptopurine (6MP), the two drugs most commonly used for maintenance treatment of childhood leukemia, are both potent hepatotoxins. In order to assess MTX-6MP-induced damage, we obtained biopsies from 11 children with acute lymphocytic leukemia (ALL) for light microscopic and transmission electron microscopic study. Prednisone, vincristine, and L-asparaginase were used for induction of remission in all patients. Although light microscopic findings were minimal, we found significant ultrastructural abnormalities in all patients. Changes included nuclear abnormalities, disruption of rough and smooth endoplasmic reticulum, a variety of mitochondrial changes, steatosis, fibrosis, and changes in peroxisomes and lysosomes. These abnormalities could not have been predicted from liver function tests or histopathology. Three of the eleven patients studied had also received cyclophosphamide and cytosine arabinoside during maintenance therapy. The ultrastructural abnormalities in this group were not distinguishable from those observed in the group that did not receive these additional chemotherapeutic agents. The long-term clinical significance of these findings is not known.
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PMID:Hepatic ultrastructure in leukemic children treated with methotrexate and 6-mercaptopurine. 668 21

Two girls, each less than 2 yr of age, developed acute megakaryoblastic leukemia (malignant myelosclerosis). Both presented with anemia, severe thrombocytopenia, and a low percentage of blasts in their peripheral blood. Their marrow showed marked reticulin fibrosis with an increase in blasts and immature megakaryocytes. The blasts stained negatively for myeloperoxidase and Sudan Black B, but showed acid phosphatase (ACP) and alpha-naphthyl acetate esterase (ANAE) activity inhibitable by sodium fluoride. They were identified as megakaryoblasts by the platelet peroxidase reaction. Cytogenetic studies showed multiple chromosomal abnormalities in both cases. Chemotherapy with vincristine, prednisone, and L-asparaginase was without effect, while daunorubicin and cytosine arabinoside induced a complete remission in one case. The second case responded to a combination of cytosine arabinoside, daunorubicin, and 6-thioguanine. This article documents that acute megakaryoblastic leukemia occurs in early childhood and describes its clinical, pathologic, and cytogenetic features. Previous reports of childhood "myelofibrosis" are reviewed, and their possible relationship with acute megakaryoblastic leukemia is discussed.
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PMID:Acute megakaryoblastic leukemia in early childhood. 686 Jul 97

The histidine ammonia-lyase from bacterial strain CAMR 5315 was partially purified to assess its effect on the growth of murine tumours. This strain was selected as the source after an extensive screening programme for histidine ammonia-lyases. The enzyme was partially purified by ammonium sulphate fractionation, chromatography on DEAE-cellulose and Sephadex G-150. The enzyme reduced circulating L-histidine levels in Wistar rats and in mice persisted with a half-life of 6-7 h. Neither LDH virus nor chemical modification with ethylacetimidate increased the half-life as observed with L-asparaginase and L-glutaminase. The enzyme was tested in mice against Ehrlich carcinoma, L5178Y lymphoblastic leukaemia, Mc/S sarcoma, B16 melanoma, P8157 mastocytoma, P1798 lymphosarcoma and the Gardner 6C3HED lymphosarcoma. The only tumours to show sensitivity to the enzyme were the Mc/S sarcoma against which a 65% increase in life span was observed at the highest enzyme dose, 1000 U/kg on alternate days over 14 days and the Ehrlich ascites carcinoma where cures were obtained at 250 U/kg on alternate days over 14 days, but only at inocula levels of 10(5) and 10(3) cells/animal respectively.
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PMID:The effect of histidine ammonia-lyase on some murine tumours. 688 63

Sudden cerebrovascular insults occurred during or immediately following remission induction therapy in 4 children with acute lymphoblastic leukemia. In 3, cerebral infarction was due to thrombosis. In the fourth, an intracerebral hematoma developed representing either frank hemorrhaging or a hemorrhagic infarction. None of the patients had central nervous system leukemia or extreme leukocytosis at the time of diagnosis. Symptoms were obtundation, hemiparesis, seizures, and headache. The induction chemotherapy included L-asparaginase which causes deficiencies of antithrombin, plasminogen, fibrinogen, and factors IX and XI. These hemostatic abnormalities may explain the thromboses and bleeding observed in these children.
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PMID:Thrombotic and hemorrhagic strokes complicating early therapy for childhood acute lymphoblastic leukemia. 693 53

55 children suffering from acute lymphoblastic leukemia were treated wih prednisone, vincristin-sulfate, daunorubicine and L-asparaginase (1st month), 6-mercapto-purine, cytosine-arabinoside. cyclophospamide, methotrexate-i.th. and cranial irradiation (2nd month). Maintenance-therapy comprised 6-mercapto-purine, cyclophosphamide and methotrexate-i.v. Serial EEG-examination were done in most of them during the course of treatment. 4 children presented with meningeal leukemia at the time of diagnosis. Their EEGs showed moderate slowing before treatment and at the end of the first month. One of them suffered a focal convulsion two days after the last VCR/daunorubine-injection. All EEG-changes were completely reversible later on. 3 patients showed severe focal EEG-disturbances and convulsions during serious neurological complications (intracranial bleeding, rubella-encephalitis). The remaining patients were free of complications at the time of the EEG-examination. Before therapy 24% of them presented normal findings, 57% slightly and 19% moderately abnormal EEGs. At the end of the first month there was an increase of moderate and severe EEG-slowing to 37% and 23%, only 11% of findings were normal. Improvement during the second month of therapy led to 37% normal and 57% slightly abnormal EEG-findings at its end. After maintenance-therapy of 1/2--1 year duration there were 65% normal EEGs and no moderate and severe disturbances any longer. Quantitative spectral analysis of the EEG in 6 additional children revealed similar changes.
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PMID:[Serial EEG-examinations in children undergoing chemotherapy of ALL according to the Berlin-West-protocol (author's transl)]. 693 35

Acute lymphoblastic leukemia (ALL) with hand mirror cell (HMC) variant was diagnosed in a 26-year-old black man in May 1978. Hemoglobin was 3.6 g/dl; the platelet count was 19.0 x 10(9)/l; leukocyte count was 8.4 x 10(9)/l with 40% blasts, 66% of which had HMC appearance. Cytochemical studies, terminal deoxynucleotidyl transferase level, and immunologic marker studies indicated a non-T/non-B lymphoblastic origin of the leukemic population. Electron microscopic studies confirmed the hand mirror appearance. Mitochondria were more numerous in these cells compared with other lymphoid cells. Cytogenetic studies showed a 46XY karyotype. Our studies confirmed the previous studies reported by Stass, et al of lymphoblastic origin of HMC leukemia. The patient responded to treatment with vincristine, prednisone and L-asparaginase and went into complete remission. It appears that this morphologic variant of ALL does exist and is not an artifact.
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PMID:Hand mirror cell leukemia--immunologic and ultrastructural studies. 693 74

The patient was an eight-year-old black male who presented to the Children's Hospital of Philadelphia (CHP) in June 1977 with foot pain. Abnormal findings on physical examination were diffuse shotty lymphadenopathy without hepatosplenomegaly. Examination of the extremities was normal. There was no evidence of increased bruising or bleeding. Laboratory data revealed a hemoglobin of 11.2 gm/dl, white blood cell count of 26,200/cu mm, and platelet count of 21,000/cu mm. Serum uric acid level was 4.2 mg/dl. The remainder of the laboratory findings were within normal limits. Bone marrow examination revealed a hypercellular marrow replaced with lymphoblasts. Immunologic evaluation showed these cells to have no surface immunoglobin and no rosette formation with sheep red blood cells. The patient received vincristine 1.5 mg/M2 daily, oral prednisone at 40 mg/M2 daily, L-asparaginase 6,000 IU/M2 for nine intramuscular doses, and methotrexate 12 mg intrathecally. After 28 days, bone marrow aspiration showed that the leukemia was in remission. He then received 2,400 rad cranial irradiation over three weeks, along with four more doses of intrathecal methotrexate, given once weekly. Maintenance consisted of monthly pulses of vincristine (1.5 mg/M2), prednisone (40 mg/M2 for five days), daily oral 6-mercaptopurine (75 mg/M2), and weekly oral methotrexate (20 mg/M2). After six months of maintenance, the patient was given a scheduled course of reinduction therapy with vincristine, prednisone, and L-asparaginase. Eleven months after diagnosis both testes were noted to be enlarged on physical examination. Wedge biopsy of both testes revealed leukemic infiltration. Examination of the bone marrow and cerebrospinal fluid (CSF) at that time were unremarkable. The patient was treated with vincristine, prednisone, and L-asparaginase again for four weeks and received intrathecal methotrexate as central-nervous-system (CNS) prophylaxis. Twenty-four hundred rad were given to both testes at 200 rad/day with decrease in testicular size. Maintenance consisted of monthly pulses of vincristine and prednisone with oral methotrexate and 6-mercaptopurine. Seven months after his testicular relapse the patient had a bone marrow relapse. He expired eight months later with disseminated leukemia.
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PMID:Proceedings of the tumor board of the Children's Hospital of Philadelphia. Testicular leukemia: incidence and management results. 694 80

Eleven patients with leukemia and lymphoma were treated with 14 courses of E. coli L-asparaginase. Abnormalities of the coagulation screening tests and decreased fibrinogen levels were observed in all patients during treatment. Significant depressions of functional (mean 32%) and antigenic (mean 48%) antithrombin III were observed by day 14 of therapy. There was no laboratory evidence of intravascular coagulation during 11/14 courses of L-asparaginase. Crossed immunoelectrophoresis of plasma obtained at the antithrombin nadir did not demonstrate an abnormal pattern which can be associated with an abnormal antithrombin III or an increase in antithrombin III-coagulation factor complexes. The major underlying mechanism of this depression is believed to be decreased hepatic synthesis, and the low levels of antithrombin III may be associated with an increased risk of thrombosis.
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PMID:Depression of functional and antigenic plasma antithrombin III (AT-III) due to therapy with L-asparaginase. 704 2

The covalent attachment of poly-DL-alanine peptides to lysyl residues on the surface of Erwinia carotovora L-asparaginase has produced a modified enzyme which is much less immunogenic in mice and demonstrates 100-fold longer plasma half-life in the rhesus monkey. Immunogenic responses towards both the immunoglobulin G (IgG) and immunoglobulin E (IgE) antibody subclasses were evaluated in C57BL x DBA/2 F1 mice exposed to 250 rads of whole-body irradiation 4 hr prior to immunization with 5-diazo-4-oxynorvaline-inactivated native and modified L-asparaginase in complete Freund's adjuvant. Under these immunologically stressful conditions, the native enzyme evoked an IgE and IgG response which could be further amplified by a secondary immunization, whereas the modified enzyme evoked no IgE or IgG response even after a tertiary immunization. In experiments mimicking an intensive therapeutic schedule, whereby two groups of mice were given weekly injections of 5 to 10 units of either native or modified asparaginase for up to 14 weeks, neither enzyme form evoked a significant IgE response, and only the mice given injections of the native enzyme produced an IgG response. In a preliminary patient study, skin testing of a child who had shown an allergic reaction to the native enzyme resulted in a negative response after an intradermal injection of the modified enzyme, whereas a wheal and flare reaction was observed to both the native enzyme and a histamine control. All of these results suggest that the modified enzyme should show a definite reduction in immunological reactions associated with L-asparaginase treatment of childhood leukemia.
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PMID:Immunological and pharmacological characterization of poly-DL-alanyl-modified Erwinia carotovora L-asparaginase. 710 4

The influence of cytostatic drugs (busulphan, chlorambucil, prednisone, 6-mercaptopurine, L-asparaginase) on the activity of alkaline and acid phosphatase, alpha-naphtolacetate esterase and the content of glycogen and lipids in leukocytes of peripheral blood in healthy rats was investigated. No analogy was reported between the changes of cytochemical reactions in healthy population of leukocytes in rats as compared with the changes (observed in preceding papers) of cytochemical reactions in leukocytes of patients with leukemia under the influence of the same cytostatic drugs.
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PMID:Effect of cytostatics administration in rats on leukocyte cytochemical markers. 719 23


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