Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Navelbine (NVB) is a new semi-synthetic Vinca alkaloid selected on the basis of its affinity for tubulin. NVB inhibits the polymerisation of tubulin and it has significant antitumor activity on P388 and L1210 leukemias and some other experimental tumors. In the present study, 20 patients (9 carcinomas, 10 lymphomas and 1 blastic crisis of chronic myeloid leukemia) received a median of 4 weekly i.v. doses of NVB. Two patients at least received each dose level: 3.6 mg/m2 (1/10 of the LD10 dose/kg in BDF1 mice), 7.2, 12, 18, 32.4, 35 and 43 mg/m2 per week. A total of 89 doses were administered. All patients had been first heavily pretreated and 17 of them had received a Vinca alkaloid. Leukopenia (neutropenia) was the dose-limiting toxicity. There was no thrombocytopenia. Leukopenia was dose-related and first seen at 32.4 mg/m2 per week. The maximal tolerated dose appears to be about 43 mg/m2. At that dose, 2 out of 3 patients developed severe leukopenia and neutropenia. One localized allergic reaction, one case of transient hepatic dysfunction, and 2 reversible peripheral neuropathies were seen. Pharmacokinetics, studied with a radioimmunoassay (RIA) method, suggested an elimination half-life of 30 h and a plasma clearance of 75 l/h. Four patients with Hodgkin's disease and two patients with non-Hodgkin's lymphoma, all of them refractory to vincristine (VCR) and/or vinblastine (VBL), showed minor responses lasting 2-8 weeks. They had received between 4 and 12 doses of 30 and 43 mg/m2. We recommend for phase 11 trials the dose of 40 mg/m2 per week.
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PMID:Phase I pharmacologic study of a new Vinca alkaloid: navelbine. 401 23

Human spleen-conditioned medium can induce the formation in vitro of large granulocyte colonies from normal human bone marrow cells. The granulocyte colonies contained cells in various stages of differentiation, from myeloblasts to mature neutrophile granulocytes. Human spleen-conditioned medium also induced colony formation with rodent bone-marrow cells, whereas rodent spleen-conditioned medium induced colony formation with rodent bone marrow but not with human cells. This in vitro system has been used to determine the potentialities for cell differentiation in bone-marrow and peripheral blood cells from patients with a block in granulocyte differentiation in vivo. The cloning efficiency, colony size, and number of mature granulocytes in bone-marrow colonies from patients with congential neutropenia, whose bone marrow contained only 1% mature granulocytes, were not less than in people whose bone marrow had the normal level of about 40% mature granulocytes. The cloning efficiency of peripheral blood cells from patients with acute myeloid leukemia was 350 times higher, with 10 times larger colonies, than the cloning efficiency of peripheral blood cells from normal people. The cytochemical properties and number of mature granulocytes in colonies from the leukemic patients were the same as in colonies from non-leukemic people. The results indicate that a block in cell differentiation in vivo, in these cases with neutropenia and acute myeloid leukemia, was overcome in vitro, in the presence of an inducer in the conditioned medium. In patients with chronic myeloid leukemia, colony formation was induced only in some of the cases. This indicates that there are blast cells with different potentialities for the development of colonies in different patients.
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PMID:In vitro induction of granulocyte differentiation in hematopoietic cells from leukemic and non-leukemic patients. 527 78

During six-month period, 102 consecutive episodes of fever in 68 children (ranging from 1 month to 14 years of age) with malignant diseases were prospectively evaluated. Sixty-five had acute lymphoblastic leukemia, nine had acute myeloblastic leukemia, nine had malignant lymphoma (four Hodgkin and five non-Hodgkin), five had chronic myeloid leukemia, four had rhabdomyosarcoma, three had CNS tumors, two had neuroblastoma, one had Wilms, and four had other malignant tumors. Forty cases (39.2%) showed severe neutropenia (500 neutrophil/m3) during the episode. S. aureus, E. coli, and S. pyogenes were in 53% of the 75 microbiologic isolates. Twenty-two percent of the viral studies were positive. Mycologic studies were all negative, except one case with C. Albicans. Pneumonia (33 cases), cellulitis (15 cases), pharyngitis (12 cases), and varicella (11 cases) were the most common final diagnosis. Seventy-one percent of the episodes were etiologically documented (by bacterial isolate, characteristic serology, and/or typical clinic picture); 19% of the febrile episodes were probable infections, and 10% were fever of uncertain cause. Ninety percent of the cases responded well to therapy, and mortality of this series was 7%. Gentamicin, Carbenicillin, and Methicilin were the more common antibiotics employed. We conclude that in our population 1) infection is a frequent cause of morbidity in children with malignant diseases; 2) the most common cause of the febrile episodes is bacterial infection; 3) S. aureus, E. coli and S. pyrogenes are the most frequent bacterial isolates, and P. aeruginosa is infrequent; 4)viral infections are relatively frequent in this group of children; and 5) with adequate management, the mortality is low.
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PMID:Infections in children with malignant disease in Argentina. 722 35

Increased numbers of bone marrow mast cells were found in 45 (2.2%) of 2,000 bone marrow specimens obtained from patients who had hematologic disorders. Mast cells were most frequently seen in the marrows of patients who had preleukemic syndromes, lymphoproliferative disorders, and acute leukemia. The 16 patients who had preleukemic syndromes included those with refractory sideroblastic and megaloblastic anemia (with or without an excess of blasts), idiopathic pancytopenia or pure erythrocytic aplasia, paroxysmal nocturnal hemoglobinuria, idiopathic refractory neutropenia, agranulocytosis or thrombocytopenia, and persistent eosinophilia. Five of the seven patients who had acute leukemia had nonlymphoblastic leukemia; two had blastic crisis of chronic granulocytic leukemia. Of the 13 patients who had lymphoproliferative disorders, eight had chronic lymphocytic leukemia, three had macroglobulinemia, and two had non-Hodgkin's lymphoma. Three patients who had chronic renal failure associated with severe anemia and two who had chronic liver disease, splenomegaly, or hypersplenism were also encountered. In this study there appeared to be a consistent relationship between the presence of increased numbers of mast cells and the lymphocyte and plasma cell counts in the bone marrow. The significance of the presence of secondary mastocytosis in premalignant lesions, neoplasia, and, in particular, lympho- and myeloproliferative disorders, is still unclear.
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PMID:Increased bone marrow mast cells in preleukemic syndromes, acute leukemia, and lymphoproliferative disorders. 745 27

Antibodies to mature blood neutrophils and to bone marrow myeloid cells have been described in the sera of some patients with apparent autoimmune neutropenia. To further explore the prevalence and specificities of antibodies to myeloid precursor cells, we evaluated sera from 148 patients with suspected autoimmune neutropenia for the presence of antibodies to neutrophils, to cultured myeloid cell lines, and to highly purified bone marrow myeloid progenitor cells. Using an immunofluorescence flow cytometric assay, we identified IgG antibodies in 42 (28%) of these sera that bound specifically to K562 cells, a multilineage cell line originally derived from a patient with chronic myelogenous leukemia. Twenty-two (15%) of the sera also contained IgG antibodies that bound specifically to the primitive myelomonocytic leukemia cell line KG1a. Twenty-five (17%) of the sera had IgG antibodies to myeloid cell lines in the absence of antibodies to mature neutrophils. There was a trend toward more severe neutropenia in patients with antibodies to K562 cells, without antineutrophil antibodies. In further studies, antibodies from 12 sera bound to mononuclear CD34+ cells that had been purified from normal human bone marrow by an immunomagnetic separation procedure. Moreover, two of these sera suppressed the growth of granulocyte-macrophage colony-forming units (CFU-GM) in methylcellulose cultures. The presence of antibodies to primitive hematopoietic cells in the sera of some patients with suspected immune neutropenia suggests that these antibodies may have a role in the pathogenesis of the neutropenia observed.
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PMID:Antibodies to myeloid precursor cells in autoimmune neutropenia. 751 22

A case of pneumatosis intestinalis with perforation is reported in a patient after bone marrow allograft for chronic myeloid leukemia. Risk factors included the transplant, prolonged immunosuppression and neutropenia, graft-versus-host disease, extended use of corticosteroids, infection and lower gastrointestinal endoscopic biopsy. The literature is reviewed and a management plan for patients presenting with this complication is discussed.
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PMID:Pneumatosis intestinalis with free air mimicking intestinal perforation in a bone marrow transplant patient. 799 50

Prolonged exposure to low concentrations of cytarabine preferentially inhibits in vitro growth of neoplastic myeloid progenitors from patients with chronic myelogenous leukemia (CML) compared to that of normal myeloid progenitors. Continuous infusions of cytarabine in doses of 15-30 mg/m2/day were therefore administered for extended periods to patients with CML in stable phase to determine if this treatment could achieve selective cytoreduction of Philadelphia chromosome (Ph)-positive cells. Five patients demonstrating > 90% Ph-positive metaphases before treatment received a total of 43 cycles of cytarabine infusional therapy. Cytarabine was administered on an outpatient basis using a portable, battery-operated syringe pump until the total leukocyte count reached 2500/microliters or the platelet count reached 75,000/microliters. A new cycle was begun when the total leukocyte count exceeded 4,000/microliters and the platelet count exceeded 100,000/microliters. The median duration of cytarabine administration per cycle was 29 days (range 15-72 days). Leukocytosis was readily controlled by low-dose cytarabine therapy in all patients. All five patients experienced complete hematologic responses during cytarabine therapy. The fraction of Ph-positive metaphases in the marrow of the five patients was reduced to 0, 10%, 43%, 72%, and 84%, respectively, during therapy. The median time to achieve optimal cytogenetic response was 4.8 months (range 2.8-8.6 months). One patient demonstrated a complete cytogenetic response after three cycles of cytarabine. Another patient demonstrated persistent cytogenetic improvement during 20 cycles of cytarabine, with a median 38% Ph-positive marrow metaphases (range 10-53%) over 32 months. Cytarabine therapy was generally well-tolerated, but was discontinued in one patient because of persistent asymptomatic elevations in hepatic enzymes, which resolved within 2 months after discontinuing therapy. There were no episodes of fever during neutropenia, and platelet transfusions were not required. However, symptomatic anemia requiring transfusion of red cells occurred during most cycles of treatment. In summary, treatment of CML with low-dose cytarabine can induce prolonged cytogenetic improvement in some patients with acceptable toxicity. Further evaluation is needed to ascertain the effect of this treatment on duration of stable phase and overall survival.
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PMID:Hematologic remission and cytogenetic improvement after treatment of stable-phase chronic myelogenous leukemia with continuous infusion of low-dose cytarabine. 834 58

The clinical course of patients with hematological disease, especially after treatment, is often complicated by gastrointestinal infections. Between 1986 and 1990 a total of 18 patients affected with hematologic disease and presenting with an acute abdomen were admitted to the surgery department at the University of Rome "La Sapienza". Most patients were affected with acute or chronic myeloid leukemia (61%) and lymphoma. Five patients with acute appendicitis, three with necrotizing enterocolitis, three with spontaneous hemoperitoneum, three with cholecystitis, two splenic infarctions and two intestinal occlusions were diagnosed. Symptoms were often vague and non specific and blood counts revealed neutropenia in all but two patients, while anemia was characteristic in spontaneous hemoperitoneum and in neutropenic enterocolitis. Fungemia occurred in only two cases while bacteremia was present in seven. The most critical patients were those affected by neutropenic enterocolitis and acute cholecystitis. Sonography was meaningful in the diagnosis of hemoperitoneum, splenic infarct and acute cholecystitis. All patients underwent surgical procedures within 48 hours of admission to the department. In all cases peritoneal washing was performed and at least one peritoneal drainage was left. In all cases of necrotizing enterocolitis, intestinal resections, either ileal or colonic, were followed by an immediate anastomosis in two layers. Intensive hematological and antibiotic post surgical care was performed in all patients. Seven patients presented minor complications (38.8%), and only one died (5.5%). Emergency surgical treatment may be safely carried out in patients with hematological diseases presenting with an acute abdomen. Intensive postsurgical care is mandatory for the recovery of patients and the patient's critical condition should not be a deterrent to surgical intervention.
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PMID:The surgical choice in neutropenic patients with hematological disorders and acute abdominal complications. 847 83

We report the case of a patient having Philadelphia-negative, bcr-abl-positive chronic myeloid leukemia. In situ hybridization showed the presence of the bcr-abl fusion on the chromosome 9 long arm in all mitoses observed. Stability of the disease was very difficult to obtain because of serious adverse effects to interferon and chemotherapy, mainly grade IV neutropenia, and a blast crisis occurred 12 months after diagnosis. Only three other patients with such presentation (Philadelphia negative, bcr-abl positive with bcr-abl fusion on the chromosome 9 long arm) have been reported, with a poor therapeutic response and outcome in two of them. Translocation of BCR to chromosome 9 may therefore have a worse prognosis than translocation of ABL to chromosome 22 in Philadelphia-negative chronic myeloid leukemia.
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PMID:Translocation of BCR to chromosome 9 in a Philadelphia-negative chronic myeloid leukemia. 853 45

Fourteen patients with high-risk leukemia (six with relapsed AML, three with relapsed ALL, one with AML-M0, four with CML in myeloid blastic crisis) were treated with a combination chemotherapy of carboplatin (200-300 mg/m2/day) and cytosine arabinoside (100 mg/m2/day) by 24 h continuous infusion for 5-7 days. Five patients (35.7%) achieved complete remission including two patients complicated with myelofibrosis (one with AML-M0 and one with CML in myelo-megakaryocytic crisis). Thirteen patients had nausea and vomiting, five patients had severe, prolonged neutropenia for which it was necessary to administer granulocyte colony-stimulating factor and six patients had severe thrombocytopenia. We concluded that this regimen is effective for the treatment of high-risk leukemia.
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PMID:Combination chemotherapy of carboplatin and cytosine arabinoside for high-risk leukemia: a pilot study. 863 58


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