RESUMEN
Associations between bladder cancer risk and NAT2 and GSTM1 polymorphisms have emerged as some of the most consistent findings in the genetic epidemiology of common metabolic polymorphisms and cancer, but their interaction with tobacco use, intensity and duration remain unclear. In a New England population-based case-control study of urothelial carcinoma, we collected mouthwash samples from 1088 of 1171 cases (92.9%) and 1282 of 1418 controls (91.2%) for genotype analysis of GSTM1, GSTT1 and NAT2 polymorphisms. Odds ratios and 95% confidence intervals of bladder cancer among New England Bladder Cancer Study subjects with one or two inactive GSTM1 alleles (i.e. the 'null' genotype) were 1.26 (0.85-1.88) and 1.54 (1.05-2.25), respectively (P-trend = 0.008), compared with those with two active copies. GSTT1 inactive alleles were not associated with risk. NAT2 slow acetylation status was not associated with risk among never (1.04; 0.71-1.51), former (0.95; 0.75-1.20) or current smokers (1.33; 0.91-1.95); however, a relationship emerged when smoking intensity was evaluated. Among slow acetylators who ever smoked at least 40 cigarettes/day, risk was elevated among ever (1.82; 1.14-2.91, P-interaction = 0.07) and current heavy smokers (3.16; 1.22-8.19, P-interaction = 0.03) compared with rapid acetylators in each category; but was not observed at lower intensities. In contrast, the effect of GSTM1-null genotype was not greater among smokers, regardless of intensity. Meta-analysis of the NAT2 associations with bladder cancer showed a highly significant relationship. Findings from this large USA population-based study provided evidence that the NAT2 slow acetylation genotype interacts with tobacco smoking as a function of exposure intensity.
Asunto(s)
Arilamina N-Acetiltransferasa/genética , Glutatión Transferasa/genética , Fumar/efectos adversos , Neoplasias de la Vejiga Urinaria/etiología , Acetilación , Adulto , Anciano , Estudios de Casos y Controles , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Riesgo , Neoplasias de la Vejiga Urinaria/genéticaRESUMEN
We designed a protocol that included 2 months of intensive Cytoxan (cyclophosphamide; Bristol-Myers Co, Evansville, IN), high-dose methotrexate (MTX), high-dose cytarabine (ara-C), and vincristine (HiC-COM) to improve event-free survival (EFS) for patients with advanced-stage Burkitt's lymphoma and B-cell acute lymphoblastic leukemia (ALL). We also wished to test the feasibility of rapidly cycling Cytoxan and high-dose ara-C based on signs of early marrow recovery. Twenty patients including 12 with stage III Burkitt's lymphoma and eight with stage IV Burkitt's lymphoma or B-cell ALL were entered onto this pilot study. The rate of complete remission was 95%. Four patients have relapsed. The 2-year actuarial EFS was 75% (median follow-up, 37 months). Two of the initial five patients developed transverse myelitis, which we believe may have been secondary to the concomitant administration of intrathecal (IT) and high-dose systemic ara-C. We conclude that this short but intensive regimen is highly effective for patients with advanced Burkitt's lymphoma and B-cell ALL. EFS has improved over previous less intensive regimens, and is comparable to regimens of longer duration.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma de Burkitt/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Linfoma de Burkitt/mortalidad , Linfoma de Burkitt/patología , Niño , Preescolar , Ciclofosfamida/administración & dosificación , Citarabina/administración & dosificación , Esquema de Medicación , Estudios de Factibilidad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Metotrexato/administración & dosificación , Estadificación de Neoplasias , Proyectos Piloto , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Inducción de Remisión , Tasa de Supervivencia , Vincristina/administración & dosificaciónRESUMEN
Five pediatric patients are described with acute lymphoblastic leukemia (ALL) who at presentation had clinical findings suggestive of B cell ALL and lymphoblasts with FAB L3 morphology and the characteristic t(8;14)(q24;q32). However, the leukemia cells of all five patients failed to express surface immunoglobulin (sIg) and kappa or lambda light chains. Based on initial immunophenotyping results consistent with B-precursor ALL, four of these cases were initially treated with conventional ALL chemotherapy. These four patients were switched to B cell ALL treatment protocols once cytogenetic results became available revealing the 8;14 translocation. The fifth case was treated with B cell ALL therapy from the outset. Four of the five patients are in complete remission at 64, 36, 29 and 13 months from diagnosis. One patient relapsed and died 6 months after initial presentation. These five unusual cases with clinical B cell ALL, the t(8;14), and FAB L3 morphology, but negative sIg, demonstrate the importance of careful and multidisciplinary evaluation of leukemic cells with morphology, cytochemistry, immunophenotyping and cytogenetic analysis. Future identification of patients with this profile will allow us to expand our knowledge regarding prognostic significance and optimal treatment for this rare subgroup of patients.
Asunto(s)
Linfocitos B/inmunología , Linfoma de Burkitt/genética , Cromosomas Humanos Par 14 , Cromosomas Humanos Par 8 , Translocación Genética , Adolescente , Antígenos CD/análisis , Linfocitos B/patología , Médula Ósea/patología , Linfoma de Burkitt/sangre , Linfoma de Burkitt/inmunología , Linfoma de Burkitt/patología , Niño , Preescolar , Mapeo Cromosómico , Femenino , Humanos , MasculinoRESUMEN
A 23-month-old female evaluated for profound anemia proved to have megakaryoblastic leukemia. The diagnosis is based on examination of bone marrow morphology, cytochemical characteristics, and immunophenotype. The chromosome complement of unstimulated blast cells in peripheral blood and bone marrow was 48,XX,+21,+21. Tetrasomy 21 is the sole clonal cytogenetic abnormality in this patient with megakaryoblastic leukemia. The constitutional complement of the patient is normal female, 46,XX.
Asunto(s)
Aneuploidia , Cromosomas Humanos Par 21 , Leucemia Megacarioblástica Aguda/genética , Femenino , Humanos , Lactante , CariotipificaciónRESUMEN
Cells cultured from individuals with neurofibromatosis, a genetic syndrome associated with a predisposition to malignancy, were studied. We examined survival as measured by colony formation in skin fibroblasts from 5 patients with neurofibromatosis after exposure to X-rays, ultraviolet light and an alkylating agent. We did not observe mutagen hypersensitivity in neurofibromatosis cells as compared to normal controls.
Asunto(s)
ADN/efectos de la radiación , Metilnitronitrosoguanidina/toxicidad , Neurofibromatosis 1/genética , Adolescente , Adulto , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/efectos de la radiación , Células Cultivadas , Niño , Femenino , Humanos , Masculino , Rayos Ultravioleta , Rayos XRESUMEN
Burkitt's lymphoma is a disease of unique cytokinetics that account for the bulky tumors, variety of presenting symptoms, and sensitivity to chemotherapy. A need to ascertain the role of surgery in the treatment of this illness prompted this review. Of nine children 5 to 12 years of age with Burkitt's lymphoma, eight had abdominal involvement. Two of the eight patients also had oral lesions and staging was done by biopsy of the oral lesion and noninvasive imaging of the abdominal tumors. The other six patients presented with abdominal complaints. One of these had diagnostic paracentesis, another had only gastroscopy, and four underwent exploratory laparotomy. The four children in whom the diagnosis was established either by biopsy of an oral lesion, biopsy of an abdominal mass, or resection of an abdominal tumor are alive without evidence of disease 6 months to 6 years after treatment. Each of these children had rapid initiation of chemotherapy. Of the other four who died, two had delayed induction of drug therapy following cytoreduction or gastroscopic biopsy. The best outcomes were associated with prompt chemotherapy. We conclude that except in rare instances in which a solitary lesion lends itself to total or near-total resection, the proper role of surgery is a simple, safe procedure to obtain enough viable tumor for accurate diagnosis and prompt chemotherapy.
Asunto(s)
Linfoma de Burkitt/cirugía , Biopsia , Linfoma de Burkitt/tratamiento farmacológico , Linfoma de Burkitt/patología , Niño , Terapia Combinada , Humanos , Masculino , Estudios RetrospectivosRESUMEN
Ten years have passed since the Chernobyl disaster. Five years ago, reports began to appear suggesting an increase in the frequency of thyroid cancer in children living or born in the areas with highest exposure to radioactive contamination. During the past year, data have been published, presented, or submitted that demonstrate the magnitude of the increase in incidence. No increase in childhood leukemia or other cancers has been documented. However, anxiety about the future persists. A rapid government response, including the distribution of potassium iodide to the highest-risk groups, pregnant women and young children, could have prevented the majority of the cases of thyroid cancer.
Asunto(s)
Neoplasias Inducidas por Radiación/epidemiología , Liberación de Radiactividad Peligrosa , Neoplasias de la Tiroides/epidemiología , Adolescente , Niño , Preescolar , Femenino , Humanos , Incidencia , Lactante , Recién Nacido , Masculino , Neoplasias Inducidas por Radiación/prevención & control , Vigilancia de la Población , Yoduro de Potasio/uso terapéutico , Embarazo , Salud Pública , Factores de Riesgo , Neoplasias de la Tiroides/prevención & control , Ucrania/epidemiologíaRESUMEN
A 3-year-old boy presented with the fever, conjunctivitis, rash, and lymphadenopathy diagnostic of Kawasaki disease. Treatment with antibiotics, aspirin, and intravenous immunoglobulin was instituted. The hematocrit decreased from 35 percent on admission to 11 percent by hospital Day 10, and the white cell count had increased from 13.7 to 42 x 10(3) per microL, and the patient had a leukoerythroblastic blood smear. The direct antiglobulin test demonstrated IgG but not complement on the red cell (RBC) surface. An acid eluate reacted (titer of 4) with all panel cells in the antiglobulin phase. Intravenous immunoglobulin from the same lot used for treatment did not contain antibody that reacted with the patient's group O RBCs or a panel of group O RBCs, but did contain IgG anti-A and -B (titer of 4). The patient received a transfusion and was given methylprednisone. The direct antiglobulin test and acid eluate were negative 4 days later. The patient had an uneventful recovery. The distinction between antibody-mediated hemolytic anemia and autoimmune hemolytic anemia is important in the treatment of this disease.
Asunto(s)
Anemia Hemolítica Autoinmune/complicaciones , Síndrome Mucocutáneo Linfonodular/complicaciones , Anemia Hemolítica Autoinmune/terapia , Transfusión Sanguínea , Preescolar , Prueba de Coombs , Humanos , Masculino , Síndrome Mucocutáneo Linfonodular/tratamiento farmacológico , Prednisona/uso terapéuticoRESUMEN
BACKGROUND: The Pediatric Oncology Group (POG) conducted a two-arm, randomized study for the treatment of children and adolescents with stage III small, non-cleaved cell lymphoma (SNCCL). Regimen A, based on the group's previous best treatment for this group of patients, included cyclophosphamide (CTX) and high-dose methotrexate (MTX), as well as vincristine (VCR), prednisone (PRED), and intrathecal (IT) chemoprophylaxis. Regimen B, based on a single institution pilot study (Total B therapy), consisted of two rapidly alternating chemotherapy combinations (CTX, VCR, doxorubicin; MTX, and cytarabine (Ara-C) plus coordinated IT chemotherapy. PROCEDURE: One hundred thirty-four consecutive patients were entered on this study. Seventy patients were randomized to Regimen A, and 64 patients to Regimen B. One hundred and twenty-two patients are eligible for response. RESULTS: Complete remission (CR) was achieved by 81% (52/64) of patients on Regimen A, and 95% (55/58) of patients on Regimen B (p=0.014 one-sided). The two-year event-free survival (EFS) is 64% (SE=6%) on Regimen A, and 79% (SE=6%) on Regimen B (p=0.027 by one-sided logrank test). No patient has relapsed on either regimen after a year from diagnosis, although one patient had a second malignancy at day 371. Severe, but manageable, hematologic toxicity was seen in the majority of patients on both regimens, but was more frequent on Regimen B. CONCLUSIONS: We conclude that the cure rate in stage III SNCCL is significantly improved with the use of a short, six-month chemotherapy regimen of fractionated CTX alternated with coordinated MTX and Ara-C. Results suggest that drug schedule, not simple drug selection, influences outcome.