RESUMEN
BACKGROUND: Leptomeningeal metastasis (LM) in breast cancer is associated with a poor prognosis. Although no randomised trial has demonstrated that intrathecal chemotherapy actually prolongs survival, this treatment is considered standard of care in this setting. The prognosis of patients with LM is poor, with a median overall survival time of less than 6 months. METHODS: Herein, we report a case of a young woman with breast cancer who presented with LM at the time of relapse and was subsequently treated with two lines of intrathecal chemotherapy that prolonged survival. RESULTS: A 28-year old woman without a significant past medical history was diagnosed with triple-negative invasive ductal carcinoma. Eight months after adjuvant treatment she developed multiple brain metastases and LM developed subsequently 1 month after finishing whole brain irradiation. Initially, she was treated with a combination of methotrexate, cytarabine and dexamethasone intrathecally but after 3 months she presented with a worsening clinical status and increased numbers of cancer cells in cerebrospinal fluid. Subsequently, she received a combination of thiotepa and methotrexate intrathecally, which resulted in a prolonged response lasting 10 months. The patient died 32 months after initial diagnosis and 18 months from LM infiltration due to disease progression in the liver and lungs as well as LM. CONCLUSION: The prognosis of patients with LM remains poor because of the limited effectiveness of currently available therapies; however, intrathecal chemotherapy could substantially prolong survival in selected patients.
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Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias Meníngeas/tratamiento farmacológico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias de la Mama/patología , Femenino , Humanos , Inyecciones Espinales , Neoplasias Meníngeas/secundario , PronósticoRESUMEN
Reciprocal communication between hematopoietic cells and their surrounding bone marrow stroma is crucial for normal progression of hematopoiesis. This complex network of cell-to-cell signals in the microenvironment involves both cell contact-mediated and paracrine cues. In hematological malignancies the intricate balance is, however, disrupted to support cancer progression. In order to detect altered microenvironmental reactivity of a hematopoietic cell sample, cellular functional assays can be designed to measure the cells' capacity to modulate stromal stress reactions, such as inflammation.Recently, we showed that human leukemic cell lines of monocytic origin can actively participate in modulation of stromal inflammation. In order to further functionally evaluate the hematopoietic cells' capacity to modulate stromal inflammation, we utilized an in vitro model of nemosis-induced inflammation of fibroblasts in a three-dimensional culture setting. This process of stromal inflammation in fibroblast aggregates is consistent, requires both cell-contact and paracrine signals, and can be produced on a large scale to support dose-dependent analyses. To extend our previous observations, we evaluated the effect of a wide panel of leukemia cell lines on cyclooxygenase- 2 induction in fibroblast aggregates in co-culture. We also assessed the feasibility of the model to support clinical functional testing by utilizing the hematopoietic fraction of leukemia patients' bone marrow aspirates after immunophenotyping. Our results suggest that the stromal inflammation-modulating activity of these samples is differently modulated in cancer and in normal bone marrow. Moreover, differences in the samples' anti-inflammatory activity may reflect disease state.
Asunto(s)
Antiinflamatorios/metabolismo , Médula Ósea/patología , Ciclooxigenasa 2/metabolismo , Fibroblastos/patología , Células Madre Hematopoyéticas/patología , Leucemia/patología , Microambiente Tumoral , Adolescente , Adulto , Médula Ósea/enzimología , Médula Ósea/inmunología , Comunicación Celular , Células Cultivadas , Niño , Preescolar , Técnicas de Cocultivo , Dermis/enzimología , Dermis/inmunología , Dermis/patología , Femenino , Fibroblastos/enzimología , Fibroblastos/inmunología , Citometría de Flujo , Células Madre Hematopoyéticas/enzimología , Células Madre Hematopoyéticas/inmunología , Humanos , Immunoblotting , Inmunofenotipificación , Lactante , Leucemia/enzimología , Leucemia/inmunología , Masculino , Persona de Mediana Edad , Células del Estroma/enzimología , Células del Estroma/inmunología , Células del Estroma/patología , Adulto JovenRESUMEN
In this report, we describe a rare 5q--/CML association in a patient with Ph-positive chronic myelogenous leukemia (CML) who achieved complete cytogenetic response on interferon-alpha (IFN-alpha) treatment, but who developed a new clone in the blastic crisis. The patient was treated with interferon-alpha beginning in 1996 and a serial chromosome and molecular study was performed over the clinical course of the disease. The patient remained in complete hematologic and cytogenetic remission until November 1998, when a reverse transcriptase PCR study performed on the bone marrow and peripheral blood cells was negative for chimeric BCR/ABL mRNA. The treatment was discontinued until April 1999, when the patient developed acute transformation of the disease. In June 1999, cytogenetic examination showed the development of a new clone, consisting of the deletion of the long arm of chromosome 5 in addition to the standard Ph translocation. The unusual association of a Ph with an abnormality usually observed in a secondary myeloproliferative disease raises the question of whether the new finding is treatment-induced or part of the disease process and casually related to the acute transformation.
Asunto(s)
Deleción Cromosómica , Cromosomas Humanos Par 5 , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Adulto , Antineoplásicos/uso terapéutico , Crisis Blástica , Células de la Médula Ósea/patología , Bandeo Cromosómico , Mapeo Cromosómico , Diagnóstico Diferencial , Femenino , Humanos , Hibridación Fluorescente in Situ , Interferón-alfa/uso terapéutico , Cariotipificación , Leucemia Mielógena Crónica BCR-ABL Positiva/sangre , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
By flow cytometry (FC) and an extensive panel of markers we characterized leukemia cells from the peripheral blood (PB) and bone marrow (BM) of 13 symptomatic patients with hairy cell leukemia (HCL). Hairy cells (HCs) identified in the large cell gate always expressed B-cell markers - CD19, CD20, CD22, HLA-DR, and 'HCL-restricted' markers - CD22+CD11c, CD25 and CD103. Other markers, not followed regularly, were occasionally expressed, such as CD34, CD38, CD71, CD15, CD10 and kappa/lambda light chains. Furthermore, in one patient with suspect but not proved HCL in PB or BM, neither morphologically nor immunologically, we confirmed the diagnosis of HCL. Only the immunophenotyping of splenic cells after splenectomy confirmed HCL diagnosis. Flow cytometry was repeated at 3-5 month intervals, after treatment with 2-Chlorodeoxyadenosine (CdA) or less frequently alpha-interferon (IFN). We investigated serially lymphocyte subsets after treatment and we found profound and persistent CD4+ lymphopenia in majority of studied patients after CdA treatment. Simultaneously we investigated the value of FC to detect minimal residual disease (MRD) and to establish, whether MRD+ could predict relapse. Detection of MRD in our series predicted hematological relapse only in one case with persistent MRD+, in majority of cases with occasionally found MRD+ phenotype, did not. Using quantitative immunophenotyping we observed significantly higher values of molecule numbers of hairy cell B-cell markers, comparing to B-cells in nonleukemic gate of the same sample. Our study showed 1) the diagnostic value of FC in management of HCL patients, 2) long-lasting response in the majority of patients after CdA, 3) a profound and persistent CD4+ lymphopenia in CdA treated patients, 4) some correlation between persistent MRD staining and hematological relapse, and 5) further, till now not described activated feature of HCs, given by the increased values of molecular numbers (molecules of equivalent soluble fluoresceine - MESF) in B-cell antigens of HCL.
Asunto(s)
Células Sanguíneas/citología , Células de la Médula Ósea/citología , Moléculas de Adhesión Celular , Citometría de Flujo/métodos , Cadenas alfa de Integrinas , Lectinas , Leucemia de Células Pilosas/diagnóstico , Leucemia de Células Pilosas/terapia , Subgrupos Linfocitarios/citología , Adulto , Anciano , Antígenos CD/biosíntesis , Antígenos de Diferenciación de Linfocitos B/biosíntesis , Antineoplásicos/uso terapéutico , Linfocitos B/metabolismo , Antígenos CD4/biosíntesis , Cladribina/uso terapéutico , Femenino , Humanos , Inmunofenotipificación , Interferón-alfa/uso terapéutico , Antígeno de Macrófago-1/biosíntesis , Masculino , Persona de Mediana Edad , Fenotipo , Receptores de Interleucina-2/biosíntesis , Lectina 2 Similar a Ig de Unión al Ácido SiálicoRESUMEN
Twelve cases of Trichosporon spp. fungemias occurring in a national cancer institution within 10 years are described. The trend of hematogenous trichosporonosis within the last 10 years is increasing. While no cases occurred in 1988-1991, after 1991, Trichosporon spp. was the most common species among non-Candida spp. fungemias in 1993-1997. The 12 cases of fungemia included 5 that started while the patients were receiving prophylaxis with oral itraconazole, and 2 appeared despite empiric therapy with amphotericin B. Five of the 12 fungemias were catheter associated. Risk factors for fungemia were: central venous catheter, broad-spectrum antibiotics (third-generation cephalosporins plus aminoglycoside); all but 1 had neutropenia and were receiving antineoplastic chemotherapy. All but 2 of the patients died of systemic fungal infection (83.3% mortality). Amphotericin B was administered to all but 1 patient, who was not treated because he died the day after his culture was found to be positive for T. beigelii, before antifungals were administered. All cases infected with T. pullulans were catheter related, and all these patients died. One of the remaining 9 fungemias was caused by T. capitatum (Blastoschizomyces capitatus), and 8 by T. beigelii. Only 2 patients were cured, 1 with a combination therapy with amphotericin B plus fluconazole, and 1 with amphotericin B monotherapy. Several risk factors (neutropenia, acute leukemia, prior therapy or prophylaxis with antifungals and catheter as source of fungemia, breakthrough fungemia) were significantly associated with Trichosporon spp. fungemia, in comparison to 63 C. albicans candidemia occurring in the same period at the same institution. Attributable mortality of hematogenous trichosporonosis was also significantly higher (83.3% vs. 15.8%, P<0.001) than that of hematogenous candidiasis.
Asunto(s)
Antifúngicos/uso terapéutico , Fungemia/microbiología , Itraconazol/uso terapéutico , Micosis/etiología , Neoplasias/complicaciones , Infecciones Oportunistas/etiología , Trichosporon , Administración Oral , Adulto , Anciano , Anciano de 80 o más Años , Aminoglicósidos , Anfotericina B/administración & dosificación , Anfotericina B/uso terapéutico , Antibacterianos/uso terapéutico , Antifúngicos/administración & dosificación , Candidiasis/etiología , Cateterismo Venoso Central/efectos adversos , Cateterismo Venoso Central/instrumentación , Cateterismo Periférico/efectos adversos , Cateterismo Periférico/instrumentación , Causas de Muerte , Cefalosporinas/uso terapéutico , Quimioprevención , Femenino , Fungemia/prevención & control , Humanos , Itraconazol/administración & dosificación , Masculino , Persona de Mediana Edad , Micosis/prevención & control , Neoplasias/tratamiento farmacológico , Neutropenia/complicaciones , Infecciones Oportunistas/prevención & control , Factores de Riesgo , Trichosporon/clasificación , Trichosporon/efectos de los fármacosRESUMEN
For exact determination of lineage assessment there is a need of surface membrane and intracellular (cytoplasmic and nuclear) immunophenotyping performed by flow cytometry. We evaluated in detail the results of surface and intracellular immunophenotyping of 34 T-ALL cases. The great heterogeneity of T-cell differentiation markers has been observed which did not allow relevant subclassification of T-ALL according to the existing subclassification schemes and the proposed three-stage model of physiological T-cell differentiation. Therefore, a simplified classification based on the CD3 marker expression either on cell membrane or in cytoplasm has been created with allocation of T-ALL into two main phenotypic groups. From 34 in detail examined T-ALL cases a great deal-27 (79%) belonged to an immature phenotype (Stage I) and only 7 (21%) expressed more mature phenotype (Stage II). Simultaneously the presence of atypical/aberrant T-cell phenotypes has been studied. We showed that in T-ALL it was possible to specify some cases with leukemia-associated phenotype with coexistence of atypical markers which are absent in nonleukemic cells. In a majority of cases early B-lineage marker (CD10) and in a smaller proportion of them non-lineage associated marker (CD34) were observed. Myeloid marker CD13 was observed in one case of the immature T-ALL, together with CD10 and CD34. As these atypical markers were present through all differentiation stages of T-ALL we obtained a strong evidence that they might represent an abnormal rather than an immature phenotype. The prognostic significance of T-ALL subtypes and aberrant markers coexpression have been discussed. Simultaneously it was shown that quantitative immunofluorescence could provide an additional important diagnostic marker also in T-ALL cases.
Asunto(s)
Antígenos de Superficie/análisis , Leucemia-Linfoma Linfoblástico de Células Precursoras/clasificación , Anticuerpos Monoclonales , Antígenos CD/análisis , Biomarcadores de Tumor/análisis , Linaje de la Célula , Variación Genética , Antígenos HLA/análisis , Humanos , Inmunofenotipificación , FenotipoRESUMEN
A patient with a constitutional chromosomal abnormality who developed acute nonlymphocytic leukemia (ANLL-M4) at the age of 31 is presented. At the time of diagnosis the only acquired chromosomal change was the presence of a small marker chromosome. The patient was studied periodically for 11 years during his illness with no evidence of karyotypic progression, until the last study, when a deletion of the long arm of chromosome 7 was detected.
Asunto(s)
Aberraciones Cromosómicas , Leucemia Mieloide Aguda/genética , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Progresión de la Enfermedad , Humanos , Cariotipificación , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/patología , Masculino , RecurrenciaRESUMEN
Five cases of fungaemia due to Fusarium spp. in cancer patients are described. Two were breakthrough cases, despite ongoing therapy with amphotericin B. Three were caused by Fusarium solani, one by F. oxysporum and one by F. dimerum. Four patients died, three of them despite therapy with amphotericin B for between 5-37 days. We describe only the second reported case of F. dimerum fungaemia. Since 1972, 93 cases of systemic infection with Fusarium spp. have been described: 43 had positive blood cultures and the overall mortality was 72%.
Asunto(s)
Infección Hospitalaria/etiología , Fungemia/etiología , Fusarium , Neoplasias/complicaciones , Adulto , Anciano , Resultado Fatal , Femenino , Fusarium/clasificación , Humanos , Control de Infecciones , Masculino , Persona de Mediana Edad , Neutropenia/complicaciones , Factores de RiesgoAsunto(s)
Deleción Cromosómica , Cromosomas Humanos Par 7/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Cromosoma Filadelfia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Humanos , Cariotipificación , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , MasculinoRESUMEN
High cardiac output failure/state (HCOF) is regular feature of some illnesses e.g. thiamine deficiency, hyperthyroidism, severe anemia, Paget's disease or arteriovenous fistulae. HCOF in multiple myeloma is reported quite rarely. 31-year-old man was admitted because of fatigue, dyspnea and subfebrilities. Heart rate was 116/min, sinus rythm blood pressure 110/60 mmHg. Chest film showed cardiomegaly with sings of interstitial pulmonary edema, echocardiography mild dilatation of the left ventricle with hyperkinetic wall motion and small pericardial effusion. Hemoglobin was 104 g/l, leukocyte count 13.5 x 10(9)/l with 30% of plasmatic cells. Serum protein electrophoresis demonstrated a monoclonal gammapathy, X ray studies of the skelet multiple osteolytic lesions. Diagnosis of plasmocytic leukemia-form of multiple myeloma was established and chemotherapy (vincristine + adriamycine + dexamethason) was started. Patient cardiac status deteriorated. Cardiac catheterisation demonstrated mean righ atrial pressure of 25 mmHg, mean pulmonary artery pressure of 28 mmHg and pulmonary artery wedge pressure of 24 mmHg. Co was 20.0 l/min (C.I. 11.5 l/min/m2). In continuing of chemotherapy and symptomatic therapy for heart failure patients status gradually improved and complete remission of the myeloma and normalisation of cardiac parameters was achieved. Heart failure in multiple myeloma patients has been attributed to amyloidosis of myocardium, hyperviscosity syndrome, co-existing CAD or anthracycline toxicity. HCOF should be considered in patients with clinical evidence of heart failure and normal left ventricular function.
Asunto(s)
Gasto Cardíaco Elevado/complicaciones , Gasto Cardíaco Bajo/etiología , Leucemia de Células Plasmáticas/complicaciones , Adulto , Humanos , MasculinoAsunto(s)
Candidiasis/tratamiento farmacológico , Cateterismo Venoso Central/efectos adversos , Fungemia/tratamiento farmacológico , Itraconazol/uso terapéutico , Leucemia Mieloide Aguda/microbiología , Trichosporon/aislamiento & purificación , Adulto , Fungemia/prevención & control , Humanos , Leucemia Mieloide Aguda/complicaciones , MasculinoRESUMEN
The incidence, aetiology and treatment of fungal infections in a 60-bed department of clinical oncology over 2 years is reported. During the second year, after the moving of the department from an old to a new building with an improved epidemiologic regimen, the incidence decreased rapidly, although the mortality due to systemic disseminated mycosis did not change.
Asunto(s)
Antifúngicos/uso terapéutico , Micosis/epidemiología , Neoplasias/complicaciones , Aspergilosis/epidemiología , Instituciones Oncológicas , Candidiasis/epidemiología , Checoslovaquia/epidemiología , Humanos , Incidencia , Mucormicosis/epidemiología , Micosis/tratamiento farmacológico , Infecciones Oportunistas/epidemiología , Estudios RetrospectivosRESUMEN
Fifty patients with advanced (Stage III and IV) large cell and immunoblastic lymphoma were treated with eight 4-week courses of chemotherapy. The first two identical A courses were composed of high dose cyclophosphamide, vincristine, 5-day administration of bleomycin, 2-week prednisone, and methotrexate with calcium leucovorin. The next two "B" courses were composed of vincristine, 3-day administration of doxorubicin together with bleomycin, and prednisone. The next two "C" courses were composed of cyclophosphamide, vincristine, bleomycin, prednisone, methotrexate, and calcium leucovorin. The last two "D" courses were the same as "B" courses. CNS prophylaxis was done with intrathecal methotrexate. Fourty-two patients (84%) achieved complete remission, 7 patients entered partial remission, and 1 patient failed to respond. The median survival of all groups was 80 + months (range 2-181 + months). Nine patients relapsed (21%), and seven patients died in complete remission, three of them died of toxicity. The most frequent toxicity was myelosuppression, mostly leukopenia, frequently followed by infection, sometimes severe. Neurotoxicity and stomatitis were frequent, but usually not severe. Two patients developed secondary malignancies. Most of the patients (54%) are alive without evidence of disease at present.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma Inmunoblástico de Células Grandes/tratamiento farmacológico , Adulto , Anciano , Bleomicina/administración & dosificación , Bleomicina/efectos adversos , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Femenino , Humanos , Leucovorina/administración & dosificación , Leucovorina/efectos adversos , Masculino , Metotrexato/administración & dosificación , Metotrexato/efectos adversos , Persona de Mediana Edad , Prednisona/administración & dosificación , Prednisona/efectos adversos , Vincristina/administración & dosificación , Vincristina/efectos adversosRESUMEN
The authors present in a retrospective study the results of treatment of infections in 290 immunodeficient patients, mostly with haematological malignancies. As compared with classical empirical combined treatment (aminoglycoside + IIIrd generation cephalosporins), combinations of quinolones and amoxycillin, amoxycillin clavulanate or vancomycin proved more satisfactory.
Asunto(s)
Antibacterianos/administración & dosificación , Infecciones Bacterianas/tratamiento farmacológico , Leucemia/complicaciones , Linfoma/complicaciones , Antibacterianos/uso terapéutico , Infecciones Bacterianas/complicaciones , HumanosRESUMEN
Eighty patients with advanced Hodgkin's disease were randomized either to treatment with combination of doxorubicin, bleomycin, vinblastine, and prednisone (ABVP), alternating with lomustine, vincristine, procarbazine, and prednisone (LOPP)--Group A, or to combination of cyclophosphamide, vincristine, procarbazine, prednisone, and low dose of bleomycin (COPP-Bleo)--Group B. Thirty-nine out of 41 patients (95%) in Group A achieved complete remission (CR) as compared to 25 CR in 39 patients (64%) in Group B. Patients with systemic symptoms, bulky disease, and nodular sclerosis achieved significantly more CR after treatment with ABVP/LOPP regimen than with COPP-Bleo regimen. Ninety percent of patients are alive in Group A (median observation time 97+ months) as compared to 58% in Group B (median observation time 97+ months). Ninety-two percent of complete responders are in CR in Group A as compared to 53% of complete responders in Group B. These differences between both groups are significant. More serious (WHO grade III and IV) myelosuppression as well as stomatitis and alopecia were observed in Group A. Gastrointestinal toxicity and neurotoxicity was more frequent in Group A. No patient died due to toxicity in Group A as compared to one patient in Group B. Non-cross-resistant alternating regimen ABVP/LOPP was more effective in the treatment of advanced Hodgkin's disease than the COPP-Bleo regimen, especially for patients with advanced Stage IVB Hodgkin's disease.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Enfermedad de Hodgkin/tratamiento farmacológico , Adolescente , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bleomicina/administración & dosificación , Bleomicina/uso terapéutico , Causas de Muerte , Ciclofosfamida/uso terapéutico , Doxorrubicina/uso terapéutico , Resistencia a Medicamentos , Femenino , Enfermedad de Hodgkin/mortalidad , Humanos , Lomustina/uso terapéutico , Masculino , Persona de Mediana Edad , Prednisolona/uso terapéutico , Prednisona/uso terapéutico , Procarbazina/uso terapéutico , Tasa de Supervivencia , Vincristina/uso terapéuticoRESUMEN
Fifty-three patients with advanced Hodgkin's disease, most of them previously treated, received 8 to 16 courses of modified MOPP regimens (nitrogen mustard replaced by trichlormethine in arm A, with addition of vinblastine to the 4-drug regimen in arm B, and alternation of three drugs--trichlormethine, vincristine, and prednisone--with probably non-cross resistant two drugs--vinblastine and procarbazine in arm C). Thirty patients (57%) achieved complete remission. Higher complete remission rate and longer survival was recorded in patients treated with 5-drug regimens (arms B and C) as compared to the 4-drug regimen (arm A), but the differences were not significant. Higher complete remission rates were observed in asymptomatic patients, females, and patients with lymphocyte predominance and nodular sclerosis subtypes of Hodgkin's disease. Besides expected short-term toxicity, 4 out of 30 complete responders developed secondary malignancies (two acute myeloblastic leukemias, one hepatocellular carcinoma, and one cerebellar astrocytoma). Several other patients had serious toxicity which could be attributed to chemotherapy. Twenty-eight percent of the patients has been alive 15 to 18 years since the start of this study.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Enfermedad de Hodgkin/tratamiento farmacológico , Adolescente , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Femenino , Enfermedad de Hodgkin/mortalidad , Enfermedad de Hodgkin/patología , Humanos , Masculino , Mecloretamina/administración & dosificación , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Compuestos de Mostaza Nitrogenada/administración & dosificación , Prednisona/administración & dosificación , Procarbazina/administración & dosificación , Inducción de Remisión , Tasa de Supervivencia , Vinblastina/administración & dosificación , Vincristina/administración & dosificaciónRESUMEN
This is a ten-year study of a cohort of 1088 Hungarian men aged 40-59 at entry, with a 99% baseline response rate and complete ascertainment of cases and follow-up. The methods were state of the art for the period the survey was performed, with quality control for standard procedure and training. Zero, five- and ten-year examinations were carried out and standard risk factors measured and analysed in relation to the ten-year experience, ie, age, blood cholesterol, blood pressure, smoking, body mass, vital capacity, and skinfolds. Risk factor levels were high relative to the Mediterranean and Oriental populations in the Seven Countries Study. The five-year coronary heart disease rates were intermediate between the low rates in Yugoslavia and Greece and high rates in Finland. Ten-year events were significantly and linearly related to quintile values of serum cholesterol and of 3, 4, 6, and 9 risk factors in the Walker-Duncan logistic model. Discrimination was not substantially improved beyond three factors apart from age. The maximal prediction concentrated 62% of events in the upper 20% of multifactor risk, and up to 80% in the upper 40% of risk. The authors conclude, from this separate but comparable study to the Seven Countries Study, that the results are not greatly different from that study or from the US Pooling Project. Unique features of the study, and its results, are the eastern European population, the absence of a strong CHD relationship with smoking, and the strong independent relationship with body mass.
Asunto(s)
Enfermedad Coronaria/epidemiología , Población Rural , Adulto , Factores de Edad , Presión Sanguínea , Peso Corporal , Colesterol/sangre , Humanos , Hungría , Masculino , Persona de Mediana Edad , Riesgo , FumarRESUMEN
Surface proteins radiolabeled by lactoperoxidase catalyzed radioiodination and/or sialoglycoproteins tritium-labeled by sodium metaperiodate/NaB3H4 technique, obtained from neoplastic cells of more than 50 patients with malignant hemopoietic disease have been analyzed with acrylamide gradient gel electrophoresis under denaturing conditions (SDS-PAGE). Electrophoretic protein and glycoprotein patterns were essentially similar within the group of examined chronic lymphocytic leukemia (CLL) patients with major surface glycoproteins gp44 and gp29,35. Glycoprotein gp29,35 corresponds by its electrophoretic mobility to Ia-like (HLA-DR antigen), which was identified on some CLL cells also by immunoprecipitation with a conventional anti-Ia antigen serum and subsequent electrophoretic analysis of immuno-precipitated antigen. Electrophoretic patterns of cell surface proteins and glycoproteins of CLL cells were markedly different from those of acute lymphoblastic leukemia (ALL) and acute myeloblastic leukemia (AML) cells which possessed a characteristic major cell surface glycoprotein gp95 (with relative molecular weight of 95-105k). This glycoprotein was markedly decreased or absent on examined CLL cells. Electrophoretic glycoprotein patterns revealed variations in the expression of several glycoproteins, as well as in the electrophoretic mobility of major glycoprotein gp95 also within the examined groups, particularly in acute myeloblastic leukemia.
Asunto(s)
Glicoproteínas/análisis , Leucemia/metabolismo , Proteínas de Neoplasias/análisis , Electroforesis en Gel de Poliacrilamida , Antígenos HLA-DR , Antígenos de Histocompatibilidad Clase II/análisis , Humanos , Técnicas para Inmunoenzimas , Leucemia Linfoide/metabolismo , Leucemia Mieloide Aguda/metabolismo , Monocitos/análisis , Ácido PeryódicoRESUMEN
Thirty eight patients with acute lymphoblastic leukemia were treated protocol 0171 (VCR, PRED, MTX, cyclophosphamide +/- +/- 6-MP) and protocol 0276/A (VRC, PRED, L-ASP, MTX, 6-MP, cyclophosphamide). Overall complete remission rate in both studies was 84--85%, and additional treatment in protocol 0171 resulted in complete remission rate of 92%. Median duration of complete remission in protocol 0171 was 23 months and median survival of all patients was 33 months. Six patients randomized to regimen "A" (without 6-MP in intensification) had median duration of complete remission 8 months and media survival was 13 months. Seventeen patients treated with regimen "B" (with 6-MP in intensification) had median duration of complete remission 25 months and median survival was 39 months. Median survival of patients allocated on protocol 0276/A in 21+ months and median duration of complete remission is 23 months at present. Twelve percent of patients treated with the best regimen have survived more than 66 months in continuous complete remission. The incidence of drug related death in complete responders was 6%. The relapses were most frequent during the first two years of remission. Extramedullary leukemia as the initial site of relapse was observed in 9% of patients.