RESUMEN
AIM: to evaluate the ocular hypotensive efficacy of systemic beta-blockers in primary glaucoma patients suffering from arterial hypertension (AH). MATERIAL AND METHODS: The study included 29 patients with POAG (58 eyes) aged from 47 to 83 years. Patients with stage I-III POAG received instillations of prostaglandin analogs and carbonic anhydrase inhibitors. All POAG patients also suffered from arterial hypertension and were prescribed selective beta-blockers (metoprolol, bisoprolol, or nebivalol) as monotherapy or as part of combination therapy (if the target arterial pressure had not been achieved under the initial treatment). After the start of oral beta-blockers therapy, the patients were re-examined at 2 and 4 weeks, 3 months, 6 months, and 1 year. RESULTS: A clinically significant reduction of IOP in the most seriously affected eye - by 3.3 mmHg (p<0.05), or 14% - occurred four weeks after the start of selective beta-blockers. Over three months of combination therapy, IOP in the 'worst' eye decreased by 4.4 mmHg (18.5%). At 1 year, IOP in the 'worst' eye was 6.2 mmHg (26%) lower than at baseline (p<0.05). CONCLUSION: Aged and senile patients with primary glaucoma usually suffer from polypathy (on average, they have 6.3±0.6 concurrent somatic diseases). To reduce the risk of polypharmacy and the frequency of side effects in the treatment of POAG and AH patients, it is advised that the treatment includes oral selective beta-blockers able to provide target levels of arterial pressure and IOP. In this study, oral beta-blockers in POAG and AH patients enabled IOP reduction as great as 18.5%-26% of baseline values over a 1-year follow-up period.
Asunto(s)
Antagonistas Adrenérgicos beta , Inhibidores de Anhidrasa Carbónica , Glaucoma , Hipertensión/tratamiento farmacológico , Presión Intraocular/efectos de los fármacos , Prostaglandinas Sintéticas , Antagonistas Adrenérgicos beta/administración & dosificación , Antagonistas Adrenérgicos beta/clasificación , Antagonistas Adrenérgicos beta/farmacocinética , Anciano , Antihipertensivos/administración & dosificación , Antihipertensivos/farmacocinética , Disponibilidad Biológica , Inhibidores de Anhidrasa Carbónica/administración & dosificación , Inhibidores de Anhidrasa Carbónica/farmacocinética , Interacciones Farmacológicas , Monitoreo de Drogas , Quimioterapia Combinada , Femenino , Glaucoma/complicaciones , Glaucoma/diagnóstico , Glaucoma/tratamiento farmacológico , Glaucoma/fisiopatología , Humanos , Hipertensión/complicaciones , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Prostaglandinas Sintéticas/administración & dosificación , Prostaglandinas Sintéticas/farmacocinética , Tonometría Ocular/métodosRESUMEN
The effects of general anesthetics ketamine and midazolam, the drugs that cause neuroapoptosis at the early stages of CNS development, on electrical activity of the somatosensory cortex in newborn rats were studied using extracellular recording of local field potentials and action potentials of cortical neurons. Combined administration of ketamine (40 mg/kg) and midazolam (9 mg/kg) induced surgical coma and almost completely suppressed early oscillatory patterns and neuronal firing. These effects persisted over 3 h after injection of the anesthetics. We concluded that general anesthesia induced by combined administration of ketamine and midazolam profoundly suppressed cortical activity in newborn rats, which can trigger neuroapoptosis in the developing brain.
Asunto(s)
Encéfalo/efectos de los fármacos , Ketamina/administración & dosificación , Ketamina/efectos adversos , Midazolam/administración & dosificación , Midazolam/efectos adversos , Anestésicos/administración & dosificación , Anestésicos/efectos adversos , Animales , Animales Recién Nacidos , Ratas , Corteza Somatosensorial/efectos de los fármacosRESUMEN
AIM: To analyse clinical implications of chromosome 8 trisomy in Ph-negative cells of the bone marrow in patients with chronic myeloid leukemia (CML) treated with inhibitors of tyrosinkinases (ITK). MATERIAL AND METHODS: A total of 386 patients with CML (chronic phase--288, acceleration phase--77) received imatinib (400-800 mg/day). Because of resistance and/or intolerance some patients were switched to ITK II (nilotinib, dasatinib, bozutinib). This study included 8 CML patients (7 in a chronic phase, 1 in acceleration phase) treated with BCR-ABL ITK inhibitors of the first (imatinib) and the second line (ITK-II). The standard cytogenetic examination, on demand--investigation of the interphase nuclei with FISH, in some cases morphological, cytochemical and histological examinations of the bone marrow were made. RESULTS: The existence of a Ph-negative clone with trisomy of chromosome 8 had no negative effect on the course of the disease. The patients showed a stable hematological and cytogenetic response and no need in changing treatment policy. In long-term follow-up Ph-negative clone with trisomy of the chromosome 8 persisted without a clear trend to rise in most patients. CONCLUSION: Detection of a Ph-negative clone with chromosome 8 trisomy at early stages suggests parallel existence of Ph-positive and Ph-negative clones. None of the patients had myelodisplasia.
Asunto(s)
Células de la Médula Ósea/efectos de los fármacos , Cromosomas Humanos Par 8/genética , Proteínas de Fusión bcr-abl/antagonistas & inhibidores , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Cromosoma Filadelfia/efectos de los fármacos , Inhibidores de Proteínas Quinasas/uso terapéutico , Trisomía , Adulto , Benzamidas , Células de la Médula Ósea/enzimología , Células de la Médula Ósea/patología , Esquema de Medicación , Femenino , Humanos , Mesilato de Imatinib , Cariotipificación , Leucemia Mielógena Crónica BCR-ABL Positiva/enzimología , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Masculino , Persona de Mediana Edad , Piperazinas/administración & dosificación , Piperazinas/uso terapéutico , Inhibidores de Proteínas Quinasas/administración & dosificación , Pirimidinas/administración & dosificación , Pirimidinas/uso terapéutico , Factores de TiempoRESUMEN
AIM: To study feasibility of hemopoiesis clonality determination in assessment of remission completeness in patients with chronic myeloid leukemia (CML) using polymerase chain reaction (PCR HUMARA). MATERIAL AND METHODS: We have examined 28 patients with newly diagnosed CML, 10 CML patients with a complete cytogenetic response (CCR) to therapy with imatinib mesilate and/or alpha-interferon, 24 healthy control females. Twelve patients with untreated CML were homozygous by HUMARA gene (human androgenic receptor gene) and were withdrawn from the study. Leukocytes of peripheral blood from all the patients were investigated with PCR HUMARA for mono- or polyclonal hemopoiesis. Clonality was defined as allele proportion (a/p) of polymorphic loci of HUMARA gene. Remission completeness was confirmed cytogenetically and by molecular methods. RESULTS: The value a/p in 10 patients with CCR varies from 0.69 to 1.33 and is similar to those in the control group. CONCLUSION: The PCR HUMARA technique adequately assesses reduction of Ph-positive clone in CML patients with CCR and points to polyclonal hemopoiesis.
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ADN de Neoplasias/genética , Hematopoyesis/fisiología , Leucemia Mielógena Crónica BCR-ABL Positiva/sangre , Polimorfismo Genético , Receptores Androgénicos/genética , Recuperación de la Función/genética , Adolescente , Adulto , Anciano , Alelos , Antineoplásicos/uso terapéutico , Benzamidas , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Mesilato de Imatinib , Factores Inmunológicos/uso terapéutico , Interferón-alfa/uso terapéutico , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Persona de Mediana Edad , Piperazinas/uso terapéutico , Reacción en Cadena de la Polimerasa , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Pirimidinas/uso terapéutico , Receptores Androgénicos/sangre , Inducción de Remisión/métodos , Resultado del TratamientoRESUMEN
AIM: To reveal prognostically significant factors affecting efficacy of glivek therapy in untreated (duration of the disease < or = 6 months) and pretreated (duration of the disease > 6 months) patients with chronic myeloid leukemia (CML) in a chronic phase. MATERIAL AND METHODS: A total of 338 patients (64 untreated and 274 pretreated) with a chronic-phase CML on glivek therapy entered the trial. RESULTS: Five-year survival on glivek was high (89, 98 and 88% in untreated and pretreated patients, respectively). Incidence of transformation in the acceleration phase and blast crisis was low both in untreated and pretreated patients (1.6 and 11%, respectively) and correlated with the rate of a complete cytogenetic response (CCR). Untreated patients had no factors affecting treatment efficacy negatively, CCR probability was 96%. Blastemia, thrombocytosis and splenomegaly reduced CCR probability significantly in pretreated patients. Slow reduction of the tumor mass, late achievement of a complete hematological response and a cytogenetic response decreased probability of CCR. CONCLUSION: Glivek is a drug of choice for patients with chronic-phase CML. High probability of CCR both in untreated and pretreated patients lowers the risk of the disease transformation into the phase of acceleration/blast crisis and raises overall survival in both groups.
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Antineoplásicos/uso terapéutico , Leucemia Mieloide de Fase Crónica/tratamiento farmacológico , Piperazinas/uso terapéutico , Pirimidinas/uso terapéutico , Adolescente , Adulto , Anciano , Benzamidas , Crisis Blástica/epidemiología , Crisis Blástica/patología , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Hematopoyesis/efectos de los fármacos , Humanos , Mesilato de Imatinib , Incidencia , Leucemia Mieloide de Fase Crónica/mortalidad , Leucemia Mieloide de Fase Crónica/patología , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Pronóstico , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Factores de Riesgo , Federación de Rusia/epidemiología , Tasa de Supervivencia/tendencias , Factores de TiempoRESUMEN
AIM: To quantitatively determine minimal residual disease (MRD) by real-time polymerase chain reaction (PCR) in patients with a chronic phase (CP) of chronic myeloid leukemia (CML). MATERIALS AND METHODS: A molecular response was analyzed in 53 CML CP patients with incomplete and complete cptogenetic response (ICR and CCR) during imatinib therapy (median follow-up 36 months). BCR-ABL gene type p210 expression was quantitatively determined by real-time PCR under the TaqMan technology (an ICycler IQ device). The beta2 microglobulin (beta2M) gene was used as a reference gene. The results were expressed as the ratio: the number of BCR-ABL copies to that of beta2M x 10(5), as well as the difference of the common logarithm (lg) of the baseline expression level (BEL) and the result obtained: CEL lg-result lg. RESULTS: The study revealed a correlation of the results of real-time PCR with those of cytogenetic analysis and showed it possible to study not only bone marrow, but also peripheral blood. Some negative real-time PCR results were checked using more sensitive PCR techniques. MRD was identified in most CML patients showing ICR and CCR during imatinib therapy. The reduction in BCR-ABL transcript levels by less than 2 lg (as compared to BEL) was associated with a cytogenetic recurrence and that by less than 3 lg was associated with a permanent high cytogenetic response. In patients with a cytogenetic recurrence, the median of BCR-ABL transcript levels was higher than that in patients with a permanent stable or unstable cytogenetic response. An elevation of BCR-ABL transcript levels over time antedated the development of a cytogenetic recurrence. CONCLUSION: Quantitative monitoring by real-time PCR gives additional information on the dynamics of MRD in CML patients treated with glivec and permits improvement of study protocols for patients with CML at complete clinicohematological and cytogenetic remission.
Asunto(s)
Biomarcadores de Tumor/genética , Proteínas de Fusión bcr-abl/genética , Regulación Leucémica de la Expresión Génica/efectos de los fármacos , Genes abl/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/diagnóstico , Microglobulina beta-2/genética , Adulto , Antineoplásicos/administración & dosificación , Antineoplásicos/uso terapéutico , Benzamidas , Biomarcadores de Tumor/sangre , Médula Ósea/patología , Femenino , Proteínas de Fusión bcr-abl/sangre , Humanos , Mesilato de Imatinib , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Masculino , Neoplasia Residual , Piperazinas/administración & dosificación , Piperazinas/uso terapéutico , Pirimidinas/administración & dosificación , Pirimidinas/uso terapéutico , ARN Mensajero/genética , ARN Neoplásico/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Sensibilidad y Especificidad , Microglobulina beta-2/sangreRESUMEN
We evaluated the efficiency of transplantation of cultured human allofibroblasts onto tympanic membrane damaged by mine explosion in combination with Tampograss dressing (Paul Hartman). Transplantation of cultured human allofibroblasts was effective in 100% cases. Application of the film with fibroblasts onto perforation occupying from 1/4 to 1/2 of the tympanic membrane was more effective by 15% (by 59% in subtotal perforation) than tympanoplasty with amnion membrane. The mean duration of tympanic membrane restoration after spontaneous healing and amnionoplasty is virtually the same, while transplantation of allofibroblasts accelerated the process in comparison with other groups in perforation of any size; in subtotal defect the duration of tympanic membrane restoration was shorter by 14 +/- 1 days.
Asunto(s)
Trasplante de Células/métodos , Explosiones , Fibroblastos/citología , Perforación de la Membrana Timpánica/terapia , Membrana Timpánica/citología , Accidentes de Trabajo , Adolescente , Adulto , Femenino , Fibroblastos/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Membrana Timpánica/patología , Perforación de la Membrana Timpánica/patología , Cicatrización de HeridasRESUMEN
AIM: To estimate detectability and characteristic features of chromosomal aberrations in bone marrow cells of patients with aplastic anemia (AA). MATERIAL AND METHODS: The trial covered 155 AA patients admitted to the Hematological Research Center in 1987-2002. Cytogenetic study by G-differential staining was performed in 58 patients with AA and 5 patients with AA transforming into myelodysplastic syndrome (MDS) or acute leukemia (AL). Cytogenetic and morphological specimens of the latter's bone marrow were studied retrospectively using fluorescent in situ hybridization (FISH) with DNA probes for detection of monosomia 7 and deletion 7q. RESULTS: Clonal chromosomal aberrations were detected in 4 out of 28 patients. Further examinations revealed no aberrations. Clonal diseases developed in 7 (4.5%) of 155 patients. In 2 patients the disease transformed into paroxysmal nocturnal hemoglobinuria, 5 (3.2%) patients developed variants of MDS and AL. Monosomia 7 or deletion 7q were diagnosed in 3 cases of MDS/AL. In retrospective study of bone marrow specimens of patients with transformation in MDS/AL with monosomia 7, FISH recognized a small elevation over control values in 2 cases. CONCLUSION: Stable clonal chromosomal aberrations are not characteristic of AA. Some AA patients with subsequent MDS/AL may have minor neoplastic clone in the disease onset.
Asunto(s)
Anemia Aplásica/genética , Transformación Celular Neoplásica , Aberraciones Cromosómicas , Cromosomas Humanos Par 7 , Síndromes Mielodisplásicos/genética , Adolescente , Adulto , Anemia Aplásica/tratamiento farmacológico , Anemia Aplásica/patología , Células de la Médula Ósea/patología , Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/patología , Deleción Cromosómica , Células Clonales/patología , Femenino , Humanos , Cariotipificación , Masculino , Persona de Mediana Edad , Monosomía , Síndromes Mielodisplásicos/patologíaRESUMEN
AIM: To analyse incidence rate of chromosomal aberrations in myelodysplastic syndromes (MDS), specification of clinicomorphological features of some cytogenetic variants. MATERIAL AND METHODS: Chromosomal analysis by the method of G-differential staining of chromosomes was made in 209 patients with different variants of MDS. RESULTS; Clonal chromosomal aberrations occured in 60.8%. The following aberrations were found most frequently: deletion of the long arm of the chromosome 5 (del(5q)) - 34.6%, trisomy of chromosome 8 (14.1%), monosomy of chromosome 7 (13.4%), aberrations 3q21q26 (12.6%), aberrations of a long arm of X-chromosome (4.7%), the absence of Y-chromosome (3.1%). Complex aberrations of karyotype were found in 13.5% cases. Chromosomal aberrations determined not only clinical and morphological features but also the prognosis of the disease. CONCLUSION: Cytogenetic examination is an essential component of MDS patients examination. It allows more precise classification of MDS variant and prognostification of the disease course.
Asunto(s)
Aberraciones Cromosómicas , Cromosomas Humanos Par 5/genética , Cromosomas Humanos Par 7/genética , Cromosomas Humanos Par 8/genética , Cromosomas Humanos X/genética , Cromosomas Humanos Y/genética , Síndromes Mielodisplásicos/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Aberraciones Cromosómicas/estadística & datos numéricos , Análisis Citogenético , Femenino , Humanos , Cariotipificación , Masculino , Persona de Mediana Edad , Monosomía/genética , Monosomía/patología , Síndromes Mielodisplásicos/clasificación , Síndromes Mielodisplásicos/diagnóstico , Pronóstico , Estudios Retrospectivos , Trisomía/genética , Trisomía/patologíaRESUMEN
AIM: Clinical practice with the drug glivek (imatinibe mesilate, ST1571) blocking activity of oncoprotein p210 shows that a cytogenetic response can be reached in 50-60% of patients with chronic myeloid leukemia (CML), in a late chronic phase (CP) in resistance to or intolerance of interferon alpha (IF-alpha) and in 24-43% of patients in the acceleration phase (AP). This study aimed at assessment of the rate and stability of a cytogenetic response (CR) and long-term results of survival in CML patients on glivek. MATERIAL AND METHODS: Glivek was given to 195 CML patients (median of the treatment duration was 42 months, 1-156 months, of the patients' age--46 years). 79 patients were in CP, 116--in AP. The doses were 400 mg/day and 116 mg/day, respectively. Karyotype was studied before the treatment and later after each 6 months. RESULTS: A considerable CR was achieved in 57% patients in CP and 44%--in AP. Of them complete CR was obtained in 48 and 35%, respectively. Marked CR is a favourable prognostic factor. Survival of patients with marked CR in CP (97% 0 and AP (89%) was significantly higher than without CR (58 and 47%, respectively, p < 0.05). Marked CR persisted in 95% cases in both phases of CML. In complete CR, a repeated study of karyotype revealed residual number of Ph+ cells both in CP and AP in 86% patients. This demonstrates necessity to take glivek continuously in achievement of a complete CR by karyotypic test. Glivek inhibits the disease progression, lowers annual lethality. 42-month (median of glivek treatment duration) overall survival reached 91 and 59% in CP and AP, respectively. CONCLUSION: CR is an integral index prognosticating CML course. Survival rose significantly in patients with marked CR both in CP and AP of CML. Marked CR is persistent in continuous glivek therapy. The rate of a CR depends much on the disease stage.
Asunto(s)
Médula Ósea/patología , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Piperazinas/uso terapéutico , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Pirimidinas/uso terapéutico , Adolescente , Adulto , Anciano , Benzamidas , Biopsia , Análisis Citogenético , Femenino , Estudios de Seguimiento , Proteínas de Fusión bcr-abl , Humanos , Mesilato de Imatinib , Cariotipificación , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/mortalidad , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de Supervivencia/tendencias , Factores de Tiempo , Resultado del TratamientoAsunto(s)
Síndrome Hipereosinofílico/etiología , Trastornos Mieloproliferativos/genética , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/genética , Factores de Escisión y Poliadenilación de ARNm/genética , Adulto , Antineoplásicos/uso terapéutico , Benzamidas , ADN de Neoplasias/genética , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Regulación Neoplásica de la Expresión Génica , Humanos , Síndrome Hipereosinofílico/tratamiento farmacológico , Síndrome Hipereosinofílico/genética , Mesilato de Imatinib , Cariotipificación , Masculino , Trastornos Mieloproliferativos/complicaciones , Trastornos Mieloproliferativos/tratamiento farmacológico , Proteínas de Fusión Oncogénica , Piperazinas/uso terapéutico , Mutación Puntual , Pirimidinas/uso terapéutico , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
AIM: To conduct molecular-cytogenetic monitoring of bone marrow cells in different regimens of chronic myeloid leukemia (CML) treatment. MATERIAL AND METHODS: A total of 651 samples of bone marrow from 319 CML patients were studied. 229 patients received polychemotherapy and 90 patients--interferon-alpha. Primary examination and monitoring of the treatment efficacy were performed using G-differential chromosome staining. Fluorescent in situ hybridization (FISH) was made in 75% cases. RESULTS: Interferon therapy resulted in a significant increase in the number of complete and significant cytogenetic responses. With aggravation of the disease the above responses occurred less frequently while minor and no response are encountered more often. Treatment with interferon-alpha in combination with chemotherapy is much more effective than monotherapy with interferon. CONCLUSION: G-differential chromosome staining karyotypes metaphases and detects clonal chromosome restructuring. Molecular-cytogenetic methods study chromosome restructuring at DNA level. FISH detects chimeric gene bcr/abl in cases when Ph-chromosome is not detectable by standard cytogenetic methods.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Células de la Médula Ósea/efectos de los fármacos , Proteínas de Fusión bcr-abl/genética , Interferón-alfa/uso terapéutico , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Cromosoma Filadelfia , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Humanos , Hibridación Fluorescente in Situ , Interferón-alfa/administración & dosificación , Interferón-alfa/farmacología , Cariotipificación , Leucemia Mielógena Crónica BCR-ABL Positiva/genéticaRESUMEN
AIM: To investigate factors determining prognosis and efficacy of induction therapy including interferon-alpha-2b (intron-A, Schering Plough) in patients at an early chronic stage of Ph-positive chronic myeloid leukemia (CML) as shown by histomorphological examination. MATERIAL AND METHODS: The analysis covered 52 CML patients treated at an early chronic phase with intron-A in a standard daily dose 5 IU/m2 in combination with low-dose cytosinearabinoside (10 mg/m2, s.c. , daily for 10 days of each month). The treatment efficacy was assessed by the international criteria of complete and partial hematological remission and cytogenetic response. The cytogenetic study employed the direct method, even and G-differential staining, fluorescent hybridization in situ (FISH). The sections were stained with hematoxilin-eosine by Gomori, van Gieson. Histological samples were examined with histomorphometry. Immunohistochemical examination was made on paraffin sections using a panel of monoclonal antibodies CD3, CD4, CD8, CD20, NK, PCNA, Ki-67 (Dako, Denmark). RESULTS: Repeated assessment of histomorphological parameters such as erythroid lineage, degree of myelofibrosis and reduction of leukemic population indicate the treatment efficacy. Estimation of the level of leukemic population proliferation in trephine biopsies from CML patients with monoclonal antibodies PCNA and Ki-67 before the treatment is prognostically significant as it further correlates with the cytogenetic response (r = 0.821, p = 0.000000). CONCLUSION: It is valid to study histomorphological picture of CML to prognosticate and assess treatment efficacy with standard doses of interferon-alpha with high probability.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Células de la Médula Ósea/efectos de los fármacos , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Células de la Médula Ósea/patología , Estudios de Cohortes , Femenino , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Interferón-alfa/administración & dosificación , Interferón-alfa/efectos adversos , Interferón-alfa/uso terapéutico , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Masculino , Persona de Mediana Edad , PronósticoAsunto(s)
Proteínas de Fusión bcr-abl/análisis , Síndrome Hipereosinofílico/tratamiento farmacológico , Trastornos Mieloproliferativos/tratamiento farmacológico , Cromosoma Filadelfia , Piperazinas/uso terapéutico , Pirimidinas/uso terapéutico , Adulto , Benzamidas , Eosinófilos/efectos de los fármacos , Humanos , Síndrome Hipereosinofílico/sangre , Síndrome Hipereosinofílico/genética , Mesilato de Imatinib , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Trastornos Mieloproliferativos/sangre , Trastornos Mieloproliferativos/genética , Piperazinas/administración & dosificación , Reacción en Cadena de la Polimerasa , Pirimidinas/administración & dosificación , Resultado del TratamientoRESUMEN
AIM: To evaluate efficacy and tolerance of glivek in chronic myeloid leukemia (CML) in patients who failed interferon-alpha (If-a) preparations. MATERIAL AND METHODS: 79 patients in a chronic phase of Ph + CML with hematological and cytogenetic resistance or intolerance of If-a. The response to glivec was assessed by achievement of a complete hematological remission and the cytogenetic effect (the degree of reduction of cell clone Ph+ in bone marrow). Tolerance and safety of the drug was studied by monthly standard clinicohematological tests. RESULTS: Not only a hematological remission (92.4%), but also partial (46.8%) or complete (27.8%) elimination of BCR-ABL +/- cells were achieved after 12 months of the treatment. Glivec was well tolerated. Hematological toxicity primarily as neutropenia and thrombocytopenia were observed in 54.4 and 42% patients, respectively. Neutropenia of the third degree which made impossible to continue the treatment was observed in 29.1% patients; throbocytopenia of the third degree was registered in 16.5% patients. Among most frequent non-hematological side effects there were moderate edema, nausea, leg muscle convulsions, weight gain, arthralgias, skin eruption. All the complications were transient, were managed in all cases with only a short-time discontinuation of glivec therapy. CONCLUSION: High activity of glivec at early stages of CML allows using this drug as a first-line therapy in patients with CML.
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Antineoplásicos/uso terapéutico , Leucemia Mieloide de Fase Crónica/tratamiento farmacológico , Piperazinas/uso terapéutico , Pirimidinas/uso terapéutico , Adulto , Anciano , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Benzamidas , Células de la Médula Ósea/efectos de los fármacos , Células de la Médula Ósea/metabolismo , Análisis Citogenético , Supervivencia sin Enfermedad , Femenino , Proteínas de Fusión bcr-abl/genética , Humanos , Mesilato de Imatinib , Cariotipificación , Leucemia Mieloide de Fase Crónica/genética , Leucemia Mieloide de Fase Crónica/mortalidad , Masculino , Persona de Mediana Edad , Piperazinas/administración & dosificación , Piperazinas/efectos adversos , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Pirimidinas/administración & dosificación , Pirimidinas/efectos adversos , Inducción de RemisiónRESUMEN
Trepanobiopsies of the bone marrow were studied in 46 patients in a chronic phase of chronic myeloid leukemia in different periods after the beginning of interferon-alpha therapy. Progression of myelofibrosis was observed in 2 cases only. Regression of myelofibrosis was observed in 14 cases of 29 (34.2%). A negative correlation between reticulin myelofibrosis and response to therapy was found. Disappearance of diffuse reticulin myelofibrosis in all cases was followed by a cytogenetic response.
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Antineoplásicos/uso terapéutico , Médula Ósea/patología , Interferón-alfa/uso terapéutico , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Mielofibrosis Primaria/tratamiento farmacológico , Adolescente , Adulto , Médula Ósea/efectos de los fármacos , Femenino , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/complicaciones , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Masculino , Persona de Mediana Edad , Mielofibrosis Primaria/etiología , Mielofibrosis Primaria/patología , PronósticoRESUMEN
AIM: To study trends in restoration of normal and tumor hemopoiesis after transplantation of allogenic and syngenic hemopoietic cells. MATERIAL AND METHODS: The examination of bone marrow before transplantation and 1, 2, 3, 6, 9 months, 1, 2 and 3 years after bone marrow transplantation (BMT) was made in 25 patients with chronic myeloid leukemia (CML) after allogenic transplantation of the bone marrow (TBM) and 4 patients after syngenic TBM. The method of G-differential staining of chromosomes and fluorescent hybridization in situ (FISH) with DNA probe to centromeric sites X/Y of chromosomes and genes BCR/ABL was used. RESULTS: 56% of CML patients after allogenic BMT were in cytogenetic and clinicohematological remission, 16% developed early cytogenetic recurrence. Single metaphase with t(9;22) were identified in 28%; 14.3% developed late cytogenetic and hematological recurrence. In patients in posttransplantation remission there were from 0.1 to 5.8% cells of the host. The number of cells of the host and the number of BCR/ABL-positive cells correlated significantly. CONCLUSION: The results of 8-year monitoring of chimerism and minimal residual disease validate application of molecular-cytogenetic methods for assessing transplant condition.
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Trasplante de Médula Ósea , Leucemia Mielógena Crónica BCR-ABL Positiva/diagnóstico , Quimera por Trasplante , Adolescente , Adulto , Análisis Citogenético , Femenino , Estudios de Seguimiento , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Leucemia Mielógena Crónica BCR-ABL Positiva/terapia , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Neoplasia Residual , Trasplante Homólogo , Trasplante IsogénicoRESUMEN
The cytogenetic study of bone marrow cells was performed in 40 patients with secondary leukemias which have arisen after application of cytostatic and/or radiotherapy for primary tumours (Hodgkin's disease, lymphomas, acute lymphoblastic leukemias, breast cancer and other solid tumours). The comparative analysis of results has shown, that the leukemias after irradiating or application of alkylating agents and irradiation, have the quite particular clinico-morphological and cytogenetic characteristics. In 70% of cases these diseases develops as smouldering leukemias with subsequent transformation in M-4, M-6, and rarely M-2 cytochemical variants. Primary cytogenetic events in 60% of researched karyotypes are the losses of long arms or whole chromosomes 5 and 7. In 20% of the researched cases normal karyotype was found, in the left 20%, the changes of a karyotype not including anomalies 5 and 7 chromosomes were detected. The obtained outcomes allow to consider the discharged complex of tags as reference for leukemias, induced by irradiating or chemical agents with similar mechanism of action (alkylating agents, benzene and its derivates). This complex of tags is typical for induced leukemias, and in a combination with definition of a level of stable aberrations in peripheral blood lymphocytes, can be utilised for abjection of radiation-induced leukemias from common mass of cases detected in regions, polluted by radionuclides. In this study in 60% of cases only specific for secondary leukemias chromosomal aberrations, including monosomy 5 and 7, rearrangements of 11q23 were found. On the base of the obtained data the differences in concepts of "secondary" and "induced" leukemias are considered.
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Leucemia Inducida por Radiación/etiología , Radioterapia/efectos adversos , Adolescente , Adulto , Anciano , Aberraciones Cromosómicas , Femenino , Humanos , Cariotipificación , Masculino , Persona de Mediana EdadRESUMEN
A comparison of chromosomal abnormalities in bone marrow leukaemic cells and of stable and unstable aberrations in lymphocytes of patients with hematological malignancies who live in areas with or without contamination by the Chernobyl nuclear accident has been made using FISH and G-banding. Healthy residents of these areas comprised the control group. No systematic cytogenetic differences of leukaemic cells between patients from contaminated and uncontaminated areas were observed. Lymphocyte aberrations, however, were generally higher in all subjects from contaminated areas. Comparison has been made with specific cytogenetic features of leukaemic cells and a high level of stable aberrations in lymphocytes of patients with secondary leukaemias that had developed after chemo- and/or radio-therapy.
Asunto(s)
Aberraciones Cromosómicas , Leucemia Inducida por Radiación/etiología , Leucemia Inducida por Radiación/genética , Liberación de Radiactividad Peligrosa , Adolescente , Adulto , Anciano , Estudios de Casos y Controles , Bandeo Cromosómico , Citogenética , Humanos , Hibridación Fluorescente in Situ , Linfocitos/efectos de la radiación , Linfocitos/ultraestructura , Persona de Mediana Edad , Neoplasias Primarias Secundarias/etiología , Neoplasias Primarias Secundarias/genética , UcraniaRESUMEN
AIM: Evaluation of clinical effectiveness of two regimens of induction therapy of an early chronic stage of Ph'-positive chronic myeloid leukemia including interferon-alpha 2b (intron-A, "Schering Plough") in a cooperative randomised trial on the protocol CML MIG-97. MATERIALS AND METHODS: 42 patients with chronic myeloid leukemia were treated either with intron-A in standard doses (5 IU/m2/day) alone or in combination with monthly 10-day courses of low-dose cytosine-arabinoside (10 mg/m2/twice a day). The effect was assessed by the international criteria of a complete and partial hematologic remission and the cytogenetic response. RESULTS: Intron-A therapy in standard doses produced a pronounced cytogenetic response in 28.6% of the patients. In low-dose interferon-alpha-2b (reaferon and intron-A, 1-3 IU/m2/day) in combination with various regimens of chemotherapy only minimal cytogenetic response was achieved. CONCLUSION: A pronounced cytogenetic response in early chronic stage of CML to standard doses of intron A holds promise in prolongation of CML patients survival and design of new effective therapy programs.