RESUMEN
The ability to switch between coagulation factors safely is of common interest to haemophilia patients and treating physicians. This is the first formal prospective comparative evaluation of safety, efficacy and incremental recovery of a plasma-derived FIX (pdFIX) and a recombinant FIX (rFIX) in the same haemophilia B patients following a switch from pdFIX Immunine® to a recently developed rFIX Bax326 product. Patients (aged <65 years) who completed a pretreatment study which prospectively documented the exposure to Immunine® and monitored FIX inhibitors while receiving prophylactic treatment were transitioned into pivotal (patients aged 12-65 years) and paediatric (patients aged <12 years) clinical studies investigating prophylaxis and treatment of bleeding episodes with Bax326. None of the 44 patients developed inhibitory or specific binding anti-FIX antibodies during the course of the studies. A total of 38 unrelated adverse events (AEs) were occurred in 20/44 (45.5%) subjects during the Immunine® study. Following a switch to Bax326, 51 AEs were reported in 25/44 (56.8%) subjects. The incidence of AEs related to Bax326 treatment (two episodes of dysgeusia in one patient) was low (2.3%); there were no serious adverse reactions. The comparison between Immunine® and Bax326 demonstrated analogous haemostatic characteristics and annualized bleeding rates. Overall, there is direct evidence indicating a safe and clinically effective transition from a pdFIX (Immunine®) to a newly developed rFIX (Bax326(1) ) for prophylaxis and treatment of bleeding in previously treated patients of all age cohorts with severe or moderately severe haemophilia B.
Asunto(s)
Coagulantes/uso terapéutico , Sustitución de Medicamentos/normas , Factor IX/uso terapéutico , Hemofilia B/tratamiento farmacológico , Proteínas Recombinantes/uso terapéutico , Adolescente , Adulto , Coagulación Sanguínea/efectos de los fármacos , Inhibidores de Factor de Coagulación Sanguínea/sangre , Niño , Coagulantes/efectos adversos , Coagulantes/farmacocinética , Estudios Cruzados , Factor IX/efectos adversos , Femenino , Hemofilia B/inmunología , Hemorragia/epidemiología , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Proteínas Recombinantes/efectos adversos , Proteínas Recombinantes/farmacocinética , Adulto JovenRESUMEN
The effects of the CYP1A1*2A genotype on susceptibility to leukemia have received particular attention in recent years because this enzyme plays a central role in the activation of carcinogens. Several polymorphisms at the CYP1A1 locus have been identified and their genotypes appear to exhibit population frequencies that depend on ethnicity. We evaluated the role of the CYP1A1*2A genotype in adults with acute lymphoblastic leukemia (ALL) by genotyping 210 patients and 228 healthy controls from the Mexican population. The frequency of the CC genotype was 8% (18/228) in the control group and 42% (88/210) in ALL patients; the frequency of the CT genotype was 39% (89/228) and 29.5% (62/210), respectively; and that of the TT genotype was 53% (121/228) and 28.5% (60/210), respectively. The odds ratio was 8.4 (95% CI, 4.7-15.5; P < 0.001). These data indicate that the CYP1A1*2A genotype contributes significantly to susceptibility to adult ALL in a sample of the Mexican population.
Asunto(s)
Citocromo P-450 CYP1A1/genética , Predisposición Genética a la Enfermedad , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Alelos , Femenino , Genotipo , Humanos , Masculino , México/epidemiología , Persona de Mediana Edad , Polimorfismo Genético , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologíaRESUMEN
Autologous peripheral blood stem cell transplantation is the therapy of choice for the treatment of multiple myeloma (MM) patients younger than 70 years old. Between August 1993 and November 2004, 54 patients with MM were autografted after conditioning with high-dose oral melphalan 140 mg/m(2) in combination with etoposide and carmustine (28 patients) or with high-dose melphalan 200 mg/m(2) I.V. (26 patients). The oral and IV melphalan groups were comparable. There were no significant differences in disease-free survival (DFS) and overall survival (OS) between the groups; however, in patients transplanted in remission, OS and DFS were better in the I.V. melphalan group. Four good-prognostic factors were identified: interval between diagnosis and transplant <18 months, number of prior chemotherapy lines < or =2, remission status (complete or partial), and the use of I.V. melphalan. In conclusion, I.V. melphalan is the therapy of choice for conditioning patients with MM who are in remission.
Asunto(s)
Melfalán/uso terapéutico , Mieloma Múltiple/terapia , Trasplante de Células Madre de Sangre Periférica/métodos , Administración Oral , Adulto , Anciano , Antineoplásicos/administración & dosificación , Antineoplásicos/uso terapéutico , Carmustina/administración & dosificación , Carmustina/uso terapéutico , Terapia Combinada , Supervivencia sin Enfermedad , Relación Dosis-Respuesta a Droga , Etopósido/administración & dosificación , Etopósido/uso terapéutico , Femenino , Humanos , Infusiones Intravenosas , Masculino , Melfalán/administración & dosificación , México , Persona de Mediana Edad , Mieloma Múltiple/patología , Inducción de Remisión , Trasplante Autólogo , Resultado del TratamientoRESUMEN
We studied the role of cytochrome P4501A1 (CYP1A1 Val/Val) genotypes in the etiology of acute lymphoblastic leukemia (ALL) in adult Mexican patients. Distributions of CYP1A1 Val/Val genotypes in peripheral blood DNA samples from 136 healthy controls and 136 adult patients with ALL were evaluated. There was an increased frequency of the CYP1A1 Val/Val genotype among ALL patients, showing a significant association between this genotype and the risk of developing ALL.
Asunto(s)
Citocromo P-450 CYP1A1/genética , Predisposición Genética a la Enfermedad , Polimorfismo Genético , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Adolescente , Adulto , Anciano , Femenino , Genotipo , Humanos , Masculino , México , Persona de Mediana EdadRESUMEN
UNLABELLED: Bone marrow transplantation has recently reached an special place as a therapeutic tool, which was not available ten years ago. AIM AND SETTING: Descriptive information about the first fifteen cases transplanted at Centro Médico Nacional de Occidente, on a third level attention in Guadalajara, Jalisco, Mexico. MATERIAL AND METHODS: Fifteen patients were transplanted, were carried out autologous transplantation in ten patients and five have received allogeneic transplant; one allogeneic transplant was performed with bone marrow aspiration donor, all next donation were taken off from peripheral blood stem cell through apheresis procedures. From autologous transplant 3 with chronic myelogenous leukemia (CML), 3 with Hodgkin's disease, 2 with solid tumor, 1 with high risk acute myelogenous leukemia and 1 large and small cell lymphoma III-B stage. Received allogeneic transplant 4 patients with CML in chronic phase and one with acute lymphoblastic leukemia Ph+. RESULTS: All patients grafted, the median time to achieve > 0.5 x 10(9)/L granulocytes was 14 days (range: 11-18) from autologous and 16 (range: 14-18) days from allogeneic transplant, whereas the median time to achieve > 20 x 10(9)/L platelets was 18 days (range: 15-35) from autologous and 22 days from allogeneic, three patients died into 100 days postprocedure, two allogeneic, from graft versus host disease III-IV degree, and one autologous from interstitial pneumonia, surviving patients have showed +30 days to +1000 days survival. CONCLUSION: With these data we show that this procedure is inexpensive, is factible and possible if it does coexist with multidisciplinary and on time support, interest, dedication on care, and enough information and desire to do it, including official decisions to perform and sponsor its continuity to the people who participate in it.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Adulto , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
The results of the treatment of 43 patients with acute promyelocytic leukemia (PML) are reported: 27 were treated initially with all-trans-retinoic acid (ATRA), whereas 16 were treated with conventional chemotherapy. All patients received myelosuppressive chemotherapy after the initial treatment. Respectively, the complete remission rate was 92% and 37% (P < 0.01), the 5-day mortality rate was 0% and 44% (P < 0.001), and the 28-day mortality rate was 4% and 44% (P < 0.001). The median disease-free survival was 12 and 1 months (P < 0.01), whereas the 12-month disease-free survival was 50% and 13% (P < 0.01) and the 36-month disease-free survival was 41% and 9% (P < 0.01). Thirteen of the patients treated with ATRA were given the treatment fully as outpatients. ATRA given as initial therapy decreased significantly early mortality in promyelocytic leukemia patients; because some promyelocytic leukemia patients given ATRA as initial therapy can be treated as outpatients, the costs of this treatment modality may be diminished.
Asunto(s)
Antineoplásicos/uso terapéutico , Leucemia Promielocítica Aguda/tratamiento farmacológico , Tretinoina/uso terapéutico , Adolescente , Adulto , Atención Ambulatoria , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Niño , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Inducción de RemisiónRESUMEN
We have prospectively performed peripheral blood stem cell autotransplants in six patients with hematological malignancies on an entirely outpatient basis. Patients were conditioned with high-dose melphalan and received a median of 4.2 x 10(8)/kg non-cryopreserved, non-purged mononuclear cells, containing a median of 3.9 x 10(6)/kg CD34 + cells. The median time to achieve > 500 granulocytes/microl was 21 days, with a range of 16 to 40, whereas the median time to achieve > 20,000 platelets/microl was 38 days, with a range of 21 to 48. Only three patients were transfused with platelets whereas packed red blood cells were transfused in two. All patients survived 60 days after the autograft and three are alive at 450, 690, and 1,950 days after the autotransplant. One patient was given an allogeneic bone marrow transplant when relapsing after the autotransplant. One patient had to be admitted to the hospital on day +10 because of fever. A median of 6,500.00 USD per patient was calculated as the total cost of each outpatient autotransplant. Since outpatient autologous transplants with non-frozen PBSC are feasible, restrictions to PBSC autotransplant programs may be overcome and costs may be diminished.
Asunto(s)
Atención Ambulatoria , Conservación de la Sangre , Trasplante de Células Madre Hematopoyéticas/métodos , Células Madre Hematopoyéticas , Adulto , Antígenos CD34/análisis , Niño , Femenino , Costos de la Atención en Salud/estadística & datos numéricos , Neoplasias Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Células Madre Hematopoyéticas/citología , Humanos , Inyecciones Intravenosas , Leucaféresis , Recuento de Leucocitos , Leucocitos Mononucleares/citología , Leucocitos Mononucleares/inmunología , Masculino , Melfalán/administración & dosificación , Persona de Mediana Edad , Acondicionamiento Pretrasplante , Trasplante Autólogo , Resultado del TratamientoRESUMEN
A second Philadelphia (Ph) chromosome is one of the most common nonrandom secondary chromosome changes in leukemias with 9;22 translocations. It has been suggested, and observed in two studies of masked t(9;22), that the second Ph chromosome is an exact duplication of the entire derivative chromosome 22. In a cytogenetic study of bone marrow cells from an acute myelogenous leukemia patient, a cell line carrying two different Ph chromosomes evidenced by a chromosome 22 centromeric heteromorphism was found. From this observation arose the question whether the second der(22) was a true Ph chromosome or whether it was a deleted chromosome derived from the normal chromosome 22 that did not contain the bcr-abl rearrangement. A fluorescent in situ hybridization (FISH) study with the t(9;22) probe revealed two bcr-abl positive signals on 60 of 100 interphase nuclei. The second Ph could have resulted from a mitotic crossing over; or, analogously to late-appearing Philadelphia chromosomes, it may be derived from a new chromatid translocation between the chromosomes 9 and 22 not involved in the initial t(9;22).
Asunto(s)
Aberraciones Cromosómicas , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Leucemia Mieloide Aguda/genética , Adolescente , Cromosomas Humanos Par 22 , Proteínas de Fusión bcr-abl/genética , Reordenamiento Génico , Humanos , Hibridación Fluorescente in Situ , Cariotipificación , MasculinoRESUMEN
PURPOSE: To compare the clinical patterns and survival of young and adult (AP) versus paediatric (PP) patients with paroxysmal nocturnal haemoglobinuria (PNH). PATIENTS AND METHODS: The clinical records of 117 patients (82% AP, 18% PP) seen in four cities of the Mexican Republic were analysed, the clinical course and survival of both groups being compared. RESULTS: No sex difference was found in the two patient-groups: 51% and 52% males, 49% and 48% females in AP and PP, respectively. The onset of PNH had similar distribution for the two groups of patients: aplastic form, 45% in AP and 62% in PP; cytopenias, 24% in AP versus 27% in PP; haemolysis, 28% in AP and 9% in PP, and thrombosis, 3% in AP versus 0% in PP. The clinical features with significant difference were: anaemic+haemorrhagic syndrome (39 AP (40%) vs 14 PP (67%), p = 0.02), initial diagnosis of immunologic thrombocytopenic purpura (7 AP (7%) vs 7 PP (33%), p = 0.003), and death rate (17 AP (18%) vs 8 PP (38%), p = 0.04). The actuarial survival curves showed significant differences between both groups (p = 0.045, Cox-Mantel), with estimated 10-year survival of 81% for AP and 55% for PP, and 15-year survivals of 64% for AP and 55% for PP. CONCLUSIONS: Seemingly, PNH in paediatric age has poorer prognosis than in adults, which is associated to higher incidence of fatal haemorrhages due to thrombocytopenia.
Asunto(s)
Hemoglobinuria Paroxística/epidemiología , Enfermedad Aguda , Adolescente , Adulto , Anemia/etiología , Anemia Refractaria con Exceso de Blastos/etiología , Médula Ósea/patología , Niño , Preescolar , Diagnóstico Diferencial , Femenino , Hemoglobinuria Paroxística/clasificación , Hemoglobinuria Paroxística/complicaciones , Hemoglobinuria Paroxística/patología , Hemorragia/etiología , Humanos , Incidencia , Lactante , Leucemia Mieloide/etiología , Tablas de Vida , Masculino , México/epidemiología , Pronóstico , Púrpura Trombocitopénica Idiopática/diagnóstico , Estudios Retrospectivos , Análisis de Supervivencia , Trombosis/etiologíaRESUMEN
The purpose of the present study was to investigate the range of micronucleated erythrocytes (MNE) in peripheral blood from splenectomized patients with and without genotoxic chemotherapy. The erythrocytes were stained with Wright and Giemsa for microscopic observation. To estimate the number of MNE, two series of 10000 erythrocytes per sample were analyzed and averaged. The results expressed as mean +/- standard deviation were as follows: control patients with genotoxic chemotherapy (n = 6) 2.5 +/- 1.5 (range 1 to 5 MNE); splenectomized patients with genotoxic chemotherapy (n = 7) 65.2 +/- 17.7 (range: 47-108) MNE and splenectomized patients without genotoxic chemotherapy (n = 13) 29.5 +/- 5.8 MNE; (range: 18.5-35.6). The MNE number in the patients treated with genotoxic chemotherapy depended on the type of drugs utilized: cyclophosphamide, mitoxantrone, vincristine, busulphan, cytosine arabinoside and hydroxyurea. Upon these results, it is suggested that splenectomized people could be useful in monitoring exposures, and the baseline MNE level would serve as each person's pre-exposure control when either chronic or acute exposure to environmental mutagens is investigated.
Asunto(s)
Antineoplásicos/efectos adversos , Eritrocitos/ultraestructura , Enfermedades Hematológicas/sangre , Micronúcleos con Defecto Cromosómico , Neoplasias/sangre , Adulto , Antineoplásicos/uso terapéutico , Femenino , Enfermedades Hematológicas/tratamiento farmacológico , Enfermedades Hematológicas/cirugía , Humanos , Masculino , Neoplasias/tratamiento farmacológico , Neoplasias/cirugía , EsplenectomíaRESUMEN
1. Following in vitro treatment with 12 microM 6-hydroxy-dopamine, 2 microM B-oestradiol, 0.1 microM propranolol and 10 microM cocaine vasa deferentia isolated from young rats (21-23 days old) showed supersensitivity to norepinephrine (NE) compared to those from adult (3 months old) rats. 2. The pA2 values for prazosin were higher in young (9.6 +/- 0.1) than in adult (8.3 +/- 0.1) rat vas deferens, with the slopes of the Schild plots not different from 1.0 (0.78 +/- 0.26 and 1.14 +/- 0.14, respectively). 3. The treatment of young rats with a single dose of testosterone abolished the supersensitivity to NE and the higher affinity for prazosin. 4. We conclude that there is a reduction of neuronal NE uptake and a decrease in the sensitivity to NE in the vas deferens as the rat matures sexually. 5. Testosterone induces a decrease in the sensitivity to NE, probably via an action on the alpha 1-adrenoceptor population and the sympathetic nerve discharge in this organ.
Asunto(s)
Compuestos de Bario , Cloruros , Músculo Liso/efectos de los fármacos , Norepinefrina/farmacología , Testosterona/farmacología , Animales , Bario/farmacología , Carbacol/farmacología , Cocaína/farmacología , Estradiol/farmacología , Técnicas In Vitro , Masculino , Contracción Muscular/efectos de los fármacos , Prazosina/farmacología , Propranolol/farmacología , Ratas , Ratas Wistar , Conducto Deferente/efectos de los fármacosRESUMEN
Ninety three patients with multiple myeloma (MM) were treated with cyclophosphamide, vincristine, melphalan, prednisone and adriamycin (C.O.M.P.A.). Their median age was 60.9 years and sixty five were males. Seven patients were in stage I-A; 25 in II-A; 33 in III-A and 28 in III-B. Complete remission (CR) was achieved in 61 (65.6%), partial remission (PR) in 18 (19.3%) and no response in 14 (15%). At present, the mean survival of the CR group, is 32.3 months (10 to 78), and of the PR 11.2 months (6 to 18). The actuarial survival of the CR group is 37.9 months. A hemoglobin level lower than 8.5 g/dL, serum creatinine higher than 2.0 mg/dL, and stage III disease were factors that together negatively influenced in both response to treatment and survival. Proteinuria did not affect response, but it was a negative factor for survival. Thirty percent of deaths were due to infection, and 24.5% to myeloma activity associated with infection. We conclude that this five drug combination (C.O.M.P.A.) achieves a high percentage of complete remissions, but does not differ significantly from other reported schemes in the mean survival obtained for multiple myeloma.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Mieloma Múltiple/tratamiento farmacológico , Adulto , Anciano , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Evaluación de Medicamentos , Femenino , Humanos , Masculino , Melfalán/administración & dosificación , Persona de Mediana Edad , Mieloma Múltiple/mortalidad , Prednisona/administración & dosificación , Inducción de Remisión , Vincristina/administración & dosificaciónRESUMEN
Twenty patients with severe aplastic anemia (SAA) were treated with low doses (1-5 mg/kg/day) of a high-potency antithymocyte globulin (ATG) produced in Mexico, shown to have at least a 10-fold potency as compared with other globulins of commercial sources. Patients received ATG within a 10-day period, every other day (5 doses) at a dose of 1 mg/kg/day (4 courses), 2 mg/kg/day (12 courses) or 5 mg/kg/day (8 courses). Four patients received 2 consecutive courses of different doses of ATG. A response rate of 42% was recorded in the group, assessed by means of increases in reticulocytes, granulocytes or platelets. One patient showed a complete remission. The 570-day survival of the group was 51%. It is concluded that the domestically produced ATG is useful in the treatment of some patients with SAA in Mexico.
Asunto(s)
Anemia Aplásica/terapia , Suero Antilinfocítico/administración & dosificación , Adolescente , Adulto , Anemia Aplásica/tratamiento farmacológico , Anemia Aplásica/mortalidad , Animales , Suero Antilinfocítico/efectos adversos , Niño , Preescolar , Esquema de Medicación , Femenino , Caballos , Humanos , Masculino , Persona de Mediana Edad , Prednisona/uso terapéutico , Inducción de RemisiónAsunto(s)
Enfermedades Autoinmunes/sangre , Enfermedades Hematológicas/etiología , Lupus Eritematoso Sistémico/sangre , Adolescente , Adulto , Anciano , Anemia Hemolítica Autoinmune/etiología , Enfermedades Autoinmunes/complicaciones , Trastornos de la Coagulación Sanguínea/etiología , Femenino , Humanos , Lupus Eritematoso Sistémico/complicaciones , Linfopenia/etiología , Masculino , Persona de Mediana Edad , Púrpura Trombocitopénica/etiologíaAsunto(s)
Autoanticuerpos/análisis , Enfermedades Autoinmunes/inmunología , Plaquetas/inmunología , Púrpura Trombocitopénica/inmunología , Retracción del Coagulo , Prueba de Coombs , Estudios de Evaluación como Asunto , Humanos , Inmunodifusión , Inmunoglobulina G/análisis , Factor Plaquetario 3/análisisRESUMEN
The effects of reserpine on the sensitivity of the isolated pacemaker from rat heart to the chronotropic effect of isoprenaline and noradrenaline were studied. A single large dose of reserpine (2.5 mg kg-1) administered to rats 24 h before killing induces supersensitivity of the isolated pacemaker to isoprenaline, leaving unaltered the responsiveness of the pacemaker to noradrenaline. Reserpine at the dose of 1.0 mg kg-1 did not alter the sensitivity of the pacemaker to the catecholamines. Only the larger dose of reserpine raised the corticosterone plasma level. It is possible that a corticosterone-mediated inhibition of the extraneuronal uptake process is responsible for the supersensitivity to isoprenaline. Large doses of reserpine should not be used in experiments aimed to study cardiac sensitivity to isoprenaline or extraneuronal uptake and metabolism of the catecholamine.