RESUMEN
A Japanese database on research and development that disaggregates an industry's intramural expenditure into 31 different product fields is used tp measure technological diversification. Sectoral patterts are identified in terms of upstream, downstream, and horizontal diversification-that is, respectively, diversification of an industry's research and development activities into product fields that are industrial inputs of that industry, into those that are outputs, and diversification that is not directed through the path of input-output relations. The pattern of the electronics industry is identified as downstream diversification whereas that of the chemical industry is identified as horizontal. The declining industry is generally making upstream diversification. Japanese corporate and governmental policies, such as trade policy, industrial policy, and the research association scheme, have accelerated technological diversification.
RESUMEN
Expression of estrogen receptor (ER) was studied in the ER-positive human breast cancer cell line MCF-7 using immunoperoxidase staining with monoclonal antibodies to ER. Using a soft agar colony assay and liquid culture, effects of growth and the antiestrogen tamoxifen were examined. Heterogeneity in expression of ER was observed between different clones in the agar cultures as well as among cells within the same clone. Clonal expression of ER increased progressively with increasing cell number within a clone. At pharmacological doses, tamoxifen significantly reduced clonal growth but also markedly reduced the expression of ER within clones that grew despite the presence of the antiestrogen. These findings are consistent with the hypothesis that ER-positive colonies arise from ER-negative progenitors and that ER expression occurs along with differentiation of cells within clones. Furthermore, the findings are consistent with tamoxifen exerting its antineoplastic action beyond the level of the tumor stem cell. Such therapy would therefore be capable of suppression but not eradication of breast cancer clonal progenitors.
Asunto(s)
Neoplasias de la Mama/patología , Antagonistas de Estrógenos/farmacología , Células Madre Neoplásicas/patología , Receptores de Estrógenos/análisis , Células Madre/patología , Neoplasias de la Mama/análisis , División Celular , Línea Celular , Femenino , Humanos , Células Madre Neoplásicas/efectos de los fármacos , Tamoxifeno/farmacologíaRESUMEN
Here we describe 2 patients with acute leukemia in whom human herpesvirus-6 (HHV-6) encephalitis developed after cord blood transplantation. In patients 1 and 2, generalized seizure and coma developed on day 62 and day 15, respectively, after cord blood transplantation, which failed to engraft in patient 1. Magnetic resonance imaging (MRI) of patient 1's brain showed low-intensity signals at the gyri of the bilateral lateral lobes on T1-weighted images and high-intensity signals on T2-weighted images. MRI of patient 2's brain showed high-intensity signals in bilateral white matter on T2-weighted images and on fluid-attenuated inversion recovery (FLAIR) images. Cerebrospinal fluid examination revealed an increased protein level with pleocytosis in patient 1 and a normal protein level without pleocytosis in patient 2. Polymerase chain reaction analysis detected HHV-6 DNA in the cerebrospinal fluid of both patients. Patient 1 recovered after administration of gancyclovir for 3 weeks. However, she again suffered from encephalitis after discontinuation of gancyclovir, and died of sepsis. Patient 2 died from an anoxic brain caused by generalized seizure. When neurological symptoms and signs appear in hematopoietic stem cell transplantation recipients, we should consider HHV-6 encephalitis and promptly and empirically treat them with gancyclovir or foscarnet.
Asunto(s)
Trasplante de Células Madre de Sangre del Cordón Umbilical/efectos adversos , Encefalitis Viral/diagnóstico , Herpesvirus Humano 6 , Leucemia Monocítica Aguda/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Infecciones por Roseolovirus/diagnóstico , Adulto , Encefalitis Viral/líquido cefalorraquídeo , Encefalitis Viral/etiología , Resultado Fatal , Femenino , Humanos , Persona de Mediana Edad , Infecciones por Roseolovirus/líquido cefalorraquídeo , Infecciones por Roseolovirus/etiologíaRESUMEN
We studied seven cases of malignant neoplasms, taken from various sites in the body, that were associated with marked granulocytosis. The seven cases were characterized clinically by marked granulocytosis with mature neutrophils, nonspecific inflammatory signs, and a rapid and progressive fatal course of the disease. The elevation of granulocyte count generally paralleled the increase in tumor size. Postmortem examination revealed no evidence of extensive bone marrow metastases or significant suppuration in any case. The bone marrows showed varying degrees of granulocytic hyperplasia with or without a shift to the left in the maturation series. Erythroid cell hyperplasia was observed in some cases, and in one instance there was an increase in immature eosinophils. The spleen showed various degrees of infiltration by neutrophils, from minimal to extremely marked; some spleens had foci of extramedullary hemopoiesis. Colony-stimulating activity was demonstrated in tumor extracts from three of these cases and from the serum in another case. Thus, it is suggested that marked granulocytosis in these patients was caused, at least in part, by colony-stimulating factor produced by the neoplastic cells.
Asunto(s)
Factores Estimulantes de Colonias/análisis , Granulocitos/patología , Neoplasias/patología , Adulto , Anciano , Autopsia , Médula Ósea/patología , Femenino , Humanos , Recuento de Leucocitos , Neoplasias Hepáticas/patología , Neoplasias Pulmonares/patología , Masculino , Neoplasias del Seno Maxilar/patología , Necrosis , Neoplasias/sangre , Neoplasias Gástricas/patología , Neoplasias Uterinas/patologíaRESUMEN
Immune reconstitution is an important component of successful allogeneic bone marrow transplantation. Immune reconstitution was evaluated for 5 years after transplantation. While the number of CD8+ T cells and CD56+ cells recovered early post transplantation, a low number of CD4+ and CD4+ CD45RA+ T cells and reversal of the CD4/CD8 ratio continued up to 5 years. Although early recovery of IgG and IgM was seen at day 100 post transplantation, serum concentration of IgA was below the normal range at 6 months and increased gradually up to 5 years. Development of acute GVHD did not affect the numbers of CD4+, CD8+, CD4+ CD45RA+ and CD4+ CD29+ T cells, but the number of CD56+ cells in patients who developed grades II-IV acute GVHD was low. The number of CD4+ CD29+ T cells had a tendency to be higher in the patients with extensive chronic GVHD than in those without chronic GVHD 2 years after transplantation whereas the number of CD4+ CD45RA+ T cells was low in spite of the absence of chronic GVHD. Serum concentration of IgA was lower in patients with extensive chronic GVHD than in those without chronic GVHD at 180 days. The number of CD4+ CD45RA+ cells in 10-19-year-old patients was higher than that in 40-49-year-old patients. Response to the Con A and PHA in 10-19-year-old patients was higher than that in older patients at 1 and 2 years. There was no significant difference in the ability of immune reconstitution between related transplant recipients and unrelated transplant recipients. These results suggest that chronic GVHD and age of patients affected immune reconstitution post transplant.
Asunto(s)
Trasplante de Médula Ósea/inmunología , Supervivencia de Injerto , Inmunidad , Adolescente , Factores de Edad , Antígenos CD/sangre , Relación CD4-CD8 , Linfocitos T CD4-Positivos/citología , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/citología , Linfocitos T CD8-positivos/inmunología , Femenino , Estudios de Seguimiento , Supervivencia de Injerto/inmunología , Enfermedad Injerto contra Huésped/sangre , Humanos , Inmunoglobulinas/sangre , Inmunoglobulinas/clasificación , Subgrupos Linfocitarios/efectos de los fármacos , Subgrupos Linfocitarios/inmunología , Masculino , Persona de Mediana Edad , Mitógenos/farmacología , Trasplante HomólogoRESUMEN
SCID mice were transplanted with H-2-incompatible C3H/He splenocytes with or without previous TBI with 2Gy to evaluate the influence of sublethal TBI on GVHD and on the graft-versus-leukemia (GVL) effect. Transplantation immediately after TBI induced lethal GVHD, but delayed donor leukocyte infusion (DLI) 5 days after TBI reduced the severity of the GVHD. SCID mice inoculated with L1210 cells after TBI received a DLI 5 days after TBI to induce the GVL effect. Survival of these mice was longer than that of control nonirradiated mice. Serum levels of tumor necrosis factor-alpha, IL-1alpha, IL-6, IL-2 and IFN-gamma were significantly elevated, and they reached maximum levels at 5 days post-transplantation. Except for IFN-gamma, all cytokine levels were higher in irradiated mice than those in nonconditioned mice. Cytotoxicity against L1210 cells mediated by splenocytes from irradiated recipients was greater than that mediated by effector cells from nonirradiated mice. All the irradiated mice survived more than 120 days after L1210 rechallenge, while all nonirradiated mice died of leukemia within 5 weeks. In conclusion, compared with control mice infused with donor splenocytes without previous TBI, SCID mice which received sublethal TBI and DLI showed superior cytotoxicity against L1210 cells and survived longer without severe GVHD.
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Trasplante de Células , Enfermedad Injerto contra Huésped/prevención & control , Reacción Injerto-Huésped , Leucemia Experimental , Bazo/trasplante , Irradiación Corporal Total , Enfermedad Aguda , Animales , Femenino , Ratones , Ratones Endogámicos C3H , Ratones SCID , Trasplante de Neoplasias , Trasplante HomólogoRESUMEN
A 42-year-old female with acute mixed lineage leukemia received a marrow transplantation from an HLA non-identical sibling. The serum of the patient showed a positive crossmatch for anti-donor lymphocytotoxic antibody and exhibited a complement-mediated cytotoxicity to donor hematopoietic progenitor cells. In an attempt to reduce the risk of graft rejection, a large volume plasma exchange was performed, which was followed by an infusion of irradiated donor lymphocytes to eliminate remaining antibodies from her serum. The level of anti-donor antibody fell below the sensitivity of the anti-human immunoglobulin lymphocytotoxicity test after the infusion of donor lymphocytes. The cytotoxic activity against donor progenitor cells also disappeared from the serum. Cyclosporin had been administered for 2 weeks before marrow infusion, and methylprednisolone and prednisolone for 1 week before the initiation of conditioning chemoradiotherapy. Conditioning comprised cytosine arabinoside 5.6 g/m2, cyclophosphamide 4500 mg/m2 and fractionated total body irradiation with 15 Gy followed by an infusion of 4.0 x 10(8) cells/kg of unmodified marrow cells. Engraftment of donor cells was documented by HLA typing of peripheral lymphocytes. A sustained engraftment may be obtained in a donor-incompatible HLA non-identical marrow transplantation with anti-donor antibody by elimination of the antibody and achieving an intensive immunosuppression in the recipient before marrow infusion.
Asunto(s)
Citotoxicidad Celular Dependiente de Anticuerpos/inmunología , Trasplante de Médula Ósea/inmunología , Antígenos HLA/inmunología , Histocompatibilidad/inmunología , Adulto , Anticuerpos/análisis , Anticuerpos/fisiología , Trasplante de Médula Ósea/patología , Femenino , Hematopoyesis/fisiología , Células Madre Hematopoyéticas/citología , Células Madre Hematopoyéticas/fisiología , Humanos , Terapia de Inmunosupresión , Linfocitos/citología , Linfocitos/inmunologíaRESUMEN
A 23-year-old woman had a normal full-term delivery 78 months after BMT for ALL. Conditioning therapy was Ara C 1.4 g/m2 x 4, CY 60 mg/kg x 2 and TBI 2.5 Gy x 5 at a dose rate of 3.5 cGy/min. Despite GVHD prophylaxis with short-term MTX and CsA, she developed grade I acute GVHD, but showed no evidence of chronic GVHD. Following amenorrhea for 4 years, menstruation recommenced spontaneously. She had a normal pregnancy 6 years after BMT resulting in a healthy infant with simple hypospadias. This and previous reports indicate that normal pregnancy is possible after BMT with TBI in excess of 10 Gy.
Asunto(s)
Trasplante de Médula Ósea , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Embarazo , Irradiación Corporal Total , Enfermedad Aguda , Adulto , Femenino , Enfermedad Injerto contra Huésped/diagnóstico , Humanos , Dosis de Radiación , Trasplante HomólogoRESUMEN
The origin of cells in almost all allogeneic donor-recipient pairs can be determined through the use of highly polymorphic minisatellite DNA probes. Single-locus probes were cloned from hypervariable fragments in a human DNA fingerprint detected with a multi-locus probe. While each probe is highly polymorphic and locus specific, they all contain repetitive sequences. The properties of single-locus probes have improved the sensitivity of detecting mixed chimerism in comparison with multi-locus probes. The use of single-locus probes permitted detection of mixed chimerism (MC) at levels as low as 0.625%, approaching that obtained by PCR methods. In the present study, five patients who received allogeneic BMT for hematologic malignancies were analyzed. Two patients exhibited MC after BMT. One developed acute GVHD and chronic GVHD and remained in CR while the second patient who had no signs of GVHD suffered a relapse.
Asunto(s)
Trasplante de Médula Ósea , Dermatoglifia del ADN , Sondas de ADN , ADN Satélite/genética , Supervivencia de Injerto , Adulto , Alelos , Femenino , Enfermedad Injerto contra Huésped , Humanos , Leucemia/patología , Leucemia/cirugía , Masculino , Quimera por Radiación , Secuencias Repetitivas de Ácidos Nucleicos , Sensibilidad y EspecificidadRESUMEN
Eighty patients receiving hematological stem cell transplantation (HCT) with a preparative regimen consisting of total body irradiation (12.5 Gy), cyclophosphamide (4000 or 4500 mg/m2), and thiotepa (400 mg/m2) were evaluated for the development of cardiac toxicity. Patients in whom the pretransplant cumulative dose of anthracycline was more than or equal to 300 mg/m2 showed a lower left ventricular ejection fraction (EF) before HCT compared to patients with less than 300 mg/m2 (0.61 +/- 0.09 vs 0.67 +/- 0.06, P = 0.0010). Patients who had undergone more than or equal to six courses of chemotherapy showed a decreased EF before HCT compared to those after less than six courses (0.67 +/- 0.05 vs 0.63 +/- 0.09, P = 0.03). Three of seven patients (43%) whose pretransplant EF had been less than or equal to 0.55 developed severe cardiac toxicity, characterized by congestive heart failure (CHF) compared with none of 83 patients (0%) whose pretransplant EF had been more than 0.55 (P = 0.00026). Of the three patients who developed severe cardiac toxicity, two were given more than 300 mg/m2 of cumulative anthracycline and underwent 23 courses and six courses of chemotherapy, while the other patient received only two courses of chemotherapy with a total dose of 139 mg/m2 of anthracycline. These results indicate that an increased cumulative dose of anthracycline and number of chemotherapy treatments are correlated with a decrease of the EF and that the EF before HCT is useful for predicting the risk of cardiac complications for recipients who have received chemotherapy.
Asunto(s)
Insuficiencia Cardíaca/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/toxicidad , Ciclofosfamida/administración & dosificación , Ciclofosfamida/toxicidad , Relación Dosis-Respuesta a Droga , Femenino , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/fisiopatología , Neoplasias Hematológicas/complicaciones , Neoplasias Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas/mortalidad , Humanos , Masculino , Valor Predictivo de las Pruebas , Pronóstico , Estudios Retrospectivos , Volumen Sistólico/fisiología , Tiotepa/administración & dosificación , Tiotepa/toxicidad , Irradiación Corporal TotalRESUMEN
To clarify the role of hepatitis G virus (HGV) infection in liver dysfunction following allogeneic BMT, we examined cryopreserved serum samples from 33 patients who had a history of blood transfusions before BMT and whose serum samples had been stored periodically, before BMT, on day 100, and thereafter for the presence of HGV-RNA and hepatitis C virus (HCV)-RNA by reverse transcription polymerase chain reaction. Nineteen patients (58%) out of 33 were positive for HGV-RNA before BMT and 10 for HCV-RNA. All patients positive for HCV-RNA were also positive for HGV-RNA. Patients were divided into three groups according to their viral status before BMT; namely, the G+C+ group (n = 10), the G+C- group (n = 9) and the G-C- group (n = 14). Two patients in the G-C- group became positive for HGV-RNA after BMT. One patient in the G+C- group suffered an acute exacerbation of hepatitis, with GPT levels reaching over 1000 IU/l, 2 and 3 years after BMT, showing quite a different clinical course from those in the G+C- group. Excluding these three patients, GPT levels of the patients in the G+C+ group were significantly higher after day 100 and remained higher than those of patients in the G+C- and G-C- groups for at least 4 years. There were no significant differences in post-transplant GPT levels between the G+C- group and the G-C- group at any time point. Of the seven patients followed-up for 5 to 10 years, three patients became HGV-RNA-negative, while four remained positive. In the absence of HCV co-infection, the behavior of GPT values post transplant in patients with HGV infection did not differ from those without HGV infection. With respect to the patient who was G+C- and showed high values of GPT 2 and 3 years post transplant, we suspect that his liver dysfunction might have been caused by some unknown virus or etiology.
Asunto(s)
Trasplante de Médula Ósea/fisiología , Flaviviridae , Hepatitis Viral Humana/fisiopatología , Hepatitis Viral Humana/transmisión , Pruebas de Función Hepática , Adolescente , Adulto , Recolección de Muestras de Sangre , Transfusión Sanguínea , Trasplante de Médula Ósea/efectos adversos , Criopreservación , Femenino , Flaviviridae/aislamiento & purificación , Estudios de Seguimiento , Hepacivirus/aislamiento & purificación , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Complicaciones Posoperatorias , ARN Viral/sangre , Estudios Retrospectivos , Factores de TiempoRESUMEN
We investigated hemostatic parameters in a prospective study of 16 patients who received bone marrow transplants (BMT). We found a significant rise in the levels of fibrinogen, plasmin-alpha2 antiplasmin inhibitor complex, tissue-plasminogen activator.plasminogen activator inhibitor complex (t-PA.PAI), von Willebrand factor antigen, and thrombomodulin on day 14 after transplant compared with values before transplant. Protein C and thrombin-antithrombin III levels did not change significantly. No significant changes in prothrombin time ratio, activated partial thromboplastin time, or protein S were detected. Patients who had grades II-IV graft-versus-host disease (GVHD) (n = 6) showed a significantly higher level of t-PA.PAI on day 14 compared with those with grades 0-I GVHD (n = 10) (P = 0.0062). Three patients with grades II-IV GVHD developed thrombotic microangiopathy (TMA) on days 19, 19 and 62. In these patients, we noted significantly lower levels of fibrinogen (P = 0.0383), and significantly higher levels of t-PA.PAI (P = 0.0008) and thrombomodulin (P = 0.0001) on day 14 compared with those patients who did not develop TMA. These results suggest that prothrombotic states and endothelial damage may be caused by the conditioning regimen and/or acute GVHD during BMT; thrombomodulin values on day 14 post BMT may be useful in surveillance for TMA because of endothelial cell injury.
Asunto(s)
Trasplante de Médula Ósea/efectos adversos , Hemostasis , Microcirculación/patología , Trombosis/diagnóstico , Adolescente , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Trombosis/sangre , Trombosis/etiologíaRESUMEN
A patient with acquired von Willebrand disease associated with multiple myeloma (IgG-lambda) is described. Mixture of his plasma or IgG fraction with washed control platelets resulted in the inhibition of aggregation with ristocetin, but mixture of control plasma or IgG fraction with washed patient platelets showed no inhibition of ristocetin-induced aggregation. Although his vWF: Ag, RCo, and factor VIII coagulant activity were all normal, inactivation of RCo was induced in normal plasma by incubation with patient plasma. Crossed immunoelectrophoretic analysis showed that vWF:Ag was composed of much more anodic component. A marked increase of Factor VIII and a rapid return of RCo to the baseline after 1-deamino-8-arginine vasopressin (DDAVP) infusion were observed. A transient increase in vWF:Ag after the infusion of DDAVP showed with less anodic forms and in the relative proportion as in normal. Treatment of the underlying disease also led to a correction of the bleeding time, improvement of platelet adhesion and ristocetin-induced aggregation, and normalization of crossed immunoelectrophoresis of vWF:Ag. The present study showed that myeloma-associated IgG interacted specifically with the antigenic sites on the von Willebrand portion of the Factor VIII complex.
Asunto(s)
Proteínas de Mieloma/inmunología , Enfermedades de von Willebrand/inmunología , Factor de von Willebrand/inmunología , Adulto , Anticuerpos Monoclonales/inmunología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Pruebas de Coagulación Sanguínea , Plaquetas/metabolismo , Factor VIII/metabolismo , Glicoproteínas/inmunología , Glicoproteínas/metabolismo , Humanos , Masculino , Melfalán/uso terapéutico , Adhesividad Plaquetaria , Agregación Plaquetaria/efectos de los fármacos , Ristocetina/antagonistas & inhibidores , Ristocetina/farmacología , Enfermedades de von Willebrand/tratamiento farmacológicoRESUMEN
Fourteen patients treated by allogeneic bone marrow transplantation for chronic myelogenous leukemia (CML) were evaluated by the polymerase chain reaction (PCR) for bcr-abl-specific transcripts. Nine patients were transplanted in the first chronic phase, three in the second chronic phase, and two in the accelerated phase. All patients achieved a complete cytogenetic and hematologic remission after bone marrow transplantation. Twelve patients are alive (median, 18 months; range, 5-54 months) and two patients died early. bcr-abl mRNA was persistently detectable for 6 to 54 months in four patients (patients 1, 3, 4, 6). From two of them, DNA fingerprint analysis showed only donor type DNA although bcr-abl mRNA was detectable. bcr-abl mRNA was never detectable posttransplant in three patients (patients 2, 5, 13). Six patients had detectable bcr-abl mRNA (patients 8-12, 14): by 6 months, all of these patients were bcr-abl mRNA negative. One patient (patient 7) had detectable full bcr-abl mRNA again at 12 months, but was then negative at 20 months. Ten patients (patients 2, 4-8, 10-13) had never detectable Philadelphia (Ph1) chromosome t(9.22) translocation, whereas four patients had detectable Ph1 (patient 1, 3, 9, 14); by 6 months, three of four cases were negative. One patient (patient 1) had detectable Ph1 at 44 months, but was negative at 50 months. Three of six patients who initially had bcr-abl mRNA detectable posttransplant (patient 7-9) became negative for bcr-abl mRNA at the time of development of chronic graft-versus-host disease (GVHD). These results suggest that the detection of subclinical Ph1 positive cells by PCR is not associated with imminent clinical or cytogenetic relapse. Moreover, graft-versus-leukemia (GVL) activity may contribute to the treatment of minimal residual disease in CML after allogeneic bone marrow transplantation.
Asunto(s)
Trasplante de Médula Ósea , Dermatoglifia del ADN , ADN de Neoplasias/análisis , Genes abl/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , ARN Mensajero/análisis , ARN Neoplásico/análisis , Adolescente , Adulto , Secuencia de Bases , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/terapia , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa/métodos , Valor Predictivo de las Pruebas , ADN Polimerasa Dirigida por ARN , Recurrencia , Sensibilidad y EspecificidadRESUMEN
A 43-year-old female with AML-M1 developed late graft failure 4 months after her first allogeneic bone marrow transplant. The patient then underwent a second transplant with peripheral blood progenitor cells obtained from the same HLA-identical brother. The donor peripheral blood progenitor cells were mobilized with granulocyte colony-stimulating factor (10 micrograms/kg daily s.c. for 6 days). The patient received horse anti-thymocyte globulin alone (15 mg/kg per day for 5 days) as the conditioning regimen. Rapid hematopoietic recovery followed a sustained engraftment. The time to reach 0.5 x 10(9)/l neutrophils and 25 x 10(9)/l platelets was 10 and 12 days, respectively. Cytogenetic analysis of bone marrow performed on day +20 demonstrated a 46XY karyotype of donor origin. There was no acute graft-versus-host disease. The patient remains in complete remission with a karnofsky score of 90% 5 months after peripheral blood progenitor cell transplantation. To treat graft failure after allogeneic bone marrow transplantation, allogeneic peripheral blood progenitor cell transplantation conditioned with anti-thymocyte globulin alone should be considered as a feasible alternative to marrow transplant.
Asunto(s)
Suero Antilinfocítico , Trasplante de Médula Ósea , Rechazo de Injerto/terapia , Trasplante de Células Madre Hematopoyéticas , Acondicionamiento Pretrasplante , Trasplante Homólogo , Adulto , Femenino , Humanos , Leucemia Mieloide Aguda/terapia , Masculino , Inducción de RemisiónRESUMEN
A 34-year-old woman of HTLV-I carrier with T-PLL, whose quality of life improved and survival was prolonged after splenectomy, is described. The patient had marked splenomegaly, generalized lymphadenopathy and marked proliferation of abnormal lymphocytes in the peripheral blood with an irregular nucleus, deeply basophilic cytoplasm and a single prominent nucleolus, which were positive for CD2, CD3, CD5, CD7, CD4 and CD8. Although the patient had serum antibody against HTLV-I, HTLV-I proviral DNA integration was not detected. She was diagnosed as an HTLV-I carrier with T-PLL and received combination chemotherapy and 15.1 Gy splenic irradiation. However, the generalized lymphadenopathy and splenomegaly did not improve. The patient underwent splenectomy to palliate abdominal distension and hypersplenism. After the operation, her symptoms improved dramatically and within a week her hemoglobin concentration and platelet count normalized. She was discharged from hospital two weeks after the splenectomy, however 11 months later, she relapsed and despite treatment with chemotherapy and alpha-interferon, she died two months after the second admission. Autopsy findings revealed that PLL cells had invaded the bone marrow, lymph nodes, liver, lungs, kidneys, uterus, ovaries and adrenal glands.
Asunto(s)
Infecciones por HTLV-I/complicaciones , Leucemia Prolinfocítica/cirugía , Esplenectomía , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Portador Sano , Terapia Combinada , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Resultado Fatal , Femenino , Humanos , Factores Inmunológicos/uso terapéutico , Inmunofenotipificación , Interferón-alfa/uso terapéutico , Leucemia Prolinfocítica/tratamiento farmacológico , Leucemia Prolinfocítica/etiología , Leucemia Prolinfocítica/patología , Leucemia Prolinfocítica/terapia , Infiltración Leucémica , Prednisona/administración & dosificación , Calidad de Vida , Esplenomegalia/etiología , Esplenomegalia/radioterapia , Esplenomegalia/cirugía , Vincristina/administración & dosificaciónRESUMEN
Between January 1990 and May 1994, 59 previously untreated adult patients with acute myeloblastic leukemia (AML) were treated with a combination of behenoyl-cytosine-arabinoside (BHAC), daunorubicin (DNR), 6-mercaptopurine (6-MP) and prednisolone (PSL). Forty one patients (69.5%) achieved complete remission (CR). The Kaplan-Meier analysis revealed an actuarial probability for remaining in remission of 36% in patients who achieved remission and a survival of 29% in all patients at 5 years. A favorable factor relative to achieving CR was performance status (P=0.04). In addition the presence of 300 cells/microl or less of residual leukemic cell counts in the bone marrow at the end point of induction therapy tended to favor remission (P=0.06) using the multivariate analysis with a multiple logistic regression model. In addition the residual leukemic cells counts of less than 300/microl in the bone marrow at the end point of induction therapy was the most significant factor for durable remission (P=0.05) by the Cox's proportional hazard model. We concluded that residual leukemic cells counts in the bone marrow at the end point of intensive induction therapy is a valuable prognostic factor for adults receiving response-oriented individualized induction therapy for AML.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Médula Ósea/patología , Leucemia Mieloide Aguda/tratamiento farmacológico , Neoplasia Residual/patología , Inducción de Remisión/métodos , Adolescente , Adulto , Anciano , Recuento de Células , Supervivencia sin Enfermedad , Femenino , Humanos , Leucemia Mieloide Aguda/mortalidad , Leucemia Mieloide Aguda/patología , Masculino , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos ProporcionalesRESUMEN
Factors predictive for central nervous system (CNS) involvement at presentation were investigated in 152 patients with non-Hodgkin's lymphoma (NHL) except for lymphoblastic cell lymphoma and small noncleaved cell lymphoma. Twelve patients developed CNS involvement during their disease course. The incidence was 7.9% of all the patients studied and 17.0% of the patients with serum LDH concentration > or = two times the upper limit of normal (2N). By univariate analysis, stage IV disease (P = .023), a serum LDH concentration > or = 2 N (P = .009), and bone marrow involvement (P = .016) were risk factors for CNS involvement. Multivariate logistic regression analysis identified a serum LDH concentration > or = 2 N (P = .032) as an independent predictor for CNS involvement. All 12 patients who developed CNS involvement were among the 126 patients with diffuse lymphoma, whereas none of the 17 patients with follicular lymphoma developed CNS involvement, although the difference was not statistically significant. The median survival of the patients with CNS involvement was only 4.5 months. We conclude that a serum LDH concentration > or = 2N at presentation is a significant predictive factor for CNS involvement for NHL patients without lymphoblastic lymphoma and small noncleaved cell lymphoma. Therefore, we would suggest that CNS prophylaxis should be considered for patients with a serum LDH concentration > or = 2N at presentation and diffuse lymphoma once a complete remission is achieved.
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Biomarcadores de Tumor/sangre , Sistema Nervioso Central/patología , L-Lactato Deshidrogenasa/sangre , Linfoma no Hodgkin/patología , Meninges/patología , Proteínas de Neoplasias/sangre , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bleomicina/administración & dosificación , Terapia Combinada , Irradiación Craneana , Ciclofosfamida/administración & dosificación , Citarabina/administración & dosificación , Doxorrubicina/administración & dosificación , Humanos , Incidencia , Leucovorina/administración & dosificación , Tablas de Vida , Linfoma no Hodgkin/clasificación , Linfoma no Hodgkin/tratamiento farmacológico , Linfoma no Hodgkin/enzimología , Linfoma no Hodgkin/mortalidad , Linfoma no Hodgkin/radioterapia , Metotrexato/administración & dosificación , Examen Neurológico , Valor Predictivo de las Pruebas , Prednisolona/administración & dosificación , Prednisona/administración & dosificación , Análisis de Supervivencia , Resultado del Tratamiento , Vincristina/administración & dosificaciónRESUMEN
Omeprazole is widely used for the treatment of Helicobacter pylori infection. It is metabolized by cytochrome P450 2C19 enzyme (CYP2C19) in the liver. Because this enzyme exhibits a genetic polymorphism, patients with low metabolic activity (poor metabolizers) may be exposed to higher concentrations of this drug than are patients who are extensive metabolizers. Eighty-six patients with cultured H. pylori-positive gastritis or peptic ulcers who completed the treatment and assessment of anti-H. pylori therapy were analyzed for CYP2C19 genotyping using a polymerase chain reaction-restriction fragment length polymorphism method [the wild-type or two mutant genes (ml in exon 5 and m2 in exon 4), or both]. Patients were classified into three groups according to the H. pylori eradication regimen: group I (n = 21; omeprazole 40mg/ day and amoxicillin 2000mg/day for 1 week); group II (n = 21; group I regimen plus sucralfate 4000mg/day, for 1 week); group III (n = 44; group I regimen plus clarithromycin 800mg/day, for 1 week). The combination of two mutant alleles (ml/ml, ml/m2, m2/m2-poor metabolizers) was observed in 13 of 86 patients (15%), and all poor metabolizer patients achieved H. pylori eradication regardless of their treatment regimens. In addition, the eradication rates of the poor metabolizers were significantly higher than those of other genotypes who carry homozygous or heterozygous normal allele (extensive metabolizers) in group I or groups I and II combined. CYP2C19 genotyping can provide a new strategy to choose an optimal regimen, and this genotyping is especially useful for Japanese, as the frequency of poor metabolizers is five times greater than that found among Caucasians.
Asunto(s)
Amoxicilina/administración & dosificación , Antibacterianos/administración & dosificación , Antiulcerosos/administración & dosificación , Hidrocarburo de Aril Hidroxilasas , Pueblo Asiatico , Sistema Enzimático del Citocromo P-450/metabolismo , Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori , Oxigenasas de Función Mixta/metabolismo , Omeprazol/administración & dosificación , Antiulcerosos/metabolismo , Claritromicina/administración & dosificación , Citocromo P-450 CYP2C19 , Sistema Enzimático del Citocromo P-450/genética , Cartilla de ADN , Esquema de Medicación , Quimioterapia Combinada , Femenino , Genotipo , Infecciones por Helicobacter/genética , Humanos , Japón , Masculino , Persona de Mediana Edad , Oxigenasas de Función Mixta/genética , Omeprazol/metabolismo , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , Sucralfato/administración & dosificación , Factores de Tiempo , Resultado del TratamientoRESUMEN
Effect of sodium nitrite on cultured FM3A cells, a C3H mouse mammary carcinoma cell line, was examined. The chromosomal preparations demonstrated that severe aberrations were induced in more than 80% of the mitotic plates at 10(-2) M and in nearly 40% at 10(-25) M after 24 and 48 h treatment. According to the results of alkaline sucrose gradient analysis sedimentation profiles of cell DNA treated at as high as 10(-1) M for 24 h scarcely changed from that of control cell DNA. Induction of 8-azaguanine-resistant mutation was demonstrated above 10(-3) M sodium nitrite.