RESUMEN
BACKGROUND: To investigate prognosis and effects of first-line therapy in elderly primary central nervous system lymphoma (PCNSL) patients. PATIENTS AND METHODS: A systematic review of studies about first-line therapy in immunocompetent patients ≥60 years with PCNSL until 2014 and a meta-analysis of individual patient data from eligible studies and international collaborators were carried out. RESULTS: We identified 20 eligible studies; from 13 studies, we obtained individual data of 405 patients, which were pooled with data of 378 additional patients (N = 783). Median age and Karnofsky Performance Score (KPS) was 68 years (range: 60-90 years) and 60% (range: 10%-100%), respectively. Treatments varied greatly, 573 (73%) patients received high-dose methotrexate (HD-MTX)-based therapy. A total of 276 patients received whole-brain radiotherapy (median 36 Gy, range 28.5-70 Gy). KPS ≥ 70% was the strongest prognostic factor for mortality [hazard ratio (HR) 0.50, 95% confidence interval (CI) 0.41-0.62]. After a median follow-up of 40 months, HD-MTX-based therapy was associated with improved survival (HR 0.70, 95% CI 0.53-0.93). There was no difference between HD-MTX plus oral chemotherapy and more aggressive HD-MTX-based therapies (HR 1.39, 95% CI 0.90-2.15). Radiotherapy was associated with an improved survival, but correlated with an increased risk for neurological side-effects (odds ratio 5.23, 95% CI 2.33-11.74). CONCLUSIONS: Elderly PCNSL patients benefit from HD-MTX-based therapy, especially if combined with oral alkylating agents. More aggressive HD-MTX protocols do not seem to improve outcome. WBRT may improve outcome, but is associated with increased risk for neurological side-effects. Prospective trials for elderly PCNSL patients are warranted.
Asunto(s)
Antimetabolitos Antineoplásicos/uso terapéutico , Neoplasias del Sistema Nervioso Central/tratamiento farmacológico , Linfoma/tratamiento farmacológico , Metotrexato/uso terapéutico , Anciano , Neoplasias del Sistema Nervioso Central/mortalidad , Humanos , Linfoma/mortalidad , Pronóstico , Tasa de SupervivenciaRESUMEN
BACKGROUND: Central nervous system (CNS) relapse is an uncommon but challenging complication in patients with mantle cell lymphoma (MCL). Survival after CNS relapse is extremely poor. Identification of high-risk populations is therefore critical in determining patients who might be candidates for a prophylactic approach. PATIENTS AND METHODS: A total of 608 patients (median age, 67 years; range 22-92) with MCL newly diagnosed between 1994 and 2012 were evaluated. Pretreatment characteristics and treatment regimens were evaluated for their association with CNS relapse by competing risk regression analysis. RESULTS: None of the patients received intrathecal prophylaxis. Overall, 33 patients (5.4%) experienced CNS relapse during a median follow-up of 42.7 months. Median time from diagnosis to CNS relapse was 20.3 months (range: 2.2-141.3 months). Three-year cumulative incidence of CNS relapse was 5.6% [95% confidence interval (95% CI) 3.7% to 8.0%]. Univariate analysis revealed several risk factors including blastoid variant, leukemic presentation, high-risk MCL International Prognostic Index and high Ki-67 (proliferation marker). Multivariate analyses revealed that Ki-67 ≥ 30 was the only significant risk factor for CNS relapse (hazard ratio: 6.0, 95% CI 1.9-19.4, P = 0.003). Two-year cumulative incidence of CNS relapse in patients with Ki-67 ≥ 30 was 25.4% (95% CI 13.5-39.1), while that in the patients with Ki-67 < 30 was 1.6% (95% CI 0.4-4.2). None of the treatment modalities, including rituximab, high-dose cytarabine, high-dose methotrexate or consolidative autologous stem-cell transplant, were associated with a lower incidence of CNS relapse. Survival after CNS relapse was poor, with median survival time of 8.3 months. There was no significant difference in the survival by the site of CNS involvement.
Asunto(s)
Neoplasias del Sistema Nervioso Central/química , Antígeno Ki-67/análisis , Linfoma de Células del Manto/química , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias del Sistema Nervioso Central/mortalidad , Neoplasias del Sistema Nervioso Central/patología , Neoplasias del Sistema Nervioso Central/terapia , Femenino , Humanos , Incidencia , Japón/epidemiología , Estimación de Kaplan-Meier , Linfoma de Células del Manto/mortalidad , Linfoma de Células del Manto/patología , Linfoma de Células del Manto/terapia , Masculino , Persona de Mediana Edad , Análisis Multivariante , Valor Predictivo de las Pruebas , Recurrencia , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenAsunto(s)
Antieméticos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Morfolinas/uso terapéutico , Náusea/tratamiento farmacológico , Prednisolona/farmacocinética , Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Aprepitant , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Interacciones Farmacológicas , Humanos , Linfoma no Hodgkin/tratamiento farmacológico , Morfolinas/farmacología , Náusea/inducido químicamente , Prednisolona/administración & dosificación , Rituximab , Vincristina/administración & dosificaciónRESUMEN
BACKGROUND: Eltrombopag is an oral, non-peptide thrombopoietin receptor agonist that has shown efficacy and safety in chronic immune thrombocytopenia (ITP). However, ethnic differences in eltrombopag exposure have been reported: area under the curve exposure to eltrombopag was 87% greater among ITP patients of East Asian descent than among ITP patients of non-East Asian ITP descent. OBJECTIVES: To evaluate the efficacy and safety of eltrombopag by using, in Japanese ITP patients, lower starting (12.5 mg) and maximum (50 mg) doses of eltrombopag than the standard starting (50 mg) and maximum (75 mg) doses approved in the USA and Europe. PATIENTS: We examined 23 Japanese patients with previously treated chronic ITP with a platelet count of < 30,000 µL(-1) in a multicenter study comprising a randomized, double-blind, placebo-controlled phase for 6-week evaluation (15 eltrombopag, and eight placebo) and an open-label phase for 6-month evaluation (23 eltrombopag). RESULTS AND CONCLUSIONS: The response rate (platelet count of ≥ 50,000 µL(-1) ) at week 6 of the 6-week double-blind phase was 60% in eltrombopag-treated patients and 0% in placebo-treated patients. Ten of 23 patients (43.5%) responded for ≥ 75% of predefined assessment visits during the 6-month open-label phase. Notably, 22% (5/23) of patients responded to 12.5 mg of eltrombopag, which was administered within the first 3 weeks of eltrombopag treatment. Bleeding decreased with eltrombopag treatment as compared with baseline. Eltrombopag was generally well tolerated; one patient experienced a transient ischemic attack on day 9. Eltrombopag (12.5-50 mg) is effective for the management of Japanese patients with chronic ITP (NCT00540423).
Asunto(s)
Pueblo Asiatico , Benzoatos/administración & dosificación , Plaquetas/efectos de los fármacos , Fármacos Hematológicos/administración & dosificación , Hemorragia/prevención & control , Hidrazinas/administración & dosificación , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Pirazoles/administración & dosificación , Administración Oral , Adulto , Anciano , Benzoatos/efectos adversos , Benzoatos/farmacocinética , Plaquetas/inmunología , Plaquetas/metabolismo , Enfermedad Crónica , Método Doble Ciego , Femenino , Fármacos Hematológicos/efectos adversos , Fármacos Hematológicos/farmacocinética , Hemorragia/sangre , Hemorragia/etnología , Hemorragia/inmunología , Humanos , Hidrazinas/efectos adversos , Hidrazinas/farmacocinética , Japón/epidemiología , Masculino , Persona de Mediana Edad , Placebos , Recuento de Plaquetas , Púrpura Trombocitopénica Idiopática/sangre , Púrpura Trombocitopénica Idiopática/etnología , Púrpura Trombocitopénica Idiopática/inmunología , Pirazoles/efectos adversos , Pirazoles/farmacocinética , Receptores de Trombopoyetina/agonistas , Receptores de Trombopoyetina/sangre , Factores de Tiempo , Resultado del TratamientoAsunto(s)
Trasplante de Médula Ósea , Linfoma de Células T/terapia , Adulto , Antígenos CD/análisis , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Terapia Combinada , Humanos , Linfoma de Células T/tratamiento farmacológico , Linfoma de Células T/inmunología , Masculino , Trasplante HomólogoRESUMEN
The brains of extremely low-birth-weight infants with periventricular leukomalacia, who survived for more than 30 days, were examined by means of neuropathologic and immunohistochemical methods. The characteristic neuropathology of the brain is comprised of spongy changes with astrogliosis, a widespread distribution (i.e., in the deep to intermediate white matter), and a diffuse distribution of associated recent lesions. Also, these lesions, both remote and recent, are located in the frontal to occipital lobes. Regarding the correlation between the lesions and transneuronal connecting fibers, the lesions involved fibers of the motor, sensory, visual, and higher cerebral functions. This involvement may cause motor and intellectual disabilities. Furthermore, immunohistochemistry demonstrated nestin-positive astrocytes, and neurons increased around the lesions, suggesting the plasticity of the brains.
Asunto(s)
Encéfalo/patología , Recién Nacido de muy Bajo Peso , Leucomalacia Periventricular/patología , Proteínas del Tejido Nervioso , Plasticidad Neuronal , Factores de Edad , Encéfalo/metabolismo , Encéfalo/fisiopatología , Química Encefálica , Preescolar , Edad Gestacional , Proteína Ácida Fibrilar de la Glía/análisis , Humanos , Inmunohistoquímica , Lactante , Recién Nacido , Proteínas de Filamentos Intermediarios/análisis , Leucomalacia Periventricular/metabolismo , Leucomalacia Periventricular/fisiopatología , NestinaRESUMEN
Seventeen cases of acute promyelocytic leukemia (APL) treated with all-trans-retinoic acid (ATRA) and combination chemotherapy at Tokyo Metropolitan Komagome Hospital between 1992 and 1999 were reviewed, and divided into 2 karyotype-based cytogenetic groups. One group comprised 7 patients with either the typical t(15;17) alone or a normal karyotype, and the other group comprised 10 patients with additional karyotypic abnormalities. No patient had received prior chemotherapy or irradiation, and no cases were complicated by a history of myelodysplastic syndrome before the diagnosis of APL. There were no significant differences in clinical characteristics at disease presentation. Complete remission was achieved in all 17 patients and karyotypes of bone marrow cells normalized in all cases. No differences were found in relapse rate, overall survival, or disease-free survival between the 2 groups. The analysis did not reveal any significant effect of additional chromosomal abnormalities on the prognosis of APL patients undergoing treatment with ATRA. However, a small number of patients were assessed in this study, and further cumulative studies are needed.
Asunto(s)
Aberraciones Cromosómicas , Leucemia Promielocítica Aguda/tratamiento farmacológico , Tretinoina/administración & dosificación , Adolescente , Adulto , Anciano , Análisis Citogenético , Femenino , Humanos , Leucemia Promielocítica Aguda/diagnóstico , Leucemia Promielocítica Aguda/genética , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
A 29-year-old woman having acute myelogeneous leukemia-M1 subtype with the chromosomal abnormality t(16;21)(p11;q22) is presented. Complete blood count at onset showed a hemoglobin level of 7.2 g/dl, a platelet count of 48 x 10(9)/l, and a white blood cell count of 161.2 x 10(9)/l with 99% blasts and 1% lymphocytes. Bone marrow aspiration revealed massive proliferation of blasts that were positive for CD13, CD33, CD34, CD56 and myeloperoxidase, and negative for other T-cell, B-cell and monocytic markers. After achieving complete remission following conventional chemotherapy, she received an HLA-matched bone marrow transplantation (BMT) from her sibling after conditioning with busulfan, etoposide and cyclophosphamide. However, 9 months later, the leukemia relapsed as a painful extramedullary mass in her left femur. In spite of intensive re-induction chemotherapy, she died of progressive disease and sepsis. Although we could not detect the TLS/FUS-ERG fusion transcripts by reverse transcriptase-polymerase chain reaction in pre-BMT remission phase, they were clearly detectable in bone marrow cells obtained 6 months after transplantation with no translocation detected by conventional cytogenetics. We consider that even high-dose chemotherapy with BMT may not be effective in the eradication of this type of leukemia, and that the detection of minimal residual disease possibly contributes to the better planning of the therapeutic strategy.
Asunto(s)
Trasplante de Médula Ósea , Cromosomas Humanos Par 16 , Cromosomas Humanos Par 21 , Leucemia Mieloide Aguda/genética , Neoplasia Residual/diagnóstico , Translocación Genética , Adulto , Antígenos CD/análisis , Antígenos CD34/análisis , Antígenos de Diferenciación Mielomonocítica/análisis , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Médula Ósea/patología , Antígenos CD13/análisis , Antígeno CD56/análisis , Resultado Fatal , Femenino , Hemoglobinas/análisis , Humanos , Cariotipificación , Leucemia Mieloide Aguda/patología , Leucemia Mieloide Aguda/terapia , Recuento de Leucocitos , Neoplasia Residual/patología , Peroxidasa/análisis , Recuento de Plaquetas , Radioterapia , Recurrencia , Inducción de Remisión , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Lectina 3 Similar a Ig de Unión al Ácido Siálico , Trasplante Homólogo , Insuficiencia del TratamientoRESUMEN
Extremely low birth weight (ELBW) infants, who died at 12 hours to 7 days after birth, with periventricular leukomalacia (PVL), were examined by means of neuropathological and immunohistochemical methods. Fourteen infants without PVL were used as controls. Anti-beta-amyloid precursor protein (APP), glial fibrillary acidic protein (GFAP), and ionized calcium-binding adaptor molecule 1 (Iba1) antibodies were used as markers for axonal damage, reactive astrocytes and activated microglia, respectively. Thirteen of 14 ELBW infants with PVL showed a widespread distribution of leukomalacia and 10 showed postnatal-onset of leukomalacia. In 12 of the 14 infants with PVL, regions of APP-reactive axons were found multifocally in the cerebral white matter, but 8 of them did not show coagulation necrosis on HE staining. GFAP-positive cells and Iba1-positive cells were markedly found in the white matter of all cases with PVL and slightly in all 14 controls. These results indicated that in ELBW infants, the distribution and formation of PVL foci are widespread and characteristic and so may involve motor and intellectual abilities in ELBW infants. Therefore, the perinatal management to maintain an appropriate cerebral circulation and oxygenation may be very important.
Asunto(s)
Enfermedades del Prematuro/patología , Recién Nacido de muy Bajo Peso , Leucomalacia Periventricular/patología , Neuroglía/patología , Degeneración Retrógrada/patología , Axones/patología , Encéfalo/patología , Femenino , Edad Gestacional , Humanos , Técnicas para Inmunoenzimas , Recién Nacido , MasculinoRESUMEN
We describe the case of a 51-year-old patient with relapsed myelodysplastic syndrome after allogeneic bone marrow transplantation (BMT), who underwent allogeneic peripheral blood stem cell transplantation (PBSCT) after conditioning with a novel regimen consisting of fludarabine, busulfan, and antithymocyte globulin. The second PBSCT was performed early, at 3 months after the initial allogeneic BMT, but it was well tolerated and complete hematologic remission was documented. The patient did not experience any early transplantation-related organ toxicity but died from opportunistic infection 6 months after the second transplantation. Our experience suggests that this novel regimen may induce remission and could be offered to patients relapsing after the first transplantation; however, the fludarabine-containing regimen might be accompanied by profound immunosuppression.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas/métodos , Síndromes Mielodisplásicos/terapia , Acondicionamiento Pretrasplante/efectos adversos , Vidarabina/administración & dosificación , Antineoplásicos/administración & dosificación , Antineoplásicos/toxicidad , Trasplante de Médula Ósea , Resultado Fatal , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Infecciones/etiología , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/complicaciones , Recurrencia , Acondicionamiento Pretrasplante/métodos , Trasplante Homólogo/efectos adversos , Trasplante Homólogo/métodos , Vidarabina/análogos & derivados , Vidarabina/toxicidadRESUMEN
Of 264 patients aged 15 years or more who underwent hematopoietic stem cell transplantation between 1989 and September 1998 at the Tokyo Metropolitan Komagome Hospital, 47 were infected by the varicella-zoster virus (VZV). In 2 patients, visceral disease preceded cutaneous dissemination. One of these patients exhibited gastrointestinal symptoms followed by disseminated skin rash 6 days later. In the other patient, epigastralgia developed and was followed by seizures secondary to meningitis; the appearance of a skin rash 5 days after these initial symptoms yielded the diagnosis. Early diagnosis and treatment of VZV infection are important, especially for patients who present with visceral symptoms suspected to be due to VZV.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas/efectos adversos , Herpes Zóster/etiología , Aciclovir/uso terapéutico , Adulto , Antivirales/uso terapéutico , Femenino , Herpes Zóster/diagnóstico , Herpes Zóster/tratamiento farmacológico , Humanos , Masculino , Resultado del TratamientoRESUMEN
Isotope dilution using [U-13C]glucose was combined with measurement of hindquarters arteriovenous difference and blood flow to examine the effect of mild cold exposure on whole-body and net hindquarters glucose metabolism in sheep. Determinations were carried out in a thermoneutral environment (20 +/- 1 degrees C) and on day 5 of mild cold exposure (4 +/- 1 degrees C). Whole-body blood glucose turnover rate was 1.56 and 1.91 mg kg-1 min-1 in the thermoneutral environment and during mild cold exposure, respectively. Net hindquarters glucose uptake was 0.79 and 1.19 mg kg-1 min-1, corresponding to 50 and 61% of whole-body turnover rate, respectively. These results suggest that in sheep the contribution of glucose uptake by the hindquarters tended to increase during mild cold exposure, even though whole-body blood glucose turnover rate did not increase significantly.