RESUMEN
PURPOSE: The use of surgery versus stomach-preserving treatment for primary gastric lymphoma has caused controversy among doctors. This retrospective, single center study aims to evaluate the efficacy and benefit of stomach-preserving treatment against surgery for early stage diffuse large B-cell lymphoma of stomach. MATERIALS AND METHODS: From August 1991 to January 2006, 43 cases of early-stage diffuse large B-cell gastric lymphoma were reviewed. RESULTS: Eleven cases were treated with chemotherapy or chemotherapy plus radiation (CT +/- RT), 17 were treated with surgery alone (OP), and 15 were treated with surgery plus adjuvant chemotherapy (OP + CT). The complete remission and response rates were 63.6% and 90.9% in those treated with CT +/- RT (7 complete responders, 3 partial responders, 1 non-responder), 100% and 100% in those treated with OP, and 100% and 100% in those treated with OP + CT, respectively. Five-year overall survival rates were 85.7%, 87.5%, and 100% in those treated by CT +/- RT, OP, and OP + CT, respectively (p=0.76). The five-year disease free survival rates were 100%, 87.5% and 100% in those treated by CT +/- RT, OP, and OP + CT, respectively (p=0.99). There was no significant difference in overall survival and disease free survival between modalities. Even though there are no definite differences in the number of complications between those treated by CT +/- RT or OP, these facts reflect little concern on complications after surgery. CONCLUSION: In preventing morbidity arising from early or late complications from surgery and promoting quality of life, chemotherapy should be a primary consideration for early stage diffuse large B-cell lymphoma of the stomach.
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Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/cirugía , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/cirugía , Adolescente , Adulto , Anciano , Quimioterapia Adyuvante/métodos , Terapia Combinada , Femenino , Humanos , Linfoma de Células B Grandes Difuso/radioterapia , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Radioterapia/métodos , Estudios Retrospectivos , Neoplasias Gástricas/radioterapia , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
Hepatitis B virus (HBV) reactivation is the frequent complication after cytotoxic chemotherapy in HBsAg-positive non-Hodgkin's lymphoma (NHL) patients. Pre-chemotherapy viral load may be a risk factor and HBeAg-positive status is associated with increased viral load. The aim of this study was to investigate the long-term treatment outcome of lamivudine in preventing HBV reactivation and its associated morbidity according to HBeAg status. Twenty-four adult HBsAg-positive NHL patients were taken 100 mg of lamivudine daily before the initiation of chemotherapy. The median duration of lamivudine therapy was 11.5 months (range: 1-54 months) and the median number of chemotherapy cycles was 6 (range: 1-16 cycles). The steroid containing chemotherapy regimens were used in 18 patients (75%), and the anti-CD20 monoclonal antibody containing chemotherapy regimen was used in 6 patients (25%). Four patients received autologous peripheral blood stem cell transplantation without resultant HBV reactivation. Hepatitis related to HBV reactivation was developed in 1 patient among 14 HBeAg-positive patients and no one among 10 HBeAg-negative. One patient developed HBV reactivation after lamivudine withdrawal, and 4 patients developed the YMDD (tyrosine-methionine-aspartate-aspartate) mutation during lamivudine therapy. There were no statistical differences in HBV reactivation rate during chemotherapy according to the HBeAg status. Our results demonstrate that lamivudine should be considered preemptively before the chemotherapy for all HBsAg-positive NHL patients to prevent HBV reactivation, regardless of pre-chemotherapy HBeAg status. Finally, compared with the chronic hepatitis B patients, similar rate of HBV reactivation after lamivudine withdrawal and development of YMDD mutation was observed in NHL patients.
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Hepatitis B/prevención & control , Lamivudine/uso terapéutico , Linfoma no Hodgkin/complicaciones , Activación Viral/efectos de los fármacos , Adulto , Anciano , Esquema de Medicación , Femenino , Hepatitis B/complicaciones , Hepatitis B/virología , Anticuerpos contra la Hepatitis B/análisis , Virus de la Hepatitis B/efectos de los fármacos , Virus de la Hepatitis B/crecimiento & desarrollo , Virus de la Hepatitis B/inmunología , Humanos , Lamivudine/administración & dosificación , Lamivudine/efectos adversos , Hígado/efectos de los fármacos , Hígado/patología , Hígado/virología , Masculino , Persona de Mediana Edad , Inhibidores de la Transcriptasa Inversa/administración & dosificación , Inhibidores de la Transcriptasa Inversa/efectos adversos , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
Autologous stem cell transplantation (ASCT) is commonly used in relapsed or refractory non-Hodgkin's lymphoma (NHL). Several trials report the role of ASCT for high risk patients. We evaluated the results and the prognostic factors influencing the therapeutic effects on the patients who were treated with high dose chemotherapy (HDC) and autologous peripheral stem cell transplantation. We analyzed the data of 40 cases with NHL who underwent ASCT after HDC. Twenty- four patients had high-risk disease, 12 cases sensitive relapse, and two cases resistant relapse or primary refractory each. The median age of patients was 34 years (range, 14-58 years). The median follow-up duration from transplantation was 16 months (range, 0.6-94 months). Estimated overall survival and progression-free survival at 5 years were 40% and 30%, respectively. Poor prognostic factors for survival included older age (>/= 45 years), poor performance status in all patient analysis, and a longer interval between first complete remission and transplantation in high risk patients. In high risk NHL patients, transplantation should be done early after first complete remission to overcome chemo-resistance.
Asunto(s)
Linfoma no Hodgkin/terapia , Trasplante de Células Madre de Sangre Periférica , Adolescente , Adulto , Terapia Combinada , Femenino , Humanos , Recuento de Leucocitos , Linfoma no Hodgkin/diagnóstico , Linfoma no Hodgkin/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Recuento de Plaquetas , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia , Trasplante AutólogoRESUMEN
Primary hepatic lymphoma is a rare disorder representing less than 1% of all extranodal lymphomas. Histological examination of a primary hepatic lymphoma usually reveals a diffuse large B-cell lymphoma; there have been few reports of primary hepatic mucosa-associated lymphoid tissue (MALT) lymphomas. A 67-year-old man was being treated for a duodenal ulcer; while receiving therapy for the ulcer, a liver mass was incidentally found on abdominal ultrasonography. The pathologic diagnosis of the hepatic mass was an extranodal marginal zone B-cell lymphoma of MALT. The patient underwent radiotherapy with a total of 4,140 cGy delivered. The patient achieved complete remission and has been followed for 6 years with no recurrence of the disease. This report reviews the case of a primary hepatic extranodal marginal zone B-cell lymphoma of MALT successfully treated by radiotherapy alone.
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Neoplasias Hepáticas/radioterapia , Linfoma de Células B de la Zona Marginal/radioterapia , Anciano , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patología , Linfoma de Células B de la Zona Marginal/diagnóstico , Linfoma de Células B de la Zona Marginal/patología , MasculinoRESUMEN
Hodgkin's disease (HD) is a hematologic malignancy which shows common features regardless of race, but racial differences may be considered with certain clinical characteristics. HD in Korea shows somewhat different characteristics when compared to cases in Western countries. We evaluated the clinical and histopathologic characteristics of HD, the outcomes of various chemotherapy regimens, and prognostic factors of HD in Korea. One hundred and five patients with initial histopathologic diagnosis of Hodgkin's disease were retrospectively reviewed 20 years after diagnosis at Yonsei University College of Medicine. Nodular sclerosis was the most common histopathologic subtype (41%) and mixed cellularity was nearly as common (40%). The overall complete remission rate (CR) was 87.6%. The disease-free survival (DFS) and overall survival (OS) rate were 79.2% and 84.8% at 5-years, 70% and 79.2% at 10- and 20-years. There were no significant differences in CR rate and DFS, but OS rates were significantly higher in m-BACOP and ABVD regimen. Univariate analysis revealed that age, B-symptom, ECOG scale, Ann Arbor stage, international prognostic index, and serum beta2-microglobulin level were significant prognostic factors for both DFS and OS. Multivariate analysis demonstrated that age, B symptoms, and ECOG scale were significant prognostic factors for OS only. In conclusion, the survival rates of HD patients in our center were superior to those of previous reports in Korea and Western countries. Considering the higher OS rate and decreased incidence of side effects, the ABVD regimen may be recommended for the initial treatment of Hodgkin's disease.
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Antineoplásicos/farmacología , Enfermedad de Hodgkin/terapia , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Enfermedad de Hodgkin/mortalidad , Humanos , Corea (Geográfico) , Masculino , Persona de Mediana Edad , Pronóstico , Inducción de Remisión , Resultado del TratamientoRESUMEN
This study aimed to analyze the overall survival period of adult lymphoblastic lymphoma patients treated with various therapeutic regimens, and to assess the determinants affecting survival outcome. Twenty-five adult patients with lymphoblastic lymphoma who had been treated at Severance Hospital, Yonsei University College of Medicine, Seoul, Korea from June 1996 to June 2005 were analyzed retrospectively. As an initial remission induction chemotherapy, the hyper-CVAD regimen was performed in eight patients, the Stanford/Northern California Oncology Group (NCOG) regimen in five, the CAVOP regimen in four, the m-BACOP regimen in three, and the CHOP regimen in one patient. Patients were divided into two groups according to their therapeutic modalities. Twenty patients received conventional chemotherapy alone and five received subsequent PBSCT after conventional chemotherapy. Four patients of the PBSCT group underwent autologous PBSCT and one underwent allogeneic PBSCT. The overall response rate was 80% (60% showing a complete response, 20% showing a partial response) and the relapse rate was 73.3%. The overall survival (OS) rate was 55.1% at 1 year, 31.5% at 5 years, and 23.6% at 9 years. The disease-free survival (DFS) rate was 46.7% at 1 year and 30.0% at 7 years. The 5-year OS rate in relation to the regimens was 60% with the Stanford/NCOG regimen, 50% with the CAVOP regimen, and 33.3% with the m-BACOP regimen. The patients treated with the hyper-CVAD regimen had an 18.2% 2-year OS rate, and other patients with CHOP or COPBLAM-V expired early in their course. The OS rate in patients treated with conventional chemotherapy alone was 19.8%, whereas patients treated with subsequent PBSCT after chemotherapy showed 50% overall survival (p=0.25). The age at presentation influenced the outcome of the patients (p=0.01). The Stanford/NCOG regimen is an effective initial choice of therapy for lymphoblastic lymphoma patients, and is superior to the hyper-CVAD regimen in complete response rate and overall survival rate (p =0.36). Addition of PBSCT after chemotherapy may be needed for achieving optimal outcomes.
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Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adolescente , Adulto , Anciano , Antineoplásicos/farmacología , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Trasplante de Células Madre/métodos , Factores de Tiempo , Resultado del TratamientoRESUMEN
PURPOSE: To elucidate the clinical behavior and treatment outcome of low-grade primary orbital lymphoma arising from mucosa-associated lymphoid tissue (MALT). METHODS AND MATERIALS: Forty-eight patients with pathologically confirmed marginal zone B-cell lymphoma of MALT were treated with radiotherapy (RT). Thirty-eight patients (79.1%) received thorough staging workup studies including bone marrow biopsy. Radiation doses ranged from 5.4 to 30.6 Gy (median, 30.6 Gy). Median follow-up period was 70 months. RESULTS: Only 2 patients revealed extraorbital lymphoma involvement (bone marrow, skin). Forty-six of 52 eye lesions showed complete response to RT. Six lesions demonstrated a partial response and showed gradual regression during the follow-up period of 39-72 months. Three patients experienced local recurrences at 34, 48, and 52 months after RT, which seemed to be related to improper use of the lens shield. Salvage re-RT was successful. The 10-year actuarial relapse-free survival, cause-specific survival, and overall survival rates were 93.1%, 97.9%, and 86.9%, respectively. CONCLUSION: Most of the MALT lymphoma of the orbit was localized at diagnosis and extraorbital relapse rarely occurred. Therefore, extensive staging workup at the time of diagnosis and follow-up studies to detect distant relapse may not be obligatory. Low-dose RT alone with proper lens shielding is the optimum treatment modality for orbital MALT lymphoma.
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Linfoma de Células B de la Zona Marginal/radioterapia , Linfoma de Células B/radioterapia , Neoplasias Orbitales/radioterapia , Adulto , Anciano , Femenino , Humanos , Linfoma de Células B/mortalidad , Linfoma de Células B/patología , Linfoma de Células B de la Zona Marginal/mortalidad , Linfoma de Células B de la Zona Marginal/patología , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/mortalidad , Neoplasias Orbitales/mortalidad , Neoplasias Orbitales/patología , Traumatismos por Radiación , Dosificación Radioterapéutica , Inducción de Remisión , Resultado del TratamientoRESUMEN
Primary splenic lymphoma (PSL) is often defined as generalized lymphoma with splenic involvement as the dominant feature. It is a rare disease that comprises approximately 1% of all malignant lymphomas. We investigated three cases of non-Hodgkin's splenic lymphoma that had different clinical features on presentation. The patients' survival times from diagnosis ranged from 59 to 143 months, without evidence of relapse after splenectomy and chemotherapy, with or without radiotherapy. This data suggest that PSL is potentially curable. Further studies are needed to evaluate the impact that different treatment modalities without splenectomy have on patient survival.
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Linfoma de Células B/diagnóstico , Linfoma de Células B Grandes Difuso/diagnóstico , Neoplasias del Bazo/diagnóstico , Femenino , Humanos , Linfoma de Células B/patología , Linfoma de Células B/terapia , Linfoma de Células B Grandes Difuso/patología , Linfoma de Células B Grandes Difuso/terapia , Masculino , Persona de Mediana Edad , Esplenectomía , Neoplasias del Bazo/patología , Neoplasias del Bazo/terapiaRESUMEN
Advanced Hodgkin's disease is usually treated with six or more cycles of combination chemotherapy. Spontaneous regression of the cancer is very rarely reported in patients with Hodgkin's disease. We present an unusual case of a patient with Hodgkin's disease who experienced complete remission with a single cycle of chemotherapy, followed by pneumonia. The case was a 36-year-old man diagnosed with stage IVB mixed cellularity Hodgkin's disease in November 2000. After treatment with one cycle of COPP-ABV (cyclophosphamide, vincristine, procarbazine, prednisone, doxorubicin, bleomycin, and vinblastine) chemotherapy without bleomycin, the patient developed interstitial pneumonia and was cared in the intensive care unit (ICU) for two months. Follow-up chest computerized tomography (CT), performed during the course of ICU care, revealed markedly improved mediastinal lymphomatous lesions. Furthermore, follow-up whole body CT and 18-fluorodeoxyglucose positron emission tomography showed complete disappearance of the lymphomatous lesions. Four years later, the patient is well and without relapse. This report is followed by a short review of the literature on spontaneous regression of Hodgkin's disease. To the best of our knowledge, this is the first case report of spontaneous remission of Hodgkin's disease in Korea.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Bleomicina/administración & dosificación , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Enfermedad de Hodgkin/complicaciones , Enfermedad de Hodgkin/tratamiento farmacológico , Neumonía/complicaciones , Prednisona/administración & dosificación , Procarbazina/administración & dosificación , Vinblastina/administración & dosificación , Vincristina/administración & dosificación , Adulto , Humanos , Masculino , Remisión EspontáneaRESUMEN
Cyclin-dependent kinase inhibitor p27Kip1 functions at the nuclear level by binding to cyclin E/cyclin-dependent kinase-2. It was shown that Akt or protein kinase B (Akt/PKB)-dependent phosphorylation of p27Kip1 led to the cytoplasmic mislocalization of p27Kip1, suggesting the potential abrogation of its activity. Here, we evaluated the localization of p27Kip1 protein in leukemic blasts in relation to Akt/PKB phosphorylation and clinical outcomes in acute myelogenous leukemia (AML). Western blot analysis of the nuclear and cytoplasmic fractions revealed a heterogenous localization pattern of p27Kip1 in AML. Cytoplasmic mislocalization of p27Kip1 was significantly associated with the constitutive serine(473) Akt/PKB phosphorylation in AML cells (P < 0.05). Transfection of U937 cells with an expression construct encoding the constitutively active form of Akt/PKB resulted in a remarkable increase in the levels of cytoplasmic p27Kip1. Whereas the transfection of U937 cells with a construct encoding dominant-negative Akt/PKB resulted in a recovery of nuclear localization of p27Kip1. Both the disease-free survival and overall survival are significantly shorter in AML cases with high cytoplasmic to nuclear ratio of p27Kip1 localization compared with the cases with low cytoplasmic to nuclear ratio (P = 0.0353, P = 0.0023, respectively). Multivariate analysis indicated that the cytoplasmic to nuclear ratio of p27Kip1 localization was an independent prognostic variable for both disease-free survival and overall survival (P = 0.043, P = 0.008, respectively). These findings additionally extend our understanding of the role of p27Kip1 in AML, and buttress the case of p27Kip1 mislocalization as a prognostic indicator and Akt/PKB/p27Kip1 pathway as a ready target for antileukemia therapy.
Asunto(s)
Proteínas de Ciclo Celular/metabolismo , Citoplasma/metabolismo , Inhibidores Enzimáticos/metabolismo , Leucemia Mieloide/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Enfermedad Aguda , Adolescente , Adulto , Anciano , Biomarcadores de Tumor , Ciclo Celular , Núcleo Celular/metabolismo , Inhibidor p27 de las Quinasas Dependientes de la Ciclina , Femenino , Genes Dominantes , Genes Supresores de Tumor , Humanos , Leucemia Mieloide/patología , Leucemia Mieloide/terapia , Masculino , Persona de Mediana Edad , Fosforilación , Pronóstico , Transporte de Proteínas , Proteínas Tirosina Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt , Fracciones Subcelulares , Tasa de Supervivencia , Células U937RESUMEN
PURPOSE: The F-box protein S-phase kinase-associated protein 2 (Skp2) positively regulates the G(1)-S phase transition by controlling the stability of several G(1) regulators, such as p27Kip1. However, the clinical significance of Skp2 in patients with acute myelogenous leukemia (AML) remains unknown. EXPERIMENTAL DESIGN: We examined the clinical and biological significance of Skp2 expression in AML and evaluated the relationship between Skp2 and p27Kip1 expression and phosphatase and tensin homologue (PTEN) phosphorylation. RESULTS: Western blot analysis showed that high Skp2 expression was observed in 57 (57.6%) cases and significantly correlated with unfavorable cytogenetics (P = 0.035) but not with age, white blood cell count, serum lactic dehydrogenase level, and the French-American-British subtype. An inverse correlation was not observed between Skp2 and p27Kip1 expression. However, p27Kip1 protein was preferentially localized to cytoplasm in the high-Skp2-expression group. The cytoplasmic to nuclear ratio of p27Kip1 expression was significantly correlated with the levels of Skp2 expression (P < 0.001). The frequency of PTEN phosphorylation was significantly higher in the high-Skp2-expression group compared with the low- Skp2-expression group (P = 0.035). The Skp2 overexpression was significantly associated with shorter disease-free survival and overall survival (P = 0.0386 and P = 0.0369, respectively). Multivariate analysis showed that Skp2 expression was an independent prognostic factor both in the disease-free survival and overall survival. CONCLUSION: These findings suggest that Skp2 expression is an independent marker for a poor prognosis in AML. The presence of a positive correlation between Skp2 and phosphorylated PTEN suggests that an aberration in the PTEN/Skp2 signaling pathway might be operating in AML.
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Leucemia Mieloide Aguda/metabolismo , Monoéster Fosfórico Hidrolasas/metabolismo , Proteínas Quinasas Asociadas a Fase-S/biosíntesis , Adolescente , Adulto , Anciano , Western Blotting , Ciclo Celular , Proteínas de Ciclo Celular/metabolismo , Línea Celular Tumoral , Núcleo Celular/metabolismo , Inhibidor p27 de las Quinasas Dependientes de la Ciclina , Citogenética , Citoplasma/metabolismo , Femenino , Fase G1 , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Fosforilación , Pronóstico , Fase S , Transducción de Señal , Factores de Tiempo , Resultado del Tratamiento , Proteínas Supresoras de Tumor/metabolismoRESUMEN
Posttransplant lymphoproliferative disorder (PTLD) is a serious complication of organ transplantation. PTLD is the disorder arising from the combined effects of Epstein-Barr virus associated lymphoid proliferation with the disruption of the normal immune control by the cytotoxic T cells. The treatment for PTLD is one of the most controversial topics in solid organ transplantation. It is well known that the initial management of PTLD is a reduction of immunosuppression. Early diagnosis and the early reduction in immunosuppression are essential even for monomorphic lymphoma. We report here on a case of the complete resolution of PTLD (diffuse large B cell lymphoma) which occurred after a drastic reduction of immunosuppression in a renal transplant recipient.
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Rechazo de Injerto/tratamiento farmacológico , Inmunosupresores/administración & dosificación , Trasplante de Riñón , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Adulto , Humanos , Corea (Geográfico) , Linfoma de Células B Grandes Difuso/diagnóstico por imagen , Masculino , Inducción de Remisión , Tomografía Computarizada de Emisión , Tomografía Computarizada por Rayos XRESUMEN
Chronic graft-versus-host disease (GVHD) of the liver usually presents as an indolent cholestatic disease. We observed 3 patients in whom chronic GVHD of the liver after allogeneic nonmyeloablative hematopoietic stem cell transplantation (HSCT) presented with marked elevations of serum aminotransferases, clinically resembling acute viral hepatitis. The liver biopsies revealed predominant diffuse lobular injury and degenerative small bile ducts. Prompt administration of high-dose immunosuppressive therapy achieved a rapid improvement of liver enzymes and bilirubin levels. We conclude that a distinct syndrome of chronic hepatic GVHD presenting as an acute hepatitis should be considered as one possible explanation for hepatic dysfunction in patients who receive nonmyeloablative allogeneic HSCT.
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Enfermedad Injerto contra Huésped/diagnóstico , Hepatitis/diagnóstico , Hepatopatías/diagnóstico , Trasplante de Células Madre de Sangre Periférica/efectos adversos , Enfermedad Aguda , Adulto , Diagnóstico Diferencial , Hepatitis/etiología , Humanos , Inmunosupresores/uso terapéutico , Linfoma no Hodgkin/terapia , Masculino , Mieloma Múltiple/terapia , Mielofibrosis Primaria/terapia , Transaminasas/sangre , Trasplante HomólogoRESUMEN
BACKGROUND: The purpose of this study was to investigate the clinical relevance of subtypes categorized by immunophenotypic analysis in primary sinonasal lymphomas. METHODS: Eighty patients with localized non-Hodgkin's lymphoma involving the nasal cavity and/or paranasal sinuses were divided into three subtypes on the basis of their immunohistochemical findings: (A) B-cell lymphoma (n = 19), (B) T-cell lymphoma (n = 27), and (C) natural killer (NK)/T-cell lymphoma (n = 34). The clinicopathologic profiles, immunophenotypic data, patterns of treatment failure, and survival data among the three patient groups were retrospectively compared. RESULTS: The nasal cavity was the predominant site of involvement in T-cell and NK/T-cell lymphoma, whereas sinus involvement without nasal disease was common in B-cell lymphoma. Systemic B symptoms were frequently observed in NK/T-cell lymphoma. Almost all patients with NK/T-cell lymphoma showed a strong association with the Epstein-Barr virus by in situ hybridization studies. Sixty-five patients (81%) patients achieved complete remission after initial treatment, but 36 (55%) of these subsequently experienced treatment failure. Although there were no significant differences in locoregional failure rates among the patients of the three groups, distant failure was far more common in B-cell or NK/T-cell lymphoma than in T-cell lymphoma (p =.005). Most B-cell lymphoma cases showed a predilection for sites of systemic failure in the nodal and extranodal sites below the diaphragm, such as the paraaortic lymph nodes or the gastrointestinal (GI) tract, whereas patients with NK/T-cell lymphoma showed an increased risk of systemic dissemination to the skin, testes, or GI tract, including the development of hemophagocytic syndrome. The 5-year actuarial and disease-free survival rates for all patients were 57% and 51%, respectively. Of the three subtypes of primary sinonasal lymphomas, T-cell lymphoma seemed to carry the most favorable prognosis and NK/T-cell lymphoma the worst. (The 5-year actuarial survival rate was 57% for B-cell lymphoma, 80% for T-cell lymphoma, 37% for NK/T-cell lymphoma; p =.02, log-rank.) By univariate and multivariate analyses, immunophenotype was identified as the most important prognostic factor. CONCLUSIONS: Our data indicate that the three subtypes of primary sinonasal lymphomas classified by immunohistochemical studies exhibit different clinical profiles, different patterns of failure, and different treatment outcomes. Given these observations, it is concluded that the recognition of these distinct subsets, diagnosed on the basis of immunophenotypic study, is very important and clinically relevant in predicting their potential behavior and prognosis.
Asunto(s)
Inmunofenotipificación , Linfoma de Células B/metabolismo , Linfoma de Células T/metabolismo , Neoplasias de los Senos Paranasales/metabolismo , Adolescente , Adulto , Anciano , Antígenos CD20/metabolismo , Antígeno CD56/metabolismo , Femenino , Humanos , Células Asesinas Naturales , Linfoma de Células B/clasificación , Linfoma de Células B/mortalidad , Linfoma de Células B/terapia , Linfoma de Células T/clasificación , Linfoma de Células T/microbiología , Linfoma de Células T/mortalidad , Linfoma de Células T/terapia , Masculino , Persona de Mediana Edad , Neoplasias de los Senos Paranasales/clasificación , Neoplasias de los Senos Paranasales/mortalidad , Neoplasias de los Senos Paranasales/terapia , Pronóstico , Estudios Retrospectivos , Análisis de Supervivencia , Insuficiencia del TratamientoRESUMEN
Thirty patients with nasal natural killer (NK)/T-cell lymphoma, who underwent systemic chemotherapy with or without involved-field radiotherapy between 1993 and 1998, were retrospectively reviewed to determine the clinical significance of P-glycoprotein immunohistochemically identified in tumor specimens. Eighty percent of previously untreated patients expressed P-glycoprotein. According to P-glycoprotein immunoreactivity, all patients with nasal NK/T-cell lymphoma were divided into 2 groups; (a) P-glycoprotein-negative group (N = 6) and (b) P-glycoprotein-positive group (N = 24). There was no significant difference in clinical profiles between both groups. Regardless of the P-glycoprotein expressions, Epstein-Barr virus genomes were almost identically detected in patients of the 2 groups. Contrary to our expectations, however, P-glycoprotein expressions were not found to be a strong predictor of chemotherapy resistance. Although 2 (33%) of 6 P-glycoprotein-negative patients and 10 (42%) of the 24 P-glycoprotein-positive patients showed a favorable response to systemic chemotherapy, 4 (67%) of 6 P-glycoprotein-negative patients did not achieve complete response (CR) to chemotherapy, which led to an early death, whereas 4 (17%) of the 24 P-glycoprotein-positive patients achieved CR to chemotherapy despite positive P-glycoprotein immunoreactivity. Overall, there were no significant differences in either CR rate or the response rate of patients in the two groups. Overall 5-year actuarial survival and disease-free survival for all patients were 44% and 47%, respectively, but no differences in survival rates were observed between 2 groups. (5-year actuarial survival rate: 33% for the P-glycoprotein-negative, 50% for the P-glycoprotein-positive) (P = 0.7093, log-rank). On univariate and multivariate analyses, P-glycoprotein expressions by immunohistochemical study were not found to be an important prognostic factor. Given these observations, we conclude that the molecular mechanisms of resistance to chemotherapy in nasal NK/T-cell lymphoma patients are not entirely dependent on P-glycoprotein, and that other complex mechanisms of drug action and resistance may be likely to be involved.
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Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Resistencia a Antineoplásicos , Células Asesinas Naturales/patología , Linfoma de Células T/tratamiento farmacológico , Linfoma de Células T/metabolismo , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/inmunología , Adulto , Anciano , Femenino , Humanos , Inmunohistoquímica , Linfoma de Células T/mortalidad , Linfoma de Células T/patología , Masculino , Persona de Mediana Edad , Pronóstico , Tasa de SupervivenciaRESUMEN
We report an unusual case of acute myelogenous leukemia in a patient who showed an extramedullary relapse in her uterus, without bone marrow recurrence, two years after an allogeneic bone marrow transplant. She complained of irregular vaginal spotting, and magnetic resonance imaging demonstrated a uterine mass. A biopsy revealed a massive infiltration of immature myeloid cells. A variable number of tandem repeats (VNTR) based on an examination of peripheral blood cells showed full donor chimerism. After receiving chemotherapy, her uterine mass had completely resolved. She has remained in complete remission for more than 6 months. This case suggests that physicians should be aware of the possibility of a uterine relapse in female bone marrow transplant recipients with acute myelogenous leukemia.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas/efectos adversos , Leucemia Mieloide Aguda/patología , Leucemia Mieloide Aguda/terapia , Sarcoma Mieloide/patología , Neoplasias Uterinas/patología , Adulto , Femenino , Humanos , Recurrencia Local de Neoplasia , Sarcoma Mieloide/etiología , Neoplasias Uterinas/etiologíaRESUMEN
BACKGROUND: High doses of corticosteroids, and the use of alkylating agents like cyclophosphamide with subsequent hypogonadism, have been implicated in the pathogenesis of chemotherapy-induced osteoporosis. In this study, we evaluated whether intravenous pamidronate can prevent bone loss and reduce vertebral fractures in patients with malignant lymphoma who were receiving chemotherapy. METHODS: We enrolled 50 patients who had newly diagnosed stage III or IV malignant lymphoma. All patients were assigned randomly to receive either intravenous pamidronate or placebo. Pamidronate (30 mg per treatment) or placebo was given at 3-month intervals for 12 months. Five patients in the control group dropped out during the trial. The main outcomes were the incidence of vertebral fractures and changes in bone mineral density of the lumbar spine and proximal femur. RESULTS: During the 12-month study, 6 (30%) of the 20 patients in the control group and 1 (4%) of the 25 patients in the pamidronate group developed new vertebral fractures (P = 0.01). In the control group, the mean percentage changes in bone mineral density were -11.2% in the lumbar spine and -4.5% in the femoral neck. In contrast, pamidronate treatment led to minor losses of bone mineral density at both sites (-2.7% at the lumbar spine; -2.3% at the femoral neck). The difference between the groups was significant at the lumbar spine (P = 0.005). CONCLUSION: Pamidronate reduces trabecular bone loss and the risk of new vertebral fractures in patients with malignant lymphoma receiving chemotherapy.
Asunto(s)
Antiinflamatorios/uso terapéutico , Antineoplásicos/efectos adversos , Densidad Ósea/efectos de los fármacos , Difosfonatos/uso terapéutico , Linfoma/tratamiento farmacológico , Fracturas de la Columna Vertebral/prevención & control , Femenino , Humanos , Linfoma/patología , Masculino , Persona de Mediana Edad , Pamidronato , Fracturas de la Columna Vertebral/inducido químicamenteRESUMEN
Apicidin, a histone deacetylase inhibitor, is a novel cyclic tetrapeptide with potent antiproliferative activity against various cancer cells. We examined whether apicidin potentiates the imatinib-induced apoptosis of Bcr-Abl-positive human leukaemia cells. In K562 cells, the co-administration of minimally toxic concentrations of imatinib and apicidin (imatinib/apicidin) for 48 h produced a marked increase in mitochondrial damage, processing of caspase cascades and apoptosis. Similar results were observed in leukaemic blasts obtained from patients with chronic myeloid leukaemia in blast crisis. Imatinib/apicidin co-treatment for 48 h resulted in a near complete loss of the full-length XIAP (X-linked inhibitor of apoptosis) protein, with a corresponding increase in the 29-kDa XIAP cleavage product. Both the degradation of XIAP and increased release of second mitochondria-derived activator of caspase/direct IAP-binding protein with low pI (Smac/DIABLO) into the cytosol were abrogated by pretreatment with the caspase-3 inhibitor DEVD-CHO. Imatinib/apicidin co-treatment for 48 h produced a prominent decrease in Bcr-Abl protein levels in a caspase-dependent manner. In summary, these data indicate that apicidin potentiates the imatinib-induced apoptosis of Bcr-Abl-positive leukaemia cells through the enhanced activation of the mitochondria-dependent caspase cascades, accompanied by caspase-dependent downregulation of Bcr-Abl and XIAP. These findings generate a rationale for further investigation of apicidin and imatinib as a potential therapeutic strategy in Bcr-Abl-positive leukaemias.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Caspasas/metabolismo , Inhibidores Enzimáticos/uso terapéutico , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Péptidos Cíclicos/administración & dosificación , Piperazinas/administración & dosificación , Pirimidinas/administración & dosificación , Apoptosis/efectos de los fármacos , Benzamidas , Western Blotting , Sinergismo Farmacológico , Genes abl , Inhibidores de Histona Desacetilasas , Humanos , Mesilato de Imatinib , Células K562 , Leucemia Mielógena Crónica BCR-ABL Positiva/enzimología , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Mitocondrias/enzimologíaRESUMEN
Low grade lymphomas are malignancies of predominantly small lymphocytes that typically have long median survival periods due to low proliferative rates. It is considered an indolent disease, but patients with low grade lymphoma can almost never be cured with conventional treatment. New low- grade lymphoma entities have been classified by the International Lymphoma Study Group (ILSG) and are also categorized into the Revised European American Lymphoma (REAL) classification. The REAL classification utilizes a multiparameter definition of clinico-pathologic and biologic entities. According to this classification, we investigated the incidence, various clinical characteristics, treatment outcome and prognostic factors of low grade lymphoma. Many clinical characteristics of low grade lymphoma in Korea differed from those of Western countries, especially in the incidence, therapeutic outcome and prognostic factors. In Korea, although the general incidence of low grade lymphoma is relatively low, the relative number of mucosa-associated lymphoid tissue lymphoma (MALToma) is very high, and the overall survival rate is better than that reported of Western countries. Thus, further investigation on treatment outcome and prognosis of low grade lymphoma entities, other than mucosa- associated lymphoid tissue lymphoma, are warranted.
Asunto(s)
Linfoma no Hodgkin/terapia , Adolescente , Adulto , Anciano , Femenino , Humanos , Inmunofenotipificación , Linfoma no Hodgkin/mortalidad , Linfoma no Hodgkin/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Resultado del TratamientoRESUMEN
The accurate staging of Hodgkin's disease (HD) and non- Hodgkin's lymphoma (NHL) is an important aspect of treatment. In this study, the authors undertook to prospectively evaluate the clinical value of 2-(fluorine-18)fluoro-2-deoxy-D- glucose position emission tomography (FDG-PET) for the staging of malignant lymphoma as compared with computed tomography and 67Ga scan. Thirty consecutive cases with biopsy-proven lymphoma (4 HD, 26 NHL) were examined by FDG-PET for the initial staging and the restaging work-up between September 2000 and April 2001. The FDG-PET and conventional study, including a CT of the neck, chest, abdomen, and of the pelvis, a bone scan, a 67Ga scan, and a bone marrow study were undertaken to investigate nodal/extranodal manifestations and bone marrow infiltration. In terms of the detection of nodal lymphoma manifestation, the sensitivities and specificities of the PET, CT, and 67Ga scan were determined to be 93.3%, 98.9%, and 25.8%, and 100%, 99.1%, and 99.8%, respectively. In terms of the detection of extranodal lymphoma manifestation, the sensitivities and specificities of the PET, CT, and 67Ga scan were 87.5%, 87.5%, and 37.5%, and 100%, 100%, and 100%, respectively. The FDG-PET proved to be very accurate for the staging of malignant lymphoma and superior to Ga-67 scan. Although the results of PET and CT were substantially comparable, both imaging studies were found to complement each other in some cases with respect to the evaluation of lymphomatous involvement.