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Circulating tumor DNA (ctDNA) carries tumor-specific genetic and epigenetic variations. To identify extranodal natural killer/T cell lymphoma (ENKTL)-specific methylation markers and establish a diagnostic and prognosis prediction model for ENKTL, we describe the ENKTL-specific ctDNA methylation patterns by analyzing the methylation profiles of ENKTL plasma samples. We construct a diagnostic prediction model based on ctDNA methylation markers with both high specificity and sensitivity and close relevance to tumor staging and therapeutic response. Subsequently, we built a prognostic prediction model showing excellent performance, and its predictive accuracy is significantly better than the Ann Arbor staging and prognostic index of natural killer lymphoma (PINK) risk system. Notably, we further establish a PINK-C risk grading system to select individualized treatment for patients with different prognostic risks. In conclusion, these results suggest that ctDNA methylation markers are of great value in diagnosis, monitoring, and prognosis, which might have implications for clinical decision-making of patients with ENKTL.
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ADN Tumoral Circulante , Linfoma Extranodal de Células NK-T , Humanos , Pronóstico , ADN Tumoral Circulante/uso terapéutico , Linfoma Extranodal de Células NK-T/diagnóstico , Linfoma Extranodal de Células NK-T/patología , Linfoma Extranodal de Células NK-T/terapia , Metilación , Estudios Retrospectivos , Células Asesinas NaturalesRESUMEN
BACKGROUND: Academic studies have proved that anti-programmed death-1 (PD-1) monoclonal antibodies demonstrated remarkable activity in relapsed/refractory classical Hodgkin lymphoma (cHL). However, most patients ultimately experienced failure or resistance. It is urgent and necessary to develop a novel strategy for relapsed/refractory cHL. The aim of this case report is to evaluate the combination approach of low-dose decitabine plus a PD-1 inhibitor in relapsed/ refractory cHL patients with prior PD-1 inhibitor exposure. CASE SUMMARY: The patient was a 27-year-old man who complained of enlarged right-sided cervical lymph nodes and progressive pain aggravation of the right shoulder over the past 3 mo before admission. Histological analysis of lymph node biopsy was suggestive of cHL. The patient experienced failure of eight lines of therapy, including multiple cycles of chemotherapy, PD-1 blockade, and anti-CD47 antibody therapy. Contrast-enhanced CT showed that the tumors of the chest and abdomen significantly shrunk or disappeared after three cycles of treatment with decitabine plus tislelizumab. The patient had been followed for 11.5 mo until March 2, 2021, and no progressive enlargement of the tumor was observed. CONCLUSION: The strategy of combining low-dose decitabine with tislelizumab could reverse the resistance to PD-1 inhibitors in patients with heavily pretreated relapsed/ refractory cHL. The therapeutic effect of this strategy needs to be further assessed.
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Interstitial pneumonia (IP) is a lethal complication in lymphoma patients undergoing chemotherapy. A total of 2212 consecutive patients diagnosed with lymphoma between 2009 and 2014 were enrolled in the present study. IP was defined as diffuse pulmonary interstitial infiltrate found on computed tomography scans. IP was observed in 106 patients. Of these, 23 patients were excluded from the study. Finally, 83 patients with IP were included in this study. The incidence of IP was 3.9% (7/287) in Hodgkin lymphoma and 2.4% (76/1925) in non-Hodgkin lymphoma (P = 0.210). The median number of chemotherapy cycles before IP was 3. The median time from the cessation of chemotherapy to IP was 17 days. Eighty-two (98.8%) patients recovered after the treatment with glucocorticoids. Sixty-six (79.5%) patients had a delay in chemotherapy, and 14 (16.9%) patients had premature termination of chemotherapy. Sixty-nine patients were re-treated with chemotherapy after remission from IP, of which 22 (31.9%) experienced IP recurrence. The incidence of IP recurrence was significantly higher in patients re-treated with a similar regimen than in those re-treated with an alternative regimen (65.4 vs. 11.6%, P < 0.001). In a multivariate Cox regression analysis, B symptoms and a history of drug allergies were identified as risk factors for IP. In conclusion, IP is a life-threatening complication in lymphoma patients. Glucocorticoid therapy with continuous monitoring of chest radiographic changes may be a favourable strategy for treating IP. However, IP may recur, especially in patients re-treated with a similar chemotherapy regimen.
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Enfermedades Pulmonares Intersticiales/diagnóstico , Enfermedades Pulmonares Intersticiales/epidemiología , Linfoma/diagnóstico , Linfoma/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Femenino , Humanos , Incidencia , Enfermedades Pulmonares Intersticiales/complicaciones , Linfoma/complicaciones , Linfoma/terapia , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Análisis de Supervivencia , Resultado del Tratamiento , Adulto JovenRESUMEN
This study was purposed to investigate the expression of latent membrane protein 1 (LMP-1) and CD68 in Hodgkin's lymphoma (HL) patients with EB virus infection and to analyze the relation of LMP-1 expression and CD68(+) tumor-associated macrophage count with clinical features and prognosis of HL patients. The expression of LMP1 and count of CD68(+) TAM were detected by immunohistochemical staining in tissue specimens of 72 HL patients; their correlation with clinical features and prognosis of HL patients was analyzed by using statistical method. The results showed that among tissue specimens of 72 HL patients, the positive rate of LMP-1 expression was 18.1% (13/72), the CD68(+) TAM count was more higher in LMP-1 positive expression [250 of CD68(+) TAM/high power field (hpf) is used as demarcation point] (P = 0.003). The statistical analysis showed that the LMP-1 positive expression was more observed in mixed type HL patients (P = 0.000); the positive rate of LMP-1 expression was much high in HL patients with albumin <40 g/L and age ≥ 45 years (P < 0.05). There was no relation of LMP-1 expression and CD68(+) TAM count with the short term therapeutic efficacy of HL patients, but the overall survival time of LMP-1 positive patients among patients followed-up for ≥ 5 years was short (P < 0.05). Moveover, no correlation of CD68(+) TAM count with the overall survival time of HL patients was found. It is concluded that the high count of CD68(+) TAM is more observed in LMP-1 positive expression of HL tissue, the LMP-1 expression states relates both with the pathological types, age and albumin level of patient with HL. The HL patients with LMP-1 positive expression have poor prognosis, suggesting that LMP-1 may be a new prognostic marker for HL patients.
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Antígenos CD/metabolismo , Antígenos de Diferenciación Mielomonocítica/metabolismo , Infecciones por Virus de Epstein-Barr , Enfermedad de Hodgkin/diagnóstico , Enfermedad de Hodgkin/virología , Proteínas de la Matriz Viral/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/metabolismo , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Adulto JovenAsunto(s)
Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Purgación de la Médula Ósea , Linfoma de Células B/terapia , Trasplante de Células Madre de Sangre Periférica , Adolescente , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Rituximab , Trasplante Autólogo , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVE: To explore the clinical characteristics and prognosis of patients with primary testicular non-Hodgkin's lymphoma. METHODS: The clinical profiles and prognostic factors of 21 cases newly diagnosed as primary testicular non-Hodgkin's lymphoma at Peking University Cancer Hospital from January 2005 to December 2012 were retrospectively analyzed. RESULTS: Their median age was 59 (34-86) years. And they were classified as Ann Arbor stage I (n = 8), stage II (n = 2) and stage IV (n = 11). There were B symptoms (n = 4), extranodal involvement outside testis (n = 12) and elevated lactate dehydrogenase (LDH) at diagnosis (n = 6). The scores of international prognostic index (IPI) were 0-1 point (n = 10), 3 points (n = 10) and 4 points (n = 1). The regimens included orchidectomy as the initial treatment (n = 15), chemotherapy followed by radiotherapy (n = 7) and CNS prophylaxis during treatment (n = 15). All patients were pathologically diagnosed as diffuse large B-cell lymphoma. And 11 cases belonged to the non-germinal center B cell-like subgroup.First-line chemotherapy was either R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone) or CHOP-like-based regimen. Complete response was achieved in 85.7% of patients. The median follow-up period was 18 (6-58) months. The 1, 2 and 3-year survival rates were 100%, 80% and 60% respectively. Statistical analysis showed that the first-line chemotherapy with rituximab was a prognostic factor (P = 0.038).Other factors included stage (P = 0.275), LDH level (P = 0.179) , ß2-microglobulin level (P = 0.229) and IPI (P = 0.275) . CONCLUSIONS: The prognosis of primary testicular non-Hodgkin's lymphoma is usually poor. The first-line chemotherapy with rituximab is a prognostic factor.
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Linfoma no Hodgkin/tratamiento farmacológico , Neoplasias Testiculares/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Inducción de Remisión , Estudios Retrospectivos , Neoplasias Testiculares/diagnósticoRESUMEN
OBJECTIVE: To explore the clinical characteristics and prognosis of patients with angioimmunoblastic T cell lymphoma (AITL). METHODS: The clinical features and prognostic factors of 42 cases newly diagnosed as AITL at Peking University Cancer Hospital from January 2007 to August 2012 were retrospectively analyzed. RESULTS: Their median age was 59(34-76) years. Among them, 97.6% cases (41/42) belonged to Ann Arbor stage III/IV, 73.8% (31/42) cases presented with B symptoms, 85.7% (36/42)cases had painless lymphadenopathy, 52.4% (22/42)cases extranodal involvement, 64.3% (27/42) cases elevated lactate dehydrogenase and 45.2% (19/42) cases elevated ß2-microglobulin at diagnosis. And 40.5% (17/42) cases had 3 points of international prognostic index (IPI) score with the highest proportion.First-line chemotherapy was predominantly CHOP (cyclophosphamide, vincristine, doxorubicin, prednisolone) or CHOP-like-based and complete response was achieved in 44.7% (17/38) of them. The median follow-up time was 40 (2-106) months The 1, 2, 5-year survival rates were 78%, 57% and 39% respectively.Statistical analysis showed that IPI was an independent prognostic factor (P = 0.009).Other factors included gender (P = 0.311), age (P = 0.263), with or without B symptoms (P = 0.102), Ki-67 index (P = 0.146) as well as the choice of first-line chemotherapy (P = 0.292) each had a tendency of affecting; the survival rate, but failed to reach statistical significance. CONCLUSIONS: Angioimmunoblastic T-cell lymphoma is a major type of peripheral T-cell lymphoma. Most AITL patients are elders with a late stage. The disease generally displays an aggressive clinical course and poor prognosis.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma de Células T/diagnóstico , Linfoma de Células T/tratamiento farmacológico , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios RetrospectivosRESUMEN
Mantle cell lymphoma(MCL), a special type of non-Hodgkin's lymphoma, is incurable through conventional treatment. This study aimed to analyze the clinical features, therapeutic responses, and prognosis of patients with MCL. Clinical data of 30 patients with MCL treated in our hospital between April 2006 and July 2011 were analyzed. Eighteen patients were treated with CHOP plus rituximab (R-CHOP) regimen, 12 underwent conventional chemotherapy. The median age of the 30 patients was 58 years, 23 were men, all patients had Cyclin D1 overexpression, 29 (96.7%) had advanced disease, 11 (36.7%) had bone marrow involvement, 9 (30.0%) had gastrointestinal involvement, and 15 (50.0%) had splenomegaly. The complete response(CR) rate and overall response rate(ORR) were significantly higher in patients undergoing R-CHOP immunochemotherapy than in those undergoing conventional chemotherapy (38.9% vs. 16.7%, P = 0.187; 72.2% vs. 41.4%, P = 0.098). The difference of 2-year overall survival rate between the two groups was not significant (P = 0.807) due to the short follow-up time. The 2-year progression-free survival (PFS) rate was higher in R-CHOP group than in conventional chemotherapy group (53% vs. 25%, P = 0.083), and was higher in patients with a lower mantle cell lymphoma international prognostic index (MIPI) (51% for MIPI 0-3, 33% for MIPI 4-5, and 0% for MIPI 6-11, P = 0.059). Most patients with MCL were elderly; in an advanced stage; showed a male predominance; and usually had bone marrow involvement, gastrointestinal involvement, or splenomegaly. R-CHOP regimen could improve the CR rate and ORR of MCL patients. MIPI can be a new prognostic index for predicting the prognosis of advanced MCL.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma de Células del Manto/tratamiento farmacológico , Linfoma de Células del Manto/patología , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Ciclina D1/metabolismo , Ciclofosfamida/uso terapéutico , Supervivencia sin Enfermedad , Doxorrubicina/uso terapéutico , Etopósido/uso terapéutico , Femenino , Estudios de Seguimiento , Humanos , Linfoma de Células del Manto/metabolismo , Linfoma de Células del Manto/terapia , Masculino , Persona de Mediana Edad , Prednisona/uso terapéutico , Inducción de Remisión , Rituximab , Trasplante de Células Madre , Tasa de Supervivencia , Vincristina/uso terapéuticoRESUMEN
OBJECTIVE: To evaluate the prognostic value of maximum standard uptake (SUVmax) on pretreatment (18)F-fluoro-2-deoxyglucose ((18)F-FDG) positron emission tomography/computed tomography (PET/CT) scan in patients with newly diagnosed diffuse large B cell lymphoma (DLBCL). METHODS: The clinical data of 39 DLBCL patients undergoing a PET/CT scan at pre-treatment from December 2009 to October 2011 were analyzed retrospectively. SUVmax on PET/CT was evaluated by SPSS 13.0 for the associations with patient characteristics, prognostic factors, treatment efficacy and survival time. RESULTS: The median SUVmax was higher in non-germinal center B cell-like (non-GCB) patients than that in GCB ones (18.0(2.2 - 40.5) vs 11.6 (5.3 - 18.7), P = 0.039). No difference of SUVmax was observed between the patients with and without bulky disease (P = 0.539). SUVmax was not associated with such patient characteristics as international protein index, age, stage, Eastern Cooperative Oncology Group performance status, lactate dehydrogenase, number of extranodal involvement and Ki-67 (all P > 0.05). No significant difference in median SUVmax existed between complete remission (CR) and non-CR patients (P = 0.312). The difference of SUVmax was insignificant for the patients with efficacy and no efficacy (P = 0.243). With the cut-off values of 10, 15, 20, the CR rate, response rate, 2-year progression-free survival (PFS) rate and 2-year overall survival (OS) rate were not different between the patients with SUVmax below and above cut-off value (all P > 0.05). CONCLUSIONS: The prognostic value of SUVmax on PET/CT is indeterminate. And it can not be used to predict the patient prognosis.
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Fluorodesoxiglucosa F18/administración & dosificación , Linfoma de Células B Grandes Difuso/diagnóstico por imagen , Tomografía de Emisión de Positrones/métodos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Tomografía de Emisión de Positrones/normas , Pronóstico , Estudios RetrospectivosRESUMEN
OBJECTIVE: To analyze the safety and adverse event profiling of pegylated L-asparaginase (PEG-asp) combined chemotherapy in the treatment of lymphoma patients. METHODS: The clinical data of 32 lymphoma patients on PEG-asp-based chemotherapy from January 2008 to March 2012 were retrospectively collected and analyzed. RESULTS: There were 22 males and 10 females with a median age of 40 years. They were diagnosed as NK/T cell lymphoma (n = 22) and lymphoblastic lymphoma (n = 10). The overall response rate was 71.9% (23/32). And complete remission was 40.6% (13/32) and partial remission 31.3% (10/32). Myelosuppression was the most common adverse event at an incidence of 81.2% (26/32). Other adverse events included a low level of fibrinogen (n = 13, 40.6%), hypoalbuminemia (n = 8, 25%) and hyperlipidemia (n = 9, 28.1%). No instance of anaphylaxis, acute pancreatitis and thrombosis occurred. CONCLUSION: PEG-asp is both effective and safe in the treatment of lymphoma and it is well-tolerated.
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Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Asparaginasa/efectos adversos , Linfoma/tratamiento farmacológico , Adolescente , Adulto , Asparaginasa/administración & dosificación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVE: To evaluate the value of (18)F-FDG PET/CT in detecting residual disease and predicting relapse following first-line treatment in patients with diffuse large B cell lymphoma (DLBCL). METHODS: The clinical data of 39 patients with DLBCL, who underwent PET/CT scan after first-line treatment, were analyzed retrospectively. Kaplan-Meier method was used to analyze the survival of patients. RESULTS: PET/CT findings were interpreted as negative, mild metabolism and positive. Seventeen patients' PET/CT findings were judged as negative, none of them relapsed with a median follow-up of 24.1 months, 13 were judged as mild metabolism, 2 of them relapsed with a median follow-up of 17.1 months. Of the rest 9 findings were judged as positive with a median follow-up of 16.3 months, 4 patients were considered as disease progression according to clinical manifestations and other radiographic results, 2 patients relapsed at the time points of 13.5 and 6.8 months after PET/CT scan respectively, the other 3 patients were diagnosed as negative by biopsy, none of them relapsed at the time points of 5.9, 9.6 and 20.0 months after PET/CT scan respectively. One-year progression-free-survival (PFS) for negative, mild metabolism and positive groups was 100%, 83% and 56%, respectively. Two-year PFS was 100%, 83% and 42%, respectively. Overall survival (OS) at 1 year for negative, mild metabolism and positive groups was 100%, 100% and 89%, respectively. Two-year OS was 100%, 100% and 63%, respectively (P = 0.004). CONCLUSION: DLBCL patients with negative and mild metabolism PET/CT following first-line treatment had good prognosis, who needed no additional therapy. While patients with positive PET/CT had poor prognosis, those patients should receive biopsy before adjusting treatment regimen because of the high false-positive rate.
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Fluorodesoxiglucosa F18 , Linfoma de Células B Grandes Difuso/diagnóstico por imagen , Linfoma de Células B Grandes Difuso/terapia , Tomografía de Emisión de Positrones/métodos , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
The objective of this study was to detect the expression levels of VEGF-C, VEGF-D, VEGFR-2 and VEGFR-3 in plasma of newly diagnosed lymphoma patients, and analyze their possible relationships with clinicopathological characteristics and prognosis. The expression levels of VEGF-C, VEGF-D, VEGFR-2 and VEGFR-3 in plasma from 86 newly diagnosed lymphoma patients were detected by enzyme-linked immunosorbent assay (ELISA). As a results, the multivariate analysis showed that VEGF-C level in non-Hodgkin's lymphoma patients was low, but high in Hodgkin's lymphoma patients; VEGFR-2 level was higher in patients > 60 years, while VEGF-D level was lower in patients with IPI > 2. The univariate analysis showed that VEGF-D level was lower in patients with IPI > 2, while VEGF-D and VEGF-C levels were higher in patients without B symptoms. Relationship analysis between these factors indicated that the relation of VEGF-D expression level with VEGFR-2 and VEGFR-3 was positive. It is concluded that VEGF-C, VEGF-D, VEGFR-2 and VEGFR-3 play important roles in the pathogenesis of lymphoma, and may be used as indicators of prognosis evaluation or even guide for the antiangiogenesis treatment of lymphoma.
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Linfoma/sangre , Linfoma/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Linfoma/diagnóstico , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Factor C de Crecimiento Endotelial Vascular/sangre , Factor D de Crecimiento Endotelial Vascular/sangre , Receptor 2 de Factores de Crecimiento Endotelial Vascular/sangre , Receptor 3 de Factores de Crecimiento Endotelial Vascular/sangre , Adulto JovenRESUMEN
OBJECTIVE: To explore the clinical features, diagnosis, treatment and prognosis of central nervous system lymphoma (CNSL). METHODS: Retrospective analysis was conducted for 31 CNSL cases from January 2007 to December 2009 in our hospital. Their clinical data were analyzed by statistical software package SPSS 16.0. RESULTS: Accounting for around 4.7% of all lymphomas at our institution, the present cohort had 21 males and 10 females with a median age of 38 years old. The major clinical manifestations were focal neurological deficits associated with the site of disease or increased intracranial pressure. Most patients were treated with chemotherapy-based regimens. The overall response rate was 67.7% (21/31) with 32.3% (10/31) complete remission rate (CR) and 35.5% (11/31) partial remission rate (PR). Involvement outside CNS or bone marrow, high international prognostic index (IPI) and B symptoms had significant effects on the therapeutic efficacy (P < 0.05). The overall survival rates were 80.7%, 74.2%, 64.5% and 58.1% at 3, 6, 12, 24 months respectively. The median survival time was 22.5 months. Univariate analysis showed that the clinical efficacy had significant effects on the overall survival of patients (OR = 0.030, 95%CI: 0.003 - 0.270, P = 0.000). CONCLUSION: The prognosis of CNSL remains poor. New diagnostic tools and treatment modality need to be explored.
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Neoplasias del Sistema Nervioso Central/diagnóstico , Neoplasias del Sistema Nervioso Central/terapia , Linfoma/diagnóstico , Linfoma/terapia , Adolescente , Adulto , Anciano , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Adulto JovenRESUMEN
OBJECTIVE: To analyze the status of hepatitis B virus (HBV) infection in non-Hodgkin lymphoma (NHL) patients. METHODS: The serum HBV markers in NHL patients were detected by enzyme-linked immunosorbent assay (ELISA). The infection rate of HBV in NHL patients was compared with that in nationwide general population. RESULTS: The positive rates of HBsAg, anti-HBs and anti-HBc in 405 cases of NHL were 11.6%, 39.8% and 47.9%, respectively, which were statistically different from those in general population (P < 0.01). The positive rates of HBsAg, anti-HBs and anti-HBc in B-cell NHL and T-cell NHL were 13.3% vs 7.1% (P = 0.083), 40.6% vs 37.5% (P = 0.567), 53.2% vs 33.9% (P = 0. 001), respectively. The HBV DNA positive rate was 23.7% in 93 cases of NHL, and was 50.0% in 38 cases of HBsAg-positive NHL while 5.5% in 55 cases of HBsAg-negative but HBcAb-positive NHL. CONCLUSIONS: The infection rate of HBV in NHL patients is higher than that in general population, in which occult hepatitis B virus infection can not be ignored. The positive rate of anti-HBc in B-cell NHL is significantly higher than that in T-cell NHL. For NHL patients infected with HBV, prophylactic anti-HBV therapy to prevent viral reactivation should be given before the anti-cancer treatment. Further study in the relationship between HBV and NHL should be carried out in the future.
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Hepatitis B/epidemiología , Linfoma no Hodgkin/virología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , ADN Viral/sangre , Femenino , Anticuerpos contra la Hepatitis B/sangre , Antígenos de Superficie de la Hepatitis B/sangre , Virus de la Hepatitis B/aislamiento & purificación , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto JovenAsunto(s)
Anemia/tratamiento farmacológico , Eritropoyetina/uso terapéutico , Leucemia Linfocítica Crónica de Células B/complicaciones , Linfoma no Hodgkin/complicaciones , Mieloma Múltiple/complicaciones , Adolescente , Adulto , Anciano , Ensayo de Inmunoadsorción Enzimática , Eritropoyetina/sangre , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: To study whether hematologic malignancy patients with anemia have a lower erythropoietin (EPO) response. METHODS: Serum EPO levels were detected by ELISA in patients with hematologic malignancies and with iron deficiency anemia (IDA). Eighty patients with hematologic malignancies, including 13 multiple myeloma (MM), 7 chronic lymphocytic leukemia (CLL) and 60 non-Hodgkin's lymphoma (NHL) were studied. Thirty of them had anemia(21 NHL,6 MM and 3 CLL). Twenty patients with IDA were studied as the control. RESULTS: Hematologic malignancy patients with anemia had higher EPO levels [(97.8 +/- 183.9) IU/L] than those with normal Hb values [(27.8 +/- 85.4) IU/L; P <0.01]. In patients with IDA, serum EPO response was inversely correlated with Hb level (r= -0.5, P <0.05) , but no such inverse correlation was found in the hematologic malignancy patients with anemia (r = -0.14). After corrected for Hb level, the serum EPO levels were significantly lower in anemic patients with hematologic malignancies than in IDA patients (P = 0.032) , indicating a decreased EPO response in the former group. CONCLUSION: Anemia associated with hematologic malignancy might result from an inappropriately low EPO response. EPO treatment for these patients may be beneficial.
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Anemia Ferropénica/sangre , Eritropoyetina/sangre , Neoplasias Hematológicas/sangre , Adolescente , Adulto , Anciano , Anemia Ferropénica/complicaciones , Ensayo de Inmunoadsorción Enzimática , Femenino , Neoplasias Hematológicas/complicaciones , Hemoglobinas/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
OBJECTIVE: To construct the gene co-expression vector of immunoglobulin heavy chain variable region (IgHV) gene and GM-CSF or IL-2 as IgHV family specific nucleic acid vaccine to lymphoma, and study the immune response of the immunized mice against lymphoma. METHODS: Six clones with significantly different length in gene fragments were selected from a gene bank constructed from normal fetal umbilical cord blood. These gene fragments in the clones were sequenced. The sequences were translated into IgHV peptides. T cell epitopes in the IgHV were predicted by bioinformatics. Meanwhile 6 clones of IgHV1 constructed before were analyzed. The most typical clone of IgHV1 and IgHV3 containing most of the T cell epitopes were selected. The IgHV gene fragments whose complementary determining region 3 (CDR3) was cut out and composed mainly of framework region were cloned into eukaryotic expression vector. The gene fragments of framework region of IgHV linking with gene of GM-CSF or IL-2 were cloned into pcDNA3.0 to form fusion genes of IgHV (FR)-GM-CSF/IL-2. Then they were transected into COS cells, African green monkey renal cells, by Lipofectin and their transient expression product was detected by ELISA. Twenty male Balb/c mice were randomly divided into 5 groups of 4 mice to be injected with different vectors at the weeks 0, 2, and 4: with IgHV3 (FR)/pcDNA3.0, with IgHV3 (FR)-IL-2/pcDNA 3.0, with blank vector pcDNA3.0 as control, with IgHV1 (FR)/pcDNA3.0, and with IgHV1 (FR)-IL-2/pcDNA3.0. At the weeks 0, 2, 4, 6, and 8 serum was collected from the mice to undergo indirect immunofluorescence examination to detect the antibodies against Namalwa cells, lymphoma cells from Africa green monkey, and normal lymphocytes. ELISA was used to examine the serum interferon (IFN)-gamma. RESULTS: About 30 of T cell epitopes existed in each IgHV peptides predicted by bioinformatics. Among the bioinformatics prediction, about 90% of the T cell epitopes were in the framework region (FR) of IgHV, and the first 10% with higher prediction score were in FR. The CDR3 of two typical IgHV sequences were cut down and the remaining sequences, mainly composed of FR, were used to construct the IgHV (FR)/pcDNA3.0 expression vectors. The 3' end of IgHV1 (FR) and IgHV3 (FR) were linked to GM-CSF or IL-2 gene successfully. The expression of GM-CSF in the group transfected with IgHV (FR)-GM-CSF/pcDNA3.0 were 200 times higher than in the group transfected with control pcDNA3.0. The expression of IL-2 in the group transfected with IgHV (FR)-IL-2/pcDNA3.0 were 60 times higher than in the group transfected with control pcDNA3.0. The antibody against IgHV1 family lymphoma cell line Namalwa could be detected since the second week in the mice immunized with IgHV1 (FR)-IL-2/pcDNA3.0. The antibody could be detected since the fourth week in the mice immunized with IgHV1 (FR). The antibody against lymphocyte line of IgHV3 family could be detected since the second week in the mice immunized with IgHV3 (FR)-IL-2/pcDNA3.0. The antibody could be detected since the fourth week in the mice immunized with IgHV3 (FR)/pcDNA3.0. The contents of serum IFN-gamma the mice immunized with IgHV1 (FR)-IL-2/pcDNA3.0 and with IgHV3 (FR)-IL-2/pcDNA3.0 was significantly higher than those of the mice immunized with IgHV (FR)/pcDNA3.0 or pcDNA3.0 (all P < 0.01). CONCLUSION: The gene fragments of IgHV (FR) can be used to construct IgHV family specific nucleic acid vaccine that induces anti-lymphoma immune response in mice by muscle injection. The expressing vectors of IgHV (FR)-GM-CSF/IL-2 induces stronger immunoreaction.
Asunto(s)
Citocinas/inmunología , Cadenas Pesadas de Inmunoglobulina/inmunología , Región Variable de Inmunoglobulina/inmunología , Linfoma/inmunología , Vacunas de ADN/inmunología , Animales , Sitios de Unión de Anticuerpos/inmunología , Citocinas/genética , ADN Recombinante/genética , ADN Recombinante/inmunología , Ensayo de Inmunoadsorción Enzimática , Técnica del Anticuerpo Fluorescente Indirecta , Factor Estimulante de Colonias de Granulocitos y Macrófagos/genética , Factor Estimulante de Colonias de Granulocitos y Macrófagos/inmunología , Humanos , Cadenas Pesadas de Inmunoglobulina/genética , Región Variable de Inmunoglobulina/genética , Interferón gamma/sangre , Interleucina-2/genética , Interleucina-2/inmunología , Linfoma/sangre , Ratones , Ratones Endogámicos BALB C , Vacunas de ADN/genéticaRESUMEN
This study was to investigate the anti-lymphocytic malignancy immunologic effects induced by two types of the idiotypic nucleic acid vaccines which were constructed from the genomic DNA and RNA of the human B lymphoma cell line respectively. Namalwa cell line and BALB/c mice were used as the models. The gene fragments of the IgH variable region (IgHV), which were obtained from the genomic DNA and RNA of Namalwa cell respectively, were cloned into the eukaryocytic expression vector pcDNA 3.0 to be used as the idiotypic nucleic acid vaccines. After transfecting COS cells with one of vaccines constructed from the genomic DNA by using LipofectAMINE, the result of transcription was identified by using RT-PCR. The experimental mice were immunized by intramuscular injection with two types of vaccines. The specific anti-idiotypic antibody was detected by indirect immunofluorescence assay. The results showed that the nucleic acid vaccine constructed from the genomic DNA can be transcribed in COS cells, the transcription product turned shorter, and the intron region of 86 bp was spliced accurately. When immunizing the mice, two vaccines both induced the anti-idiotypic antibody against Namalwa cell, the anti-idiotypic antibody could be detected since detected since after immunization, and got to the peak of titer on the sixth week. It was concluded that the nucleic acid vaccines against lymphoma can be constructed from both the genomic DNA and RNA.