Relationship between p53 rs1625895 polymorphism and prognosis in diffuse large B-cell lymphoma / 北京大学学报(医学版)

OBJECTIVE@#p53 gene, as "the guardian of the genome", is the most widely studied tumor suppressor gene. Previous studies have shown that about 50 percent of tumors have P53 dysfunction. This article aims to retrospectively analyze the correlation between p53 rs1625895 polymorphism and the prognosis of patients with diffuse large B-cell lymphoma (DLBCL).@*METHODS@#PCR combined with Sanger sequencing were used to detect rs1625895 genotype in 384 DLBCL patients. The relationship between rs1625895 polymorphisms and the clinical characteristics, first-line therapeutic effects and the prognosis of the patients were analyzed.@*RESULTS@#Among all the patients, 2 (0.5%) patients with AA genotype, 34 (8.9%) patients with AG genotype and 348 (90.6%) patients with GG genotype were identified. The patients with different rs1625895 genotypes did not have any difference in terms of age, gender, B symptoms (developing any of the following symptoms: unexplained recurrent fever (often above 38 °C), night sweats, and unexplained weight loss of 10% within 6 months ), erythrocyte sedimentation rate (ESR), international prognostic index (IPI) and molecular subtype (P>0.05). The overall response rate (ORR) was 82.9% and 82.8% in AA/AG and GG, respectively. There was no significant difference between the first-line therapeutic effects of the two groups (P>0.05). And there was also no difference between A allele carriers and homozygous G allele carriers for the 5-year progressionfree survival rate (PFS) (71.8% vs. 62.3%, χ2=1.351, P=0.245) and 5-year overall survival rate (OS) (72.2% vs. 64.1%, χ2=1.267, P=0.260). But in the subgroup with Germinal Center B-cell (GCB) type, the patients carrying A allele for rs1625895 had an obviously longer PFS (91.7% vs. 72.7%, χ2=4.493, P=0.034) and OS (91.7% vs. 76.7%, χ2=4.246, P=0.039) compared with the patients homozygous for the G allele. As for the patients with non-GCB subtype, there was no significant difference in PFS and OS between different rs1625895 genotypes (P>0.05). According to whether the first-line regimen contained rituximab or not, the patients were divided into two groups treated with cyclophosphoramide, doxorubicin, vincristine and prednisone (CHOP) or with rituximab and CHOP (R-CHOP). But in both subgroups, there was no significant difference in the 5-year PFS and OS between the AA/AG and GG patients, too (P>0.05).@*CONCLUSION@#For DLBCL patients receiving CHOP regimen chemotherapy in the first line, p53 rs1625895 cannot predict the clinical efficacy and prognosis of the patients, but in the patients with GCB subtype, this polymorphism may be a prognostic indicator.

Survival Analysis of 148 Patients with Primary Diffuse Large B Cell Lymphoma / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinical outcome of the patients with primary diffuse large B-cell lymphoma（DLBCL）.@*METHODS@#Clinical data of 148 patients with DLBCL in our hospital and cancer hospital from March 2006 to April 2016 were retrospectively analyzed. Kaplan-Meier analysis was used to estimate progression-free survival（PFS）and overall survival（OS）.@*RESULTS@#5-year OS and PFS rates were 85% and 69%，respectively. The survival analysis showed that 5-year OS rate of R-CHOP group was significantly higher than that of CHOP alone group（89% vs. 70%，P60 years），poor ECOG score（≥2），advanced stage（Ⅲ-Ⅳ），higher IPI score（≥3），CHOP alone and absence of radiotherapy related with poor survival rate. Furthermore，multivariate analysis showed that age>60 year significantly related with the worse OS.@*CONCLUSION@#Age >60 year is an important independent prognostic factor to predict worse OS or PFS.

Efectividad de Rituximab en el tratamiento de citopenias autoinmunes refractarias en adultos / Effectiveness of Rituximab in the treatment of cytopenias refractory autoimmune in adults

The term autoimmune cytopenias is referred to a heterogeneous group of diseases characterized by a reduced peripheral blood cell counts in one or more cellular series, because an immunological disorder. The first line therapy is steroids, followed by splenectomy or immunesupressant therapy in non-responders. Rituximab is an anti CD20 monoclonal antibody used as a third line in refractory patients or as an alternative to splenectomy. We present a retrospective study of nine patients with autoimmune cytopenias treated in a public hospital setting with rituximab. Five patients with the diagnosis of inmune thrombocytopenic purpura received it, all of them achieved hematological response (4 complete and one partial). The median time to the best response was 6 weeks, staying in this category after 6 months of follow up. Four patients with autoimmune hemolytic anemia received rituximab, three of them achieving partial response and one was lost from follow up. No severe adverse effects related to rituximab were registered.

Lymphangiogenesis and angiogenesis in oral cavity and lower lip squamous cell carcinoma / Linfangiogênese e angiogênese em carcinomas de células escamosas de lábio inferior e da cavidade oral

ABSTRACT INTRODUCTION: Tumors of the lip and oral cavity differ in various aspects; therefore a clarification of the distinctions among these sites may help to better understand the biologic behavior of neoplasms occurring in these locations. OBJECTIVE: Considering that angiogenesis and lymphangiogenesis are two major elements that can influence various aspects of tumor biology, we aimed to compare these factors between squamous cell carcinoma of the lower lip and oral cavity. METHODS: A total of 84 primary squamous cell carcinomas including 45 oral and 39 lower lip tumors were selected and immunohistochemically stained with monoclonal antibody against D2-40 and CD105. Mean microvessel density was assessed in tumoral tissue, while lymphatic vessel density was calculated in both neoplastic tissue and invasion front. Data were statistically analyzed using t-test and p-values of <0.05 were considered significant. RESULTS: We found a mean microvessel density ± standard deviation of 31.94 ± 18.9 in oral cavity and 27.54 ± 20.8 in lower lip squamous cell carcinomas, with no significant difference (p = 0.32). Mean lymphatic vessel density ± standard deviation was 13.05 ± 8.2 and 16.57 ± 10.79 in of oral cavity and lower lip neoplastic tissue, respectively. The corresponding values were 9.94 ± 5.59 and 12.50 ± 7.8 in the invasive front. Significant differences were not observed in either of the lymphatic vessel density variables between the two sites. CONCLUSION: According to our results, it seems that the search for additional factors other than those related to the vasculature should continue, to help clarify the differences in biologic behavior between lower lip and oral cavity squamous cell carcinomas.

Resumo Introdução: Os tumores de lábio e da cavidade oral diferem em vários aspectos; portanto, o conhecimento das diferenças entre eles pode ajudar na melhor compreensão do comportamento biológico das neoplasias que ocorrem nesses locais. Objetivo: Considerando que a angiogênese e a linfangiogênese são dois elementos importantes que podem influenciar diversos aspectos da biologia dos tumores, objetivamos comparar esses fatores entre o carcinoma de células escamosas (CCE) de lábio inferior e da cavidade oral. Método: No total, foram selecionados 84 CCEs primários (45 tumores da cavidade oral e 39 tumores de lábio). Esses tumores foram corados por processo imunohistoquímico com anticorpo monoclonal anti-D2-40 e CD105. Avaliamos a densidade média de microvasos (DMV) no tecido tumoral, enquanto que a densidade vascular linfática (DVL) foi calculada tanto no tecido neoplásico como no front de invasão. Os dados foram estatisticamente analisados com o uso do teste t e valores de p < 0,05 foram considerados significantes. Resultados: Chegamos a uma média para DMV ± DP de 31,94 ± 18,9 para CCEs na cavidade oral e de 27,54 ± 20,8 no lábio inferior, sem diferença significante (p = 0,32). As médias para DVL ± DP foram de 13,05 ± 8,2 e 16,57 ± 10,79 no tecido neoplásico da cavidade oral e lábio inferior, respectivamente. Os valores correspondentes foram 9,94 ± 5,59 e 12,50 ± 7,8 no front invasivo. Não foram observadas diferenças significantes nas duas variáveis DVL entre os dois locais. Conclusão: De acordo com os nossos resultados, a pesquisa por fatores adicionais, além daqueles relacionados à vasculatura, deve ter continuidade, para auxiliar no esclarecimento das diferenças do comportamento biológico entre CCEs no lábio inferior e na cavidade oral.

Rituximab plus Autologous Hemotopoietic Stem Cell Transplantation for The Treatment of CD5 Positive Diffuse Large B Cell Lymphoma with Autoimmune Hemolytic Anemia / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To summarize the clinical features and therapy experience of a case of CD5 positive diffuse large B cell lymphoma (CD5+ DLBCL) with autoimmune hemolytic anemia (AIHA).</p><p><b>METHODS</b>A 49-years old patient was investigated. The routine blood examination, bone marrow smear, Coombs test, serological test, chest CT, abdominal MR and immunochemistry etc were performed for this patient; and therapeutic effects of the chemotherapy regimen consisting of rituximab plus autologous hematopoietic stem cell transplantation (auto-HSCT) were observed.</p><p><b>RESULTS</b>The cervical lymphnode biopsy confirmed CD5+ DLBCL; the severe anemia, reticulocyte increase, Coombs test positive, and erythroid hyperplasia in bone marrow all suggested the occurence of autoimmune hemolytic anemia (AIHA). After plasma exchange, immune suppression using methylprednisolone, blood transfusion, one course of chemotherapy with "R-CHOP-E", the symptoms of AIHA in patient disappeared. After a continuous treatment for 3 courses of "R-CHOP-E", the bone marrow infiltration appeared, which was assessed as "PD", then the treatment was changed to the "R-ESHAP" for 4 courses, the patient was reassessed as "CR". The patient subsequently underwent auto-HSCT, followed up for 6 months, patientis still "CR".</p><p><b>CONCLUSION</b>The status of the CD5+ DLBCL patient with AIHA is severe, and the prognosis is poor. The curative effect of the chemotherapy regimen with rituximab plus auto-HSCT for this patien is well.</p>

Aidi Injection-Asisted R-CHOP Chemotherapy for the Treatment of Diffuse Large B-Cell Lymphoma / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigaate the clinical efficacy of Aidi injection-asisted R-CHOP chemotherapy for the treatment of diffuse large B-cell lymphoma (DLBCL).</p><p><b>METHODS</b>Fifty-one patients diagnosed as DLBCL in our department from February 2005 to September 2015 were randomly divided into 2 groups. Out of them, 26 patients in one group received R-CHOP chemotherapy asisted by Aidi intravenous infection (Aidi+R-CHOP group), 25 patients were in another group received only R-CHOP chemotherapy (R-CHOP group), 3 weeks for one course, to tally continuous 2 courses. The recent therapeutic efficacy, adverse events, quality of life, sIL-2R level and long-term survival rate were compared between 2 groups.</p><p><b>RESULTS</b>The efficacy of the Aidi+R-CHOP group was significantly higher than that of the R-CHOP group (P<0.05); the incidences of neutropenia and thrombocytopenia were significantly lower than the R-CHOP group (P<0.05); besides, KPS scores were significantly higher than in the R-CHOP group (P<0.05); sIL-2R level in the Aidi+R-CHOP group after treatment was significantly lower than that in the R-CHOP group (P<0.05), however, these data were not statistically different between the two groups before treatment. In addition, 3 and 5-year progression-free survival (PFS) rate in the Aidi+R-CHOP group was significantly higher than that in the R-CHOP group.</p><p><b>CONCLUSION</b>The use of Aidi injection-asisted R-CHOP chemotherapy for treating patients with diffuse large B-cell lymphoma can increase the patient's tolerance to chemotherapy, improve their quality of life, also reduce the side-effects of chemotherapy, and the trerapeutic effect is more significant than that of R-CHOP regimen alone, thus improving the overall therapeutic efficacy of patients with diffuse large B-cell lymphoma.</p>

Evaluation Value of Invasion Area PET-CT Scanning for Chemotherapeutic Efficacy and Prognosis of Patients with Lymphoma / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the evaluation value of invasion area PET-CT scanning for chemotherapeutic efficacy and prognosis of patients with lymphoma.</p><p><b>METHODS</b>A total of 98 newly diagnosed patients with lymphoma received the chemotherapy by R-CHOP protocol, the PET-CT scan of whole body and invasion area was performed after 6 cycle of chemotherapy. The invasion area was determined by PET-CT scan results before chemotherapy. The difference of clinical stage, clinical efficacy, radiation dose and scanning time were compared between PET-CT scanning of whole body and invasion area.</p><p><b>RESULTS</b>The clinical stages of PET-CT scaning of whole body and invasion area were complete consistent, the consisitent rate of clinical stages from whole body and invasion area PET-CT scaning with Ann Arbor staging was 95.9%(94/98). Whole body PET-CT scan showed that 68 cases achieved CR, 26 cases achieved PR, 1 case achieved SD, 3 cases achieved PD. PET-CT scan of invasion area showed that 68 cases achieved CR, 24 cases achieved PR, 2 cases achieved SD, and 4 cases achieved PD; the PET-CT scan results of the whole body and the invasion area was consistent with CR. In 68 patients with CR, the radiation dose of CT, PET and PET-CT was significantly lower than that of whole body PET-CT, and the scanning time was significantly less than that of whole body PET-CT (P < 0.05).</p><p><b>CONCLUSION</b>For clinical efficicacy with CR patients, the scan results of whole body and invasion area PET-CT are consistent, and the PET-CT invasion area can significantly reduce the radiation dose and scanning time; and for PR, SD and PD patients, the whole body PET-CT scan should be performed to evaluation clinical efficiency.</p>

Rituximab and Dexamethasone Combined with Cyclophosphamide for Treatment of Relapsed and Refractory Immune Thrombocytopenia / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To evaluate the efficiency and safety of rituximab and dexamethasone combined with cyclophosphamide for treating patients with relapsed and refractory immune thrombocytopenia (ITP).</p><p><b>METHODS</b>Twelve patients with relapsed and refractory immune thrombocytopenia were prospectively enrolled in this study, and received rituximab 375 mg/m(2) once a week for 4 weeks, dexamethasone 40 mg once a day for consecutive 4 days, and cyclophosphamide 500 mg/m(2) biweekly for 2 weeks. The levels of IFN-r and IL-4 in peripheral blood of patients were measured by enzyme-linked immunosorbent assay (ELISA), and the percentages of Breg, Treg and Th17 cells were detected by flow cytometry before and after treatment. Efficiency was evaluated according to platelet counts, and side effects were observed.</p><p><b>RESULTS</b>Six out of 12 patients reached to complete remission and 4 patients reached to partial remission, with the total response rate 83.33%. The platelet counts [(115.42 ± 76.60) × 10(9)/L] after treatment were significantly higher than that before treatment [(115.42 ± 76.60) × 10(9)/L] (P < 0.001). The ratio of IFN-r/ IL4 after treatment (5.89 ± 2.30) was very significantly lower than that before treatment (7.00 ± 2.73) (P = 0.002). The percentage of Breg cells after treatment [(21.27 ± 4.28)%] were much significantly higher than that before treatment [(15.48 ± 1.67)%] (P < 0.001). The ratio of Treg/Th17 after treatment (3.07 ± 1.50) was significantly higher than that before treatment (0.98 ± 0.45) (P < 0.001). Infusion reaction was observed in 1 patient, secondary hypertension and hyperglycemia were in 1 patient, and pneumonia in 2 patients.</p><p><b>CONCLUSION</b>Rituximab and dexamethasone combined with cyclophosphamide can improve the outcomes of patients with relapsed and refractory immune thrombocytopenia patients and they were well tolerated, its mechanism may be related with the balance between T cell sunsets and Treg cells.</p>

Comparison of prognostic models for patients with early-stage diffuse large B-cell lymphoma / 中华血液学杂志

<p><b>OBJECTIVE</b>To compare the prognostic value of different models in patients with early-stage diffuse large B-cell lymphoma (DLBCL).</p><p><b>METHODS</b>Early-stage DLBCL patients diagnosed from January 2000 to December 2012 were analyzed retrospectively. All patients received with at least 2 cycles of immunochemotherapy R-CHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) with or without radiotherapy. The prognostic value of international prognostic index (IPI) , revised IPI (R-IPI) and enhanced IPI (NCCN-IPI) was compared.</p><p><b>RESULTS</b>Ninety-seven cases of early-stage DLBCL were included in the study. The median age was 58 years (15-88 years) with a median follow-up of 34.7 months (range 7.3-77.4 months). The expected 5-year overall survival (OS) for entire group was 82%. There was no patient in the high risk group according to IPI or NCCN-IPI. According to IPI, the 5-year OS in the low, low intermediate, high intermediate risk groups were 95%, 38% and 60%, respectively. According to R-IPI, the 5-year OS in the very good, good, and poor risk groups were 93%, 75% and 60%, respectively. According to NCCN-IPI, the 5-year OS in the low, low intermediate, high intermediate risk groups were 92%, 85% and 29%, respectively.</p><p><b>CONCLUSION</b>NCCN-IPI would be of an ideal prognostic model for early-stage DLBCL patients.</p>

O rituximabe como uma opção para pacientes com vasculite sistêmica grave refratária à terapia convencional: relato de sete casos e revisão de literatura / Rituximab as an alternative for patients with severe systemic vasculitis refractory to conventional therapy: report of seven cases and literature review

Resumo O maior entendimento das bases fisiopatológicas e do comportamento das vasculites sistêmicas, aliado ao desenvolvimento de regimes terapêuticos com perfil de segurança e eficácia cada vezes melhores, modificou drasticamente o prognóstico dos pacientes diagnosticados com essas entidades clínicas. Recentemente, o emprego do rituximabe no tratamento de pacientes com vasculites ANCA associadas em ensaios clínicos randomizados se mostrou uma opção importante em casos selecionados, especialmente pacientes refratários ou intolerantes à terapia-padrão com ciclofosfamida e corticosteroides. O presente artigo traz o relato de sete casos de vasculites sistêmicas com tratamento bem-sucedido com rituximabe.

Abstract The greater understanding of pathophysiology and behavior of systemic vasculitis, together with the development of therapeutic regimens with increasingly better safety and efficacy profiles, dramatically changed the prognosis of patients diagnosed with these clinical entities. Recently, the use of rituximab in the treatment of patients with ANCA-associated vasculitis in randomized clinical trials showed an important alternative in selected cases, especially patients refractory or intolerant to standard therapy with cyclophosphamide and corticosteroids. This article presents the report of seven cases of systemic vasculitis successfully treated with rituximab.

Foot reflexology in feet impairment of people with type 2 diabetes mellitus: randomized trial / Reflexologia podal no comprometimento dos pés de pessoas com diabetes mellitus tipo 2: ensaio randomizado / Reflexología podal en el comprometimiento de los pies de personas con diabetes mellitus tipo 2: ensayo aleatorio

AbstractObjective: to evaluate the effect of foot reflexology on feet impairment of people with type 2 diabetes mellitus.Method: this is a randomized, controlled and blind clinical trial. The sample was comprised by people with type 2 diabetes mellitus who, after being randomized into Treated group (n = 21) and Control group (n = 24), received guidelines on foot self-care. To the Treated Group it was also provided 12 sessions of foot reflexology. The scores of impairment indicators related to skin and hair, blood circulation, tissue sensitivity and temperature were measured by means of the instrument for assessing tissue integrity of the feet of people with diabetes mellitus. Chi-square test, Fisher exact test, Mann-Whitney test and regression analyzes were applied to the data, considering a significance level of 5% (P value <0.05).Results: participants who received the therapy showed better scores in some impairment indicators related to skin and hair (hair growth, elasticity/turgor, hydration, perspiration, texture and integrity of the skin/ skin peeling).Conclusion: the foot reflexology had a beneficial effect on feet impairment of people with type 2 diabetes mellitus, which makes it a viable therapy, deserving investment. This study was registered in the Brazilian Registry of Clinical Trials - RBR-8zk8sz.

ResumoObjetivo:avaliar o efeito da reflexologia podal no comprometimento dos pés de pessoas com diabetes mellitus tipo 2.Método:trata-se de um ensaio clínico, randomizado, controlado e mascarado. A amostra foi composta por pessoas com diabetes mellitus tipo 2 que, após serem randomizadas em grupo Tratado (n=21) e Controle (n=24), receberam orientações de autocuidado com os pés. Ao Grupo Tratado também foram fornecidas 12 sessões de reflexologia podal. Foram mensurados os escores de comprometimento de indicadores relacionados à pele e pelos, circulação sanguínea, sensibilidade e temperatura tissular por meio do Instrumento para avaliação da integridade tissular dos pés de pessoas com diabetes mellitus. Aos dados foram aplicados os testes Qui-Quadrado, Exato de Fisher, Mann-Whitney e Análises de regressão, considerando-se nível de significância de 5% (Valor P<0,05).Resultados:os participantes que receberam a terapia apresentaram melhores escores de comprometimento em alguns indicadores relacionados à pele e pelos (crescimento de pelos, elasticidade/tugor, hidratação, transpiração, textura e integridade da pele/descamação cutânea).Conclusão:a reflexologia podal apresentou efeito benéfico sobre o comprometimento dos pés de pessoas com diabetes mellitus tipo 2, o que a torna uma terapia viável e que merece investimento. Este estudo foi registrado no Registro Brasileiro de Ensaios Clínicos - RBR-8zk8sz.

ResumenObjetivo:evaluar el efecto de la reflexología podal en el comprometimiento de los pies de personas con diabetes mellitus tipo 2.Método:se trata de un ensayo clínico, aleatorio, controlado y enmascarado. La muestra estuvo compuesta por personas con diabetes mellitus tipo 2 que, después de ser tratadas aleatoriamente en los grupos Tratado (n=21) y Control (n=24), recibieron orientaciones de autocuidado de los pies. También, al Grupo Tratado se le suministraron 12 sesiones de reflexología podal. Fueron medidos los puntajes de comprometimiento de indicadores relacionados a la piel y pelos, circulación sanguínea, sensibilidad y temperatura tisular por medio de instrumento para evaluación de la integridad del tejido de los pies de personas con diabetes mellitus. Los datos fueron sometidos a las pruebas Chi-cuadrado, Exacta de Fisher, Mann-Whitney y Análisis de regresión, considerando un nivel de significación de 5% (Valor p<0,05).Resultados:los participantes que recibieron la terapia presentaron mejores puntajes de comprometimiento en algunos indicadores relacionados a la piel y pelos (crecimiento de pelos, elasticidad/turgencia, hidratación, transpiración, textura e integridad de la piel/descamación cutánea).Conclusión:la reflexología podal presentó efecto benéfico sobre el comprometimiento de los pies de personas con diabetes mellitus tipo 2, lo que la torna una terapia viable y que merece inversiones. Este estudio fue registrado en el Registro Brasileño de Ensayos Clínicos - RBR-8zk8sz.

Rituximab induced left bundle branch block

Rituximab [a monoclonal antibody directed against CD 20] therapy can be acutely complicated by infusion reactions and cardiac arrhythmia on rare occasions. We report the first case of a new onset left bundle branch block [LBBB] after rituximab therapy for Wegener's vasculitis

Impact of rituximab and IPI on survival in diffuse large B cell lymphoma patients treated at a tertiary level cancer centre in Pakistan: a single-centre experience

To determine the impact of Rituximab and international prognostic index score on survival in diffuse large B-cell lymphoma patients. The retrospective study was conducted at Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, from January to May 2013 and comprised record of patients with diffuse large B-cell lymphoma who were treated from 2007 to 2010. Baseline international prognostic index score, stage at presentation were noted and the records were divided into two groups A and B on the basis of the type of chemotherapy. SPSS 19 was used for statistical analysis. Of the 93 patients in the study whose records were reviewed, 54[58%] were men. Overall median age was 43 years [range: 18-76]. Stages at presentation were stage-I 14 [15.1%], stage-II 41 [44.1%], stage-III 20 [21.5%] and stage-IV 18 [19.4%]. International prognostic index risk categorisation was low risk 59[63.4%], low intermediate risk 23[24.7%], high intermediate risk 10[10.8%] and high risk 1[1.1%]. There were 31[33%] patients in Group A and 62[67%] in Group B. Median follow-up was 3.9 years [range: 1.2-6.1]. Overall survival at 4 years was 66.4%; for Group A 65.3% and for Group B 66.7% [p<0.4]. On the basis of risk categories, overall survival was statistically significant [p<0.001] between the groups. International prognostic index risk categorisation had statistically significant impact on survival. However, there was no evidence of a significant survival benefit between types of chemotherapy. Further controlled trials are needed in this regard

Role of frontline autologous stem cell transplantation in young, high-risk diffuse large B-cell lymphoma patients

BACKGROUND/AIMS: Several studies have demonstrated the effect of autologous hematopoietic stem cell transplantation (auto-HSCT) as a salvage treatment for patients with relapsed diffuse large B-cell lymphoma (DLBCL). However, the role of auto-HSCT as a frontline treatment has not been fully investigated in the rituximab era. We validated the age-adjusted International Prognostic Index (aaIPI) score for high-risk DLBCL patients and identified a possible role for frontline auto-HSCT. METHODS: We recommended frontline auto-HSCT for high-risk DLBCL patients who satisfied the criteria of both a higher Ann-Arbor stage (III to IV) and an elevated lactate dehydrogenase (LDH) level at diagnosis with an aaIPI score > or = 2. From 2006 to 2011, among the 150 DLBCL patients aged or = 2 showed inferior overall survival (OS; p = 0.040) and progression-free survival (PFS; p = 0.007) compared to the aaIPI score 0 to 1. Between the two treatment arms among the high-risk DLBCL patients, the clinical parameters were not different. The high-risk group treated with frontline auto-HSCT showed similar OS (p = 0.392) and PFS (p = 0.670) to those in the low-risk group. Thus, frontline auto-HSCT showed superior PFS (p = 0.004), but only a trend towards favorable OS (p = 0.091) compared to R-CHOP alone. CONCLUSIONS: We identified the possible role of frontline auto-HSCT for high-risk DLBCL with a higher stage (III to IV) and elevated LDH level.

Expression of CD68, cyclin D1 and rearrangement of bcl-6 gene are adverse prognostic factors in diffuse large B-cell lymphoma / 中华病理学杂志

<p><b>OBJECTIVE</b>To study expression of CD68, cyclin D1 protein and rearrangement of bcl-6 gene impact on the prognosis of diffuse large B-cell lymphoma (DLBCL).</p><p><b>METHODS</b>Gets paraffin samples of the 105 cases DLBCL with the detailed follow-up information, and were studied by using immunohistochemical EnVision method for CD3, CD10, CD20, CD68, cyclin D1, bcl-6, MUM 1, SOX-11 immunolabeling. The DLBCL were classified into germinal center B cell-like (GCB) subtypes and non-germinal center B cell-like (non-GCB) subtypes according to Hans'algorithm. Application of fluorescence in situ hybridization (FISH) technique to detect the bcl-6 gene rearrangement. The relationship between CD68, cyclin D1 protein, the bcl-6 gene and the curative effect of chemotherapy and survival was analyzed using statistical software. Respectively by GCB type, non-GCB type immune phenotype and CHOP, R-CHOP chemotherapy group, compare the curative effects.</p><p><b>RESULTS</b>105 patients had GCB 19 cases (18.1%), non-GCB 86 cases (81.9%), CD68 expression was 18 cases (17.1%), cyclin D1 high expression 36 cases (34.3%), bcl-6 gene rearrangement in 21 cases (21.9%), there is no correlation among the three (P > 0.05). One-way analysis of variance showed that age ≤ 60 years, clinical stage I-II, IPI score 0 to 2 points, LDH (U/L) < 245 IU/L,GCB subtypes, R-CHOP therapy, the prognosis of patients with better (P < 0.05), But gender, primary site no correlation with prognosis (P > 0.05). CD68, cyclin D1 high expression, bcl-6 rearrangement had poor prognosis (P < 0.05). Stratification analysis results show GCB-type or non-GCB type with high expression of CD68 contrast alloimmune phenotype groups had a poor prognosis, non-GCB type with high expression of cyclin D1 and rearrangement of bcl-6 gene had a poor prognosis (P < 0.001, P = 0.02). Treatment scheme of layered display, the CHOP treatment, significantly correlated with overall survival with high expression of CD68, cyclin D1 (P < 0.05), the R-CHOP treatment, there was no statistically significant difference between CD68, cyclin D1 high expression and overall survival (P = 0.428 and 0.168). Multivariate COX model analysis showed that high expression of CD68 (P = 0.026), high expression of cyclin D1 (P = 0.003) and high levels of LDH (P = 0.005) were adverse prognostic factors independent.</p><p><b>CONCLUSIONS</b>high expression of CD68, cyclin D1 and rearrangement of bcl-6 gene suggests poor prognosis, CD68, cyclin D1 protein and bcl-6 gene can be used as a prognostic indicator in patients with DLBCL.</p>

The First Case Report of Composite Bone Marrow Involvement by Simultaneously Developed Peripheral T-Cell Lymphoma, Not Otherwise Specified, and Diffuse Large B-Cell Lymphoma

No abstract available.

Development of a novel reporter gene method for determination of ADCC potency of anti-CD20 monoclonal antibody / 药学学报

The biological activity of ADCC by anti-CD20 monoclonal antibody was determined by BioGlo™ Luciferase Assay System using Jurkat/NFAT-luc+FcγRIIIa cell line as effector cell and WIL2-S cell line as target cell. The developed method was verified for specificity, precision and accuracy. Anti-CD20 monoclonal antibody showed a dose-response mode by the developed method, and the determination result complied with the following four-parameter equation: y = (A-D)/[1 + (X/C)(B)] + D. The optimized parameters of the method were determined including the antibodies diluted concentration (18,000 ng·mL(-1)), dilution rate (1:5), the ratio of effector cell and target cell (6:1), and induction time (6 h). The values of eight independent tests have passed a statistical test for curve regression analysis, linear or parallelism, which showed the method possessed good specificity. Four different dilute groups of recovery rates sample were determined for 3 times, and the result showed mean relative potencies of (44.39±3.93)%, (72.74±2.78)%, (128.28±7.01)% and (168.19±2.70)% respectively, with a variation coefficient of less than 10%, and the recoveries of (88.78±7.85)%, (96.99±3.70)%, (102.63±5.61)% and (112.12±1.80)% respectively. A novel reporter gene method for determination of biological activity of ADCC by anti-CD20 monoclonal antibody was successfully developed, which showed strong specificity, good reproducibility and high accuracy, and might be used routinely.

Elderly chronic lymphocytic leukemia combined with invasive aspergillosis infection in one case / 中国实验血液学杂志

<p><b>OBJECTIVE</b>This study was aimed to investigate the morphological, immunophenotype, cytogenetic characteristics, clinical and therapy features in one elderly patient with chronic lymphocytic leukemia (CLL) combined with invasive aspergillose infection(IAI).</p><p><b>METHODS</b>The morphological features of bone marrow cells from patient were observed by light microscope, the immunophenotype were detected by flow cytometry, the cytogenetic characteristics were assayed by conventional chromosomal analysis and fluorescence in situ hybridization (FISH).</p><p><b>RESULTS</b>at onset of disease, the patient was diagnosed as B-CLL, Rai stage is II. He was treated with a course of RF(fludarabine 50 mg×5, rituximab 600 mg×5) chemotherapy, and achived complete remission (CR) lasting for five years, then the patient was treated with multiple courses of chemotherapy and maintained at a steady state of disease. After the last chemotherapy, this patient developed a fever, his temperature fluctuated at 37.2-38.7°C, the lung CT showed the presence of massive shadow, repeated 1-3-β-D-glucan test was positive,and he was considered as invasive aspergillosis infection, voriconazole was intravenously injected him for 2 months, his lung CT showed better efficacy. However, the leukemia continued progress, his hemogram was extremely low, invasive aspergillosis infection relapsed,voriconazole treatment was poor effect,ultimately this patient died of the rapid progress of leukemia and multiple organ invasive aspergillosis. Autopsy showed chronic lymphocytic leukemia with multiple metastases and multiple organ invasive aspergillosis.</p><p><b>CONCLUSION</b>invasive aspergillosis is a serious complication for CLL patients,once occurs, the prognosis is poor,so early diagnosis and prophylactic antifungal therapy may reduce fungal infection complication.</p>

A multicenter clinical trial of caffeic acid tablet in treatment of 103 primary immune thrombocytopenia patients / 中华血液学杂志

<p><b>OBJECTIVE</b>To determine the efficacy and safety of oral caffeic acid (CA) tablet in management of primary immune thrombocytopenia(ITP).</p><p><b>METHODS</b>One hundred and three ITP patients with PLT>10×10⁹/L and no serious bleeding symptoms from three centers were enrolled. According to their platelet count before CA treatment, these patients were divided into group A (PLT<30×10⁹/L), including 24 females and 27 males with median age 48(18-84)years; and group B (PLT≥30×10⁹/L), including 33 females and 19 males with median age 43(18-83)years. Patients in both groups took CA tablets orally of 300 mg three times per day for 12 consecutive weeks. Combined medicine treatment such as corticosteroids, danazol, TPO and Rituximab, which might increase the platelet count of these patients, were not allowed during CA therapy.</p><p><b>RESULTS</b>In group A, the overall response rate was 51.0%(26/51), with 2 patients achieving complete response (CR) and 24 patients achieving response(R). Of 26 patients achieving response (CR+R), the median platelet count before CA therapy was 20.5(15-28)×10⁹/L , and the median peak platelet count after CA therapy was 63(38-112)×10⁹/L. The median time to achieving response was 4(2-10) weeks. Patients with pretreatment PLT>20×10⁹/L showed significantly better response than those PLT<20×10⁹/L (68.0% vs 34.6%, P=0.017). In group B, the CR rate was 40.4%(21/52). Frequency of CA-related adverse events was 1.94%(2/103), including mild nausea in 1 case and elevation of liver enzymes in 1 case. Both were grade 1 and transient.</p><p><b>CONCLUSION</b>Caffeic acid was effective in patients with ITP with few and mild adverse effects.</p>

A single-center clinical study of 22 patients with acquired hemophilia / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the feature of underlying disorders, clinical symptoms, diagnosis and treatment strategies of patients with acquired hemophilia(AH).</p><p><b>METHODS</b>The clinical data and laboratory tests results of 22 patients with AH from March 2010 to June 2014 were retrospectively analyzed.</p><p><b>RESULTS</b>A total of 22 patients with AH were enrolled in our study, including 20 patients diagnosed as acquired hemophilia A (AHA) and 2 as acquired hemophilia B (AHB). Among the AHA patients, there were 10 males and 10 females with the median age of 37.5 (range, 2-95) years old. The median activity of FVIII (FVIII:C) of the 20 AHA patients was 1.9% (0.5%-39.0%). Soft tissue hematoma (80.0%) and subcutaneous bleeding (75.0%) were the most common clinical symptoms. Two male children were diagnosed as AHB (age 1 and 3 years old, respectively) with mild bleeding symptoms, and the activities of FIX (FIX:C) were 5.0% and 16.0%, respectively. In addition, an underlying disorder was found in 7 patients (31.8%). In laboratory testing, all patients had prolonged APTT, normal PT, decreased FVIII:C or FIX:C, positive antibody screening test or antibody titer (2-32 BU), and negative for lupus anticoagulant and anticardiolipin antibody. Nineteen out of 20 patients were treated with blood products to stop acute bleeding episodes. Corticosteroid alone was applied to 7 patients, corticosteroid combined with other immunosuppressive agents to 11 patients, rituximab to 3 patients. Nineteen patients responded well to hemostatic treatment, except 1 patient who died of fatal bleeding. The FVIII:C of 8 patients increased to a normal level with the median time of 42.5(21-145) days. After treatment, the activity of FIX:C of the 2 AHB patients achieved 35% and 24% in 48 and 60 days, respectively.</p><p><b>CONCLUSION</b>Acquired hemophilia is not an uncommon disease in clinical practices, which can occur in people of all ages. AH is a bleeding disorder with heterogeneous characteristics. Compared with adult, the clinical symptoms of children patients were mild, which lead to underdiagnosis.</p>