P53 Gene Mutations in Non-Hodgkin's Lymphoma

Summary: To understand P53 gene change of non Hodgkin's lymphoma (NHL) and human malignant lymphoma cell lines, the exons 5 7 of 29 patients with NHL and 9 kinds of human malignant lymphoma cell lines were studied by silver staining PCR SSCP technique. Three cases of P53 gene point mutation was found in 29 cases of NHL. Mutation developed in exon 5 in 2 cases, and in exon 6 in 1 case. They were all diffuse lymphoma. In mutation cases, B cell lymphoma accounted for 2 cases and the other one was T cell lymphoma. There was no P53 gene mutation in low grade follicular lymphoma. Seven strains out of 9 kinds of lymphoma cell lines had P53 gene point mutation. One strain had the mutation in exon 5; 5 strains in exon 6 and 1 strain in exons 5, 6, 7. There was a high mutation rate in lymphoma cell lines and low mutation rate in NHL patients. P53 gene plays an important role in lymphoma cell line establishment, cell regeneration and disease evolution.

Positron emission tomography/computerized tomography in the evaluation of primary non-Hodgkin's lymphoma of prostate

Primary malignant lymphoma of the prostate is exceedingly rare.Here we report a case of a 65-year-old man who presented with increased urinary frequency,urinary urgency,and urinary incontinence for two years.Benign prostatic hypertrophy was suspected at primary impression.Ultrasound revealed a hypoechoic lesion of the prostate.The total serum prostate-specific antigen was within normal range.Positron emission tomography/computerized tomography(PET/CT)showed a hypermetabolic prostatic lesion.Prostate biopsy was consistent with a non-germinal center diffuse large B cell lymphoma.There was complete remission of the prostatic lesion following six cycles of chemotherapy as shown on the second PET/CT imaging.18F-fluoro-deoxy glucose PET/CT is not only a complement to conventional imaging,but also plays a significant role in the diagnosis and evaluation of treatment response of prostatic lymphoma.

Autologous peripheral blood stem cell mobilization following dose-adjusted cyclophosphamide, doxorubicin, vincristine and prednisolone chemotherapy alone or in combination with rituximab in treating high-risk non-Hodgkin's lymphoma

Background: The regimen of cyclophosphamide, doxorubicin, vincristine, and prednisolone(CHOP) is an eicient treatment of non-Hodgkin's lymphoma(NHL). This study aimed to assess the eicacy and toxicity of dose-adjusted CHOP alone or in combination with rituximab(R-CHOP) by examining the stem cell mobilization in NHL patients. Factors afecting the collection of CD34+ cells were also explored.Methods: Our retrospective study included 39 patients eligible for autologous stem cell transplantation: 14 patients who expressed CD20 and were inancially eligible received R-CHOP for autologous peripheral blood stem cell(APBSC) mobilization; the remaining 25 patients received CHOP.Results: The median CD34+ cell yield was 7.01 × 106 cells/kg body weight(range 1.49–28.39 × 106 cells/kg body weight), with only two patients failing to meet the target CD34+ cell harvest of ber of apheresis procedures per patient was 1(range 1–3). The≥2.0 APBS× 106 cells/kg body weight. The median numC mobilization yield of the CHOP group appeared to be higher than that of the R-CHOP group(P response(CR) rate in = 0.005), whereas the success rate was similar between groups. R-CHOP elevated the completeB cell lymphoma patients as compared with CHOP(P = 0.01). No signiicant diferences in toxicity or engraftment were observed between the two groups.Conclusion: The present study demonstrated that dose-adjusted CHOP chemotherapy efectively mobilized APBSCs in NHL patients and that the addition of rituximab to dose-adjusted CHOP chemotherapy elevated the CR rate for patients with B-cell lymphoma.

Simultaneous occurrence of a hepatocellular carcinoma and a hepatic non-Hodgkin's lymphoma infi ltration

To investigate the simultaneous occurrence of hepatocellular carcinoma and non-Hodgkin's lymphoma, we report the case of a 70 year old patient with a primary diagnosis of non-Hodgkin's lymphoma in 2002. In a routine follow up investigation of his chronic lymphocytic leukemia a newly detected mass in the Couinaud's segments 2 and 3 was found. No hepatitis C virus or hepatitis B virus infection or cirrhosis was evident. After laparoscopic segmentectomy the histological examination revealed a hepatocellular carcinoma. While the relation between liver parenchyma damages and hepatocellular carcinoma or non-Hodgkin's lymphoma is well known, only a few publications have focused on the coexistence of hepatocellular carcinoma and non-Hodgkin's lymphoma. With this case we demonstrate the coexistence of these diseases without having a pre- damaged liver parenchyma.

Association of the Asp312Asn and Lys751 Gln polymorphisms in the XPD gene with the risk of non-Hodgkin's lymphoma:evidence from a meta-analysis

Polymorphisms in DNA repair genes may alter DNA repair capacity and,consequently,lead to genetic instability and carcinogenesis.Several studies have investigated the association of the Asp312 Asn and Lys751 Gln polymorphisms in the xeroderma pigmentosum complementation group D {XPD) gene with the risk of non-Hodgkin's lymphoma(NHL),but the conclusions have been inconsistent.Therefore,we performed this meta-analysis to more precisely estimate these relationships.A systematic literature search was performed using the PubMed,Embase,and Chinese Biomedical(CBM) databases.Ultimately,6 studies of Asp312 Asn,comprising 3,095 cases and 3,306 controls,and 7studies of Lys751 Gln,consisting of 3,249 cases and 3,676 controls,were included.Pooled odds ratios(ORs) and 95%confidence intervals(CIs) were calculated to assess the strength of each association.Overall,no association was observed between the Asp312 Asn polymorphism and NHL risk(homozygous:OR = 1.11,95%CI = 0.94-1.32;heterozygous:OR = 1.00,95%CI = 0.89-1.11;recessive:OR = 1.12,95%CI = 0.95-1.31;dominant:OR = 1.02,95%CI = 0.92-1.13;and allele comparison:OR = 1.04,95%CI = 0.96-1.12) or between the Lys751 Gln polymorphism and NHL risk(homozygous:OR = 0.97,95%CI = 0.83-1.15;heterozygous:OR = 0.96,95%CI = 0.86-1.06;recessive:OR = 1.00,95%CI = 0.86-1.16;dominant:OR = 0.96,95%CI = 0.87-1.06;and allele comparison:OR = 0.98,95%CI = 0.91-1.05).Furthermore,subgroup analyses did not reveal any association between these polymorphisms and ethnicity,the source of the controls,or the NHL subtype.These results indicated that neither the Asp312 Asn nor Lys751 Gln XPD polymorphism was related to NHL risk.Large and well-designed prospective studies are required to confirm this finding.

HCV infection, B-cell non-Hodgkin's lymphoma and immunochemotherapy: Evidence and open questions

There is plenty of data confirming that hepatitis C virus (HCV) infection is a predisposing factor for a B-cell non-Hodgkin's lymphoma (B-NHL) outbreak, while relatively few reports have addressed the role of HCV in affecting B-NHL patients' outcome. HCV infection may influence the short-term outcome of B-NHL because of the emergence of severe hepatic toxicity (HT) during immunochemotherapy. Furthermore, the long term outcome of HCV-related liver disease and patients' quality of life will possibly be affected by Rituximab maintenance, multiple-lines of toxicity during chemotherapy and hematopoietic stem cell transplantation. In this review, data dealing with aggressive and low-grade B-NHL were separately analyzed. The few retrospective papers reporting on aggressive B-NHL patients showed that HCV infection is a risk factor for the outbreak of severe HT during treatment. This adverse event not infrequently leads to the reduction of treatment density and intensity. Existing papers report that low-grade B-NHL patients with HCV infection may have a more widespread disease, more frequent relapses or a lower ORR compared to HCV-negative patients. Notwithstanding, there is no statistical evidence that the prognosis of HCV-positive patients is inferior to that of HCV-negative subjects. HCV-positive prospective studies and longer follow-up are necessary to ascertain if HCV-positive B-NHL patients have inferior outcomes and if there are long term sequels of immunochemotherapies on the progression of liver disease.

Hepatitis C virus and non-Hodgkin's lymphomas:Metaanalysisof epidemiology data and therapy options

Hepatitis C virus(HCV) is a global health problem affecting a large fraction of the world's population: This virus is able to determine both hepatic and extrahepatic diseases. Mixed cryoglobulinemia, a B-cell "benign" lymphoproliferative disorders, represents the most closely related as well as the most investigated HCVrelated extrahepatic disorder. Since this virus is able to determine extrahepatic [non-Hodgkin's lymphoma(NHL)] as well as hepatic malignancies(hepatocellular carcinoma), HCV has been included among human cancer viruses. The most common histological types of HCV-associated NHL are the marginal zone, the lymphoplasmacytic and diffuse large cell lymphomas. The role of the HCV in the pathogenesis of the B-cell lymphoproliferative disorders is confirmed also by the responsiveness of the NHL to antiviral therapy. The purpose of this review is to provide an overview of the recent literature and a meta analysis of the epidemiology data, to explain the role of HCV in the development of NHL's lymphoma. Furthermore, the possibility to treat these HCV-related NHL with the antiviral therapy or with other therapeutic options, like chemotherapy, is also discussed.

Hepatitis viruses and non-Hodgkin's lymphoma: A review

Non-Hodgkin's lymphoma(NHL) is among the haematological malignancies with high prevalence worldwide, causing estimated 355 900 new cases and 191 400 deaths in 2008. High prevalence of NHL is documented in economically more developed areas while low prevalence is observed in less developed areas of the globe. A wide array of environmental factors have been reported to be either directly involved or in modifying the risk of NHL development. In addition to these factors, a number of infectious agents, chiefly viruses have also been implicated in the development of NHL. This article reviews the available literature to discuss the role of hepatitis viruses in NHL development, possible mechanisms of lymphomagenesis and also identify the areas in which further research is required to better understand this disease. A brief discussion on the clinical aspects such as classification, staging, treatment approaches have also been included in this article.

Primary non hodgkin's lymphoma of lacrimal sac presented as recurrent acute dacryocystitis: A case report

Primary non Hodgkin's lymphoma of the lacrimal sac is uncommon but potentially delay in diagnosis as it may mimic the presentation of primary post saccal nasolacrimal duct obstruction. In this article, we reported a case of primary non Hodgkin's lymphoma of the lacrimal sac presented with recurrent acute dacryocystitis in a young lady. A 28 years old Malay lady had history of persistent epiphora on left eye for 4 years. Prior to presentation to our clinic, it was preceded by progressive recurrent painful medial canthal swelling for 6 months duration. Clinical diagnosis of post saccal naso lacrimal duct obstruction was made and otorhinolaryngology assessment revealed intranasal mass. Endoscopic excision was done showed diffuse large B cell lymphoma on histology. The patient was started on 6 cycles of chemotherapy which subsequently result in no recurrence of the tumour post chemotherapy. Any case of post saccal nasolacrimal duct obstruction should be investigated thoroughly as it may become as a presentation of other sinister pathology.

STUDIES OF THE CHARACTERISTIC FEATURES OF KI-1 POSITIVE NON-HODGKIN'S LYMPHOMA

The clinical histopathological and immuno-phenotypic features in 5 patients with Ki-1 positive non-Hodgkin's lymphoma (NHL) were studied. When firstseen, 4 patients presented enlargement of superficiallymph nodes, with skin lesions in 2 patients. Two patientsin stage Ⅳ with fever, hepato-splenomegaly and bonemarrow invasion, died. Histologically, the tumor cellsshowed diffused or patchy hyperplasia. The cells wererelatively large in size, rich in basophilic or slightlyeosinophilic cytoplasm with irregular-shaped nuclei,prominent nucleoli, and distinct anaplasia andpleomorphism. Some of the cells looked very much likethe Reed-Sternberg cells. Multinucleated giant cells wereseen. Immunophenotypically, all the cells were CD30 (Ki-1) and CD25 (IL-2 receptor) positive but CD15 (Leu M1)negative. Thus, the 5 patients with Ki-1 positive NHLwere all of T cell type.

Primary Non-Hodgkin’s Malignant Lymphoma of the Uterus at the Reference Hospital of Maradi/Niger: A Case Report

Malignant non-Hodgkins lymphoma (MHNL) of the uterus is uncommon. We report a case diagnosed on the basis of histologic and immunohistochemical studies of a hysterectomy specimen induced by a very painful pelvic mass in a 50-year-old patient with no previous history of the disease. It was classified as Ann Arbor IV Bb after imaging, given the medullary infiltration and signs of clinical and biological evolutivity: the patient had received two courses of chemotherapy, CHOP protocol. She died 23 days after the second treatment due to a hypertensive crisis.

Primary hepatic non-Hodgkin's lymphoma: a case report and review of the literature

Objective: To gain more data for the diagnosis and treatment for primary hepatic lymphoma(PHL). Methods: A 32-year-old man was admitted due to fatigue, anorexia, loss of weight and fever. Physical examination was carried out and bone marrow aspitation, blood culture, endoscopy of stomach and colon, chest X-ray, renal fumction and liver function test were all done. Results: Physical examination showed slight abdominal tenderness all edema of the legs, and the liver was unpalpable. Alpha- fetoprotein (AFP ) and carcinomoembryonic antigen (CEA ) were negative. Laboratory tests of rheumatic diseases such as ANA and ENA were all normal. Abdominal ultrasonography and computerized tomography showed diffuse low density or diffuse hypoechogenic changes of the liver, there was no obvious mass lesion in the liver. Conclusion: The diagnosis of PHL was affirmed, and the subtype was non-Hodgkin’s lymphoma.

Gastric amyloidoma in patient after remission of Non-Hodgkin's Lymphoma

Amyloidosis is commonly systemic,occasionally organlimited,and rarely a solitary localized mass.The latter,commonly referred to as tumoral amyloidosis,is described as occurring in nearly every organ/tissue.Only a few reports of gastric amyloidosis exist today.We describe a 72 year-old black male from Barbados presenting with 3 d of diffuse abdominal pain.His medical history included Non-Hodgkin's Lymphoma diagnosed five years ago,status-post six rounds of cyclophosphamide,adriamycin,vincristine,prednisone chemotherapy,and currently was in remission.On computed tomography scan of the abdomen,thickening and calcification of the gastric wall was noted along with pneumatosis.On esophagogastroduodenoscopy,a large circumferential friable mass was seen from the gastroesophageal junction to the body.A large nonbleeding 3 cm polyp was also seen in post bulbar area of duodenum.Biopsies were stained with Congo red and gave green birefringence under polarized light,consistent with tumoral amyloidosis.Positron emission tomography scan revealed diffuse gastric mucosa uptake compatible with gastric malignancy without metastatic foci.Treatment for gastric amyloidomas has presently been one of observation or,at most,resection of the amyloid mass.It is not known if our patient required the same approach or if this warranted the re-institutionof chemotherapy for Non-Hodgkin's Lymphoma.Until more reports of tumoral amyloidosis are made known,treatment as well as prognosis remain uncertain.

Expression of P120 Catenin mRNA in Non-Hodgkin's Lymphoma Cell Lines

To investigate p120 catenin mRNA expression in Non-Hodgkin＇s lymphoma （NHL） cell lines （U937, Raji, Jurkat and Molt4） and normal lymphocytes and explore the relationship between p120 catenin and Non-Hodgkin＇s lymphoma, total RNA sample was extracted by using TRIzol and reversely transcripted into cDNA. Polymerase chain reaction was performed to detect mRNA expression of p120 catenin in NHL cell lines U937, Raji, Jurkat and Molt4. Normal lymphocytes were used as control. It was found expressions of p120 catenin 1A and 3A mRNA were high in above-mentioned NHL cell lines, but neither p120 catenin 1A nor 3A was found in normal lymphocytes as shown by RT-PCR. It is concluded that both P120ctnlA and P120ctn3A mRNA transcripts were found in all NHL cell lines U937, Raji, Jurkat and Molt4 but they don＇t exist in normal lymphocytes, suggesting pl20cm possibly is of importance in diagnosis and therapy of lymphoma.

Extranodal Imaging Manifestations of Non-Hodgkin's Lymphoma

A series of imaging features of extranodal, multi-systemic involvements in Non-Hodgkin's lymphoma (NHL) were investigated The clinical data and imaging findings of 16 patients with pathologically proved NHL were retrospectively analyzed The related literatures were reviewed Of the 16 cases of NHL, skeletal involvement was found in 4, nasal cavity and nasal sinuses were involved in 4, too Lesion in the thorax was seen in 3 patients, hepatic involvement occurred in one case, cerebral ventricle was affected in 3 cases, mesentery was involved in one case Even though extranodal involvement of NHL exhibited extremely variable patterns, there were some relatively typical imaging findings Emphasized in this report were the relatively specific imaging manifestations of different systems, which may mimic infectious or other neoplasms of different sites The importance of imaging studies lies in the availability for diagnosis, staging and follow-up of NHL Combined with the clinical and other related information, the diagnostic accuracy can be further improved, thus, providing reliable evidence in guiding clinical management

Low-Dose Involved-Field Radiotherapy in Relapsed Low-Grade Non-Hodgkin's Lymphoma in Elderly Patients (Mansoura University Experience)

Purpose: To assess the response rate, duration of response and prognostic factors affecting response after low-dose involved-field radiotherapy in patients with relapsed low-grade B-cell non-Hodgkin lymphoma. Patients and Methods: Forty-four patients were included. Patients were treated with a total dose of 4 Gy (2 × 2 Gy) using 6 - 15 Mv photon or electron beam. Results: most patients were above age of 60 years (59%) with male predominance. Follicular lymphoma was the most common pathological type;bulky disease (>5 cm) was presented in 61.4%. Patients who received only 2 regimens were 63.7% and 31.8% had >2 involved sites. No treatment related toxicity was observed. The overall response rate was 88.7%;complete response was reached in 59.1% and stable disease in 6.8%, progressive disease in 4.5%. Median time to local progression was 33 months (95% CI 23.70 - 42.29);2-year local progression free survival was 78%. Response rate was found to be dependent on age, number of involved sites and lymph node size but independent on sex, pathological type, number of prior regimens, LDH level and time since diagnosis. Conclusion: Short-course-low dose palliative radiotherapy (2 × 2 Gy) affords an attractive option for treatment of relapsed low-grade non-Hodgkin’s lymphoma due to high response rates. However, these results had to be confirmed in a larger number of patients.

A comparative study of ^(67)Ga planar and SPECT images in diagnosis of non-Hodgkin's lymphoma

To comparatively study the sensitivity and specificity of 67Ga planar and SPECT images in diagnosis of non-Hodgkin’s lymphoma. Methods Simultaneous 67Ga planar and SPECT were conducted by using Sopha DS7 SPECF for 48 intermediate lesions in 30 patients that had been pathologically confirmed, with their healthy counterparts as controls. Results Thesensitivity of planar images in head-neck, chest and abdomen was 60.0%, 72.7% and 72.7% respectively, and that of SPECTwas 93.3%, 90.9% and 81.8% respectively. The planar imaging had a general false-neck rate of 31.3%, 2.5 times higherthan SPECF imaging (12.5%) had. Both of them had the same false-positive rate (6.3%). Conclusion SPECT imaging is superior in sensitivity to planar imaging for head-neck, chest and abdomen in detection of intermediate NHL.

Phase I study of chimeric anti-CD20 monoclonal antibody in Chinese patients with CD20-positive non-Hodgkin＇s lymphoma

Objective： This study was designed to determine the safety, pharmacokinetics and biologic effects of a humanmouse chimeric anti-CD20 monoclonal antibody （SCT400） in Chinese padents with CD20-positive B-cell non- Hodgkin＇s lymphoma （CD20 B-cell NHL）. SCT400 has an identical amino acid sequence as rituximab, with the exception of one amino acid in the CH1 domain of the heavy chain, which is common in Asians. Methods： Fifteen patients with CD20＋ B-cell NHL received dose-escalating SCT400 infusions （250 mg/m2： n=3; 375 mg/m2： n=9; 500 mg/m2： n=3） once weekly for 4 consecutive weeks with a 24-week follow-up period. The data of all patients were collected for pharmacoklnetics and pharmacodynamics analyses. Results： No dose-limiting toxicities were observed. Most drug-related adverse events were grade 1 or 2. Two patients had grade 3 or 4 ncutropenia. Under premedication, the drug-related infusion reaction was mild. A rapid, profound and durable depletion of circulating B cells was observed in all dose groups without significant effects on T cell count, natural killer （NK） cell count or immunoglobulin levels. No patient developed anti- SCT400 antibodies during the course of the study. SCT400 serum half-life （Tin）, maximum concentration （Cmax and area under the curve （AUC） generally increased between the first and fourth infusions （P〈0.05）. At the 375 mg/m2 dose, the T1/2 was 122.5±46.7 h vs. 197.0,75.0 11, respectively, and the Cmax was 200.6±20.2 pg/mL vs. 339.1±71.0 ng/mL, respectively. From 250 mg/m2 to 500 mg/m2, the Cmax and AUC increased significantly in a dose-dependent manner （P〈0.05）. Patients with a high tumor burden had markedly lower serum SCT400 concenmations compared with those without or with a low tumor burden. Of the 9 assessable patients, 1 achieved complete response and 2 achieved partial responses. Conclusions; SCT400 is well-tolerated and has encouraging preliminary efficacy in Chinese patients with CD20＋ B-cell NHL.

Correlation between Increased Circulating Endothelial Progenitor Cells and Stage of non-Hodgkin Lymphoma

This study aims to examine the levels of circulating endothelial progenitor cells （cEPCs） in the peripheral blood of patients with non-Hodgkin lymphoma （NHL） and their correlation with the tumor stage. Forty-one patients with biopsy-proven NHL and 16 healthy individuals were recruited. Pe- ripheral blood mononuclear cells （PBMCs） were isolated by density gradient centrifugation, and cEPCs were characterized by triple staining using antibodies against CD133, CD34 and vascular endothelial growth factor receptor-2 （VEGFR-2, CD309） and quantified by flow cytometry. In NHL patients, the number of cEPCs was significantly greater than in control group （P=-0.000）. The cEPCs counts in patients with NHL of stage III-1V were significantly greater than in stage I -II （P=-0.010）. FACS analysis revealed that the number of cEPCs in NHL patients had no correlation with the gender （P=0.401） or the pathological category （P=0.852）. It was suggested that the over-expression of cEPCs in NHL patients may serve as a novel biomarker for disease progression in NHL.

Expression of survivin in Human Non-Hodgkin Lymphoma and Its Correlation with Proliferation and Angiogenesis

In order to investigate the expression change of survivin in non-Hodgkin lymphoma （NHL） and its possible effects on NHL development, the expression of survivin, Ki-67, caspase3 and FⅧRAg in reactive lymphoid hyperplasia （RH） and NHL was detected by immunohistochemical assay, and apoptosis index （AI） in RH and NHL by TUNEL analysis. The results showed that the expression of survivin is significantly higher in aggressive NHL than in indolent NHL （P〈0.01）, while there was no statistically significant difference between RH and indolent NHL （P〉0.05）. The expres- sion of survivin had a significantly positive correlation with the expression of Ki-67 and FVSRAg （r=0.6495, 0.6635, respectively, both P〈0.01）, and a negative correlation with the expression of caspase3 and AI （r=-0.5820, -0.6013, respectively, P〈0.01）. It was suggested that survivin may contribute to the progression of NHL by playing an important role in promoting cell proliferation, inhibiting cell apoptosis and enlisting angiogenesis. Survivin expression is closely related to malignant grade and therefore may be considered an important prognostic factor of NHL.