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.

The expression of cyclooxygenase-2 （COX-2） and p16 in non-Hodgkin＇s lymphomas and its clinical significance

目的将在 non-Hodgkin 的淋巴瘤(NHL ) 和他们与它的开始和进步的关系调查 cyclooxygenase-2 (COX-2 ) 和 p16 蛋白质的表示。COX-2 和 p16 蛋白质的表达式被流动血细胞计数与非恶意的疾病从 60 个 NHL 病人和 10 个控制病人在淋巴结织物学习的方法。结果在 NHL 纸巾的 COX-2 蛋白质表示的积极的率(63.3% ， 38/60 ) 在在纸巾的正常单桅单甲板平底船比那高(0， 0/10 ) 。差别在二个组之间是重要的(P 【 0.01 ) 。COX-2 蛋白质的表示与 NHL 的临床的阶段被联系。在舞台我 + II 病人，它显著地更低(35.0%+54.6%) 比那在阶段 III + IV 病人(84.6%+87.5%)(P 【 0.01 ) 。在不同性别，变老，恶意的度，国际新闻学会等级，额外的节的参与和 B 症状组织的肿瘤， COX-2 表示的差别不是统计上重要的(P 】 0.05 ) 。p16 蛋白质表示的积极的率(41.7% ， 25/60 ) 在正常淋巴瘤在 NHL' 是比那统计上低的(100% ， 10/10 )(P 【 0.01 ) 。p16 蛋白质的表示与 NHL 的恶意的度有关。在低恶意的度纸巾的 p16 蛋白质的积极的率(64.7% ， 11/17 ) 在高恶意的度纸巾比那高(14.3% ， 2/14 )(P 【 0.05 ) 。在不同性别，年龄，国际新闻学会等级，额外的节的参与，临床的阶段和 B 症状的 NHL 纸巾的 p16 蛋白质的积极的率不是统计上重要的(P 】 0.05 ) 。在 COX-2 积极病人的 p16 蛋白质表示是 47.4%(18/38 ) ，并且在否定病人，它是 31.8%(7/22 ) 。有没有统计上他们之间的差别(P 】 0.05 ) 。在那里揭示的关联分析不是在 COX-2 和 p16 蛋白质的表示之间的关联。COX-2 和 p16 蛋白质都可以与开始有关系并且 NHL 进行的结论。在 NHL 的 COX-2 蛋白质的表示可以是差的预示的指示物。COX-2 和 p16 蛋白质可能在 NHL 的开始和进步有不同机制。他们的关系第一在这篇文章被提出并且需要推进学习。

Bruton’s tyrosine kinase inhibitors in primary central nervous system lymphoma:New hopes on the horizon

In this editorial,we comment on the article by Wang et al.This manuscript explores the potential synergistic effects of combining zanubrutinib,a novel oral inhibitor of Bruton’s tyrosine kinase,with high-dose methotrexate(HD-MTX)as a therapeutic intervention for primary central nervous system lymphoma(PCNSL).The study involves a retrospective analysis of 19 PCNSL patients,highlighting clinicopathological characteristics,treatment outcomes,and genomic biomarkers.The results indicate the combination’s good tolerance and strong antitumor activity,with an 84.2%overall response rate.The authors emphasize the potential of zanubrutinib to modulate key genomic features of PCNSL,particularly mutations in myeloid differentiation primary response 88 and cluster of differentiation 79B.Furthermore,the study investigates the role of circulating tumor DNA in cerebrospinal fluid for disease surveillance and treatment response monitoring.In essence,the study provides valuable insights into the potential of combining zanubrutinib with HD-MTX as a frontline therapeutic regimen for PCNSL.The findings underscore the importance of exploring alternative treatment modalities and monitoring genomic and liquid biopsy markers to optimize patient outcomes.While the findings suggest promise,the study’s limitations should be considered,and further research is needed to establish the clinical relevance of this therapeutic approach for PCNSL.

Non Hodgkin’s Lymphoma with Right Atrial Intra Cardiac Metastases

Background: Diffuse Large B-Cell Lymphoma (DLBCL) is the most variant of Non-Hodgkin’s Lymphoma (NHL) and also the most common variant with secondary intracardiac masses. Case summary: 7 years old child presented to emergency with acute decompensated cardiac failure, ascites and tender hepatomegaly. 2D echo evaluation was suggestive of large intracardiac mass in the right atrium almost completely obstructing Tricuspid valve orifice, gross pericardial effusion and dilated Inferior Vena Cava (IVC). Emergency tumor excision surgery was performed which revealed 4 × 4 cm pinkish firm mass arising from anterior Tricuspid annulus which was completely excised. Child was extubated on postoperative day (POD) 0 and was on minimal inotropic support. Ascites reduced significantly on POD1 allowing abdominal palpation which revealed a mass in the epigastric region. This prompted evaluation by pediatrician and oncology workup suggestive of increased 18-Flouro Deoxy Glucose (18-FDG) uptake in the mediastinum, abdomen, bilateral proximal thighs, all mediastinal lymph nodal stations, bilateral lung hilar stations 10R, 10L involving all encasing the heart and great vessels with pleural deposits, Celiac trunk, superior Mesenteric Artery (SMA), Portal vein, IVC and abdominal aorta. Histo pathology Examination (HPE) and Immuno Histo Chemistry (IHC) of intracardiac mass revealed DLBCL which is metastatic in nature. Chemotherapy was started as per (French American British Lymphomes Malins B) FAB LMB-96 protocol with the child currently in the Induction phase having poor prognosis and less survival interval. Conclusion: Surgery can be considered a treatment option for metastatic intracardiac masses during emergency scenarios like cardiogenic shock to relieve obstruction along the pathway of blood flow in the heart even though we may not be able to completely excise the tumor surgically.

Prognostic Value of Semi-Quantitative 18F-FDG PET/CT Parameters in Hodgkin’s Lymphoma

Objective:To assess the prognostic value of maximum standardized uptake value(SUVmax),metabolic tumor volume(MTV),and total lesion glycolysis(TLG)determined by 18F-fluorodeoxyglucose positron emission tomography-computed tomography(18F-FDG PET/CT)imaging in Hodgkin’s lymphoma patients.Methods:A total of 148 Hodgkin’s lymphoma patients diagnosed with lymph node biopsy from October 2014 to October 2015 were retrospectively analyzed followed by categorizing into good(125 cases)and poor(23 cases)prognosis groups.The chi-squared test was used to analyze the clinicopathological characteristics of Hodgkin’s lymphoma patients with the semi-quantitative 18F-FDG PET/CT parameters;the Spearman method was used to analyze the correlation between the semi-quantitative parameters and clinicopathological features of Hodgkin’s lymphoma;receiver operating characteristic curve was used to analyze the predictive value of the semi-quantitative parameters for poor prognosis of Hodgkin’s lymphoma patients.Results:Mean SUVmax,MTV,and TLG of the 148 cases of Hodgkin’s lymphoma were 7.26±2.38,12.46±3.14 cm3,and 76.83±18.56 g,respectively.Significant variations in the Ann Arbor stage and clinical classification were observed with different levels of semi-quantitative parameters(P<0.05).The semi-quantitative parameters were not correlated with age and gender(P>0.05)but positively correlated with Ann Arbor stage and clinical classification(P<0.05).These parameters in the poor prognosis group were higher than those in the good prognosis group(P<0.05).The area under the curve(AUC)of SUVmax,MTV,and TLG in predicting the poor prognosis group was 0.881,0.875,and 0.838,with cut-off values of 7.264,12.898 cm3,and 74.580g,as well as specificity of 88.8%,84.0%,and 78.4%,and sensitivity of 87.0%,87.0%,and 78.3%,respectively;the AUC of the combined prediction was 0.986,with a specificity of 97.6%and sensitivity of 86.3%.Conclusion:The semi-quantitative 18F-FDG PET/CT parameters provide valuable insights for Hodgkin’s lymphoma prognosis assessment.

Comparison of Dose-dense ABVD and Standard ABVD in the Treatment of Early Unfavorable and Advanced Hodgkin's Lymphoma: A Retrospective Analysis

This retrospective analysis compared standard regimen of doxorubicin, bleomycin, vin- blastine, and dacarbazine （ABVD） with the dose-dense ABVD regimen （ABVD-21） in terms of effi- cacy and toxicity. Patients who had early-stage unfavorable or advanced Hodgkin＇s lymphoma （HL） according to German Hodgkin Study Group criteria from March 1999 to February 2011 were ana- lyzed for treatment response, long-term survival and hematological toxicity. There were 85 patients in the ABVD-21 group and 118 patients in the ABVD group respectively. The complete remission rates aider completion of treatment were 92.9% and 90.7% for ABVD-21 and ABVD, respectively. During a median follow-up period of 62 months, no significant difference was found in projected 10-year progression-free survival （PFS） and overall survival （OS） rates （84.7% and 94.1% respectively for ABVD-21; 81.4% and 91.5% for ABVD）. Subgroup analyses showed that ABVD-21 was signifi- cantly better than ABVD for patients with IPS〉3 in terms of PFS and OS rates. Grade 3 to 4 leuko- penia （51.8% vs. 28.8%, P=0.001） and neutropenia （57.6% vs. 39.0%, P=0.009） were more common with ABVD-21. We were led to conclude that dose-dense ABVD did not result in better tumor con- trol and overall survival than did ABVD for early-stage unfavorable HL. However, patients at high risk, for example, with IPS〉3, may benefit from dose-dense ABVD.

Waldenstrom's macroglobulinemia associated with Hodgkin's lymphoma:a case report

Waldenstrom＇s macroglobulinemia/lymphoplasmacytic lymphoma （WM/LPL） is a low-grade B-cell non- Hodgkin＇s lymphoma with an indolent clinical course. Higher-grade non-Hodgkin lymphoma （NHL） and therapy- related myelodysplasia/acute leukemia （t-MDS/AML） have been reported in patients with WM/LPL in previous studies. However, only two cases with WM/LPL were reported to develop to Hodgkin lymphoma （HL）. Here, we report the first case of WM/LPL who developed classical HL simultaneously 3 years after initial nucleoside analog-based chemotherapy.

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.

Composite diffuse large B-cell lymphoma and classical Hodgkin's lymphoma of the stomach:Case report and literature review

The combination of classical Hodgkin’s lymphoma(cHL)and non-Hodgkin lymphoma coexisting in the same patient is not common,especially in one extranodal location.Here we present a rare case of composite diffuse large B-cell lymphoma(DLBCL)and cHL occurring simultaneously in the stomach of a 53-year-old female who presented with upper abdominal discomfort and gas pain.Surgery was performed and the disease was diagnosed pathologically as composite lymphoma of DLBCL and cHL using hematoxylin-eosin and immunohistochemical staining.Epstein-Barr virus(EBV)infection was not detected by in situ hybridization for EBV-encoded RNA or immunohistochemistry for EBV latent membrane protein-1.Polymerase chain reaction analysis from the two distinct components of the tumor demonstrated clonal immunoglobulinκlight chain gene rearrangements.The patient died approximately 11 mo after diagnosis in spite of receiving eight courses of the CHOP and two courses of the rituximab-CHOP(RCHOP) chemotherapy regimen.This case report showed that the two distinct components,DLBCL and cHL,appeared to originate from the same clonal progenitor cell,and that EBV infection was not essential for transformation during the course of tumorigenesis.

Epstein Barr virus-positive mucocutaneous ulcer of thecolon associated Hodgkin lymphoma in Crohn＇s disease

Epstein Barr virus （EBV） positive mucocutaneous ulcers（EBVMCU） form part of a spectrum of EBV-associatedlymphoproliferative disease. They have been reportedin the setting of immunosenescence and iatrogenicimmunosuppression, affecting the oropharyngeal mucosa,skin and gastrointestinal tract （GIT）. Case reports andseries to date suggest a benign natural history respondingto conservative management, particularly in the GIT. Wereport an unusual case of EBVMCU in the colon, arisingin the setting of immunosuppression in the treatment ofCrohn＇s disease, with progression to Hodgkin lymphoma18 mo after cessation of infliximab. The patient presentedwith multiple areas of segmental colonic ulceration,histologically showing a polymorphous infiltrate withEBV positive Reed-Sternberg-like cells. A diagnosisof EBVMCU was made. The ulcers failed to regressupon cessation of infliximab and methotrexate for 18mo. Following commencement of prednisolone for herCrohn＇s disease, the patient developed widespreadHodgkin lymphoma which ultimately presented as alife-threatening lower GIT bleed requiring emergencycolectomy. This is the first report of progression ofEBVMCU to Hodgkin lymphoma, in the setting of ongoingiatrogenic immunosuppression and inflammatory boweldisease.

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.

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 gastric non-Hodgkin lymphomas:Recent advances regarding disease pathogenesis and treatment

Primary gastric lymphomas(PGLs)are distinct lymphoproliferative neoplasms described as heterogeneous entities clinically and molecularly.Their main histological types are diffuse large B-cell lymphoma(DLBCL)or mucosaassociated lymphoma tissue.PGL has been one of the main fields of clinical research of our group in recent years.Although gastric DLBCLs are frequent,sufficient data to guide optimal care are scarce.Until today,a multidisciplinary approach has been applied,including chemotherapy,surgery,radiotherapy or a combination of these treatments.In this minireview article,we provide an overview of the clinical manifestations,diagnosis and staging of these diseases,along with their molecular pathogenesis and the most important related clinical published series.We then discuss the scientific gaps,perils and pitfalls that exist regarding the aforementioned studies,in parallel with the unmet need for future research and comment on the proper methodology for such retrospective studies.Aiming to fill this gap,we retrospectively evaluated the trends in clinical presentation,management and outcome among 165 patients with DLBCL PGL who were seen in our institutions in 1980-2014.The study cohort was divided into two subgroups,comparing the main 2 therapeutic options[cyclophosphamide doxorubicin vincristine prednisone(CHOP)vs rituximab-CHOP(R-CHOP)].A better outcome with immunochemotherapy(R-CHOP)was observed.In the next 2 mo,we will present the update of our study with the same basic conclusion.

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.

A case of primary isolated non-Hodgkin’s lymphoma of the esophagus in an immunocompetent patient

Primary non-Hodgkin’s lymphoma of the esophagus is a rare disease.A case of primary isolated nonHodgkin’s lymphoma of the esophagus in a 77-yearold man without acquired immunodeficiency syndrome is presented.We describe the clinical features and the imaging findings(barium swallow,endoscopic ultrasonography and CT)of a biopsy proven B-cell lymphoma with diffuse transmural involvement of the esophagus wall,which was discovered incidentally.We also briefly review the literature.

Sternal Hodgkin’s lymphoma: A case report and review of literature

BACKGROUND Sternal tumors are difficult to diagnose, and usually need to be differentiated from other diseases such as tuberculosis, osteosarcoma, intrathoracic thyroid and thymoma. The sternum is a rare site of Hodgkin’s lymphoma, which is often misdiagnosed as tuberculosis on routine histopathology.CASE SUMMARY We reported a 47-year-old female patient with chest pain in the upper sternum for 1 mo. Chest computed tomography found a mass in the upper sternum.Pathology and immunohistochemistry of the biopsy confirmed the diagnosis of typical Hodgkin’s lymphoma(mixed cellularity subtype). Patient was diagnosed with primary sternal Hodgkin’s lymphoma and administered 6 cycles of adriamycin, bleomycin, vinblastine, and dacarbazine chemotherapy. Patient had no tumor recurrence and progression at a follow-up visit 2 years later.CONCLUSION This study highlights the rarity of primary sternal Hodgkin’s lymphoma and the challenges of its diagnosis. A Pub Med and Web of Science search revealed 10 reported cases of sternal involvement in Hodgkin’s lymphoma.