Lymphoma The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . All rights reserved. FoxP3-Positive T-Regulatory Cells in Lymph Nodes with Mycosis Fungoides and Sézary Syndrome Tue, 11 Nov 2014 08:03:41 +0000 Mycosis fungoides and Sézary syndrome are indolent cutaneous T-cell lymphomas, with skin-associated peripheral lymph nodes being the most frequent extracutaneous site of involvement. Acquisition of functional properties of regulatory T-cells by malignant T-cells in advanced disease may contribute to immunosuppression. Whereas previous studies examining FoxP3 protein expression in mycosis fungoides and Sézary syndrome have focused on skin specimens, little data are available on lymph nodes from patients with these conditions. In this study we examined FoxP3+ regulatory T-cells in lymph nodes from 26 patients with mycosis fungoides and Sézary syndrome and correlated the findings with clinical data, molecular assays for T-cell clonality, and flow cytometry. Except for one case of Sézary syndrome in which malignant T-cells expressed FoxP3 protein, a significantly lower number of FoxP3-expressing cells occurred in lymph nodes that were clearly involved with lymphoma as compared to uninvolved nodes. Cox proportional hazards model showed that lymph node rating and histological evidence of transformation, but not number of FoxP3+ cells, were factors significantly associated with adverse prognosis. We speculate that modulation of FoxP3+ cells in lymph nodes involved with lymphoma might play a role in disease progression. Attainment of a regulatory T-cell phenotype by a subset of lymphoma cells might signal a poor prognosis. Rekha Bhat, Bhavna Khandpur, Eric C. Vonderheid, and J. Steve Hou Copyright © 2014 Rekha Bhat et al. All rights reserved. Rituximab Induced Interstitial Lung Disease in Patients with Non-Hodgkin’s Lymphoma: A Clinical Study of Six Cases and Review of the Literature Mon, 15 Sep 2014 11:10:58 +0000 Background. Rituximab-induced lung disease (R-ILD) is a rare entity that should be considered in patients treated with rituximab who present with dyspnea, fever, and cough but no clear evidence of infection. Aim. The aim of this prospective longitudinal study is to describe the clinical presentation, management, and response to rechallenge in patients diagnosed with rituximab induced ILD over a period of one year. Results. Out of sixteen patients with CD20 positive non-Hodgkin’s lymphoma who received rituximab along with standard chemotherapy, six patients developed features suggestive of R-ILD. Four (66.6%) of these patients had diffuse large B cell lymphoma. The median time of presentation of R-ILD was after the 3rd cycle of chemotherapy. Three patients (50%) presented with acute onset of high fever, dyspnea, and dry cough while the remaining three presented with insidious onset of dyspnea and dry cough. An infectious etiology for the respiratory illness was ruled out in all patients with an exhaustive work-up. Four patients (66.6%) responded to corticosteroid treatment and supplemental oxygen. One patient required mechanical ventilation and succumbed to ILD while another required prolonged supplemental oxygen. Two (33.3%) of patients were successfully rechallenged with rituximab under cover of corticosteroids. Conclusions. Rituximab induced lung disease is a rare but potentially fatal pulmonary toxicity which requires a high index of suspicion for early diagnosis and treatment. Uma Maheswari Krishnaswamy, Vinayak V. Maka, Murali Subramanian, Rohith Chitrapur, and Nalini Kilara Copyright © 2014 Uma Maheswari Krishnaswamy et al. All rights reserved. Impact of BMI and Gender on Outcomes in DLBCL Patients Treated with R-CHOP: A Pooled Study from the LYSA Thu, 16 Jan 2014 07:58:18 +0000 In diffuse large B-cell lymphoma (DLBCL), the age-adjusted International Prognostic Index (aaIPI) score is currently used to predict patient outcomes and to choose the best therapeutic treatment. Body mass index (BMI) and gender are occasionally sited as prognostic factors; however, their value has never been studied in a large series of patients included in prospective clinical trials in the rituximab era. To assess the impact of BMI and gender on OS and PFS independently of the aaIPI score, we pooled 985 patients that were prospectively included in GELA studies and uniformly treated with R-CHOP. Univariate analysis indicated that high aaIPI and male gender were associated with a worse PFS, whereas high (>25) or low (<18.5) BMI scores were not. High aaIPI score was the only factor predictive for OS. In a multivariate analysis, including aaIPI score, gender, BMI, and interaction between BMI and gender, aaIPI remained the strongest predictive factor, and BMI < 18.5 was significantly associated with a worse OS but not PFS. In conclusion, in the rituximab era, the aaIPI score remains the major predictor of outcome in DLBCL patients; however, male gender and low BMI seem to impact outcome. Clémentine Sarkozy, Nicolas Mounier, Alain Delmer, Achiel Van Hoof, Jean Michel Karsenti, Emmanuel Fleck, Marie Maerevoet, Jean Claude Eisenmann, Richard Delarue, Michel Fabbro, and Bertrand Coiffier Copyright © 2014 Clémentine Sarkozy et al. All rights reserved. Primary Non-Hodgkin’s Lymphoma of Stomach: To Report 54 Patients and Analysis of Major Reported Series Wed, 23 Oct 2013 11:21:57 +0000 Introduction. This study aimed to report the characteristics, prognostic factors, and treatment outcomes of 54 patients with primary gastric lymphoma. Materials and Methods. This retrospective study was carried out by reviewing the medical records of 54 adult patients diagnosed at a tertiary academic hospital. All the patients were treated with curative intent. Forty-four patients (81.5%) underwent gastrectomy followed by adjuvant chemotherapy and/or radiotherapy, whereas 10 ones (18.5%) were treated with chemotherapy alone or with radiotherapy. Results. The study was conducted on 25 males and 29 females with the median age of 50 years. Diffuse large B-cell lymphoma (DLCL) (67%) and Mucosa Associated Lymphoid Tissue (MALT) lymphoma (26%) were the most common histologic types. Besides, 36 (59%), 16 (30%), 5 (9%), and 1 (2%) patients were in stages I, II, III, and IV, respectively. The 5-year disease-free survival and overall survival were 64.7% and 67%, respectively. In univariate analysis for overall survival, International Prognostic Index (IPI) (), the WHO performance status (), Ann Arbor stage (), age (), and LDH serum level () were the prognostic factors. Conclusion. Gastric lymphoma tends to present in early stage of the disease and has a favorable outcome. Mansour Ansari, Hamid Nasrolahi, Amir Abbas Kani, Seyed Hasan Hamedi, Samira Razzaghi, Niloofar Ahmadloo, Mohammad Mohammadianpanah, Shahpour Omidvari, and Ahmad Mosalaei Copyright © 2013 Mansour Ansari et al. All rights reserved. Therapy-Related Late Adverse Events in Hodgkin’s Lymphoma Thu, 11 Apr 2013 15:09:43 +0000 Hodgkin's lymphoma (HL) is one of the most curable hematologic diseases with an overall response rate over 80%. However, despite this therapeutic efficacy, HL survivors show a higher morbidity and mortality than other people of the same age because of long-term therapy-related events. In the last decades, many efforts have been made to reduce these effects through the reduction of chemotherapy dose, the use of less toxic chemotherapeutic agents, and the introduction of new radiation techniques. In this paper, we will describe the main long-term effects related to chemotherapy and radiotherapy for HL, the efforts to reduce toxicity made in the last years, and the clinical aspects which have to be taken into consideration in the followup of these patients. Manuel Gotti, Valeria Fiaccadori, Elisa Bono, Benedetta Landini, Marzia Varettoni, Luca Arcaini, and Maurizio Bonfichi Copyright © 2013 Manuel Gotti et al. All rights reserved. Is There Any Relationship between Human Herpesvirus-8 and Multiple Myeloma? Tue, 26 Feb 2013 11:36:18 +0000 Background. Human herpesvirus-8 (HHV-8) is associated with some human diseases including Kaposi’s sarcoma and also some B-cell lymphoproliferative disorders. Few studies have highlighted the potential role of HHV-8 in the development of multiple myeloma (MM) which is known as a malignant proliferation of plasma cells derived from a single clone. Aims. The aim of this study was to find a relationship between HHV-8 and MM using polymerase chain reaction (PCR) method. Materials and Methods. This study was conducted on 30 formalin-fixed, paraffin-embedded (FFPE) bone marrow biopsies of multiple myeloma and 30 normal FFPE bone marrow biopsies. After the sample preparation, Deoxyribonucleic acid (DNA) was extracted by nonheating procedure. PCR for HHV-8 virus was carried out with commercial kit and the PCR products were visualized by gel electrophoresis. Finally, the statistical analysis was performed. Results. HHV-8 virus was not detected by PCR from FFPE blocks of multiple myeloma samples, while only one of the controls showed DNA band of the corrected molecular weights. Fisher’s exact test showed that no statistical differences were found between the two groups (). Conclusion. Our report adds to the body of evidence that there is no association between HHV- 8 and MM against a major role of HHV-8 infection in the pathogenesis of clonal plasma cell proliferation. Mohammad Hadi Sadeghian, Maryam Mohammadnia Avval, Hossein Ayatollahi, Mohammad Reza Keramati, Bahram Memar, Saeed Amel Jamedar, Maryam Sheikhi, and Gohar Shaghayegh Copyright © 2013 Mohammad Hadi Sadeghian et al. All rights reserved. Polo-Like Kinase 1: A Novel Target for the Treatment of Therapy-Resistant Mantle Cell Lymphoma Thu, 21 Feb 2013 08:59:06 +0000 Mantle cell lymphoma (MCL) is a B-cell non-Hodgkin lymphoma (NHL) which is one of the most aggressive lymphomas. Despite recent improvements in therapies, the development of therapy-resistance is still a major problem; therefore, in order to understand the molecular basis of therapy-resistance, stable therapy-resistant MCL cell lines have been established by us. Based on the gene expression profiles of these cell lines, Polo-like kinase 1 (PLK1) was chosen as a therapeutic target. In this paper, we demonstrate a significant antilymphoma effect of targeting PLK1 in therapy-resistant MCL cells and primary MCL cells from refractory patients. PLK1 knockdown with the antisense oligonucleotide (ASO)/or small molecule inhibitor BI2536 showed significantly decreased proliferation and increased apoptosis in therapy-resistant MCL cell lines and MCL primary cells. Additionally, the direct protein-protein interaction partners of PLK1 were mapped using ingenuity pathway and confirmed the level of association of these partners with PLK1 based on their expression changes following PLK1 knockdown using real-time PCR. Results suggest that PLK1 is a viable target for the treatment of therapy-resistant MCL. Adam K. Ahrens, Nagendra K. Chaturvedi, Ashima Shukla, Tara M. Nordgren, Ganapati V. Hegde, Julie M. Vose, and Shantaram S. Joshi Copyright © 2013 Adam K. Ahrens et al. All rights reserved. The Development and Validation of a Measure of Health-Related Quality of Life for Non-Hodgkin’s Lymphoma: The Functional Assessment of Cancer Therapy—Lymphoma (FACT-Lym) Wed, 20 Feb 2013 08:21:02 +0000 Background. The individual concerns of non-Hodgkin’s lymphoma (NHL) patients require identification and assessment during clinical research proposing to measure patients’ outcomes. The FACT-Lym was developed as part of the FACIT measurement system to address health-related quality-of-life (HRQL) issues for NHL patients. Patients and Methods. Items for the FACT lymphoma subscale (LymS) were generated from healthcare provider interviews, published literature, and content validity patient interviews. The FACT-Lym was validated on a sample of 84 NHL patients, with additional measures at baseline (T1), 3–7 days (T2), and 8–12 weeks (T3). Results. Item correlations, expert relevance ratings, and patient input on content shortened the initial 22-item LymS to 15 items. The validation sample included 56% female, 76.2% white, 60% indolent disease, and 85% receiving treatment. Internal consistency coefficients for the 15-item LymS (.79, .85, and .84 T1–T3) and test-retest stability (.84) indicated good reliability. Correlations between LymS and SF-36 physical () and mental () summary scores reflect concurrent validity. Responsiveness to ECOG performance status and treatment status exceeded established FACT subscale scores. The FACT-LymS differentiated patients’ retrospective ratings of change in each of the three groups (better; unchanged; worse), . Conclusions. These results support the validity of the FACT-Lym and suggest it will be a useful targeted endpoint in NHL clinical research. Fay J. Hlubocky, Kimberly Webster, John Cashy, Jennifer Beaumont, and David Cella Copyright © 2013 Fay J. Hlubocky et al. All rights reserved. Clinical Features and Prognosis of CD20 Negative Aggressive B-Cell Non-Hodgkins Lymphoma Thu, 03 Jan 2013 09:47:30 +0000 Cluster designation (CD) 20 antigen is expressed on most B-cell lymphomas and serves as a therapeutic target for rituximab. A small minority of aggressive B-cell lymphomas, predominantly plasmablastic variants, do not express CD 20. We systematically reviewed all cases of aggressive B-cell lymphomas diagnosed at our institution over a period of 13 years. Of the 232 cases, 7 did not express CD 20. Five of these were plasmablastic lymphomas while two were unclassifiable B-cell lymphomas. While most of the plasmablastic lymphomas responded to chemotherapy, patients with unclassifiable lymphomas were primarily refractory or relapsed soon after chemotherapy. Sumit Gaur, Osvaldo Padilla, and Zeina Nahleh Copyright © 2013 Sumit Gaur et al. All rights reserved. Analysis of NF-B Pathway Proteins in Pediatric Hodgkin Lymphoma: Correlations with EBV Status and Clinical Outcome—A Children's Oncology Group Study Sun, 30 Dec 2012 09:31:36 +0000 Constitutively active nuclear factor-B (NF-B) is integral to the survival of Hodgkin/Reed-Sternberg cells (H/RS) in Hodgkin lymphoma (HL). To investigate NF-B pathway proteins in pediatric HL, we utilized a tissue microarray compiled from 102 children enrolled in the Children's Oncology Group intermediate-risk clinical trial AHOD0031 (56 male, 78 Caucasian, median age 15 years (range 1–20 years), 85 nodular sclerosing subtype, 23 Epstein-Barr virus (EBV) positive, and 24 refractory/relapsed disease). We examined the intensity, localization, and pathway correlations of NF-B pathway proteins (Rel-A/p65, Rel-B, c-Rel, NF-B1, NF-B2, IB-, IKK-, IKK-, IKK-/NEMO, NIK, and A20), as well as their associations with EBV status and clinical outcome. NF-B pathway proteins were overexpressed in pediatric HL patients compared to controls. Patients with EBV− tumors, or with rapid early therapy response, had tightly coordinated regulation of NF-B pathway proteins, whereas patients with EBV+ tumors, or slow early therapy response, had little coordinated NF-B pathway regulation. High NIK expression was associated with a slow response to therapy and decreased EFS. Elevated Rel-B, NIK, and the NF-B inhibitor A20 were associated with decreased EFS in multivariate analysis. These studies suggest a pivotal role for the NF-B pathway in therapy response and patient survival in Hodgkin lymphoma. Terzah M. Horton, Andrea M. Sheehan, Dolores López-Terrada, Robert E. Hutchison, Sonia Narendra, Meng-Fen Wu, and Hao Liu Copyright © 2012 Terzah M. Horton et al. All rights reserved. Diagnostic Workup of Small B Cell Lymphomas: A Laboratory Perspective Tue, 20 Nov 2012 09:50:06 +0000 Small B cell lymphoma is a morphological designation to a group of B cell lymphomas which are composed of a clonal population of small lymphoid cells. The subtypes of this category have diagnostically distinct characteristics and different clinical behaviors and treatment. Correct diagnosis and classification of these subsets depend on the integration of morphologic, immunophenotypic, and molecular genetic features. In this paper, differential diagnosis of this category of tumors and a practical approach based on biomarker evaluation are discussed. Kathryn Rizzo and Mehdi Nassiri Copyright © 2012 Kathryn Rizzo and Mehdi Nassiri. All rights reserved. Successful Treatment in Children with Hodgkin Lymphoma in Greece; A 20-Year Experience in a Single Institution Thu, 04 Oct 2012 18:00:51 +0000 During the last 30 years, combined chemotherapy regimens with radiotherapy or not significantly improved the prognosis for patients with Hodgkin lymphoma. We retrospectively studied 58 children (35 boys and 23 girls) with Hodgkin lymphoma who were treated at our institution during the period 1987–2006 and we correlated age, sex, stage, histology, and therapy with the outcome of patients. Of our patients, 9 children were 8 years old or younger. Nodular sclerosis was the predominant histology subtype (69%), whereas 26 patients (45%) had advanced disease (stage III or IV). Chemotherapy (CT) with various drug combinations, according to the period of treatment plus low-dose involved field radiation therapy (IFRT), was used in all patients. Five children experienced relapse and in 3 other patients second or third malignancies were documented. The overall survival was found to be 98%. No factors related to the outcome could be detected. The prognosis of children with Hodgkin lymphoma is excellent with CT combined with low dose IFRT but in long-time survivors late effects of the combined modality treatment are still issues of major concern. Longer followup of a greater number of patients is necessary to detect prognostic factors related to the outcome of children with Hodgkin lymphoma and to identify some patients who would be treated without radiation. Apostolos Pourtsidis, Dimitrios Doganis, Margarita Baka, Despina Bouhoutsou, Maria Varvoutsi, Maria Synodinou, Katerina Strantzia, and Helen Kosmidis Copyright © 2012 Apostolos Pourtsidis et al. All rights reserved. Combination Phototherapy with a Histone Deacetylase Inhibitor and a Potent DNA-Binding Bibenzimidazole: Effects in Haematological Cell Lines Thu, 27 Sep 2012 18:56:07 +0000 Current treatment for cutaneous T-cell lymphoma includes phototherapy, which involves either the use of narrowband ultraviolet B light or in combination with a psoralen photosensitiser. Therapy typically involves administration of the photosensitiser followed by topical exposure to . A different approach is extracorporeal photopheresis, an ex vivo strategy which is used for more advanced stages of disease. Further, histone deacetylase inhibitors are emerging as potent anticancer agents with suberoylanilide hydroxamic acid and depsipeptide, having received FDA approval for the treatment of cutaneous T-cell lymphoma. We have developed Sens, an extremely potent, DNA minor groove-binding sensitizer for potential use in phototherapy. We have previously demonstrated the extreme photopotency of Sens in human erythroleukemic K562 cells. Here we have extended those studies by investigating the photopotency of Sens in four haematological cell lines, namely, K562, T-cell leukaemic CEM-CCRF, P-glycoprotein overexpressing R100, and transformed B-lymphoblastoid cell lines (LCL) cells. In addition, we investigated the effects of suberoylanilide hydroxamic acid in combination with Sens. Using γH2AX as the endpoint, our findings indicate that Sens-induced phototoxicity in all four of the haematological cell lines. The addition of suberoylanilide hydroxamic acid augmented the photopotency of Sens highlighting the potential clinical applicability of combination therapies. Annabelle L. Rodd, Katherine Ververis, and Tom C. Karagiannis Copyright © 2012 Annabelle L. Rodd et al. All rights reserved. Current and Emerging Therapeutics for Cutaneous T-Cell Lymphoma: Histone Deacetylase Inhibitors Thu, 16 Aug 2012 09:05:01 +0000 Cutaneous T-cell lymphoma is a term that encompasses a spectrum of non-Hodgkin’s T-cell lymphomas with primary manifestations in the skin. It describes a heterogeneous group of neoplasms that are characterised by an accumulation of malignant T cells of the CD4 phenotype that have the propensity to home and accumulate in the skin, lymph nodes, and peripheral blood. The two most common variants of cutaneous T-cell lymphoma include mycosis fungoides and the leukemic variant, the Sézary syndrome. While numerous treatments are available for cutaneous T-cell lymphoma and have shown to have success in those with patch and plaque lesions, for those patients with tumour stage or lymph node involvement there is a significant decline in response. The relatively new therapeutic option with the use of histone deacetylase inhibitors is being advanced in the hope of decreasing morbidity and mortality associated with the disease. Histone deacetylase inhibitors have been shown to induce changes in gene expression, affecting cell cycle regulation, differentiation, and apoptosis. The aim of this paper is to discuss CTCL in the context of advances in CTCL treatment, specifically with HDAC inhibitors. Annabelle L. Rodd, Katherine Ververis, and Tom C. Karagiannis Copyright © 2012 Annabelle L. Rodd et al. All rights reserved. AIDS-Related Non-Hodgkin's Lymphoma in Sub-Saharan Africa: Current Status and Realities of Therapeutic Approach Thu, 12 Jul 2012 13:23:39 +0000 Today AIDS-related non-Hodgkin's lymphoma (AR-NHL) is a significant cause of morbidity and mortality in HIV-infected patients the world over, and especially in sub-Saharan Africa. While the overall incidence of AR-NHL since the emergence of combination antiretroviral therapy (cART) era has declined, the occurrence of this disease appears to have stabilized. In regions where access to cART is challenging, the impact on disease incidence is less clear. In the resource-rich environment it is clinically recognized that it is no longer appropriate to consider AR-NHL as a single disease entity and rather treatment of AIDS lymphoma needs to be tailored to lymphoma subtype. While intensive therapeutic strategies in the resource-rich world are clearly improving outcome, in AIDS epicenters of the world and especially in sub-Saharan Africa there is a paucity of data on treatment and outcomes. In fact, only one prospective study of dose-modified oral chemotherapy and limited retrospective studies with sufficient details provide a window into the natural history and clinical management of this disease. The scarcities and challenges of treatment in this setting provide a backdrop to review the current status and realities of the therapeutic approach to AR-NHL in sub-Saharan Africa. More pragmatic and risk-adapted therapeutic approaches are needed. Peter M. Mwamba, Walter O. Mwanda, Naftali W. Busakhala, R. Matthew Strother, Patrick J. Loehrer, and Scot C. Remick Copyright © 2012 Peter M. Mwamba et al. All rights reserved. An Unusual Presentation of Liver Failure in a Patient with Primary Gastrointestinal Hodgkin's Lymphoma Thu, 25 Nov 2010 14:22:50 +0000 Introduction. Hodgkin's lymphoma (HL) presenting either with primary bowel involvement or with cholestasis is unusual. The combination of primary gastrointestinal HL presenting with cholestasis and ductopenia has not been previously described. Case Report. We present a case of primary gastrointestinal HL with evidence of liver involvement, but also with prominent ductopenia on liver biopsy and associated intrahepatic cholestasis. A 50-year-old man with a history of Crohn's disease presented with a bowel obstruction, for which he underwent a small bowel resection. Histology revealed HL. His course was complicated by cholestatic liver failure. A subsequent liver biopsy revealed both focal involvement by lymphoma and ductopenia, resembling vanishing bile duct syndrome (VBDS). He was treated with chemotherapy with improvement in his cholestasis, but he eventually succumbed due to further complications of his disease and treatment toxicities. Conclusion. This case of primary gastrointestinal HL associated with ductopenia does not meet classic criteria for VBDS, but the clinical presentation and pathology are suggestive of a VBDS-like paraneoplastic process. Therapies for HL in the setting of cholestatic liver failure require special consideration, but some reports of durable remissions and recovery of liver function have been reported. Gabrielle B. Rocque, Jeffrey T. Malik, David T. Yang, and Julie E. Chang Copyright © 2011 Gabrielle B. Rocque et al. All rights reserved.