Management Of non-Hodgkin Lymphoma Research Articles

Evaluation of clinicians' knowledge and practice regarding pharmacotherapy of Non-Hodgkin's lymphoma: A multi-center study in Yemen.

Non-Hodgkin lymphoma (NHL) is a hematological malignancy that requires effective pharmacotherapy for optimal management. There is limited information regarding Yemeni clinicians' knowledge and practice of NHL pharmacotherapy. This study aims to assess the knowledge and practice of physicians and nurses in Yemen regarding pharmacotherapy of NHL. A cross-sectional study was conducted in Sana'a, Yemen, from January 1, 2022, to January 31, 2023. Two self-administrated and validated questionnaires were distributed to 99 physicians and 164 nurses involved in pharmacotherapy for NHL in different oncology centers and units across Yemen. Convenience samples were used to recruit participants. A binary logistic regression analysis was performed to identify factors associated with nurses' and physicians' knowledge and practice. The correlation coefficient was used to examine the relationship between knowledge and practice. A total of 77 physicians and 105 nurses completed the questionnaires. The results showed that 54.3% of nurses and 66.2% of physicians had poor knowledge of NHL pharmacotherapy. In terms of practice, 83.8% of nurses and 75.3% of physicians exhibited poor practice regarding NHL pharmacotherapy. Multivariable logistic regression analysis identified that nurses who received sufficient information about chemotherapy displayed a significant association with good knowledge, while nurses working in the chemotherapy administration department were significant predictors of good practice. Among physicians, those working in the National Oncology Center (NOC) in Sana'a demonstrated good practice. Correlation analysis revealed a positive relationship between nurses' knowledge and their practice. The study's results confirm deficiencies in knowledge and practice of pharmacotherapy for NHL among physicians and nurses in Yemen. Efforts should be made to enhance their understanding of treatment guidelines and to improve patient care. Improvement in educational programs and training opportunities may contribute to improving patient outcomes in the management of NHL.

An An Overview of the Treatment of Non-Hodgkin Lymphoma with The Novel Cellular Therapies: CAR-T and Bispecific Monoclonal Antibodies

The management of non-Hodgkin lymphoma (NHL), including refractory and relapsed high grade and low-grade NHL has been significantly improved in recent years with the development of cellular therapies which harness the powerful anti-cancer effects of the immune system. These include the ground-breaking and now established technology of chimeric antigen receptor cell therapy as well as the promising new range of bispecific monoclonal antibody therapies. This article will give a summary of the currently available cellular and bi-specific antibody therapies for the treatment of NHL in licenced use and clinical trials, including an overview of their proven efficacy and characteristic side-effect profiles which distinguish them from conventional immunochemotherapy. The relative strengths and weaknesses of these comparable therapies will also be discussed together with consideration of where they may fit into the treatment sequence of NHL in the future. The article will also address the challenges of delivering these innovative technologies in different healthcare settings and how they may alter the future of therapy for patients with this form of cancer.

Immunophenotypic characterisation of non-Hodgkin lymphomas at a tertiary hospital in Ghana.

Non-Hodgkin lymphomas (NHLs) are a heterogeneous group of clonal lymphoid tumours originating from lymphocytes. They constitute about 90% of an estimated 3%-4% worldwide distribution of malignant lymphomas among various cancers. Despite the continuous rise and associated deaths, research on NHLs, and in particular the area of immunophenotypic spectrum is limited in Ghana and sub-Saharan Africa. A retrospective, descriptive study in which archived tissue blocks of histologically diagnosed NHLs at a tertiary hospital in Accra, Ghana, were used. Antigenic phenotypes were determined by immunohistochemistry. A total of 66 cases of NHLs, with a mean age of 50.2 ± 16.1 years, were selected for the study. Among the targeted markers, cluster of differentiation 20 (CD20) was the most commonly expressed in 89.4% (59) cases. Immunohistochemistry studies revealed a greater proportion of B cell lymphomas of 89.4%. Five subtypes were successfully identified, of which diffuse large B cell lymphoma constitutes the predominant group (40.9%). A significant association was observed between phenotypic cell types and outcomes of NHLs (p = 0.011). Adult NHLs were mostly due to the malignant transformation of B cells with diffuse large B cell lymphoma being the commonest subtype. The present study therefore serves as preliminary data for further research towards the adoption of an improved treatment regimen and management of NHLs.

Diagnosis and Follow Up of Non Hodgkin Lymphoma in Dakar, Senegal

Introduction: The management of Non-Hodgkin Lymphoma (NHL) in Senegal is challenging due to the lack of exploration tools and the inaccessibility of anticancer drugs. This study aimed to identify the prognostic factors at diagnosis and to assess their outcome under treatment. Methodology: We conducted a descriptive and analytical prospective study range from 1st January 2018 to 3rd July 2020 covering NHL cases. Initial prognostic factors were assessed according to the International Prognostic Index for diffuse large cell B lymphoma and T-cell lymphoma, the Mantle Cell Lymphoma International Prognostic Index and the Follicular Lymphoma International Index for mantle cell lymphoma and small cell lymphoma respectively. B-cell lymphomas were treated with polychemotherapy with or without rituximab, T-cell lymphomas were treated with polychemotherapy alone. Progression was assessed on the basis of response to treatment, toxicity and survival. Results: We included 40 patients, 30 males and 10 females with a sex ratio of 3. The mean age was 43.38 years +15.87. The mean time from symptom onset to diagnostic confirmation was 7.4 months. The total follow-up time of the cohort was 30.5 patient-years. B-cell lymphomas accounted for 57.5% of cases, T-cell lymphomas for 27.5% of cases. Twenty-five patients (67.6% of cases) were at an advanced stage at diagnosis. The initial prognosis was unfavourable in 29.7% of cases, all histological types combined. The overall survival at 30 months was 70%. Conclusion: Our patients were diagnosed with advanced disease stage. The overall survival at 30 months was short. Early diagnosis and better access to immunochemotherapy could improve these results.

FDG PET/CT versus Bone Marrow Biopsy for Diagnosis of Bone Marrow Involvement in Non-Hodgkin Lymphoma: A Systematic Review

The management of non-Hodgkin lymphoma (NHL) patients requires the identification of bone marrow involvement (BMI) using a bone marrow biopsy (BMB), as recommended by international guidelines. Multiple studies have shown that [18F]FDG positron emission tomography, combined with computed tomography (PET/CT), may provide important information and may detect BMI, but there is still an ongoing debate as to whether it is sensitive enough for NHL patients in order to replace or be used as a complimentary method to BMB. The objective of this article is to systematically review published studies on the performance of [18F]FDG PET/CT in detecting BMI compared to the BMB for NHL patients. A population, intervention, comparison, and outcome (PICO) search in PubMed and Scopus databases (until 1 November 2021) was performed. A total of 41 studies, comprising 6147 NHL patients, were found to be eligible and were included in the analysis conducted in this systematic review. The sensitivity and specificity for identifying BMI in NHL patients were 73% and 90% for [18F]FDG PET/CT and 56% and 100% for BMB. For aggressive NHL, the sensitivity and specificity to assess the BMI for the [18F]FDG PET/CT was 77% and 94%, while for the BMB it was 58% and 100%. However, sensitivity and specificity to assess the BMI for indolent NHL for the [18F]FDG PET/CT was 59% and 85%, while for the BMB it was superior, and equal to 94% and 100%. With regard to NHL, a [18F]FDG PET/CT scan can only replace BMB if it is found to be positive and if patients can be categorized as having advanced staged NHL with high certainty. [18F]FDG PET/CT might recover tumors missed by BMB, and is recommended for use as a complimentary method, even in indolent histologic subtypes of NHL.

Evidence that PKCα inhibition in Dalton’s Lymphoma cells augments cell cycle arrest and mitochondrial-dependent apoptosis

Protein kinase Cα (PKCα), belonging to ser/thr protein kinase, perform various biological functions. Overexpression of PKCα has been observed in multiple human malignancies including lymphoma. However, the molecular pathogenesis and involvement of PKCα in Non-Hodgkin lymphoma (NHL) are not clearly understood. Hence, deciphering the role of PKCα in NHL management may provide a better therapeutic option. In the present study, we used selective pharmacological inhibitors Gö6976 and Ro320432 that potentially inhibit PKCα-mediated signaling in DL cells, resulting in the inhibition of cell growth and mitochondrial-dependent apoptosis. PKCα inhibition by these inhibitors also displays cell cycle arrest at the G1 phase and causes growth retardation of DL cells. Our results extended the mechanism of PKCα in NHL, and provided potential implications for its therapy.

Development of Novel CAR Therapies for Diffuse Large B-Cell Lymphoma Using Genome-Wide Overexpression Screens

Despite recent therapeutic advances in the management of non-Hodgkin lymphoma (NHL), up to 50% of patients with diffuse large B-cell lymphoma (DLBCL) relapse after first line therapy, and for DLBCL patients who relapse within 12 months after subsequent stem cell transplant (SCT), the median overall survival (OS) is 6.3 months. Recently, chimeric antigen receptor (CAR) T-cell therapy has shown remarkable activity in relapsed DLBCL with complete response (CR) rate of 40% and 54% for the two of the FDA-approved CAR T-cell products, tisagenlecleucel and axicabtagene ciloleucel, respectively. However, at a median follow-up of 18 months, only 36% of patients treated with tisagenlecleucel remained in CR; with longer follow-up for axicabtagene ciloleucel the median progression free survival (PFS) was 5.9 months. Immune escape and immune evasion are primary mechanisms of CAR-T resistance; clearly improvements are needed to increase response rate and cure.While CRISPR-based loss-of-function screens have shown promise for high-throughput identification of genes that modulate T-cell response, these methods have been limited thus far to negative regulators of T-cell functions, and raise safety concerns due to the permanent nature of genome modification. Here we identify positive T-cell regulators via overexpression of ~12,000 barcoded human open reading frames (ORFs). Using this genome-scale ORF screen, we found modulator genes which increased primary human CD4+ and CD8+ T-cell proliferation, including activation markers like CD25 and CD40L, and secretion of key cytokines like interleukin-2 and interferon-gamma. In addition, we developed a single-cell genomics method (OverCITE-seq) for high-throughput quantification of the transcriptome and surface proteome in ORF-engineered T-cells.The top-ranked ORF, lymphotoxin beta receptor (LTBR), is typically expressed in a subset of myeloid cells but absent in lymphocytes. When expressed in T-cells, LTBR induces a profound transcriptional remodelling, resulting in increased resistance to exhaustion and activation-induced apoptosis, as well as upregulation of a plethora of proinflammatory cytokines, co-stimulatory molecules and antigen presentation machinery. In order to investigate the mechanism of action of LTBR, we developed an epistasis assay which allows for simultaneous gene knockout and LTBR overexpression in primary T cells. Thus, LTBR appears to induce both canonical and non-canonical NFkB pathways - but the phenotype observed in T cells is dependent only on the former.Finally, we co-expressed several top-ranked genes, including LTBR, with FDA approved CD19-targeting CARs utilizing either 4-1BB or CD28 co-stimulatory domains. In line with previous results, co-expression of top-ranked ORFs increased proinflammatory cytokine secretion and cytotoxicity against CD19+ positive cancer cell lines. This functional improvement was also observed when top-ranked ORFs and CARs were delivered to T cells isolated from DLBCL patients as shown in Figure 1. Our results provide several strategies for improving next generation CAR T-cell therapies via induction of new synthetic cell programs which may optimize immune activation and enhance the efficacy of these important therapies, a high priority for patients with relapsed and refractory DLBCL and other lymphomas. [Display omitted] DisclosuresMimitou: Immunai: Current Employment. Smibert: Immunai: Current Employment. Diefenbach: Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; IMab: Research Funding; Gilead: Current equity holder in publicly-traded company; Celgene: Research Funding; AbbVie: Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Merck Sharp & Dohme: Consultancy, Honoraria, Research Funding; IGM Biosciences: Research Funding; Morphosys: Consultancy, Honoraria, Research Funding; MEI: Consultancy, Research Funding; Perlmutter Cancer Center at NYU Langone Health: Current Employment; Incyte: Research Funding; Trillium: Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Genentech, Inc./ F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Research Funding. Sanjana: Qiagen: Consultancy; Vertex: Consultancy.

PCN89 Estimating the costs of the management of non-Hodgkin’s lymphoma at a tertiary health institution

Diffuse large B-cell lymphoma (DLBCL) is an aggressive and common type of non-Hodgkin’s lymphoma(NHL). It is of public health importance in Zimbabwe due to the high burden of HIV. The treatment of CD20-positive DLBCL include cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) with or without rituximab (R-CHOP). Adding rituximab results in additional drug and diagnostic costs. Estimating treatment costs is important for budgeting. The aim of this study was to estimate the costs of managing NHL. The medical records of NHL patients at Parirenyatwa Hospital in 2015 were reviewed to determine personnel, drugs, laboratory procedures and other hospital services that were utilized. Micro costing method was used to aggregate the resources, determine unit costs and estimating the total cost of managing NHL. The costing was done from a healthcare provide perspective. The 2015 cost figures were adjusted for inflation to 2019 and reported in United States Dollars. A total of 89 patient records were reviewed with patients having a mean age of 41[4-76] and 64% were male. The majority 87% of the patients treated with CHOP and 17% on R-CHOP. The average cost for managing NHL with CHOP was $1235 per patient per cycle with diagnostic procedures contributing 52% to the figure. R-CHOP costed $2950 per patient per cycle with medications contributing 60%. The management of NHL is associated with substantial healthcare costs. Adding rituximab to CHOP results in significant increase in drug-related costs.

ABCL-154: Problems in the Management of Non-Hodgkin Lymphoma (NHL) in the Hematology Department of CHU of Conakry (Guinea)

Introduction: Non-Hodgkin lymphomas are characterized by monoclonal malignant proliferation of B or T lymphoid cells, rarely NK. The objective of the study was to determine the main difficulties in the management of patients being followed for non-Hodgkin lymphoma. Methodology: This was a descriptive cross-sectional study carried out at the Hematology Department of the Conakry University Hospital. It took place over a period from January 2015 to September 2019. It consisted of data collection from the records of patients meeting the inclusion criteria during the study period. Results: We included 49 cases in which NHL accounted for 51.12% of all hematological malignancies. The M/F sex ratio was 2.11. The mean age was 43 years with extremes of 17 and 75 years. The most affected age group was 45-59 years of age. Diagnosis was made on the basis of: histology (93.88%), immunohistochemistry (4.08%), cytology (2.04%). The diagnostic delay was less than 6 months (10.20%), between 6 and 12 months (42.85%) and more than 12 months (46.95%). The most frequent histological type was diffuse large cell lymphoma (41%), followed by Burkitt lymphoma (20.41%) and marginal zone lymphoma (19%). Treatment was mainly CHOP21 (61.02%), COP (14.28%), and the rest of the patients were untreated. For those treated, the therapeutic plan was respected in 38.25% of cases. Conclusion: Diagnostic delay, unavailability of immunohistochemistry and specific drugs, low socioeconomic status, and illiteracy for some patients were the main problems found in the management of non-Hodgkin lymphoma in our exercise setting. Non-Hodgkin lymphomas are characterized by monoclonal malignant proliferation of B or T lymphoid cells, rarely NK. The objective of the study was to determine the main difficulties in the management of patients being followed for non-Hodgkin lymphoma. This was a descriptive cross-sectional study carried out at the Hematology Department of the Conakry University Hospital. It took place over a period from January 2015 to September 2019. It consisted of data collection from the records of patients meeting the inclusion criteria during the study period. We included 49 cases in which NHL accounted for 51.12% of all hematological malignancies. The M/F sex ratio was 2.11. The mean age was 43 years with extremes of 17 and 75 years. The most affected age group was 45-59 years of age. Diagnosis was made on the basis of: histology (93.88%), immunohistochemistry (4.08%), cytology (2.04%). The diagnostic delay was less than 6 months (10.20%), between 6 and 12 months (42.85%) and more than 12 months (46.95%). The most frequent histological type was diffuse large cell lymphoma (41%), followed by Burkitt lymphoma (20.41%) and marginal zone lymphoma (19%). Treatment was mainly CHOP21 (61.02%), COP (14.28%), and the rest of the patients were untreated. For those treated, the therapeutic plan was respected in 38.25% of cases. Diagnostic delay, unavailability of immunohistochemistry and specific drugs, low socioeconomic status, and illiteracy for some patients were the main problems found in the management of non-Hodgkin lymphoma in our exercise setting.

IBCL-313: Challenges in the Management of Non-Hodgkin Lymphoma in Low-Income Countries: The Case of Haiti

Context: Non-Hodgkin lymphoma (NHL) is the second most common hematological malignancy in Haiti [1]. Its optimal management is mainly hampered by the unavailability of rituximab, a medication that significantly increases overall survival (OS) in NHL patients [2,3]. Objective: To describe the epidemiological and clinical features of NHL at Innovating Health International (IHI), a cancer clinic in Haiti, and to estimate the OS in this suboptimal setting. Design: This is a chart-based retrospective study on patients aged 15 years or older managed for NHL at IHI's cancer clinic in Port-au-Prince, Haiti from January 1, 2015 to December 31, 2019. Variables such as age, gender, date of admission, histology, staging, baseline ECOG, treatment status, outcome, and date of death were collected for this study. Main outcome measures: Overall survival of patients treated for NHL and all cases combined according to the main histological subtypes as of December 31, 2019. Results: Of the 78 patients with the clinical diagnosis of lymphoma, 48 (61.5%) had a confirmed histological diagnosis. The mean age was 49.9 years [range: 17–79] for 30 males and 18 females. Forty-two patients (87.5%) had B-cell lymphoma and 6 (12.5%) T-cell lymphoma, with diffuse large B-cell lymphoma (DLBCL) (n=16) and small lymphocytic lymphoma (SLL) (n=15) as the most common histologic subtypes. Eight cases (16.7%) were extranodal lymphomas, 67.5% of the patients (n=40) had stage III or IV disease, and 89.7% (n=39) had an ECOG of 2 or less. Baseline lactate dehydrogenase (LDH) was elevated for 77.3% of the patients (n=22). In addition, 72.9% of the patients received chemotherapy (mostly CHOP as first-line, rarely CVP; ICE and GEMOX as second- or third-line; rarely chlorambucil and prednisone for SLL). The overall mortality rate was 52.1%, and 4 patients (8.3%) were lost to follow-up. OS for treated patients was 19.4 months, 14.6 months for DLBCL, 19.4 months for SLL, and 27.2 months for non-specified NHL. Conclusions: NHL patients treated over this five-year period have a high mortality rate and decreased OS due to advanced stage and suboptimal treatment. Rituximab needs to be available and accessible in Haiti to improve survival of patients with NHL.

Shifting Treatment Paradigms in Non-Hodgkin Lymphomas

Despite significant therapeutic advances in the treatment of patients with non-Hodgkin lymphoma (NHL), a significant proportion experience relapse or progression following standard immunochemotherapy (ICT). The introduction of novel targeted immunotherapy agents has potentially ushered in a new era in the management of NHL. Emerging approaches to treatment, including chemo-free regimens, targeted therapies, and immunotherapy for follicular lymphoma (FL), mantle cell lymphoma (MCL), and diffuse large B-cell lymphomas (DLBCL), have become increasingly important. Furthermore, genomic tools and biomarkers support subtyping of lymphomas and contribute greatly to identifying patients likely to respond to therapy and predict treatment outcome, thus offering a subset-specific precision medicine approach to managing NHL to both prevent and treat relapse. The latest development in the management of NHL is the use of checkpoint inhibitors to prevent cell–cell communication and tumour growth. Despite limited evidence to date, checkpoint inhibitors in combination with existing ICT may fundamentally shift the NHL treatment algorithm towards personalised immunotherapy.

Management of Non-Hodgkin Lymphoma: ICMR Consensus Document.

Hitherto poor outcomes, paucity of data and heterogeneity in International approach to Pediatric NHL (Non-Hodgkin Lymphoma) prompted the need for guidelines for Indian population with vast variability in access, affordability and infrastructure across the country. These guidelines are based on consensus among the experts and best available evidence applicable to Indian setting. Evaluation of NHL should consist of easily doable and rapid tissue diagnosis (biopsy or flow cytometry of peripheral blood/malignant effusions), St Jude/IPNHLSS (International Pediatric Non-Hodgkin Lymphoma Staging System) and risk grouping with CSF (Cerebro-spinal fluid), bone marrow, whole body imaging [CECT (Contrast enhanced computerized tomography)±MRI (Magnetic resonance imaging)] and blood investigations for LDH (Lactate dehydrogenase), TLS (Tumor lysis syndrome) and organ functions. Life threatening complications like SVCS (Superior vena cava syndrome)/Mediastinal syndrome and TLS need to pre-empted and promptly managed. All children with poor general condition, co-morbidities, metabolic or obstructive complications should receive a steroid or chemotherapy pro-phase first. For mature B-NHL (B cell - Non-Hodgkin lymphoma), in centres with good infrastructure and methotrexate levels, FAB-LMB-96 (French-American-British/Lymphomes Malins B) or BFM (Berlin-Frankfurt-Münster)-NHL-95 protocols may be used. In centres with limited infrastructure and/or no methotrexate levels; CHOP (Cyclophosphamide-hydroxydaunomycin-oncovin-prednisolone) (early stage) or MCP (Multi-centre protocol)-842 [all stages except CNS (Central nervous system) disease] may be used. Patients with poor early response should have escalated therapy. High-Risk B-NHL will benefit with addition of Rituximab to standard chemotherapy. Radiotherapy (RT) is not warranted. For lymphoblastic lymphoma, in centres with good infrastructure and methotrexate levels, BFM-95 protocol may be used. In centres with limited infrastructure and/or no methotrexate levels; modified MCP-841 with cytarabine, modified BFM-90 protocol with reduced-dose methotrexate or I-BFM 2009 protocol using Capizzi methotrexate may be considered. For ALCL (Anaplastic large cell lymphoma), in centres with good infrastructure and methotrexate levels, ALCL-99 protocol may be considered. In centres with limited infrastructure and/or no methotrexate levels; CHOP (limited-stage only), modified MCP-842 protocol or APO (Adriamycin-prednisolone-oncovin) regimen may be used.

A concise review of lenalidomide therapy for follicular lymphoma

ABSTRACTIntroduction: Lenalidomide, first introduced for the treatment of multiple myeloma in 2008, has been used in the treatment of various subtypes of non-Hodgkin lymphoma (NHL). Considering its mechanism of action, it has been associated with rituximab, showing strong activity in follicular lymphomas (FL). As the chemo-free treatments are a topic of great relevance we decided to prepare a concise review mainly directed to clinicians involved in the management of NHL patients.Areas covered: This article reviews the clinical trials published since 2008 utilizing lenalidomide alone or in combination for treating relapsed/refractory or treatment naïve patients with FL.Expert opinion: With current rituximab plus chemotherapy treatments, almost all patients will relapse from the disease over time. The introduction of lenalidomide in the management of FL showed good efficacy in particular in combination with rituximab (R2). The high rates of durable responses obtained with the R2 combination were similar to those previously observed with standard chemotherapy plus rituximab. If the results of the ongoing multicenter pivotal phase 3 trial (NCT01476787) are favorable for R2 combination, we may move towards a chemotherapy-free approach in the management of FL, which would finally turn a dream into reality.

The Use of the Cytokines EMAP-II, IL-19 and IL-10 as Biomarkers to Determine Prognosis of Non Hodgkin?s Lymphoma

Objectives: Establishing diagnostic and prognostic factors are very important in the management of Non-Hodgkin Lymphoma (NHL). Our aim was to evaluate the clinical significance of serum EMAP-II, IL-19, and IL–10 in NHL patients for assessing treatment response and prognosis of patients. Methods: Serum EMAP-II, IL-19, and IL-10 levels were measured in the serum of 64 NHL patients before and after treatment with CHOP-based chemotherapy by enzyme-linked immunosorbent assay. Correlations of marker levels to the laboratory, clinicopathological and immunophenotyping markers were performed. Results: Serum levels of EMAP-II and IL-10 were higher before therapy and decreased significantly thereafter (P<0.001). High EMAP-II and IL-10 were correlated with serum ALT and blood urea respectively (P=0.043, P=0.020). Significantly higher levels of IL-19 were demonstrated in patients with relapse (P<0.001). A significant association was found between serum IL-19 and AST, CD23 and B-cl2 (P=0.032, P=0.015, P=0.024 respectively). There was a significant correlation between EMAP-II and IL-10 in NHL patients (r=0.827, P<0.001). Conclusion: EMAP-II, IL-19, and IL-10 can all serve as useful diagnostic markers in NHL patients. They assessed response to therapy. IL-19 proved to be the most sensitive predictor of advanced disease and poor prognosis.

The interpretation of Castleman disease in non-Hodgkin lymphoma practice guidelines (2015.V2)

Updated guidelines on the management of non-Hodgkin lymphoma (2015.V2) have been issued by the National Comprehensive Cancer Network (NCCN) in March 3, 2015. The Castleman disease (CD) is included for the first time. References from relevant publications, the standards for diagnosis and treatment of CD are described in detail and it also provides professional healthcare with clear guidance on the management of patients with CD. Key words: Castleman disease; Guidelines

Curability of Advanced Indolent or Low-Grade Follicular Lymphomas: Time for a New Paradigm?

Curability of Advanced Indolent or Low-Grade Follicular Lymphomas: Time for a New Paradigm?

Prenyltransferases Regulate CD20 Protein Levels and Influence Anti-CD20 Monoclonal Antibody-mediated Activation of Complement-dependent Cytotoxicity

Anti-CD20 monoclonal antibodies (mAbs) are successfully used in the management of non-Hodgkin lymphomas and chronic lymphocytic leukemia. We have reported previously that statins induce conformational changes in CD20 molecules and impair rituximab-mediated complement-dependent cytotoxicity. Here we investigated in more detail the influence of farnesyltransferase inhibitors (FTIs) on CD20 expression and antitumor activity of anti-CD20 mAbs. Among all FTIs studied, L-744,832 had the most significant influence on CD20 levels. It significantly increased rituximab-mediated complement-dependent cytotoxicity against primary tumor cells isolated from patients with non-Hodgkin lymphomas or chronic lymphocytic leukemia and increased CD20 expression in the majority of primary lymphoma/leukemia cells. Incubation of Raji cells with L-744,832 led to up-regulation of CD20 at mRNA and protein levels. Chromatin immunoprecipitation assay revealed that inhibition of farnesyltransferase activity was associated with increased binding of PU.1 and Oct-2 to the CD20 promoter sequences. These studies indicate that CD20 expression can be modulated by FTIs. The combination of FTIs with anti-CD20 mAbs is a promising therapeutic approach, and its efficacy should be examined in patients with B-cell tumors.

Proteasome inhibition and combination therapy for non-Hodgkin's lymphoma: from bench to bedside.

Although patients with B-cell non-Hodgkin's lymphoma (NHL) usually respond to initial conventional chemotherapy, they often relapse and mortality has continued to increase over the last three decades in spite of salvage therapy or high dose therapy and stem cell transplantation. Outcomes vary by subtype, but there continues to be a need for novel options that can help overcome chemotherapy resistance, offer new options as consolidation or maintenance therapy postinduction, and offer potentially less toxic combinations, especially in the elderly population. The bulk of these emerging novel agents for cancer treatment target important biological cellular processes. Bortezomib is the first in the class of proteasome inhibitors (PIs), which target the critical process of intracellular protein degradation or recycling and editing through the proteasome. Bortezomib is approved for the treatment of relapsed or refractory mantle cell lymphoma. The mechanisms of proteasome inhibition are very complex by nature (because they affect many pathways) and not fully understood. However, mechanisms of action shared by bortezomib and investigational PIs such as carfilzomib, marizomib, ONX-0912, and MLN9708 are distinct from those of other NHL treatments, making them attractive options for combination therapy. Preclinical evidence suggests that the PIs have additive and/or synergistic activity with a large number of agents both in vitro and in vivo, from cytotoxics to new biologicals, supporting a growing number of combination studies currently underway in NHL patients, as reviewed in this article. The results of these studies will help our understanding about how to best integrate proteasome inhibition in the management of NHL and continue to improve patient outcomes.

High-dose thiotepa, etoposide and carboplatin as conditioning regimen for autologous stem cell transplantation in patients with high-risk non-Hodgkin lymphoma

High-dose chemotherapy conditioning regimens followed by autologous stem cell transplantation generally provide good results in non-Hodgkin lymphoma. We have evaluated the effects of a high-dose regimen comprising thiotepa, etoposide and carboplatin. After debulking and mobilization with high-dose cyclophosphamide or other schedules, forty-five patients at various disease stages were conditioned with thiotepa, etoposide and carboplatin prior to autologous stem cell transplantation. The overall response rate was 77.8% (30 CR, 66.7%; 5 PR, 11.1%). Ten patients (22.2%) did not respond. Two patients (4.4%) died from transplant-related complications. The mean 5-year overall survival was 71.1%: 12 patients relapsed within the first 5 years of follow-up. The overall response rate and 5-year overall survival were better for patients with an International Prognostic Index (IPI) 1 at diagnosis than for those with IPI 2 and IPI 3 (P<0.005 for all). The thiotepa, etoposide and carboplatin conditioning regimen for autologous stem cell transplantation in non-Hodgkin lymphoma has a good anti-lymphoma effect and provides encouraging results in terms of response to treatment and 5-year overall survival. Its good tolerance and acceptable toxicity suggest that it may a very useful in the management of non-Hodgkin lymphoma.

&amp;lt;p&amp;gt;The Role of Plerixafor in the Management of Non-Hodgkin&amp;rsquo;s Lymphoma and Hematopoietic Stem Cell Transplantation&amp;lt;/p&amp;gt;&amp;lt;p&amp;gt;&amp;nbsp;&amp;lt;/p&amp;gt;

Autologous hematopoietic stem cell transplantation (HSCT) is an established treatment for relapsed chemotherapy sensitive non-Hodgkin’s lymphoma (NHL) and an important component of anti-myeloma therapy. Recovery of bone marrow function after autologous HSCT is dependant on the dose of infused hematopoietic stem cells (HSCs) after bone marrow ablation. Despite the use of chemotherapy and granulocyte colony-stimulating factor (G-CSF) based mobilization regimens, some patients are unable to mobilize adequate numbers of CD34+ HSCs and cannot undergo potentially lifesaving autologous HSCT. Plerixafor (AMD3100 or Mozobil) is a newly licensed drug which is used with G-CSF to mobilize CD34+ HSCs for autologous HSCT, reducing apheresis requirements, and the rate of primary mobilization failure. Plerixafor and G-CSF “rescue” protocols allow the successful mobilization of HSCs in patients that have failed standard G-CSF based mobilization protocols. Hematopoietic stem cell biology and the use of Plerixafor in the management of NHL are reviewed.