Introduction: The modern treatment of patients with primary central nervous system lymphoma (PCNSL) consists of two phases: induction, currently represented by a high-dose-methotrexate-based polychemotherapy, and consolidation. The optimal consolidation therapy has not been defined yet, but several strategies, such as whole-brain radiotherapy (WBRT), high-dose chemotherapy supported by autologous stem cell transplantation (HDC/ASCT) or nonmyeloablative chemotherapy, have been addressed in important randomized trials.
Areas Covered: This review provides an overview of the current role of consolidation strategies in young and fit patients with newly diagnosed PCNSL.
Primary adrenal lymphoma (PAL) and primary renal lymphoma (PRL) are rare extranodal lymphomas, predominantly of diffuse large B-cell lymphoma subtype. Primary adrenal and renal lymphomas (PARL) exhibit a high predilection for the central nervous system (CNS). Therefore, current guidelines support the use of CNS prophylaxis in PARL, particularly in cases of high-risk Central Nervous System International Prognostic Index (CNS-IPI).
View Article and Find Full Text PDFIn the last decades some bacteria have been associated with a various extent with marginal zone (extra nodal, nodal and splenic types) lymphomas are frequently associated with chronic infections, with important clinical, molecular, biological, and therapeutic implications. The well-known correlation between Helicobacter pylori and gastric MALT-lymphoma, the recently reported links between Chlamydia psittaci and ocular adnexal MALT-lymphoma and Borrelia burgdorferi and cutaneous MALT lymphoma constitute the most studied examples; in addition, Campylobacter jejuni and some more recent associations encompassing Achromobacter xylosoxidans and Haemophilus influenzae will be further reported. Biological and clinical features, therapeutic implications and future perspectives of these lymphoma-microbial associations are discussed in this review.
View Article and Find Full Text PDFBest Pract Res Clin Haematol
October 2017
Ocular adnexal marginal zone lymphoma (OAML) represents 1-2% of all non Hodgkin lymphomas. In the last few years many advances in understanding the pathogenesis and the molecular basis involved in its development have been done. Many potential risk factors have been proposed; a dysregulation of immune response in association with a chronic antigenic stimulation, have been hypothesized as possible pathogenic mechanism.
View Article and Find Full Text PDFBackground: Patients with relapsed diffuse large B-cell lymphoma (DLBCL) not eligible for autologous stem cell transplantation (ASCT) or having relapse after ASCT have a low likelihood of cure. Single-drug maintenance after salvage therapy might be an attractive strategy to prolong survival in these patients. Lenalidomide is a suitable candidate for long-lasting maintenance as it is an oral drug, active against DLBCL that can be taken for years with an acceptable toxicity profile.
View Article and Find Full Text PDFPurpose The benefit of high-dose chemotherapy with autologous stem-cell transplantation (ASCT) as first-line treatment in patients with diffuse large B-cell lymphomas is still a matter of debate. To address this point, we designed a randomized phase III trial to compare rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP)-14 (eight cycles) with rituximab plus high-dose sequential chemotherapy (R-HDS) with ASCT. Patients and Methods From June 2005 to June 2011, 246 high-risk patients with a high-intermediate (56%) or high (44%) International Prognostic Index score were randomly assigned to the R-CHOP or R-HDS arm, and 235 were analyzed by intent to treat.
View Article and Find Full Text PDFIt has been well established that nuclear factor kappa-B (NF-κB) activation is important for tumor cell growth and survival. RelA/p65 and p50 are the most common NF-kB subunits and involved in the classical NF-kB pathway. However, the prognostic and biological significance of RelA/p65 is equivocal in the field.
View Article and Find Full Text PDFPurpose: To assess the predictive value of F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) for disease recurrence after immunochemotherapy (R-CHT) and mediastinal irradiation (RT), using the recently published criteria of the Lugano classification to predict outcomes for patients with primary mediastinal large B-cell lymphoma.
Methods And Materials: Among 125 patients prospectively enrolled in the IELSG-26 study, 88 were eligible for central review of PET/CT scans after completion of RT. Responses were evaluated using the 5-point Deauville scale at the end of induction R-CHT and after consolidation RT.
CD37 (tetraspanin TSPAN26) is a B-cell surface antigen widely expressed on mature B cells. CD37 is involved in immune regulation and tumor suppression but its function has not been fully elucidated. We assessed CD37 expression in de novo diffuse large B-cell lymphoma (DLBCL), and investigated its clinical and biologic significance in 773 patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and 231 patients treated with CHOP.
View Article and Find Full Text PDFChronic lymphocytic leukaemia (CLL) is the most common leukaemia among the adults in the Western World. CLL (and the corresponding nodal entity small lymphocytic lymphoma, SLL) is classified as a lymphoproliferative disorder characterised by the relentless accumulation of mature B-lymphocytes showing a peculiar immunophenotype in the peripheral blood, bone marrow, lymph nodes and spleen. CLL clinical course is very heterogeneous: the majority of patients follow an indolent clinical course with no or delayed treatment need and with a prolonged survival, while others experience aggressive disease requiring early treatment followed by frequent relapses.
View Article and Find Full Text PDFThe eye is a rare site for the development of malignant lymphoma. Based on cell type and involved intraocular structures, which as a whole represent an immune-privileged site, several subtypes of primary intraocular lymphoma need to be discerned. Primary vitreoretinal lymphoma (PVRL), the most common form, is an aggressive B-cell malignancy and considered a subtype of primary central nervous system (CNS) lymphoma.
View Article and Find Full Text PDFBackground: Standard treatment for patients with primary CNS lymphoma remains to be defined. Active therapies are often associated with increased risk of haematological or neurological toxicity. In this trial, we addressed the tolerability and efficacy of adding rituximab with or without thiotepa to methotrexate-cytarabine combination therapy (the MATRix regimen), followed by a second randomisation comparing consolidation with whole-brain radiotherapy or autologous stem cell transplantation in patients with primary CNS lymphoma.
View Article and Find Full Text PDFBackground: Primary central nervous system lymphoma (PCNSL) is a highly aggressive Non-Hodgkin lymphoma (NHL) with rising incidence over the past 30 years in immunocompetent patients. Although outcomes have improved, PCNSL is still associated with inferior prognosis compared to systemic NHL. Many questions regarding the optimal therapeutic approach remain unanswered.
View Article and Find Full Text PDFThe role of p53 family member p63 in oncogenesis is the subject of controversy. Limited research has been done on the clinical implications of p63 expression in diffuse large B-cell lymphoma (DLBCL). In this study, we assessed p63 expression in de novo DLBCL samples (n=795) by immunohistochemistry with a pan-p63-monoclonal antibody and correlated it with other clinicopathologic factors and clinical outcomes.
View Article and Find Full Text PDFPrimary central nervous system lymphoma (PCNSL) treatment includes 2 phases: induction and consolidation. Induction consists of high-dose methotrexate-based polychemotherapy for most patients, with regimen and dose variations according to patient characteristics and country. Several strategies have been proposed for the consolidation phase, with whole-brain irradiation (WBRT) the most common.
View Article and Find Full Text PDFExtranodal marginal zone lymphoma of the mucosa-associated lymphoid tissue (MALT lymphoma) accounts for 7% to 8% of newly diagnosed lymphomas. Because of its association with infectious causes, such as Helicobacter pylori (HP) or Chlamydophila psittaci (CP), and autoimmune diseases, it has become the paradigm of an antigen-driven malignancy. MALT lymphoma usually displays an indolent course, and watch-and-wait strategies are justified initially in a certain percentage of patients.
View Article and Find Full Text PDFDouble-hit B-cell lymphoma is a common designation for a group of tumors characterized by concurrent translocations of MYC and BCL2, BCL6, or other genes. The prognosis of concurrent MYC and BCL6 translocations is not well known. In this study, we assessed rearrangements and expression of MYC, BCL2 and BCL6 in 898 patients with de novo diffuse large B-cell lymphoma treated with standard chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab).
View Article and Find Full Text PDFMYC dysregulation, including MYC gene rearrangement and Myc protein overexpression, is of increasing clinical importance in diffuse large B-cell lymphoma (DLBCL). However, the roles of MYC and the relative importance of rearrangement vs overexpression remain to be refined. Gaining knowledge about the tumor biology associated with MYC dysregulation is important to understand the roles of MYC and MYC-associated biology in lymphomagenesis.
View Article and Find Full Text PDFIntroduction: Primary Central Nervous System (CNS) lymphomas are a rare group of malignancies with peculiar clinical and biologic features, aggressive course, and unsatisfactory outcome in contrast with other aggressive lymphomas. Despite a high chemo- and radiosensitivity, remissions are frequently short lasting, mainly because the blood-brain barrier limits the access of many drugs to the CNS, preventing a homogeneous treatment of all CNS tissues. Moreover, survivor patients are at high risk of developing severe treatment-related toxicity, mainly disabling neurotoxicity for elderly ones, raising the question of whether to intensify therapy to improve the cure rate or to downgrade treatment to reduce side effects.
View Article and Find Full Text PDFDysregulated NF-κB signaling is critical for lymphomagenesis. The regulation, function, and clinical relevance of c-Rel/NF-κB activation in diffuse large B-cell lymphoma (DLBCL) have not been well studied. In this study we analyzed the prognostic significance and gene-expression signature of c-Rel nuclear expression as surrogate of c-Rel activation in 460 patients with de novo DLBCL.
View Article and Find Full Text PDFPurpose: Treatment of secondary CNS dissemination in patients with aggressive lymphomas remains an important, unmet clinical need. Herein, we report the final results of a multicenter phase II trial addressing a new treatment for secondary CNS lymphoma based on encouraging experiences with high doses of antimetabolites in primary CNS lymphoma and with rituximab plus high-dose sequential chemoimmunotherapy (R-HDS) in relapsed aggressive lymphoma.
Patients And Methods: HIV-negative patients with aggressive B-cell lymphoma and secondary CNS involvement at diagnosis or relapse, age 18 to 70 years, and Eastern Cooperative Oncology Group performance status ≤ 3 were enrolled and treated with high-doses of methotrexate and cytarabine, followed by R-HDS (cyclophosphamide, cytarabine, and etoposide) supported by autologous stem-cell transplantation (ASCT).
Survivin, a member of the inhibitor of apoptosis protein family, is overexpressed in a variety of human neoplasms. The prognostic significance of survivin expression in diffuse large B-cell lymphoma patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) is unclear. We used standard immunohistochemistry methods to quantify survivin expression in 463 patients with de novo diffuse large B-cell lymphoma who received the R-CHOP.
View Article and Find Full Text PDF