Should rituximab replace splenectomy in the management of splenic marginal zone lymphoma?

Background: SMZL is a relatively rare low grade B-cell lymphoma, characterized usually by an indolent clinical behavior. Since there is no prospective randomized trials to establish the best treatment approach, decision on therapeutic management should be based on the available retrospective series. Based on these data, rituximab and splenectomy appear to be the most effective. Splenectomy represented the standard treatment modality until early 2000s. More than 90% of the patients present quick amelioration of splenomegaly related symptoms along with improvement of cytopenias related to hypersplenism. The median progression free survival was 8.25 years in the largest series of patients published so far, while the median 5- and 10- year OS were 84% and 67%, respectively. Responses to splenectomy are not complete since extrasplenic disease persists. Patients with heavy bone marrow infiltration, lymphadenopathy or other disease localization besides the spleen are not good candidates for splenectomy. Furthermore splenectomy is a major surgical procedure accompanied by acute perioperative complications as well as late toxicities mainly due to infections. For that reasons splenectomy is not appropriate for elderly patients or patients with comorbidities with a high surgical risk. On the other hand rituximab monotherapy displays high efficacy with minimal toxicity. Several published series have shown an ORR more than 90%, with high CR rates (∼50%). The 10-year PFS and OS were 63% and 85%, respectively in a series of 104 SMZL patients. The role of rituximab maintenance has been investigated by only one group. Based on these data, maintenance with rituximab further improved the quality of responses by increasing significantly the CR rates (from 42% at the end of induction to 71% at the end of maintenance treatment), as well as the duration of responses: 7-year PFS was 75% for those patients who received maintenance vs 39% for those who did not (p < 0.0004). However no difference in OS has been noticed between the two groups, so far. Summarizing the above data, it is obvious that Rituximab monotherapy is associated with high response rates, long response duration and favorable safety profile, rendering it as the treatment of choice in SMZL. © 2017 Elsevier Lt

Current and emerging treatment approaches for splenic marginal zone lymphoma

Introduction: Splenic marginal zone lymphoma (SMZL) represents a distinct entity within the spectrum of marginal zone lymphomas (MZL). Due to its rarity, treatment is not standardized. Areas covered: Currently two therapeutic options have been associated with the best outcome: splenectomy and rituximab. Splenectomy is associated with high response rates (~90%) with a median PFS>5 years. However, responses are not complete and it is associated with increased surgical risk as well as increased risk of septic episodes. Rituximab has shown significant efficacy with minimal toxicity in SMZL. The ORR is > 90%, with half of these responses being complete with a long duration of response. For the small proportion of SMZL with more aggressive clinical behavior, not responding or relapsing shortly after rituximab, novel agents are required. Several new drugs have shown significant activity in other low grade lymphomas. However, there is currently no trial testing the role of these agents specifically in SMZL. Expert opinion: Rituximab monotherapy currently represents the best choice for first line treatment for SMZL. Randomized studies are required in order to improve the outcome, especially for the small proportion of cases with the more aggressive clinical behavior. © 2016 Informa UK Limited, trading as Taylor & Francis Group

Hodgkin lymphoma transformation of chronic lymphocytic leukemia under ibrutinib therapy: Chance association or therapy-related?

The established treatment algorithms for chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) are currently challenged by novel classes of drugs, with ibrutinib being one of the most effective. Published data suggest that patients with early progression under ibrutinib often emerge as having Richter's transformation (RT) with a rapidly fatal prognosis, mostly developing diffuse large B-cell lymphoma (DLBCL). In this respect, it is known that RT to large DLBCL occurs in about 5% of patients with CLL during the disease course and less frequently to Hodgkin lymphoma (HL). Here, we report a patient with CLL who presented with HL transformation while still receiving therapy with ibrutinib stressing the need for clinical vigilance in any case with persisting or enlarging lymph nodes during treatment with this agent, as prompt modification of therapy is most important

Angiogenesis in chronic lymphocytic leukemia

Data concerning angiogenesis in chronic lymphocytic leukaemia (CLL) indicate that CLL patients are characterized by various abnormalities in the angiogenic profile including increased microvessel density in lymph nodes and in bone marrow and increased levels of certain pro-angiogenic vascular growth factors. Vascular endothelial growth factor (VEGF) and its receptors, basic fibrobast growth factor (bFGF) and matrix metalloproteinases(MMPs) were found to be highly expressed in CLL patients while there was no difference in angiogenin expression between CLL patients and healthy individuals. VEGF is implicated in CLL pathogenesis through various mechanisms. Enhanced angiogenesis in CLL has been associated in several reports with disease characteristics and patients' survival. Various anti-angiogenic agents targeting angiogenesis related pathways such as immunomodulatory drugs and receptor tyrosine kinase inhibitors have already been entered in clinical trials. Among them lenalidomide is the most promising antiangiogenic drug showing a significant efficacy in relapsed/refractory CLL patients. © 2013 Bentham Science Publishers

Composite lymphomas: A challenging entity

Composite lymphomas (CLs) are characterized by the rare occurrence of two or more morphologically and/or immunophenotypically different lymphomas in the same anatomic tissue site. Many different combinations of lymphoma have been reported including multiple B-cell lymphomas, B-cell and T-cell non Hodgkin lymphomas, non Hodgkin lymphomas and Hodgkin lymphoma and complex B-cell, T-cell and Hodgkin lymphoma cases. The two lymphoma components usually are not clonally related but the use of thorough molecular techniques revealed that in some cases the two components are clonally related suggesting origin from a common progenitor cell. Pathogenesis of these lymphomas remains not well defined and the etiology differs according to the types of lymphomas involved. Composite B-cell lymphomas with two distinct low grade components are rare and usually are characterized by the existence of two different unrelated progenitors. CLs consisting of two types of non Hodgkin lymphomas of the same lineage, mostly B-cells, represent in most of the cases tumor progression and transformation from an indolent B-cell lymphoma to diffuse large B-cell lymphoma (DLBCL) and the low grade and high grade components in this type of CL are often clonally related while a clonal link has also been reported in cases of CLs containing Hodgkin lymphoma with various non Hodgkin lymphomas. CLs must be carefully diagnosed because the containing disease entities may not only have different natural course but also may differ in prognosis and treatment. © 2014 Bentham Science Publishers

New Insights into Monoclonal B-Cell Lymphocytosis

Monoclonal B-cell lymphocytosis (MBL) is a premalignant condition characterized by the presence of less than 5000/L circulating clonal B cells in otherwise healthy individuals. Three subcategories have been identified according to the immunophenotypic features: CLL-like, CD5(+) atypical, and CD5(-) MBL. CLL-like MBL is by far the most frequent and best studied category and further divided in low-count [LC] and high-count [HC] MBL, based on a cutoff value of 500/L clonal B cells. LC-MBL typically remains stable and probably does not represent a truly premalignant condition, but rather an age-related immune senescence. On the other hand, HC-MBL is closely related to CLL-Rai0, bearing similar immunogenetic profile, and is associated with an annual risk of progression to CLL requiring therapy at a rate of 1.1%. Currently there are no reproducible factors for evaluating the risk of progression to CLL. CD5(-) MBL is characterized by an immunophenotype consistent with marginal zone origin and displays many similarities with marginal zone lymphomas (MZL), mainly the splenic MZL. The cutoff value of 5000/L clonal B cells cannot probably be applied in CD5(-) MBL, requiring a new definition to describe those cases. © 2014 Christina Kalpadakis et al

Normalization of the serum angiopoietin-1 to angiopoietin-2 ratio reflects response in refractory/resistant multiple myeloma patients treated with bortezomib

Neoangiogenesis is involved in the pathophysiology of multiple myeloma and angiopoietins possibly contribute to myeloma-induced neovascularization. Bortezomib's antineoplastic potential includes an anti-angiogenic effect. We determined serum levels of angiopoietin-1 and angiopoietin-2 with ELISA pre- and post-bortezomib administration in 35 patients with relapsed/refractory multiple myeloma. Pre-bortezomib, serum angiopoietin-1 levels did not differ in patients and in healthy individuals, while serum angiopoietin-2 levels were elevated. Corresponding serum angiopoietin-1/angiopoietin-2 ratio was reduced in patients compared with controls. After treatment, serum angiopoietin-1 levels increased, while serum angiopoietin-2 levels decreased, therefore the angiopoietin-1/ angiopoietin-2 ratio increased and normalized. This increase was significant in patients who responded to treatment. In conclusion, angiopoietin-1/angiopoietin- 2 ratio normalization reflected response to bortezomib. ©2008 Ferrata Storti Foundation