Prognostic assessment in patients with indolent B-cell lymphomas.

2012

Arcaini L, Rattotti S, Gotti M, Luminari S.

Source

Division of Hematology, Department of Hematology and Oncology, Fondazione IRCCS Policlinico San Matteo, University of Pavia, 27100 Pavia, Italy.

Abstract

Follicular lymphoma (FL) is an indolent lymphoma with long median survival. Many studies have been performed to build up prognostic scores potentially useful to identify patients with poorer outcome. In 2004, an international consortium coordinated by the International Follicular Lymphoma Prognostic Factor project was established and a new prognostic study was launched (FLIPI2) using progression-free survival (PFS) as main endpoint and integrating all the modern parameters prospectively collected. Low-grade non-Hodgkin lymphomas were once considered as a heterogenous group of lymphomas characterized by an indolent clinical course. Each entity is characterized by unique clinicobiologic features. Some studies have been focused on prognostic factors in single lymphoma subtypes, with the development of specific-entity scores based on retrospective series, for instance splenic marginal zone lymphoma (SMZL). A widely accepted prognostic tool for clinical usage for indolent non-follicular B-cell lymphomas is largely awaited. In this paper we summarized the current evidence regarding prognostic assessment of indolent follicular and non-follicular lymphomas.

Scientific World Journal

Isolated mononeuropathy multiplex-a rare manifestation of intravascular large B-cell lymphoma.

Sept 2012

Lynch KM, Katz JD, Weinberg DH, Lin DI, Folkerth RD.

Source

*Department of Neurology, St Elizabeth's Medical Center, Boston, MA †Department of Neuropathology, Brigham and Women's Hospital, Boston, MA.

Abstract

ABSTRACT: Intravascular large B-cell lymphoma, also known as angiotrophic large cell lymphoma, is a rare disorder where neoplastic lymphoid cells proliferate within the walls of small- to medium-sized blood vessels. Peripheral neuropathy and other neurological manifestations, including stroke and dementia, are common, but cases of isolated multiple mononeuropathies in the absence of systemic symptoms are distinctly rare. We present an unusual case of biopsy-proved angiotrophic large cell lymphoma presenting exclusively with multiple mononeuropathies.

PubMed

The Relationship between Exposure to Pesticides and the Occurrence of Lymphoid Neoplasm.

June 2012

Zakerinia M, Namdari M, Amirghofran S.

Source

Department of Internal Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.

Abstract

BACKGROUND:

The etiology of malignant lymphoma is still largely unknown. This study determines the relationship between exposure to pesticides and the occurrence of lymphoid neoplasms in Shiraz, Southern Iran.

METHODS:

Between 2007 and 2008, in a case control study conducted in Nemazee Hospital in Shiraz, Southern Iran, 200 subjects diagnosed with lymphoma according to the World Health Organization (WHO) classification were enrolled. Controls (n=200) were frequency matched to the cases by sex, age, and center. Subjects who were a farmer were compared with all other occupations.

RESULTS:

Out of the 200 cases that were diagnosed as lymphoid neoplasms, 100 were non-Hodgkin's lymphoma, 54 Hodgkin's lymphoma and 46 multiple myeloma. Seventy two percent of the NHL's were of the B-cell type, 15% of the T-cell type and the rest were not classified. Furthermore, subjects exposed to pesticides were at an increased risk of non-Hodgkin lymphoma and MM, but not Hodgkin lymphoma.

CONCLUSION:

Risk of non-Hodgkin lymphoma and MM was highest for exposure to pesticides, among them, insecticide's risk was confirmed.

PubMed

Murine models of B-cell lymphomas: promising tools for designing cancer therapies.

2012

Donnou S, Galand C, Touitou V, Sautès-Fridman C, Fabry Z, Fisson S.

Source

Institut National de la Santé et de la Recherche Médicale (INSERM), UMRS 872, Équipe Microenvironnement Immunitaire des Tumeurs, Centre de Recherche des Cordeliers, 75006 Paris, France.

Abstract

Human B-cell lymphomas, the fourth most common hematologic malignancy, are currently the subject of extensive research. The limited accessibility of biopsies, the heterogeneity among patients, and the subtypes of lymphomas have necessitated the development of animal models to decipher immune escape mechanisms and design new therapies. Here, we summarize the cell lines and murine models used to study lymphomagenesis, the lymphoma microenvironment, and the efficacy of new therapies. These data allow us to understand the role of the immune system in the fight against tumors. Exploring the advantages and limitations of immunocompetent versus immunodeficient models improves our understanding of the molecular and cellular mechanisms of tumor genesis and development as well as the fundamental processes governing the interaction of tumors and their host tissues. We posit that these basic preclinical investigations will open up new and promising approaches to designing better therapies.

Hindawi Publishing

MLL Duplication in a Pediatric Patient With B-Cell Lymphoblastic Lymphoma.

Nov 2011

Mater DV, Goodman BK, Wang E, Gaca AM, Wechsler DS.

Source

*Division of Pediatric Hematology-Oncology, Department of Pediatrics †Department of Pathology ‡Department of Radiology, Duke University, Durham, NC.

Abstract

Lymphoblastic lymphoma is the second most common type of non-Hodgkin lymphoma seen in children. Approximately, 90% of lymphoblastic lymphomas arise from T cells, with the remaining 10% being B-cell-lineage derived. Although T-cell lymphoblastic lymphoma most frequently occurs in the anterior mediastinum (thymus), B-cell lymphoblastic lymphoma (B-LBL) predominates in extranodal sites such as skin and bone. Here, we describe a pediatric B-LBL patient who presented with extensive abdominal involvement and whose lymphoma cells displayed segmental duplication of the mixed lineage leukemia (MLL) gene. MLL duplication/amplification has been described primarily in acute myeloid leukemia and myelodysplastic syndrome with no published reports of discrete MLL duplication/amplification events in B-LBL. The MLL gene duplication noted in this case may represent a novel mechanism for tumorigenesis in B-LBL.

Lippincott, Williams & Wilkins

Intravascular large B-cell lymphoma.

Mar 2012

Orwat DE, Batalis NI.

Abstract

A rare type of diffuse large B-cell lymphoma, intravascular large B-cell lymphoma primarily affects the middle-aged to elderly population, with a slight predominance in men. By the time of presentation, most patients have advanced, disseminated disease, and often the diagnosis is made at autopsy. Patients may present with any of a myriad of symptoms, with any tissue potentially being infiltrated. Central nervous system and cutaneous involvement is common, as is the presence of B symptoms including fever, weight loss, and night sweats. Morphologically, growth of neoplastic cells is restricted to the lumen of small vessels. The cells are large, with 1 or more prominent nucleoli, scant cytoplasm, and frequent mitotic figures, and are commonly positive for cluster of differentiation markers 79a, 20, and 19, as well as MUM1/IRF4 and Bcl-2. Intravascular large B-cell lymphoma is aggressive, and without treatment is rapidly fatal.

Full Text Article

Archives of Pathology & Laboratory Medicine

Aurora A inhibitor (MLN8237) plus Vincristine synergizes with Rituximab as a potential curative therapy in aggressive B-cell non-Hodgkin lymphoma.

Feb 2012

Mahadevan D, Stejskal A, Cooke LS, Manziello A, Morales C, Persky DO, Fisher RI, Miller TP, Qi W.

Source

Hematology/Oncology, The University of Arizona Cancer Center.

Abstract

PURPOSE:

Aurora A and B are oncogenic serine/threonine kinases that regulate mitosis. Over-expression of Auroras promotes resistance to microtubule targeted agents. We investigated mechanistic synergy by inhibiting the mitotic spindle apparatus in the presence of MLN8237 [M], an Aurora A inhibitor with either vincristine [MV] or docetaxel [MD] in aggressive B-NHL. The addition of rituximab [R] to MV or MD was evaluated for synthetic lethality.

EXPERIMENTAL DESIGN:

Aggressive B-NHL cell subtypes were evaluated in vitro and in vivo for target modulation and anti-NHL activity with single agents, doublets and triplets by analyzing cell proliferation, apoptosis, tumor growth, survival and mechanisms of response/relapse by gene expression profiling with protein validation.

RESULTS:

MV is synergistic while MD is additive for cell proliferation inhibition in B-NHL cell culture models. Addition of R to MV is superior to MD but both significantly induce apoptosis compared to doublet therapy. Mouse xenograft models of mantle cell lymphoma showed modest single agent activity for M, R, D and V with tumor growth inhibition (TGI) of ~10-15%. Of the doublets, MV caused tumor regression, while TGI was observed with MD (~55-60%) and MR (~25-50%) respectively. Although MV caused tumor regression, mice relapsed 20 days after stopping therapy. In contrast, MVR was curative, while MDR led to TGI of ~85%. PCNA, Aurora B, cyclin B1, cyclin D1 and Bcl-2 proteins of harvested tumors confirmed response and resistance to therapy.

Clinical Cancer Research