ntralesional Rituximab in the Treatment of Indolent Primary Cutaneous B-Cell Lymphomas. An Epidemiologic Observational Multicentre Study: the Spanish

Intralesional Rituximab in the Treatment of Indolent Primary Cutaneous B-Cell Lymphomas. An Epidemiologic Observational Multicentre Study: the Spanish Working Group on CutaneousLymphoma.

2012

Peñate Y, Hernández-Machín B, Pérez-Méndez LI, Santiago F, Rosales B, Servitje O, Estrach T, Fernández-Guarino M,Calzado L, Acebo E, Gallardo F, Salar A, Izu R, Ortiz-Romero PL, Pujol RM, Fernández-de-Misa R.

Source

Dermatology Department. Complejo Hospitalario Universitario Insular Materno-Infantil. Gran Canaria Dermatology Department. Hospital Virgen de los Reyes. El Hierro Research Unit. Hospital Universitario Nuestra Señora de Candelaria. Universidad de La Laguna. Tenerife Dermatology Department. Hospital del Mar. Universitat Autònoma de Barcelona. Barcelona. Dermatology Department. Hospital Universitario 12 de Octubre. Madrid. Dermatology Department. Hospital Universitari de Bellvitge. IDIBELL. Barcelona. Dermatology Department. Hospital Clínico. University of Barcelona. Barcelona Dermatology Department. Hospital Universitario Ramón y Cajal. Madrid. Dermatology Department. Hospital Universitario Fundación Alcorcón. Madrid. Dermatology Department. Hospital de Cruces. Baracaldo. Dermatology Department. Hospital de Basurto. Bilbao. Research Unit - Dermatology Department. Hospital Universitario Nuestra Señora de Candelaria. Universidad de La Laguna. Tenerife.

Abstract

Background: 

Intravenous, rituximab is a safe and effective option for the treatment of systemic non-Hodgkin B-cell lymphoma. The effectiveness of intralesional rituximab (ILR) in primary cutaneous B-cell lymphomas (PCBL) has been described in a small number of patients.

Objectives: 

To evaluate the effectiveness, tolerance and adverse effects of ILR in patients with follicle centre (FCL) and marginal zone (MZL) PCBL.

Methods: 

This was an epidemiologic observational multicentre study of patients with PCBL treated with ILR..

Results: 

Seventeen patients with MZL and 18 with FCL PCBL were included. The median number of lesions treated was 2 per patient. The treatment regimen used in 74% of the patients was courses of 3 injections in a single week at 1-month intervals. The dose per lesion and day of treatment was 10 mg in 71% of the patients. The median cumulative dose of rituximab per lesion was 60 mg (range, 13-270) and per patient was 150 mg (range, 20-360 mg). Complete response (CR) and partial response were achieved in 71% and 23% of patients, respectively.

The median time to CR in patients who received 10 mg of ILR per lesion was 8 weeks. Similar response rates were observed in MZL and FCL. Median disease-free survival was 114.1 weeks. No parameters that significantly predicted CR were identified. Adverse reactions were recorded in 19 patients. The most frequent was localised pain at the injection site. Median follow-up was 21 months.

Conclusions: 

ILR is a well tolerated and effective treatment for FCL and MZL PCBL. It should be considered a useful alternative in patients with recurrent lesions and in which the sequelae of radiotherapy or surgery would be significant.

British Association of Dermatologists.

Incidence, risk factors and outcome of histological transformation in follicular lymphoma.

Feb. 2012

Conconi A, Ponzio C, Lobetti-Bodoni C, Motta M, Rancoita PM, Stathis A, Moccia AA, Mazzucchelli L, Bertoni F,Ghielmini M, Cavalli F, Zucca E.

Source

Oncology Institute of Southern Switzerland (IOSI), Bellinzona, Switzerland.

Abstract

Histological transformation (HT) into diffuse large B-cell lymphoma (DLBCL) was documented in 37 of the 281 (13%; 95% CI, 9-18) follicular lymphoma (FL) patients treated at our institute from 1979 to 2007. HT occurred at a median of 2·75 years from initial FL diagnosis and HT rate was 15% at 10 years and 26% at 14 years, with a plateau from that point onward. Patients with bulky or extranodal disease, or those diagnosed before 1990 had a significantly higher risk of HT. When initial treatment strategies were taken into account, a reduced HT risk was seen in the patients initially managed with a 'watch and wait' policy, while the risk appeared significantly increased in the small subset of 18 patients initially managed with rituximab plus chemotherapy (P = 0·0005). HT was associated with a significantly shorter cause-specific survival (P = 0·0002). Predictors of survival after HT were the Follicular Lymphoma International Prognostic Index at diagnosis, as well as age and performance status at the time of HT. Our data confirm the adverse clinical outcome of FL after HT. In keeping with previous isolated reports, our findings suggest that there is a subgroup of patients in whom HT may not occur.

PubMed

Ten antibodies, six colors, twelve parameters: A multiparameter flow cytometric approach to evaluate leptomeningeal disease in B-cell non-Hodgkin's ly

Ten antibodies, six colors, twelve parameters: A multiparameter flow cytometric approach to evaluate leptomeningeal disease in B-cell non-Hodgkin's lymphomas.

Nov 2011

Ten antibodies, six colors, twelve parameters: A multiparameter flow cytometric approach to evaluate leptomeningeal disease in B-cell non-Hodgkin's lymphomas.

Stacchini A, Aliberti S, Demurtas A, Benevolo G, Godio L.

Source

Flow Cytometry Unit, Department of Pathology, Molinette Hospital, Turin Italy. astacchini@molinette.piemonte.it.

Abstract

BACKGROUND:

Flow cytometry (FC) is considered a sensitive and specific technique for the detection of occult lymphomacells in cerebrospinal fluid (CSF).

METHODS:

The diagnostic sensitivity of a FC approach which uses a combination of 10 antibodies, a single-tube evaluation, and a six-color instrument, was evaluated and compared to conventional cytology (CC) for the detection of lymphomatous cells in the CSF of 44 patients affected by B-cell non-Hodgkin's lymphoma (B-NHL) considered at high risk of central nervous system spread.

RESULTS:

The CSF obtained from 36 newly diagnosed and 8 relapsed patients affected by B-cell lymphoma was assessed by FC and CC on a total of 62 samples; 52/62 (82.6%) were considered paucicellular as they had fewer than 10 cells/μl. All cases were evaluated by both methods. FC gave 15/62 (24%) positive results, CC 10/62 (16%) positive results; none of the samples evaluated had a positive CC with a negative FC result.

CONCLUSIONS:

The use of a multiparameter FC approach, which collects an elevated number of monoclonal antibodies in a single tube and identify different cell populations with a selective gating strategy analysis, allows for the evaluation of lymphocyte subsets and the detection of leptomeningeal disease in B-NHL, even in the presence of paucicellularity of samples.

PubMed

Elevated serum IL-10 levels in diffuse large B-cell lymphoma: a mechanism of aberrant Janus kinase 2 activation.

Feb 2012

Gupta M, Han JJ, Stenson M, Maurer M, Wellik L, Hu G, Ziesmer S, Dogan A, Witzig TE.

Source

Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, United States;

Abstract

Cytokines are deregulated in cancers and can contribute to tumor growth. In patients with diffuse large cell lymphoma(DLBCL), we observed higher levels of JAK/STAT pathway related serum cytokines (IL-6, IL-10, EGF, IL-2) vs controls. Of these, only IL-10 activated the JAK2 pathway in lymphoma cells in vitro. Patients with high serum IL-10 had shorter event free survival (EFS) than patients with low levels (p>0.01) and high IL-10 correlated with high LDH (p=0.0085) and higher International Prognostic Index scores (p=0.01). To explore the mechanism by which IL-10 may contribute to an inferior EFS, we investigated the effect of IL-10 on the JAK2 pathway and found that the IL-10/IL-10R complex upregulated JAK2 signaling. Neutralizing antibody to IL-10 inhibited constitutive as well as IL-10-induced JAK2/STAT3 phosphorylation. JAK2 inhibition dephosphorylated JAK2 and STAT3 and caused an inhibitory effect on phospho-JAK2 positive DLBCL cells; there was minimal effect on phospho-JAK2 negative cells. Apoptosis induced by JAK2 inhibition was dependent upon inhibition of autocrine IL-10 and c-myc expression and independent of Bcl-2 family expression. These results provide the rationale for testing JAK2 inhibitors in DLBCL patients and indicate that serum IL-10 may be a biomarker to identify patients more likely to respond to JAK2-targeted therapy.

Blood Journal

Serum C-reactive protein as an important prognostic variable in patients with diffuse large B cell lymphoma.

Feb 2012

Serum C-reactive protein as an important prognostic variable in patients with diffuse large B cell lymphoma.

Cao Y, Shi YX, Chen JO, Tan YT, Cai YC, Luo HY, Qiu MZ, Cai XY, Jin Y, Sun YL, Jiang WQ.

Source

State Key Laboratory of Oncology, South China, Guangzhou, Guangdong, 510060, People's Republic of China.

Abstract

C-reactive protein (CRP) is an acute-phase reactant that is a promising biomarker in patients with cancer of many kinds. The aim of this retrospective study was to evaluate significant changes in CRP levels as a parameter for the response effect and long-term survival of patients with diffuse large B cell lymphoma (DLBCL). Serum CRP data were collected in 94 patients with DLBCL from October 2006 to August 2009 in Cancer Center, Sun Yat-Sen University. Results were correlated with clinical data. The median CRP serum level in patients with DLBCL was 30.91 ± 53.35 in male and 22.39 ± 29.89 mg/L in female. Base line CRP levels were correlated with International Prognostic Index (IPI) scores (p = 0.03). Among the patients with an IPI score of 1-2, base line CRP levels were correlated with long-term survival (p = 0.001). Base line CRP levels were also correlated with OS (p = 0.001) and varied with different clinical stages (p = 0.03). The corresponding CRP levels in the patients with 2 cycles of chemotherapy were correlated with short-term treatment response (p = 0.003) and OS (p = 0.04) or TTP (p = 0.03). CRP serum levels can be used as additional prognostic parameter in patients with diffuse large B cell type lymphoma.

PubMed

The lymph system and lymphoid tissue

The lymph system and lymphoid tissue

To know what lymphoma is, it helps to understand the body's lymph system.

The lymph system (also known as the lymphatic system) is composed mainly of lymphoid tissue, lymph vessels, and a clear fluid called lymph. Lymphoid tissue includes the lymph nodes and related organs that are part of the body's immune and blood-forming systems, such as the spleen and bone marrow.

Lymphocytes

Lymphoid tissue is made up of several types of immune system cells that help the body fight infections. Most of the cells in lymphoid tissue are lymphocytes, a type of white blood cell. The 2 main types of lymphocytes are B lymphocytes (B cells) and T lymphocytes (T cells). Normal B cells and T cells do different jobs within the immune system.

B lymphocytes: B cells normally help protect the body against germs (bacteria or viruses) by making proteins called antibodies. The antibodies attach to the germs, marking them for destruction by other immune system cells. Antibodies also attract certain blood proteins that can kill bacteria.

T lymphocytes: There are several types of T cells, each with a special job. Some T cells can directly destroy cells infected with viruses, fungi, or certain kinds of bacteria. T cells can also release substances that attract other types of white blood cells, which then digest the infected cells. Some types of T cells play a role in either boosting or slowing the activity of other immune system cells.

Both types of lymphocytes can develop into lymphoma cells, but B-cell lymphomas are much more common in the United States than T-cell lymphomas. Different types of lymphoma can develop from each type of lymphocyte, based on how mature the cells are when they become cancerous and other factors.

Treatment for each lymphoma depends on which type it is, so determining the exact type of lymphoma is important.

Organs that have lymphoid tissue

Lymphoid tissue is found in many places throughout the body. Because lymphoid tissue is in many parts of the body, lymphomas can start almost anywhere. The major sites of lymphoid tissue are:

Lymph nodes: Lymph nodes are bean-sized organs found throughout the body, including inside the chest, abdomen, and pelvis. They can sometimes be felt under the skin in the neck, under the arms, and in the groin. Lymph nodes are made up mainly of lymphocytes.

The lymph nodes in the body are connected by a system of lymph vessels. These vessels are like veins, except that instead of carrying blood, they carry lymph and lymphocytes.

Lymph nodes get bigger when they fight infection. Lymph nodes that grow in reaction to infection are called reactive nodes or hyperplastic nodes and are often tender to the touch. An enlarged lymph node is not always a sign of a serious problem. People with sore throats or colds often feel enlarged lymph nodes in the neck. But a large lymph node is also the most common sign of lymphoma. Lymph node enlargement is discussed more in the section, "How is non-Hodgkin lymphoma diagnosed?"

Spleen: The spleen is an organ under the lower part of the rib cage on the left side of the body. An average adult spleen weighs about 5 ounces. The spleen makes lymphocytes and other immune system cells to help fight infection. It also stores healthy blood cells and filters out damaged blood cells, bacteria, and cell waste.

Thymus: The thymus is a small organ behind the upper part of the breastbone and in front of the heart. Before birth, the thymus plays a vital role in development of T lymphocytes. The thymus shrinks and becomes less important over the first 20 years of life. Despite this, it continues to play a role in immune system function.

Adenoids and tonsils: These are collections of lymphoid tissue at the back of the throat. They help make antibodies against germs that are breathed in or swallowed. They are easy to see when they become enlarged during an infection or if they become cancerous.

Digestive tract: The stomach and intestines as well as many other organs also have lymphoid tissue.

Bone marrow: The bone marrow (the soft inner part of certain bones) makes red blood cells, blood platelets, and white blood cells. Red blood cells carry oxygen from the lungs to the rest of the body. Platelets plug up small holes in blood vessels caused by cuts or scrapes. White blood cells' main job is fighting infections. The 2 main types of white blood cells are granulocytes and lymphocytes. Bone marrow lymphocytes are primarily B cells. Lymphomas sometimes start from bone marrow lymphocytes.

Cancer.org