MedWorm: Lymphoma

Neuroimaging of infections of the central nervous system

Seminars in Neurology — Thu, 09 Oct 2008 16:38:55 +0100

Semin Neurol 2008; 28: 511-522DOI: 10.1055/s-0028-1083688ABSTRACTNeuroimaging plays a crucial role in the diagnosis and therapeutic management of neurologic infections. This article summarizes imaging findings in brain abscesses, ventriculitis, viral diseases, and opportunistic infections. In cases of uncomplicated meningitis, cranial computed tomography is sufficient to exclude brain edema, hydrocephalus, and skull base pathology. Magnetic resonance imaging (MRI) is superior in depicting complications (e.g., empyema, vasculitis). Diffusion-weighted imaging (DWI) shows parenchymal complications of meningitis earlier and is of help in differentiation of pyogenic abscess from other ring-enhancing lesions. Proton magnetic resonance spectroscopy can produce specific peak-patterns in cases of abscess, such as the presence of lactate and cytosolic amino acids. In toxoplasmosis, DWI may help to differentiate from lymphoma, showing no restriction of water diffusion. In patients with viral encephalitis, DWI allows earlier lesion detection. MRI has revolutionized the rapid diagnosis of spinal abscess.[...]© Thieme Medical PublishersGet connected:Table of contents | Abstract | Full text (Source: Seminars in Neurology)

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Editorial comment

The Journal of Urology — Thu, 09 Oct 2008 15:01:49 +0100

Nieder et al demonstrate an increased risk of bladder cancer following all forms of radiation and of rectal cancer following external beam radiation for prostate cancer. This study is novel in that it determines the secondary malignancy risk of different radiation therapies during the PSA era. The authors appropriately point out some limitations of the SEER database including absence of smoking data, short followup (median 49 months) and unknown radiation doses. The risk of malignancy is known to increase with radiation dose and time following exposure. Although lymphoma and leukemia may peak in 4 to 9 years, bladder and rectal cancer may require longer to develop (10 to 20 years) (reference 7 in article). This may partially explain the low malignancy risk in this study. Patients treated with radiation at a young age are at highest risk and should be followed closely to determine the long-term incidence of secondary malignancy. (Source: The Journal of Urology)

The international myeloma foundation congratulates friend and collaborator dr. luc montagnier for being awarded the nobel prize

Health News from Medical News Today — Thu, 09 Oct 2008 13:00:00 +0100

The International Myeloma Foundation (IMF) - supporting research and providing education, advocacy, and support for myeloma patients, families, researchers, and physicians - today congratulated French researcher Dr. Luc Montagnier as co-recipient of the 2008 Nobel Prize in medicine. Dr. (Source: Health News from Medical News Today)

Epicept receives ceplene(r) marketing approval in europe

Health News from Medical News Today — Thu, 09 Oct 2008 12:00:00 +0100

EpiCept Corporation (Nasdaq and OMX Nordic Exchange: EPCT) today announced that the European Commission has granted a full marketing authorization in the form of a positive Commission Decision, for Ceplene® (histamine dihydrochloride) for the remission maintenance and prevention of relapse in adult patients with Acute Myeloid Leukemia (AML) in first remission. (Source: Health News from Medical News Today)

New characteristics discovered in hodgkin lymphoma

Health News from Medical News Today — Thu, 09 Oct 2008 12:00:00 +0100

Researchers are still discovering new characteristics of Hodgkin lymphoma, a common form of cancer of the lymphatic system. The malignant cells are derived from white blood cells (B cells), but have lost a considerable part of the B cell-specific gene expression pattern. The phenotype and the characteristics of Hodgkin lymphoma cells are therefore unique. BjÃ¶rn Lamprecht and Dr. (Source: Health News from Medical News Today)

Important step in understanding the initiation of human cancer at a cellular level

Health News from Medical News Today — Thu, 09 Oct 2008 12:00:00 +0100

A family of cancer-fighting molecules helps blood stem cells in mice decide when and how to divide, say researchers at the Stanford University School of Medicine. Blocking the molecules' function spurs the normally resting cells to begin proliferating strangely - making too much of one kind of cell and not enough of another. (Source: Health News from Medical News Today)

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Dr. ernest beutler dies at 80; scripps physician and researcher pioneered bone marrow transplants

Los Angeles Times - Science — Thu, 09 Oct 2008 07:00:00 +0100

Dr. Ernest Beutler, a Scripps Research Institute physician and researcher who was one of the country's leading experts on diseases of the blood and iron metabolism, died Sunday of lymphoma at Scripps Green Hospital in La Jolla. He was 80. (Source: Los Angeles Times - Science)

Lymphoma cell adhesion-induced expression of b cell-activating factor of the tnf family in bone marrow stromal cells protects non-hodgkin's b lymphoma cells from apoptosis

Leukemia — Thu, 09 Oct 2008 04:00:00 +0100

Lymphoma cell adhesion-induced expression of B cell-activating factor of the TNF family in bone marrow stromal cells protects non-Hodgkin's B lymphoma cells from apoptosis Leukemia advance online publication, October 9, 2008. doi:10.1038/leu.2008.266 Authors: T Lwin, L A Crespo, A Wu, S Dessureault, H B Shu, L C Moscinski, E Sotomayor, W S Dalton & J Tao (Source: Leukemia)

Lipopolysaccharide activates nf-{kappa}b by tlr4-bcl10-dependent and independent pathways in colonic epithelial cells

AJP: Gastrointestinal and Liver Physiology — Thu, 09 Oct 2008 04:00:00 +0100

In colonic epithelium, one of the pathways of lipopolysaccharide (LPS) activation of NF-B and IL-8 is via Toll-like receptor (TLR)4, MyD88, IRAK1/4, and B-cell CLL/lymphoma 10 (Bcl10). However, this innate immune pathway accounts for only ~50% of the NF-B activation, so additional mechanisms to explain the LPS-induced effects are required. In this report, we identify a second pathway of LPS-induced stimulation, mediated by reactive oxygen species (ROS), in human colonic epithelial tissue cells in tissue culture and in ex vivo mouse colonic tissue. Measurements of IL-8, KC, Bcl10, phospho-IB, nuclear NF-B, and phosphorylated Hsp27 were performed by ELISA. The TLR4-Bcl10 pathway was inhibited by Bcl10 siRNA and in studies with colonic tissue from the TLR4-deficient mouse. The ROS pathway was inhibited by Tempol, a free radical scavenger, or by okadaic acid, an inhibitor of Hsp27 dephosphorylation by protein phosphatase 2A (PP2A). The ROS pathway was unaffected in the TLR4-deficient tissue or by silencing of Bcl10. The combination of exposure to the free radical scavenger Tempol and of TLR4 or Bcl10 suppression was required to completely inhibit the LPS-induced activation. The ROS pathway was associated with dephosphorylation of Hsp27. LPS appears to activate both the regulatory component of the IB-kinase (IKK) signalosome through Bcl10 interaction with Nemo (IKK) and the catalytic component through Hsp27 interaction with IKKβ. Since LPS exposure is associated with septic shock and the systemic inflammatory response syndrome, distinguishing between these two pathways of LPS activation may facilitate new approaches to prevention and treatment. (Source: AJP: Gastrointestinal and Liver Physiology)

Cats and dogs cut their owners' cancer risk by a third, researchers say

the Mail online | Health — Wed, 08 Oct 2008 19:35:21 +0100

Owning a cat or a dog can reduce by nearly a third the chances of developing non-Hodgkin's lymphoma, a rapidly rising form of cancer, claim researchers. (Source: the Mail online | Health)

Cats and dogs cut their owners' cancer risk by a third, researchers say

the Mail online | Diet — Wed, 08 Oct 2008 19:35:21 +0100

Owning a cat or a dog can reduce by nearly a third the chances of developing non-Hodgkin's lymphoma, a rapidly rising form of cancer, claim researchers. (Source: the Mail online | Diet)

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Stockguru announces profile coverage of pharmacom biovet, inc.

Medical News (via PRIMEZONE) — Wed, 08 Oct 2008 16:42:00 +0100

DALLAS, Oct. 8, 2008 (GLOBE NEWSWIRE) -- John Pentony, Publisher of StockGuru.com, announced today that the company has initiated profile coverage of PharmaCom BioVet, Inc. (Pink Sheets:PHMB). PharmaCom BioVet is dedicated to advancing the medical care industry for companion animals by establishing state-of-the-art treatment centers for lymphoma and other forms of cancer throughout the country. The purpose of these centers is to help prolong the quality of life for companion animals with cancer, and pursue the potential for a complete cure. These centers will also operate under the philosophy of providing a compassionate care environment for both the animal patients and their owners. (Source: Medical News (via PRIMEZONE))

Intracranial aspergillus infection associated with an amyloid tumor and lymphoma

Skull Base — Wed, 08 Oct 2008 14:19:37 +0100

Skull BaseDOI: 10.1055/s-0028-1087222ABSTRACTIntracranial aspergillus infection is an uncommon finding. The importance of a high index of clinical suspicion, coupled with an early diagnosis, can potentially be lifesaving. We illustrate the case in a patient who developed right-sided visual disturbance and facial paresthesia, where radiological diagnosis was meningioma but histopathology revealed an amyloid tumor with synchronous aspergillus infection and lymphoma at the same site. This diagnosis should always be considered, especially in immunodeficient patients, using a combination of neurological and thoracic imaging and histopathology of a resected specimen.[...]© Thieme Medical PublishersGet connected:Table of contents | Abstract | Full text (Source: Skull Base)

Pharmacom biovet, inc. announces corporate vision to research, treat and compassionately care for companion animals afflicted with cancer

Veterinary News From Medical News Today — Wed, 08 Oct 2008 12:00:00 +0100

PharmaCom BioVet, Inc. (PINKSHEETS: PHMB) is pleased to announce their corporate vision to research, treat and compassionately care for companion animals afflicted with cancer. PharmaCom BioVet, Inc. is dedicated to advancing the medical care industry for companion animals by establishing state-of-the-art treatment centers for lymphoma and other forms of cancer throughout the country. (Source: Veterinary News From Medical News Today)

Can chronic recurrent multifocal osteomyelitis predispose to lymphoma of bone? a case report.

Journal of Pediatric Orthopaedics B — Wed, 08 Oct 2008 11:45:29 +0100

Page: 329DOI: 10.1097/BPB.0b013e32830cc390Authors: Jellicoe, Paul; Hopyan, Sevan (Source: Journal of Pediatric Orthopaedics B)

Igg4-producing marginal zone b-cell lymphoma.

International Journal of Hematology — Wed, 08 Oct 2008 04:00:00 +0100

IgG4-producing marginal zone B-cell lymphoma.

Int J Hematol. 2008 Oct 8;

Authors: Sato Y, Takata K, Ichimura K, Tanaka T, Morito T, Tamura M, Yoshino T

IgG4-related disease is a recently proposed clinical entity with several unique clinicopathological features. A chronic inflammatory state with marked fibrosis, which can often be mistaken for malignancy, especially by clinical imaging analyses, unifies these features. Little is known about lymphomagenesis in the context of IgG4-related disease, we recently first reported the ocular adnexal marginal zone B-cell lymphomas arising from IgG4-related disease. To the best of our knowledge, no existing study has ever established the neoplastic potential of IgG4-producing cells. In the present report, we describe the first IgG4-producing lymphoma. The patient was a 72-year-old male who was being followed for an asbestos-related pleural plaque. During follow-up, computed tomography revealed bilateral renal masses and multiple swollen retroperitoneal lymph nodes. A retroperitoneal lymph node biopsy was performed. Histologically, the interfollicular areas were expanded by medium to large plasmacytoid cells. These plasmacytoid cells showed nuclear pleomorphism and had prominent Russell bodies. Immunohistochemistry and double immunofluorescence staining of these cells revealed IgG4 positivity and monotypic lambda-light chain predominance. A portion of these cells were partially positive for CD20, negative for CD3, and somewhat faintly positive for CD138. In addition, serum IgG4 was elevated. Southern blot analysis of the lymph node specimen detected immunoglobulin heavy chain gene rearrangement. The present study indicates that, not only can malignant lymphomas occur in the setting of IgG4-related disease, but IgG4-producing cells can also be neoplastic.

PMID: 18839275 [PubMed - as supplied by publisher]

(Source: International Journal of Hematology)

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Primary cardiac lymphoma: case report and brief review of the literature

Echocardiography — Wed, 08 Oct 2008 04:00:00 +0100

Primary cardiac lymphoma is defined as a non-Hodgkin's lymphoma mainly located in the heart and/or the pericardium. It is rare and affects elderly men. Common manifestations are pericardial effusion and heart failure. Diagnosis is usually late and prognosis is poor. We report a case of a patient with a large primary cardiac lymphoma who presented with chest pain and negative T-waves in electrocardiogram. Transthoracic echocardiogram showed a large mass in the right atrium and right ventricle while transesophageal echocardiogram also revealed the presence of large mobile masses in the right atrium, which were considered to be thrombi. Tissue biopsy showed a high-grade B-cell diffuse lymphocytic lymphoma. The patient was treated with chemotherapy and radiation with complete remission and prolonged survival. (ECHOCARDIOGRAPHY, Volume **, ************) (Source: Echocardiography)

Images in clinical medicine: lymphadenopathy

New England Journal of Medicine — Wed, 08 Oct 2008 04:00:00 +0100

A 61-year-old man with small lymphocytic lymphoma-chronic lymphocytic leukemia presented with neck stiffness and bilateral axillary discomfort associated with increasing, diffuse lymphadenopathy. He had received the diagnosis of small lymphocytic ... (Source: New England Journal of Medicine)

[lymphoma and myeloma] prediction of survival in multiple myeloma based on gene expression profiles reveals cell cycle and chromosomal instability signatures in high-risk patients and hyperdiploid signatures in low-risk patients: a study of the intergroupe francophone du myelome

Journal of Clinical Oncology — Wed, 08 Oct 2008 04:00:00 +0100

Purpose Survival of patients with multiple myeloma is highly heterogeneous, from periods of a few weeks to more than 10 years. We used gene expression profiles of myeloma cells obtained at diagnosis to identify broadly applicable prognostic markers. Patients and Methods In a training set of 182 patients, we used supervised methods to identify individual genes associated with length of survival. A survival model was built from these genes. The validity of our model was assessed in our test set of 68 patients and in three independent cohorts comprising 853 patients with multiple myeloma. Results The 15 strongest genes associated with the length of survival were used to calculate a risk score and to stratify patients into low-risk and high-risk groups. The survival-predictor score was significantly associated with survival in both the training and test sets and in the external validation cohorts. The Kaplan-Meier estimates of rates of survival at 3 years were 90.5% (95% CI, 85.6% to 95.3%) and 47.4% (95% CI, 33.5% to 60.1%), respectively, in our patients having a low risk or high risk independently of traditional prognostic factors. High-risk patients constituted a homogeneous biologic entity characterized by the overexpression of genes involved in cell cycle progression and its surveillance, whereas low-risk patients were heterogeneous and displayed hyperdiploid signatures. Conclusion Gene expression–based survival prediction and molecular features associated with high-risk patients may be useful for developing prognostic markers and may provide basis to treat these patients with new targeted antimitotics. (Source: Journal of Clinical Oncology)

[lymphoma and myeloma] del(6)(q22) and bcl6 rearrangements in primary cns lymphoma are indicators of an aggressive clinical course

Journal of Clinical Oncology — Wed, 08 Oct 2008 04:00:00 +0100

Purpose Primary CNS lymphoma (PCNSL) is an aggressive lymphoma but clinically validated biologic markers that can predict natural history to tailor treatment according to risk are lacking. Several genetic changes including BCL6 rearrangements and deletion of 6q22, containing the putative tumor suppressor gene PTPRK, are potential risk predictors. Herein we determined the prevalence and survival impact of del(6)(q22) and BCL6, immunoglobulin heavy chain (IGH), and MYC gene rearrangements in a large PCNSL cohort treated in a single center. Patients and Methods Interphase fluorescence in situ hybridization was performed using two-color probes for BCL6, MYC, IGH-BCL6, and del(6)(q22) on thin sections of 75 paraffin-embedded samples from 75 HIV-negative, immunocompetent patients newly diagnosed with PCNSL. Survival data were analyzed using Kaplan-Meier survival curves, log-rank tests, and proportional hazards regression adjusting for age, deep structure involvement, and high-dose methotrexate (HDMTX) treatment. Results The prevalence of del(6)(q22) and BCL6, IGH, and MYC translocations was 45%,17%, 13%, and 3%, respectively. The presence of del(6)(q22) and/or a BCL6 translocation was associated with inferior overall survival (OS; P = .0097). The presence of either del(6)(q22) alone or a BCL6 translocation alone was also associated with inferior OS (P = .0087). Univariable results held after adjusting for age, deep structure involvement, and HDMTX. Conclusion Del (6)(q22) and BCL6 rearrangements are common in PCNSL and predict for decreased OS independent of deep structure involvement and HDMTX. Unlike systemic diffuse large B-cell lymphoma, del(6)(q22) is common and IGH translocations are infrequent and usually involve BCL6 rather than BCL2, suggesting a distinct pathogenesis. (Source: Journal of Clinical Oncology)

[review article] aids-related malignancies: state of the art and therapeutic challenges

Journal of Clinical Oncology — Wed, 08 Oct 2008 04:00:00 +0100

Despite the impact of combination antiretroviral therapy (cART) on HIV-related mortality, malignancy remains an important cause of death in the current era. Although the advent of cART has resulted in reductions in the incidence of Kaposi's sarcoma and non-Hodgkin's lymphoma, non–AIDS-defining malignancies present an increased risk for HIV-infected patients, characterized by some common clinical features, generally with a more aggressive behavior and a more advanced disease at diagnosis, which is responsible for poorer patient outcomes. Specific therapeutic recommendations are lacking for these new nonopportunistic malignancies, such as Hodgkin's lymphoma, anal cancer, lung cancer, hepatocarcinoma, and many others. Antiretroviral agents have a propensity for causing drug interactions as a result of their ability to either inhibit or induce the cytochrome P450 (CYP) enzyme system. Because many antineoplastic drugs are also metabolized by the CYP system, coadministration with cART could result in either drug accumulation with increased toxicity, or decreased efficacy of one or both classes of drugs. Further research delineating the combined safety and pharmacokinetics of antiretrovirals and antineoplastic therapy is necessary. Special considerations of these AIDS-related and non–AIDS-related malignancies and their clinical and therapeutic aspects constitute the subject of this review. (Source: Journal of Clinical Oncology)

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[diagnosis in oncology] anaplastic large-cell lymphoma presenting as an endobronchial polypoid tumor

Journal of Clinical Oncology — Wed, 08 Oct 2008 04:00:00 +0100

(Source: Journal of Clinical Oncology)

Hodgkin lymphoma -- new characteristics discovered

EurekAlert! - Cancer — Wed, 08 Oct 2008 04:00:00 +0100

(Helmholtz Association of German Research Centres) Researchers are still discovering new characteristics of Hodgkin lymphoma, a common form of cancer of the lymphatic system. Björn Lamprecht and Dr. Stephan Mathas (Max Delbrück Center for Molecular Medicine, MDC, Berlin-Buch and Charité -- Universitätsmedizin Berlin, Germany) have now demonstrated the production of interleukin 21 in the tumor cells of Hodgkin lymphoma. IL-21 promotes the growth of cancer cells and helps them evade immune system detection. (Source: EurekAlert! - Cancer)

Biogen drug has strong clinical showing as leukemia medicine

bizjournals.com Health Care:Biotechnology headlines — Tue, 07 Oct 2008 18:57:21 +0100

A lymphoma treatment developed by Biogen Idec has shown strong promise in a late-stage human clinical trial as a leukemia treatment. (DNA) (Source: bizjournals.com Health Care:Biotechnology headlines)

Biogen drug has strong clinical showing as leukemia medicine

bizjournals.com Health Care:Pharmaceuticals headlines — Tue, 07 Oct 2008 18:57:21 +0100

Oral cancer drug revlimid(r) receives marketing authorization from health canada for treatment of multiple myeloma

Health News from Medical News Today — Tue, 07 Oct 2008 16:00:00 +0100

Celgene International Sarl (NASDAQ: CELG) announced that its oral cancer drug REVLIMID (lenalidomide) has received marketing authorization approval from Health Canada for use in combination with dexamethasone as a treatment for patients with multiple myeloma who have received at least one prior therapy. Multiple myeloma is the second most commonly diagnosed blood cancer worldwide. (Source: Health News from Medical News Today)

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Extraocular muscle involvement in marginal zone b-cell lymphomas of the orbit.

Orbit — Tue, 07 Oct 2008 15:54:52 +0100

Extraocular muscle involvement in marginal zone B-cell lymphomas of the orbit.

Orbit. 2008;27(5):345-9

Authors: Izambart C, Robert PY, Petellat F, Petit B, Gastaud P, Lagier J, Labrousse F, Adenis JP

Introduction: Marginal zone B-cell lymphoma is the most frequent ocular adnexal lymphoma. It may involve the conjunctiva, lacrimal gland, eyelid, extraocular muscle, and orbital connective tissue. Extraocular muscle infiltration is rare. Methods: We report here a series of 5 patients presenting with extraocular muscle infiltration due to marginal zone B-cell lymphoma, extracted from a retrospective study of 39 patients with primitive ocular adnexal marginal zone B-cell lymphoma presenting within a 15-year period, from 1993 to 2007, at two university hospitals. Results: Out of 39 patients, two females and three males presented with extraocular muscle involvement (one levator muscle, one medial rectus muscle, one lateral rectus muscle, one inferior rectus muscle, and one inferior oblique muscle). In 4 cases, the right eye was involved. The median age of presentation was 60 years. Proptosis and diplopia were the main clinical signs. A mean duration of symptoms was 12 months before diagnosis was given. Three patients were stage IE at the diagnosis, according to Ann Arbor classification, and one was at stage IV. Three patients received radiotherapy and two received chemotherapy. Three patients underwent local relapses at a median time of 40 months. The patients with relapses were treated with chemotherapy alone in one case, radiotherapy alone in one case, and immunotherapy and chemotherapy in one case. The mean follow-up period was 54 months. Discussion: When compared to other locations of marginal zone B-cell lymphomas of the orbit, extraocular involvement occurred in younger patients and had similar prognosis. Conclusion: Extraocular muscle involvement is a rare location of marginal zone B-cell lymphoma that had to be known and can simulate thyroid orbitopathy.

PMID: 18836931 [PubMed - in process]

(Source: Orbit)

Biogen idec’s rituxan showing promise to treat leukemia

bizjournals.com Health Care:Biotechnology headlines — Tue, 07 Oct 2008 14:49:35 +0100

Phase iii study showed rituxan combined with chemotherapy improved progression-free survival in patients with relapsed chronic lymphocytic leukemia

Lymphoma / Leukemia News From Medical News Today — Tue, 07 Oct 2008 13:00:00 +0100

Genentech, Inc. (NYSE:DNA) and Biogen Idec (Nasdaq:BIIB) announced that a global Phase III study of Rituxan® (rituximab) in combination with fludarabine and cyclophosphamide chemotherapy met its primary endpoint of improving progression-free survival (PFS), as assessed by investigators, in patients with previously treated CD20-positive chronic lymphocytic leukemia (CLL) compared to chemotherapy alone. There were no new or unexpected safety signals reported in the study. (Source: Lymphoma / Leukemia News From Medical News Today)

New stanford diagnostic test for rare leukemia seems to provide faster results, study finds

Lymphoma / Leukemia News From Medical News Today — Tue, 07 Oct 2008 13:00:00 +0100

A new twist on a well-known cell sorting technique may allow physicians to diagnose rare leukemias in hours instead of weeks, according to a study by researchers at the Stanford University School of Medicine and UC-San Francisco. The clinical promise of the Stanford-developed approach, which eavesdrops on individual cells to decipher potentially dangerous molecular conversations, is likely to extend to many other disorders in which cell-signaling pathways are disrupted. (Source: Lymphoma / Leukemia News From Medical News Today)

Dkms, whole foods and the deerfield community band together to help save chicago father in need of a bone marrow transplant

Lymphoma / Leukemia News From Medical News Today — Tue, 07 Oct 2008 11:00:00 +0100

Come to the Bone Marrow Donor Drive and Become a Life-Saver DKMS, Whole Foods and the Deerfield community are joining forces to help save the life of Jon Simon, a Deerfield resident of 30 years, whose only chance of survival is a bone marrow transplant.Â So far, no matches have been found. Jon, a devoted husband and father, has been fighting Non-Hodgkin Lymphoma (NHL), a type of blood cancer, for more than one year. (Source: Lymphoma / Leukemia News From Medical News Today)

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High-dose therapy and autologous stem cell transplantation for follicular lymphoma undergoing transformation to diffuse large b-cell lymphoma

European Journal of Haematology — Tue, 07 Oct 2008 04:00:00 +0100

The transformation of follicular lymphoma (FL) to high-grade histology occurs in up to 70% of patients. The role of hematopoietic stem cell transplantation (HSCT) in transformed FL is poorly defined. Twenty-four FL patients with histologically confirmed transformation to diffuse large B-cell lymphoma underwent unpurged autologous HSCT at our institution. Their median age was 56 yr. The median number of prior chemotherapies was 2 (range 1[ndash]6). Thirteen patients had residual nodal disease measuring more than 2 cm and four patients had bulky disease at the time of HSCT. Six patients had refractory disease at transplantation. At a median follow-up of 38 months, 3-yr progression-free survival following autologous HSCT was 40%. The 3-yr overall survival was 52%. The cumulative incidence of relapse and non-relapse mortality rate was 41% and 25%, respectively. (Source: European Journal of Haematology)

High incidence of dna mutations and gene amplifications of the alk gene in advanced sporadic neuroblastoma tumours

BJ Gene — Tue, 07 Oct 2008 04:00:00 +0100

Anaplastic lymphoma kinase (ALK) is oncogenic in several tumours and recently identified as a predisposition gene for familial neuroblastoma (NB) harbouring mutations in the tyrosine kinase domain (TKD). We have analysed a large set of sporadic human NB primary tumours of all clinical stages for chromosomal re-arrangements using array-CGH (n=108) and mutations of the ALK gene (n=90), and expression of ALK and related genes (n=19). ALK amplification or in-gene re-arrangements were found in 5% of NB tumours and mutations in 11% including two novel not previously published mutations in the TKD; c.3733T>A and c.3735C>A. DNA mutations in the TKD and gene amplifications were only found in advanced large primaries or metastatic tumours and correlated with the expression levels of ALK and downstream genes as well as other unfavourable features and poor outcome. Our data support that the ALK protein contribute to NB oncogenesis providing a highly interesting putative therapeutic target in a subset of unfavourable NB tumours. (Source: BJ Gene)

P53 mutations in lymphomas: position matters

Blood — Tue, 07 Oct 2008 04:00:00 +0100

(Source: Blood)

Risk of lymphoproliferative disorders among first-degree relatives of lymphoplasmacytic lymphoma/waldenstrom macroglobulinemia patients: a population-based study in sweden

Blood — Tue, 07 Oct 2008 04:00:00 +0100

A role for genetic factors in the etiology of lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (LPL/WM) is implicated based on prior findings from multiply affected families and small case-control and cohort studies. We identified 2144 LPL/WM patients (1539 WM [72%] and 605 LPL [28%]) diagnosed in Sweden, 8279 population-based matched controls, and linkable first-degree relatives of patients (n = 6177) and controls (n = 24 609). Using a marginal survival model, we calculated relative risks and 95% confidence intervals as measures of familial aggregation. We found first-degree relatives of LPL/WM patients to have 20-fold (4.1-98.4), 3.0-fold (2.0-4.4), 3.4-fold (1.7-6.6), and 5.0-fold (1.3-18.9) increased risks of developing LPL/WM, non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL), and monoclonal gammopathy of undetermined significance (MGUS), respectively. However, there was no evidence of an increased risk of developing multiple myeloma or Hodgkin lymphoma. In analyses stratified by type of first-degree relative (parent, sibling, offspring), age at diagnosis of the probands (greater or less than 70 years), and sex of the first-degree relative, we did not observe the risk estimates to be significantly different compared with the overall analyses. Our findings of highly increased risks of developing LPL/WM, NHL, CLL, and MGUS support the operation of shared susceptibility genes that predispose to LPL/WM and other lymphoproliferative disorders. (Source: Blood)

Clinical features and treatment outcome of nasal-type nk/t-cell lymphoma of waldeyer ring

Blood — Tue, 07 Oct 2008 04:00:00 +0100

The clinical characteristics and prognosis remain unclear for nasal-type NK/T-cell lymphoma of Waldeyer ring (WR-NKTL). The aim of this study is to determine the clinical features and outcome. Ninety-one patients with WR-NKTL were reviewed. According to the Ann Arbor system, 15, 56, 12, and 8 patients had stage I, II, III, and IV. Of patients with stage I and II, 54 received combined chemotherapy and radiotherapy (CMT), 13 received radiotherapy alone, and 4 patients received chemotherapy alone. All 20 patients with stage III/IV received primary chemotherapy. The disease is characterized by predominance in young males, good performance, a propensity for nodal involvement, frequent stage II through IV diseases, low frequency of elevated LDH, low-risk international prognostic index (IPI), high sensitivity to radiotherapy, and intermediate sensitivity to chemotherapy. The 5-year overall survival and progression-free survival for all patients were 65% and 51%, respectively. The age, B symptoms, stage, and IPI were important prognostic factors. CMT tended to improve the survival compared with radiotherapy alone for patients with stage I and II diseases. Both nodal involvement and distant extranodal dissemination were the primary failure patterns. WR-NKTL appears to have distinct clinical characteristics and favorable outcomes. (Source: Blood)

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Long-term outcomes of patients with advanced-stage cutaneous t-cell lymphoma and large cell transformation

Blood — Tue, 07 Oct 2008 04:00:00 +0100

Although mycosis fungoides (MF) is typically an indolent disease, patients with advanced-stage disease (stages IIB-IVB), including Sézary syndrome (SS), often have a poor outcome. A 31-year, retrospective analysis of our cutaneous lymphoma database, of 297 patients with MF and SS, was undertaken to study long-term outcomes and identify clinical predictors of outcome in patients with advanced-stage disease (ASD, n = 92) and large cell transformation (LCT, n = 22). Two-thirds of patients with ASD presented with de novo ASD. The median overall survival (OS) for ASD was 5 years with a 10-year predicted OS of 32%. Age at initial diagnosis (P = .01), tumor stage (P = .01), and clinical stage (P = .001) were found to be significant predictors of outcome. Patients who presented with de novo ASD demonstrated better outcomes that were not statistically significant than those with a prior diagnosis of early-stage MF (P = .25). Transformation developed in 22 of the 297 MF/SS patients (7.4%), with a transformation rate of only 1.4% in patients with early-stage disease, compared with stage IIB (27%) and stage IV (56%-67%) disease. The median OS from diagnosis of LCT was 2 years. We confirm that the incidence of LCT is strongly dependent on tumor stage at diagnosis, and we demonstrate a much lower overall risk of LCT than previously reported. (Source: Blood)

Structural profiles of tp53 gene mutations predict clinical outcome in diffuse large b-cell lymphoma: an international collaborative study

Blood — Tue, 07 Oct 2008 04:00:00 +0100

The purpose of this study is to correlate the presence of TP53 gene mutations with the clinical outcome of a cohort of patients with diffuse large B-cell lymphoma (DLBCL) assembled from 12 medical centers. TP53 mutations were identified in 102 of 477 patients, and the overall survival (OS) of patients with TP53 mutations was significantly worse than those with wild-type TP53 (P < .001). However, subsets of TP53 mutations were found to have different effects on OS. Mutations in the TP53 DNA-binding domains were the strongest predictors of poor OS (P < .001). Mutations in the Loop-Sheet-Helix and Loop-L3 were associated with significantly decreased OS (P = .002), but OS was not significantly affected by mutations in Loop-L2. A subset of missense mutations (His158, His175, Ser245, Gln248, His273, Arg280, and Arg282) in the DNA-binding domains had the worst prognosis. Multivariate analysis confirmed that the International Prognostic Index and mutations in the DNA-binding domains were independent predictors of OS. TP53 mutations also stratified patients with germinal center B cell–like DLBCL, but not nongerminal center B cell–like DLBCL, into molecularly distinct subsets with different survivals. This study shows the prognostic importance of mutations in the TP53 DNA-binding domains in patients with DLBCL. (Source: Blood)

The presence of tp53 mutation at diagnosis of follicular lymphoma identifies a high-risk group of patients with shortened time to disease progression and poorer overall survival

Blood — Tue, 07 Oct 2008 04:00:00 +0100

The International Prognostic Index and the Follicular Lymphoma International Prognostic Index are widely used for the risk assessment of follicular lymphoma (FL). Although molecular studies have provided insight into the biology of FL, no molecular marker has impacted on treatment stratification. Because TP53 mutations are associated with poor prognosis in hematologic malignancies, we investigated the prognostic value of TP53 mutation at diagnosis in FL. Heterozygous TP53 mutation was detected in 12 of 185 (6%) analyzed cases. Mutation was associated with older age (P = .02) and higher International Prognostic Index score (P = .04). On multivariate analysis, TP53 mutation correlated with shorter progression-free survival (P < .001) and overall survival (P = .009). TP53 mutation was associated with low expression of the immune-response 1 gene expression signature (P = .016) and with an unfavorable gene expression-based survival predictor score (P < .001), demonstrating for the first time that molecular features of the malignant cell may correlate with the nature of the immune response in FL. (Source: Blood)

Targeting bcl-2 family proteins modulates the sensitivity of b-cell lymphoma to rituximab-induced apoptosis

Blood — Tue, 07 Oct 2008 04:00:00 +0100

The chimeric monoclonal antibody rituximab is the standard of care for patients with B-cell non-Hodgkin lymphoma (B-NHL). Rituximab mediates complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity of CD20-positive human B cells. In addition, rituximab sensitizes B-NHL cells to cytotoxic chemotherapy and has direct apoptotic and antiproliferative effects. Whereas expression of the CD20 antigen is a natural prerequisite for rituximab sensitivity, cell-autonomous factors determining the response of B-NHL to rituximab are less defined. To this end, we have studied rituximab-induced apoptosis in human B-NHL models. We find that rituximab directly triggers apoptosis via the mitochondrial pathway of caspase activation. Expression of antiapoptotic Bcl-xL confers resistance against rituximab-induced apoptosis in vitro and rituximab treatment of xenografted B-NHL in vivo. B-NHL cells insensitive to rituximab-induced apoptosis exhibit increased endogenous expression of multiple antiapoptotic Bcl-2 family proteins, or activation of phosphatidylinositol-3-kinase signaling resulting in up-regulation of Mcl-1. The former resistance pattern is overcome by treatment with the BH3-mimetic ABT-737, the latter by combining rituximab with pharmacologic phosphatidylinositol-3-kinase inhibitors. In conclusion, sensitivity of B-NHL cells to rituximab-induced apoptosis is determined at the level of mitochondria. Pharmacologic modulation of Bcl-2 family proteins or their upstream regulators is a promising strategy to overcome rituximab resistance. (Source: Blood)

Aberrant expression of the th2 cytokine il-21 in hodgkin lymphoma cells regulates stat3 signaling and attracts treg cells via regulation of mip-3{alpha}

Blood — Tue, 07 Oct 2008 04:00:00 +0100

The malignant Hodgkin/Reed-Sternberg (HRS) cells of classical Hodgkin lymphoma (HL) are derived from mature B cells, but have lost a considerable part of the B cell–specific gene expression pattern. Consequences of such a lineage infidelity for lymphoma pathogenesis are currently not defined. Here, we report that HRS cells aberrantly express the common cytokine-receptor -chain (c) cytokine IL-21, which is usually restricted to a subset of CD4+ T cells, and the corresponding IL-21 receptor. We demonstrate that IL-21 activates STAT3 in HRS cells, up-regulates STAT3 target genes, and protects HRS cells from CD95 death receptor–induced apoptosis. Furthermore, IL-21 is involved in up-regulation of the CC chemokine macrophage-inflammatory protein-3 (MIP-3) in HRS cells. MIP-3 in turn attracts CCR6+CD4+CD25+FoxP3+CD127lo regulatory T cells toward HRS cells, which might favor their immune escape. Together, these data support the concept that aberrant expression of B lineage–inappropriate genes plays an important role for the biology of HL tumor cells. (Source: Blood)

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The majority of cutaneous marginal zone b-cell lymphomas expresses class-switched immunoglobulins and develops in a t-helper type 2 inflammatory environment

Blood — Tue, 07 Oct 2008 04:00:00 +0100

Extranodal marginal zone B-cell lymphomas (MZBCLs) arise on a background of chronic inflammation resulting from organ-specific autoimmunity, infection, or by unknown causes. Well-known examples are salivary gland MZBCL in Sjögren's sialadenitis and gastric MZBCL in Helicobacter pylori gastritis. MZBCLs express CXCR3, a receptor for interferon-–induced chemokines highly expressed in the chronic inflammatory environment. The immunoglobulin (Ig) variable heavy/light chain (IgVH/IgVL) gene repertoire of salivary gland and gastric MZBCL appears restricted and frequently encodes B-cell receptors with rheumatoid factor reactivity. Primary cutaneous marginal zone B-cell lymphomas (PCMZLs) are regarded as the skin-involving counterparts of extranodal MZBCLs. Although PCMZLs have been associated with Borrelia burgdorferi dermatitis, PCMZLs generally arise because of unknown causes. We studied an extensive panel of PCMZLs and show that PCMZLs do not conform to the general profile of extranodal MZBCL. Whereas most noncutaneous MZBCLs express IgM, PCMZLs in majority express IgG, IgA, and IgE and do not show an obvious immunoglobulin repertoire bias. Furthermore, the isotype-switched PCMZLs lack CXCR3 and seem to arise in a different inflammatory environment, compared with other extranodal MZBCLs. (Source: Blood)

K-rasg12d-induced t-cell lymphoblastic lymphoma/leukemias harbor notch1 mutations and are sensitive to {gamma}-secretase inhibitors

Blood — Tue, 07 Oct 2008 04:00:00 +0100

To study the impact of oncogenic K-Ras on T-cell leukemia/lymphoma development and progression, we made use of a conditional K-RasG12D murine knockin model, in which oncogenic K-Ras is expressed from its endogenous promoter. Transplantation of whole bone marrow cells that express oncogenic K-Ras into wild-type recipient mice resulted in a highly penetrant, aggressive T-cell leukemia/lymphoma. The lymphoblasts were composed of a CD4/CD8 double-positive population that aberrantly expressed CD44. Thymi of primary donor mice showed reduced cellularity, and immunophenotypic analysis demonstrated a block in differentiation at the double-negative 1 stage. With progression of disease, approximately 50% of mice acquired Notch1 mutations within the PEST domain. Of note, primary lymphoblasts were hypersensitive to -secretase inhibitor treatment, which is known to impair Notch signaling. This inhibition was Notch-specific as assessed by down-regulation of Notch1 target genes and intracellular cleaved Notch. We also observed that the oncogenic K-Ras-induced T-cell disease was responsive to rapamycin and inhibitors of the RAS/MAPK pathway. These data indicate that patients with T-cell leukemia with K-Ras mutations may benefit from therapies that target the NOTCH pathway alone or in combination with inhibition of the PI3K/AKT/MTOR and RAS/MAPK pathways. (Source: Blood)

Gene expression predicts overall survival in paraffin-embedded tissues of diffuse large b-cell lymphoma treated with r-chop

Blood — Tue, 07 Oct 2008 04:00:00 +0100

Gene expression profiling (GEP) on frozen tissues has identified genes predicting outcome in patients with diffuse large B-cell lymphoma (DLBCL). Confirmation of results in current patients is limited by availability of frozen samples and addition of monoclonal antibodies to treatment regimens. We used a quantitative nuclease protection assay (qNPA) to analyze formalin-fixed, paraffin-embedded tissue blocks for 36 previously identified genes (N = 209, 93 chemotherapy; 116 rituximab + chemotherapy). By qNPA, 208 cases were successfully analyzed (99.5%). In addition, 15 of 36 and 11 of 36 genes, representing each functional group previously identified by GEP, were associated with survival (P < .05) in the 2 treatment groups, respectively. In addition, 30 of 36 hazard ratios of death trended in the same direction versus the original studies. Multivariate and variable cut-off point analysis identified low levels of HLA-DRB (< 20%) and high levels of MYC (> 80%) as independent indicators of survival, together distinguishing cases with the worst prognosis. Our results solve a clinical research problem by demonstrating that prognostic genes can be meaningfully quantified using qNPA technology on formalin-fixed, paraffin-embedded tissues; previous GEP findings in DLBCL are relevant with current treatments; and 2 genes, representing immune escape and proliferation, are the common features of the most aggressive DLBCL. (Source: Blood)

Tun et al. pathway analysis of primary central nervous system lymphoma. blood. 2008; 111:3200-3210.

Blood — Tue, 07 Oct 2008 04:00:00 +0100

(Source: Blood)

Plasmablastic lymphoma: a review

Oral Diseases — Tue, 07 Oct 2008 04:00:00 +0100

Plasmablastic lymphoma (PBL) has been recently characterised as an aggressive subtype of non-Hodgkin's lymphoma, most frequently arising in the oral cavity of HIV-infected patients. To date, approximately 60 cases fulfilling the clinico-pathological characteristics of PBL have been reported. PBLs are composed of large cells with eccentrically located nuclei and deeply basophilic cytoplasm with a paranuclear hof. The tumour cells are invariably immunoreactive for the plasma cell marker CD138, and show monoclonal rearrangement of the immunoglobulin heavy chain gene (IgH) and/or clonal restriction of the Ig light chain (IgL) gene expression in most of the cases. Similar to other types of AIDS-related lymphomas, there is evidence that Epstein[ndash]Barr virus and Kaposi-sarcoma associated Human Herpes Virus 8 may play a relevant role in the pathogenesis of PBL. PBL patients have been treated heterogeneously, with a combination of chemotherapy, radiotherapy and/or surgery, and their prognosis is usually poor, with a death rate of approximately 60% at 1 year. (Source: Oral Diseases)

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Evolution of ptld following renal transplantation in a child

Pediatric Transplantation — Tue, 07 Oct 2008 04:00:00 +0100

Markert E, Siebolts U, Habbig S, Odenthal M, Dienes HP, Stippel DL, Hoppe B, Wickenhauser C. Evolution of PTLD following renal transplantation in a child.Pediatr Transplantation 2008. © 2008 Wiley Periodicals, Inc.Abstract: We report the case of an eight-yr-old child with early onset PTLD half a year after renal transplantation. The patient developed gastrointestinal pain and bowel biopsies revealed imposing lymphoid infiltrates with small spots of lymphoid blasts in the colonic mucosa. These findings were interpreted as transplantation associated B-cell stimulation. However, the persistent severe abdominal pain led to the resection of a jejunal segment. Here, gut wall perforation caused by a tumor mass was seen. Histologically, a blastic lymphoid cell proliferation of B-cell origin with high proliferation rate and EBV association could be demonstrated. IgH rearrangement analysis and in situ hybridization revealed an oligoclonal B-cell pattern. Reduction of immunosuppression and treatment with rituximab led to lymphoma remission and conversion of EBV serology four wk later. The report presented herein demonstrates the evolution of an oligoclonal lymphoproliferation with direct disease progression towards EBV associated PTLD by analyzing different stages of the disease. (Source: Pediatric Transplantation)

Changes in cancer incidence in teenagers and young adults (ages 13 to 24 years) in england 1979-2003

Cancer — Tue, 07 Oct 2008 04:00:00 +0100

Cancer for teenagers and young adults represents a major source of morbidity and mortality. Trends in cancer incidence can provide pointers concerning how changes in the environment and in personal behavior affect cancer risks.Data on 39,129 neoplasms in individuals ages 13 to 24 years who were diagnosed in England from 1979 to 2003 were analyzed. Variability in incidence by time period and differences in the time trends by age group, sex, and geographic region were analyzed using generalized linear models.Incidence rates of leukemias, lymphomas, central nervous system, bone, and germ cell tumors; melanoma; and carcinomas of the thyroid, ovary, cervix, and colon/rectum increased over time (all P < .01); whereas the incidence of carcinomas of the stomach and bladder decreased (both P < .01). These changes were consistent by age, sex, and region for most neoplasms. Melanoma incidence stabilized in southern England by 1993 but continued to increase in northern England (P = .001). The increase in non-Hodgkin lymphoma was greater in individuals ages 20 to 24 year than in younger individuals, but the increase in Hodgkin lymphoma was confined to individuals ages 13 to 14 years.The changes in incidence rates may have been caused in part by environmental changes and in part by behavioral changes in young individuals. Some of these results can be used to inform public health campaigns, which can be constructed to encourage better lifestyle choices by young individuals. Cancer 2008. © 2008 American Cancer Society. (Source: Cancer)

Epstein-barr virus-associated b-cell lymphoma secondary to fcd-c therapy in patients with peripheral t-cell lymphoma.

International Journal of Hematology — Tue, 07 Oct 2008 04:00:00 +0100

Epstein-Barr virus-associated B-cell lymphoma secondary to FCD-C therapy in patients with peripheral T-cell lymphoma.

Int J Hematol. 2008 Oct 7;

Authors: Weisel KC, Weidmann E, Anagnostopoulos I, Kanz L, Pezzutto A, Subklewe M

Epstein-Barr virus (EBV)-associated B-cell lymphoproliferative disorders occur at an increasing frequency in various hereditary and acquired states of immune dysfunction. In a few cases of T-cell lymphoma, especially in angioimmunoblastic T-cell lymphoma (AILT), EBV-associated B-cell lymphoproliferative disorders have been reported. Here, we present two cases of EBV-associated B-cell lymphoma after treatment of T-cell lymphoma (AILT and peripheral T-cell lymphoma, unspecified, PTCL-NOS) with a regimen containing alemtuzumab and fludarabine. Conventional and immunohistological tissue staining showed the typical features of highly proliferating diffuse large B-cell lymphoma in both cases. The monoclonal B-cell population displayed EBV latency type III. At the time of diagnosis the cellular immune status of both patients was severely compromised with an absolute CD4 T-cell count below <120 mul(-1). Our observation supports the notion that combination of cytotoxic drugs and immunosuppressive antibodies in patients with T-cell lymphoma may severely aggravate the already present immunodeficiency. We suggest to monitor the cellular immune status in combination with the EBV load in high risk patients for early detection-and possibly intervention-of EBV-associated lymphoma.

PMID: 18839273 [PubMed - as supplied by publisher]

(Source: International Journal of Hematology)

Hydroxamic acid derivatives of mycophenolic acid inhibit histone deacetylase at the cellular level.

Bioscience, Biotechnology, and Biochemistry — Tue, 07 Oct 2008 04:00:00 +0100

Hydroxamic Acid Derivatives of Mycophenolic Acid Inhibit Histone Deacetylase at the Cellular Level.

Biosci Biotechnol Biochem. 2008 Oct 7;

Authors: Batovska DI, Kim DH, Mitsuhashi S, Cho YS, Kwon HJ, Ubukata M

Mycophenolic acid (MPA, 1), an inhibitor of IMP-dehydrogenase (IMPDH) and a latent PPARgamma agonist, is used as an effective immunosuppressant for clinical transplantation and recently entered clinical trials in advanced multiple myeloma patients. On the other hand, suberoylanilide hydroxamic acid (SAHA), a non-specific histone deacetylase (HDAC) inhibitor, has been approved for treating cutaneous T-cell lymphoma. MPA seemed to bear a cap, a linker, and a weak metal-binding site as a latent inhibitor of HDAC. Therefore, the hydroxamic acid derivatives of mycophenolic acid having an effective metal-binding site, mycophenolic hydroxamic acid (MPHA, 2), 7-O-acetyl mycophenolic acid (7-O-Ac MPHA, 3), and 7-O-lauroyl mycophenolic hydroxamic acid (7-O-L MPHA, 4) were designed and synthesized. All these compounds inhibited histone deacetylase with IC(50) values of 1, 0.9 and 0.5 muM, and cell proliferation at concentrations of 2, 1.5 and 1 muM, respectively.

PMID: 18838793 [PubMed - as supplied by publisher]

(Source: Bioscience, Biotechnology, and Biochemistry)