Diffuse large B-cell non-Hodgkin lymphoma in the very elderly: challenges and solutions.

Feb 2013

Latta S, Cygan PH, Fried W, Nabhan C.

Source

Department of Medicine, Advocate Lutheran General Hospital, Park Ridge, Illinois 60068, USA.

Abstract

Diffuse large B-cell non-Hodgkin lymphoma (DLBCL) is a disease of the elderly, but our current guidelines and treatment paradigms for this disease are based on studies that have mainly enrolled younger patients. Because the number of people living beyond the age of 80 increased by more than 250% between 1960 and 2000, and since it is expected that the population over the age of 75 will triple by 2030, understanding how these elderly patients should be treated is paramount to improving outcomes for this potentially curable lymphoma. In this review, we outline the scope of the problem; we define "the elderly" and identify challenges in assessing this patient population. We also summarize pivotal studies that have been conducted in these elderly patients and suggest an algorithm to aid clinicians in making treatment decisions when faced with DLBCL patients older than 80.

PubMed

Comment in

• The following popper user interface control may not be accessible. Tab to the next button to revert the control to an accessible version.
  Destroy user interface controlWhen can R-CHOP not be used in an elderly patient? [Oncology (Williston Park). 2013]
• 
  
• The following popper user interface control may not be accessible. Tab to the next button to revert the control to an accessible version.
  Destroy user interface controlFffuse large B-cell lymphoma in the very elderly: the case for refining our clinical trials. 
• 
  
• [Oncology (Williston Park). 2013]
• 
  
• The following popper user interface control may not be accessible. Tab to the next button to revert the control to an accessible version.
  Destroy user interface controlDiffuse large B-cell lymphoma in the elderly: leaving our old way(s) behind? [Oncology (Williston Park). 2013]

Nonstereotyped Lymphoma B Cell Receptors Recognize Vimentin as a Shared Autoantigen.

Mar 2012

Cha SC, Qin H, Kannan S, Rawal S, Watkins LS, Baio FE, Wu W, Ong J, Wei J, Kwak B, Kim S, Popescu MS, Paick DS,Kim K, Luong A, Davis RE, Schroeder HW Jr, Kwak LW, Neelapu SS.

Source

Division of Cancer Medicine, Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX 77030;

Abstract

Ag activation of the BCR may play a role in the pathogenesis of human follicular lymphoma (FL) and other B cellmalignancies. However, the nature of the Ag(s) recognized by tumor BCRs has not been well studied. In this study, we used unbiased approaches to demonstrate that 42 (19.35%) of 217 tested FL Igs recognized vimentin as a shared autoantigen. The epitope was localized to the N-terminal region of vimentin for all vimentin-reactive tumor Igs. We confirmed specific binding to vimentin by using recombinant vimentin and by performing competitive inhibition studies. Furthermore, using indirect immunofluorescence staining, we showed that the vimentin-reactive tumor Igs colocalized with an anti-vimentin mAb in HEp-2 cells. The reactivity to N-terminal vimentin of IgG FL Igs was significantly higher than that of IgM FL Igs (30.4 versus 10%; p = 0.0022). However, vimentin-reactive FL Igs did not share CDR3 motifs and were not homologous. Vimentin was expressed in the T cell-rich regions of FL, suggesting that vimentin is available for binding with tumor BCRs within the tumor microenvironment. Vimentin was also frequently recognized by mantle cell lymphoma and multiple myeloma Igs. Our results demonstrate that vimentin is a shared autoantigen recognized by nonstereotyped FL BCRs and by the Igs of mantle celllymphoma and multiple myeloma and suggest that vimentin may play a role in the pathogenesis of multiple B cellmalignancies. These findings may lead to a better understanding of the biology and natural history of FL and other B cell malignancies.

PubMed

Treatment Strategies for Patients with Diffuse Large B-Cell Lymphoma: Past, Present, and Future.

Apr 2012

Sinha R, Nastoupil L, Flowers CR.

Source

Department of Hematology/Medical Oncology, Winship Cancer Institute, 1365 C Clifton Road, Ste 4005, Atlanta, GA 30322, Office: 404-778-1827.

Keywords:Diffuse Large B-Cell Lymphoma, Lymphoma, Non-Hodgkin Lymphoma, chemoimmunotherapy, rituximab, treatment

Abstract

Diffuse large B-cell lymphoma (DLBCL) is the most commonly occurring lymphoma in the Western world. DLBCL is a clinically, biologically, and pathologically heterogeneous entity with biologically distinct subtypes that have different expected treatment outcomes. The addition of rituximab to combination chemotherapy has improved outcomes for all patients with DLBCL and can produce cure for many individuals. Relapsed DLBCL is generally managed with salvage chemo-immunotherapy followed by high dose therapy and autologous stem cell transplantation which can cure additional patients. 

However, outcomes for patients who relapse early after upfront rituximab and chemotherapy have a poorer prognosis. Novel therapies and strategies are desperately needed for these patients and several emerging treatments hold promise for improving DLBCL treatment outcomes in the future.

PubMed

R-CHOP therapy alone in limited stage diffuse large B-cell lymphoma.

Feb 2013

Tomita N, Takasaki H, Miyashita K, Fujisawa S, Ogusa E, Matsuura S, Kishimoto K, Numata A, Fujita A, Ohshima R,Kuwabara H, Hagihara M, Hashimoto C, Takemura S, Koharazawa H, Yamazaki E, Fujimaki K, Taguchi J, Sakai R,Ishigatsubo Y.

Source

Department of Internal Medicine and Clinical Immunology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.

Abstract

Long-term observation has identified a pattern of continuing relapse in limited stage diffuse large B-cell lymphoma (DLBCL) treated by three cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) plus involved-field irradiation. We retrospectively analysed 190 untreated patients with limited stage DLBCL treated by R-CHOP alone. All the patients were scheduled to undergo primary therapy with six cycles of full-dose R-CHOP. Cases with a dose reduction of more than 20% were excluded from the study. Additional local irradiation was allowed in patients with partial response (PR). Five patients received additional local irradiation after PR at the end of the R-CHOP therapy. The median observation period was 52 months. Median age at diagnosis was 63 years. The responses to therapy were 180 complete responses, eight PR, and two progression of disease (PD). The 5-year progression-free survival and 5-year overall survival rates were 84% and 90%, respectively, both in plateau. During the observation period, 29 patients experienced PD. The progression sites were the primary sites in 15 patients, outside the primary sites in 10, and undetermined in four patients. These results suggest that the 'standard' strategy of three cycles of R-CHOP followed by involved-field radiotherapy for limited stage DLBCL could be effectively replaced by six cycles of R-CHOP alone.

PubMed

HHV8-Negative Primary Effusion Lymphoma of B-Cell Lineage: Two Cases and a Comprehensive Review of the Literature.

2013

Saini N, Hochberg EP, Linden EA, Jha S, Grohs HK, Sohani AR.

Source

Department of Internal Medicine, North Shore Medical Center, Salem, MA 01970, USA.

Abstract

Primary effusion lymphoma (PEL) is a rare extranodal lymphoma that typically presents in a body cavity in the absence of a detectable tumor mass and that occurs predominantly in immunosuppressed individuals. The neoplastic lymphoid cells are frequently infected with human herpes virus 8 (HHV8), also known as Kaposi sarcoma herpes virus (KSHV). We describe two HIV-negative patients who presented with primary effusion lymphoma of B-cell lineage involving the pleural cavity, but whose tumor cells lacked infection by HHV8. We review the English language literature of HHV8-negative PEL of B-cell lineage and compare these lymphomas to HHV8-associated PEL with regard to clinical and pathological characteristics, therapy, and outcome.

Full Text Article

Case Reports in Oncological Medicine

High MET gene copy number predicted poor prognosis in primary intestinal diffuse large B-cell lymphoma.

Feb 2013

Huang WT, Chuang SS.

Abstract

BACKGROUND: MET is a proto-oncogene with its copy number (CN) alterations been reported in some cancers, but not in primary intestinal diffuse large B-cell lymphoma (PI-DLBL) yet.

METHODS:

In this retrospective study, we performed histology and chart reviews, immunohistochemistry and quantitative polymerase chain reaction for MET CN alterations on 28 surgically resected PI-DLBLs.

RESULTS:

There were 12 men and 16 women with a median age of 70 and a mean follow-up of 32 months. The median MET CN was 2.20 (range, 1.04 to 3.35). CN gain was observed in 11 cases, including 5 with CN greater than 3. Nine patients (32%) had diploid CN and eight (29%) with CN loss. Patients with gain or diploid CN showed significantly worse prognosis (P = 0.046) than those with CN loss. Furthermore, MET CN greater than 3 was associated with an adverse outcome (P = 0.003). Intestinal perforation at presentation was the sole clinicopathological factor associated with a poor prognosis (P = 0.004) and perforation was correlated with CN greater than 3 (P = 0.002).

CONCLUSIONS:

Our finding of MET CN gain as a poor prognostic factor in PI-DLBL patients might serve as the rationale for targeting MET signaling pathway in the treatment of these patients. Virtual slide The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1637072378895873.

Diagnostic Pathology

Prognostic value of (18)F-FDG PET/CT after first-line treatment in patients with diffuse large B cell lymphoma

2012

[Article in Chinese]

Ying ZT, Wang XJ, Song YQ, Zheng W, Wang XP, Xie Y, Lin NJ, Tu MF, Ping LY, Liu WP, Deng LJ, Zhang C, Yang Z, Zhu J.

Source

Peking University Cancer Hospital & Institute, Department of Lymphoma, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing 100142, China.

Abstract

OBJECTIVE:

To evaluate the value of (18)F-FDG PET/CT in detecting residual disease and predicting relapse following first-line treatment in patients with diffuse large B cell lymphoma (DLBCL).

METHODS:

The clinical data of 39 patients with DLBCL, who underwent PET/CT scan after first-line treatment, were analyzed retrospectively. Kaplan-Meier method was used to analyze the survival of patients.

RESULTS:

PET/CT findings were interpreted as negative, mild metabolism and positive. Seventeen patients' PET/CT findings were judged as negative, none of them relapsed with a median follow-up of 24.1 months, 13 were judged as mild metabolism, 2 of them relapsed with a median follow-up of 17.1 months. Of the rest 9 findings were judged as positive with a median follow-up of 16.3 months, 4 patients were considered as disease progression according to clinical manifestations and other radiographic results, 2 patients relapsed at the timepoints of 13.5 and 6.8 months after PET/CT scan respectively, the other 3 patients were diagnosed as negative by biopsy, none of them relapsed at the timepoints of 5.9, 9.6 and 20.0 months after PET/CT scan respectively. One-year progression-free-survival (PFS) for negative, mild metabolism and positive groups was 100%, 83% and 56%, respectively. Two-year PFS was 100%, 83% and 42%, respectively. Overall survival (OS) at 1 year for negative, mild metabolism and positive groups was 100%, 100% and 89%, respectively. Two-year OS was 100%, 100% and 63%, respectively (P = 0.004).

CONCLUSION:

DLBCL patients with negative and mild metabolism PET/CT following first-line treatment had good prognosis, who needed no additional therapy. While patients with positive PET/CT had poor prognosis, those patients should receive biopsy before adjusting treatment regimen because of the high false-positive rate.

PubMed

The diagnosis and management of ocular lymphoma.

Feb 2013

Vollmer L.

Source

*OD, FAAO Nova Southeastern University, Fort Lauderdale, Florida.

Abstract

PURPOSE:

Lymphoma is the most common malignancy of the ocular adnexa. Most of the ocular adnexa lymphomas are non-Hodgkin B-cell lymphomas. The most common type of ocular adnexa lymphoma is primary extranodal marginal zone B-cell lymphoma of the MALT (mucosa-associated lymphoid tissue). Most of these neoplasms are primary extranodal lymphomas, although 10% to 32% are secondary tumors from disseminated disease.

CASE REPORT:

A 58-year-old woman presented for a comprehensive examination, with the chief complaint of ocular discomfort in both eyes. Anterior segment examination revealed bilateral salmon-colored lesions of the inferior and superior conjunctivae. The patient was referred for systemic evaluation and histopathology of the conjunctival lesions. She was diagnosed as having marginal zone lymphoma of the MALT and underwent radiation therapy (RT).

CONCLUSIONS:

Ocular lymphoma may present on routine examination or with mild symptoms. Although most commonly a primary extranodal neoplasm, the condition may be associated with disseminated lymphoma and requires thorough evaluation and staging of the disease for determination of appropriate treatment. The primary eye care provider plays an important role in the identification and staging of the disease, as well as managing complications from RT. It is also important to recognize that concurrent conditions requiring treatment with topical medications, such as glaucoma, may be complicated after treatment because of the inflammation and ocular surface irritation after RT. The necessity and benefit of the addition of intraocular pressure medications during that time should be measured on a case-by-case basis. Patients should be followed closely after treatment for relapse of disease and identification of complications from ocular RT.

PubMed

Stereotyped B cell receptors in B cell leukemias and lymphomas.

2013

Darzentas N, Stamatopoulos K.

Source

Medical Genomics Research Group, Molecular Medicine Program, CEITEC/Central European Institute of Technology, Masaryk University, Brno, Czech Republic.

Abstract

Recent research has revealed the existence of subsets (clusters) of patients with different types of B-cell lymphomas and leukemias with restricted, "stereotyped" immunoglobulin (IG) variable heavy complementarity-determining region 3 (VH CDR3) sequences within their B cell receptors (BcR), suggesting selection by common epitopes or classes of structurally similar epitopes. BcR stereotypy was initially described in chronic lymphocytic leukemia (CLL), where it constitutes a remarkably frequent feature of the IG repertoire, and subsequently identified in other malignancies, including mantle cell lymphoma and splenic marginal-zone lymphoma. Of note, at least in CLL, emerging evidence indicates that the grouping of cases into distinct clusters with stereotyped BcR is functionally and prognostically relevant. Hence, the reliable identification of BcR stereotypy may assist in the investigation of the nature of the selecting antigens and immune pathways leading to lymphom adevelopment, and also potentially pave the way for tailored treatment strategies applicable to each major stereotyped subset. In this chapter, we provide an overview of BcR stereotypy in human B-cell malignancies, and outline previous and current methodological approaches used for its identification.

PubMed

Interim FDG PET/CT as a prognostic factor in diffuse large B-cell lymphoma.

Interim FDG PET/CT as a prognostic factor in diffuse large B-cell lymphoma.

Jan 2013

Fuertes S, Setoain X, Lopez-Guillermo A, Carrasco JL, Rodríguez S, Rovira J, Pons F.

Source

Nuclear Medicine Department, Clinic University Hospital, Barcelona, Spain, sfuertes75@hotmail.com.

Abstract

PURPOSE:

Interim (18)F-FDG PET performed early during the course of therapy in diffuse large B-cell lymphoma (DLBCL) is a good predictor of outcome. However, interpretation criteria for interim PET for the evaluation of tumour response are still not clearly defined. The study aim was to assess whether interim PET can predict overall survival (OS) and progression-free survival (PFS) in DLBCL patients following three different sets of parameters, two qualitative (visual) methods and one semiquantitative.

METHODS:

A total of 50 newly diagnosed DLBCL patients were prospectively enrolled in this study. All patients had a PET/CT scan at diagnosis and an interim PET/CT scan after the second or third cycle of chemotherapy. Three methods of evaluation for the interim PET/CT were used: a qualitative three-point scoring (3-PS) method, a qualitative 5-PS method and a semiquantitative method (ΔSUV(max)). The degree of correlation between therapy response seen on FDG PET and PFS and OS was determined.

RESULTS:

The analysis of the visual 3-PS method showed no statistically significant difference in PFS and OS. The estimated 5-year PFS and OS were 79 % and 92 %, respectively, in patients with an interim PET scan showing uptake not greater than in the liver versus 50 % in patients with uptake greater than in the liver, and this difference was statistically significant. The optimal cut-off value of ΔSUV(max) that could predict the PFS and OS difference in patients with DLBCL was 76 % (95 % CI 62.7-89.2 %) and 75 % (95 % CI, 54.6-95.4 %), respectively.

CONCLUSION:

Our results support the use of liver uptake as an indicator in the qualitative evaluation of interim PET, or a ΔSUV(max) greater than 75 % in semiquantitative analysis. Interim PET may predict PFS and OS and could be considered in the prognostic evaluation of DLBCL.

Springer Link

Pathophysiology and molecular aspects of diffuse large B-cell lymphoma.

2012

Gouveia GR, Siqueira SA, Pereira J.

Source

Hospital das Clínicas da Faculdade de Medicina, Universidade de São Paulo - USP, São Paulo, SP, Brazil.

Abstract

Diffuse large B-Cell lymphoma is the most common subtype of non-Hodgkin lymphoma in the West. In Brazil, it is the fifth cause of cancer, with more than 55,000 cases and 26,000 deaths per year. At Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo - HCFMUSP, diffuse large B-Cell lymphoma represents 49.7% of all non-Hodgkinlymphoma cases. Initially, the classification of non-Hodgkin lymphoma was based on morphology, but advances in immunology and molecular medicine allowed the introduction of a biological classification for these diseases. As for other cancers, non-Hodgkin lymphoma involves patterns of multifactorial pathogenesis with environmental factors, as well as genetic, occupational and dietary factors, contributing to its development. Multiple lesions involving molecular pathways of B-cell proliferation and differentiation may result in the activation of oncogenes such as the BCL2, BCL6, and MYC genes and the inactivation of tumor suppressor genes such as p53 and INK4, as well as other important transcription factors such as OCT-1 and OCT-2. A dramatic improvement in survival was seen after the recent introduction of the anti-CD20 monoclonal antibody. The association of this antibody to the cyclophosphamide, hydroxydaunorubicin, oncovin and prednisolone (CHOP) regimen has increased overall survival of diffuse large B-Cell lymphoma and follicular lymphoma patients by 20%. However, 50% of all diffuse large B-Cell lymphoma patients remain incurable, creating a demand for more research with new advances in treatment. Thus, it is important to know and understand the key factors and molecular pathways involved in the pathogenesis of diffuse large B-Cell lymphoma.

PubMed

Primary diffuse large B cell lymphoma of the cranial vault.

2012

Rezaei-Kalantari K, Samimi K, Jafari M, Karimi MA, Ansari K, Davoodi M, Nabi-Meybodi M, Gorjian M.

Source

Department of Radiology, Hazrat Rasoul-e-Akram Hospital, Tehran University of Medical Sciences, Tehran, Iran.

Abstract

Primary non-Hodgkin's lymphoma of the cranial vault is extremely rare. This case report presents a 42-year-old man with a painless subcutaneous scalp mass which extended intracranially associated with recent mild headache. Initial computed tomography and magnetic resonance imaging revealed two lesions emanating from the skull. Biopsy revealed a diagnosis of diffuse large B cell lymphoma (DLBCL). A thorough work-up revealed no other point of involvement. This case is concerned about considering lymphoma in the differential diagnosis of calvarial lesions with both intra- and extra cranial extensions but without obvious intervening bony destruction.

PubMed

Intravascular large B-cell lymphoma with leukemic component.

Nov 2012

1. Armin Rashidi and 
2. Michele R. Roullet

1. A 59-year-old man presented with acalculous cholecystitis and hepatomegaly. Routine laboratory tests were remarkable for thrombocytopenia (125 × 10⁹/L), alanine aminotransferase 95 U/L, aspartate aminotransferase 760 U/L, alkaline phosphatase 223 U/L, and lactate dehydrogenase 3755 U/L. A peripheral smear showed morphologically normal red blood cells and large atypical lymphoid cells (panel A and inset). Cholecystectomy, liver biopsy, and bone marrow biopsy were performed. Flow cytometry on bone marrow and peripheral blood demonstrated a population of λ-restricted B cells that were positive for CD19, CD20, and CD22, and coexpressed CD5 and CD10. Histologic sections showed large atypical lymphoid cells within small subserosal vessels of the gallbladder, as well as within hepatic (panel C) and bone marrow sinusoids (panel B). Immunohistochemistry showed strong positivity for CD20, PAX-5, CD5, CD10, and Ki-67. Fluorescent in situ hybridization revealed a distal deletion of BCL6 and 3 to 5 copies of BCL2. Cerebrospinal fluid examination was unremarkable.
   Intravascular large B-cell lymphoma (IVLBCL) is a rare subtype of extranodal large B-cell lymphoma characterized by intraluminal growth of lymphoma cells within small vessels. Circulating lymphoma cells in the peripheral blood happens occasionally. Once called the oncologist's “great imitator,” IVLBCL can mimic, because of its intrinsically widespread nature, diseases in almost any organ and diagnosis requires high vigilance.
   BloodJournal

Low-grade B-cell lymphoma presenting as a uvular mass.

Dec 2012

Walker R, Heffelfinger R.

Source

Department of Otolaryngology-Head and Neck Surgery, University of Rochester Medical Center, 601 Elmwood Ave., Box 629, Rochester, NY 14642, USA. RyanD_Walker@urmc.rochester.edu.

Abstract

Uvular enlargement may occur acutely as a result of infection, allergy, or trauma. Squamous cell carcinoma may present as a progressively enlarging uvular mass. Primary MALT (mucosa-associated lymphoid tissue) lymphoma of the uvula and a neuroendocrine tumor of the parapharyngeal space presenting as a uvular mass have each been previously described in the literature. Here we present a case of low-grade B-cell lymphoma presenting as a uvular mass in a 55-year-old patient with progressive throat swelling and dysphagia.

PubMed