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]
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• 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. 
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• [Oncology (Williston Park). 2013]
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• 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