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

Dose-densified chemoimmunotherapy followed by systemic central nervous system prophylaxis for younger high-risk diffuse large B-cell/follicular grade 3 lymphoma patients: results of a phase II Nordic Lymphoma Group study.

Dec 2012

Holte H, Leppä S, Björkholm M, Fluge O, Jyrkkiö S, Delabie J, Sundström C, Karjalainen-Lindsberg ML, Erlanson M, Kolstad A, Fosså A, Ostenstad B, Löfvenberg E, Nordström M, Janes R, Pedersen LM, Anderson H, Jerkeman M, Eriksson M.

Source

Department of Oncology, Oslo University Hospital, Oslo, Norway.

Abstract

Background

Many patients with aggressive B-cell lymphomas and high clinical risk score still die of lymphoma after conventional R-CHOP chemoimmunotherapy. We hypothesized that intensified chemoimmunotherapy including systemic central nervous system (CNS) prophylaxis improves outcome and reduces the incidence of CNS-related events.Patients and methodsInclusion criteria were age 18-65 years, primary diffuse large B-cell lymphoma or grade III follicular lymphoma without clinical signs of CNS disease and negative cerebrospinal fluid cytology, age-adjusted International Prognostic Index 2-3 and WHO performance score 0-3. Treatment consisted of six courses of R-CHOEP-14 followed by a course of high-dose cytarabine and a course of high-dose methotrexate. Primary end point was failure-free survival (FFS) at 3 years.ResultsA total of 156 eligible patients with a median age of 54 years (range 20-64) were included. Three toxic deaths were observed. Three-year overall survival (OS) and FFS rates (median observation time 52 months for survivors) were 81% and 65%, respectively. Seven patients experienced CNS relapse, all within 6 months.ConclusionsThe results are promising with favorable 3-year OS and FFS rates, a low toxic death rate and a lower than expected number of CNS events. CNS progression might be further reduced by earlier CNS prophylaxis.CinicalTrials.gov. identifierNCT01502982.

Oxford Journal - Annals of Oncology

Bone Marrow Histopathology in the Diagnostic Evaluation of Splenic Marginal-zone and Splenic Diffuse Red Pulp Small B-cell Lymphoma: A Reliable Substitute for Spleen Histopathology?

Nov 2012

Ponzoni M, Kanellis G, Pouliou E, Baliakas P, Scarfò L, Ferreri AJ, Doglioni C, Bikos V, Dagklis A, Anagnostopoulos A,Ghia P, Stamatopoulos K, Papadaki T.

Source

*Pathology Unit †Unit of Lymphoid Malignancies ¶Medical Oncology Unit, Department of Oncology, San Raffaele Scientific Institute ∥Laboratory of B cell Neoplasia, Università Vita-Salute San Raffaele, Milan, Italy ‡Hematopathology Department, Evangelismos Hospital, Athens §Hematology Department-HCT Unit, G. Papanicolaou Hospital #Institute of Agrobiotechnology, Center for Research and Technology, Thessaloniki, Greece.

Abstract

Primary splenic small B-cell lymphomas mostly comprise the distinct entity of splenic marginal-zone lymphoma (SMZL) and the provisional category of splenic lymphoma/leukemia unclassifiable, mainly represented by the hairy cell leukemia variant and splenic diffuse red pulp small B-cell lymphoma (SDRL). Until recently, histopathologic examination of splenectomy specimens was considered mandatory for the diagnosis of SMZL. However, nowadays, mainly because of advances in chemoimmunotherapy, splenectomy is performed much less frequently. We evaluated the diagnostic efficacy of bone marrow biopsy (BMB) histopathology in the diagnostic approach toward SMZL and SDRL and tested whether it may serve as a substitute for spleen histopathology in the differential diagnosis between these 2 entities. To this end, we conducted a paired assessment of BMB and spleen diagnostic samples from 46 cases with a diagnosis of SMZL (n=32) or SDRL (n=14) based on spleen histopathology. We demonstrate that detailed immunohistopathologic BMB evaluation offers adequate evidence for the confirmation of these entities and their differential diagnosis from other small B-cell lymphoma histotypes. Notably, the immunophenotypical profile of SMZL and SDRL was identical in both BMB and spleen specimens for 21 evaluated markers. Paired assessment of BMB and spleen specimens did not identify discriminating patterns of BMB infiltration, cytology, and/or immunohistology between SMZL and SDRL. Accordingly, bone marrow histopathology contributes significantly in confirming the diagnosis of SMZL and SDRL. However, presently it is not possible to distinguish SMZL from SDRL on the basis of BMB evaluation alone; hence, histopathologic examination of the spleen remains the "gold standard" approach.

PubMed