Radiation and Dose-densification of R-CHOP in Aggressive B-cell Lymphoma With Intermediate Prognosis: The UNFOLDER Study.

UNFOLDER (Unfavorable Young Low-Risk Densification of R-Chemo Regimens) is an international phase-3 trial in patients 18-60 years with aggressive B-cell lymphoma and intermediate prognosis defined by age-adjusted International Prognostic Index (aaIPI) of 0 and bulky disease (≥7.5 cm) or aaIPI of 1. In a 2 × 2 factorial design patients were randomized to 6× R-CHOP-14 or 6× R-CHOP-21 (rituximab, cyclophosphamide, doxorubicin, vincristine, and prediso[lo]ne) and to consolidation radiotherapy to extralymphatic and bulky disease or observation.

Radiation and Dose-densification of R-CHOP in Primary Mediastinal B-cell Lymphoma: Subgroup Analysis of the UNFOLDER Trial.

UNFOLDER (NCT00278408, EUDRACT 2005-005218-19) is a phase-3 trial in patients with aggressive B-cell lymphoma and intermediate prognosis, including primary mediastinal B-cell lymphoma (PMBCL). In a 2 × 2 factorial design, patients were randomized to 6× R-CHOP-14 or R-CHOP-21 (rituximab, cyclophosphamide, doxorubicin, vincristine, and prediso(lo)ne) and to consolidation radiotherapy to extralymphatic/bulky disease or observation. Response was assessed according to the standardized criteria from 1999, which did not include F-18 fluordesoxyglucose positron emission tomography/computed tomography (FDG-PET) scans.

Molecular Cytogenetic Profiling Reveals Similarities and Differences Between Localized Nodal and Systemic Follicular Lymphomas.

Recently, we have developed novel highly promising gene expression (GE) classifiers discriminating localized nodal (LFL) from systemic follicular lymphoma (SFL) with prognostic impact. However, few data are available in LFL especially concerning hotspot genetic alterations that are associated with the pathogenesis and prognosis of SFL. A total of 144 LFL and 527 SFL, enrolled in prospective clinical trials of the German Low Grade Lymphoma Study Group, were analyzed by fluorescence in situ hybridization to detect deletions in chromosomes 1p, 6q, and 17p as well as translocations to determine their impact on clinical outcome of LFL patients.

Rituximab With Involved Field Irradiation for Early-stage Nodal Follicular Lymphoma: Results of the MIR Study.

The MabThera and Involved field Radiotherapy study investigated efficacy and safety of involved field (IF) radiotherapy in combination with the anti-CD20 antibody Rituximab for early-stage follicular lymphoma (FL) in a prospective, single-arm multicenter phase 2 design. Eighty-five stage I-II FL patients received 8 cycles of Rituximab (375 mg/m) and IF irradiation (30/40 Gy). The primary endpoint was progression-free survival (PFS) 2 years from treatment start.

Localized- and advanced-stage follicular lymphomas differ in their gene expression profiles.

The genetic background of follicular lymphomas (FLs) diagnosed in advanced clinical stages III/IV, and which are frequently characterized by t(14;18), has been substantially unraveled. Molecular features, as exemplified in the clinicogenetic risk model m7FLIPI, are important tools in risk stratification. In contrast, little information is available concerning localized-stage FL (clinical stages I/II), which accounts for ∼20% of newly diagnosed FL in which the detection rate of t(14;18) is only ∼50%.

Therapy of nodal Follicular Lymphoma (WHO grade 1/2) in clinical stage I/II using response adapted Involved Site Radiotherapy in combination with Obinutuzumab (Gazyvaro) - GAZAI Trial (GAZyvaro and response adapted Involved-site Radiotherapy): a study protocol for a single-arm, non-randomized, open, national, multi-center phase II trial.

Background: Large field irradiation had been standard for early-stage follicular lymphoma (FL) for a long time. Although involved field radiotherapy (IF-RT) was recently favored because of the toxicity of large field irradiation, smaller irradiation fields have been accompanied with an increased risk of out-of-field recurrence. The MIR (MabThera and Involved field Radiation) trial has shown that the combination of IF-RT at a dose of 30-40 Gy with the anti-CD20 antibody rituximab has led to similar efficacy compared with large field irradiation but with markedly reduced side effects.

Allogeneic haematopoietic cell transplantation offers the chance of cure for patients with transformed follicular lymphoma.

Purpose: In patients with follicular lymphoma, secondary transformation to aggressive lymphoma (tFL) implies a poor prognosis. In principle, allogeneic haematopoietic cell transplantation (allo-HCT) offers a chance of cure for tFL but is rarely practiced. Aim of this retrospective multicenter study was to define the actual significance of allo-HCT in treatment of tFL.

Anti-CD20 antibody treatment of non-Hodgkin lymphomas.

The CD20 antigen characteristic for mature B-cell is also expressed on B-cell Non-Hodgkin lymphomas (NHL). It thus presents a possible target for immunotherapy. NHL respond readily to radio- and/or chemotherapy but this standard treatment bears a high risk of relapse.

Long-term follow-up of pediatric patients receiving total body irradiation before hematopoietic stem cell transplantation and post-transplant survival of >2 years.

Background: Total body irradiation (TBI) treatment eradicates malignant cells and suppresses the immune system before hematopoietic stem cell transplantation (HSCT). The radiation dose is limited by its toxicity to healthy organs. Many reports describe long-term sequelae from TBI in adults, but comparable data for pediatric patients are scarce.

The composition of the microenvironment in follicular lymphoma is associated with the stage of the disease.

The role of regulatory and follicular helper T-cells as prognostic markers in follicular lymphoma was evaluated within the setting of prospective, randomized trials because the previously published results were contradictory. Two hundred sixty-four diagnostic tissue specimens from patients suffering from follicular lymphoma who received therapy within prospective randomized trials of the German Low Grade Lymphoma Study Group were analyzed immunohistochemically for FoxP3 and PD-1 expression to detect regulatory and follicular helper T-cells, respectively. We did not find any correlation between the content of regulatory and follicular helper T-cells and the time to treatment failure or overall survival in patients with advanced stages of follicular lymphoma in need of treatment.

Advanced-stage III/IV follicular lymphoma: treatment strategies for individual patients.

Background: In patients with advanced-stage III/IV follicular lymphoma (FL), there are many treatment options available. The current challenge is to choose the optimal strategy for the individual patient.

Methods: The literature was reviewed with respect to treatment strategies in patients with advanced FL by screening the PubMed databank.

Nodal follicular lymphoma: the role of radiotherapy for stages I and II.

Purpose: To clarify the role of external-beam radiotherapy (RT) in patients with stage I and II nodal follicular lymphoma (FL).

Methods: The literature was reviewed with respect to different treatment strategies in patients with stage I and II nodal FL by screening the PubMed databank.

Results: In patients with stage I and II nodal FL, RT alone with different irradiation techniques (involved-field [IFI]/extended-field [EFI]/total nodal [TNI]/total lymphoid irradiation [TLI]) produces excellent local disease control (approximately 95%) resulting in disease-free survival and overall survival (OS) rates of 37-94% and 40-93% at 5-15 years, respectively.

Long-term in vivo effects of cisplatin on gamma-H2AX foci signaling in peripheral lymphocytes of tumor patients after irradiation.

Purpose: This study determined the effects of cis-diamminedichloroplatinum(II) on radiation-induced foci formation of gamma-H2AX and Rad51 in lymphocytes.

Experimental Design: Twenty-eight cancer patients were irradiated for intrathoracic, pelvic, or head and neck tumors and received simultaneous cisplatin containing chemotherapy. The effect of cisplatin on radiation-induced gamma-H2AX and Rad51 foci as a response to ionizing radiation-induced DNA double-strand breaks was measured in lymphocytes after in vivo and in vitro radiochemotherapy.

Improvement of overall survival in advanced stage mantle cell lymphoma.

Purpose: Mantle cell lymphomas (MCLs) represent a clinically aggressive lymphoma subtype with a poor prognosis. To explore a potential progress in outcome a historical comparison was performed using data from the Kiel Lymphoma Study Group (KLSG; 1975 to 1986) and the German Low Grade Lymphoma Study Group (GLSG; 1996 to 2004).

Patients And Methods: All patients with the histologically confirmed diagnosis of advanced-stage nonblastoid MCL were eligible.

gamma-H2AX foci formation in peripheral blood lymphocytes of tumor patients after local radiotherapy to different sites of the body: dependence on the dose-distribution, irradiated site and time from start of treatment.

Purpose: To evaluate the relationship between an estimated integral total body radiation dose delivered and phosphorylated histone H2AX protein (gamma-H2AX) foci formation in peripheral blood lymphocytes of cancer patients.

Material And Methods: gamma-H2AX formation was quantified as the mean number of foci per lymphocyte (N(meanH2AX)) and the percentage of lymphocytes with > or =n foci. The integrated total body radiation dose was estimated from the dose volume histogram of patient's body corrected for the proportion of the body scanned by computed tomography for 3D treatment planning.