Outcomes following watchful waiting for stage II-IV follicular lymphoma patients in the modern era.

To examine the effectiveness of an initial management strategy of watchful waiting for follicular lymphoma (FL) in clinical practice, we compared outcomes for patients diagnosed 2004-2007 in the United States initially managed with watchful waiting with outcomes following initial rituximab monotherapy and chemoimmunotherapy. In total, 1754 stage II-IV patients in the National LymphoCare Study underwent watchful waiting (n = 386), rituximab monotherapy (n = 296) or rituximab plus chemotherapy (n = 1072) as initial management strategy. Female patients and those who received treatment in the Northeast or in an academic setting more commonly underwent watchful waiting versus initial chemoimmunotherapy; whereas patients with grade 3 histology, anaemia, elevated lactate dehydrogenase, extranodal involvement, B symptoms or performance status ≥1 more commonly received chemoimmunotherapy.

A Phase 2 Trial of Fludarabine Combined With Subcutaneous Alemtuzumab for the Treatment of Relapsed/Refractory B-Cell Chronic Lymphocytic Leukemia.

Background: Alemtuzumab is effective in fludarabine-refractory patients with chronic lymphocytic leukemia. We performed a phase 2 study of alemtuzumab in combination with fludarabine in patients with relapsed disease.

Patients And Methods: Patients received alemtuzumab and fludarabine daily on days 1 to 5 of a 28-day cycle for up to 6 cycles with the primary objective of determining the rate of complete response.

Combination of GM-CSF With Fludarabine-Containing Regimens in Chronic Lymphocytic Leukemia and Indolent Non-Hodgkin Lymphoma.

Background: Granulocyte-monocyte colony stimulating factor (GM-CSF) is a hematopoietic cytokine with immunomodulatory activity that has preclinical evidence for enhancement of antitumor immunity when administered in combination with chemotherapy. We evaluated the utility of GM-CSF with chemoimmunotherapy in patients with indolent non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL) in a pilot study.

Patients And Methods: Patients with previously untreated, relapsed, or refractory indolent NHL or CLL were treated with GM-CSF, rituximab, fludarabine, and cyclophosphamide or mitoxantrone for a maximum of 6 cycles.

A phase II study of bortezomib added to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone in patients with previously untreated indolent non-Hodgkin's lymphoma.

Bortezomib-containing combinations are active in non-Hodgkin lymphoma (NHL) although peripheral neuropathy can limit their dose intensity. Based on our phase I findings, we conducted a phase II trial of bortezomib in combination with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) with a modified dose of vincristine. Patients with untreated indolent NHL received bortezomib (1·6 mg/m(2) ) on days 1 and 8 of a 21-day cycle for up to 8 cycles and R-CHOP with a 1·5 mg cap of vincristine.

Comparison of the effectiveness of frontline chemoimmunotherapy regimens for follicular lymphoma used in the United States.

To compare the effectiveness of frontline rituximab-chemotherapy regimens in clinical practice, we examined outcomes for patients with low-grade, stage III/IV follicular lymphoma receiving rituximab (R) with cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP), R with cyclophosphamide, vincristine and prednisone (R-CVP) or R with a fludarabine-based regimen (R-Flu) as frontline therapy. In total, 611 patients meeting these criteria were identified in the National LymphoCare Study: 47% receiving R-CHOP (n = 287), 31% receiving R-CVP (n = 187) and 22% receiving R-Flu (n = 137). Overall response rates were high (R-CVP 87%, R-CHOP 93%, R-Flu 94%; p = 0.

Intensive chemotherapy and consolidation with high dose therapy and autologous stem cell transplant in patients with mantle cell lymphoma.

Mantle cell lymphoma (MCL) remains incurable with conventional chemotherapy without consensus on the optimal initial treatment. We examined our single center experience with frontline therapy for patients with MCL in consecutive cases diagnosed 1995-2011. Among 81 patients, median age was 59 (28% were ≥65 years of age), 95% had stage III/IV disease and 54% had a low risk MCL International Prognostic Index score.

The use and effectiveness of rituximab maintenance in patients with follicular lymphoma diagnosed between 2004 and 2007 in the United States.

Background: The authors examined the "real-world" effectiveness of rituximab (R) maintenance therapy (R-maintenance) compared with observation after R-based induction therapy in patients with previously untreated follicular lymphoma (FL) in the United States.

Methods: The National LymphoCare Study is a prospective, multicenter, observational study that enrolled > 2700 untreated patients with FL diagnosed from 2004 to 2007 at 265 sites in the United States. Among these, patients who achieved at least stable disease after R-based induction therapy were eligible for the current analysis.

Vinorelbine, paclitaxel, etoposide, cisplatin, and cytarabine (VTEPA) is an effective second salvage therapy for relapsed/refractory Hodgkin lymphoma.

Background: For Hodgkin lymphoma (HL) patients with refractory or relapsed (R/R) disease after primary therapy, the standard of care is a salvage regimen followed by autologous stem cell transplant (ASCT). However, patients who fail to respond to a salvage regimen have limited options. Our phase I study of cytarabine combined with fixed doses of vinorelbine, paclitaxel, etoposide, and cisplatin (VTEPA) for patients with R/R lymphoma showed an overall response rate (ORR) of 33%.

Single-agent lenalidomide in patients with mantle-cell lymphoma who relapsed or progressed after or were refractory to bortezomib: phase II MCL-001 (EMERGE) study.

Purpose: Although dose-intensive strategies or high-dose therapy induction followed by autologous stem-cell transplantation have improved the outcome for patients with mantle-cell lymphoma (MCL), most eventually relapse and subsequently respond poorly to additional therapy. Bortezomib (in the United States) and temsirolimus (in Europe) are currently the only two treatments approved for relapsed disease. Lenalidomide is an immunomodulatory agent with proven tumoricidal and antiproliferative activity in MCL.

The role of chemotherapy in managing chronic lymphocytic leukemia: optimizing combinations with targeted therapy.

For many years, alkylating agents were the standard treatment for chronic lymphocytic leukemia (CLL). The advent of purine analogs improved response rates, but not overall survival, and although the monoclonal antibody rituximab is generally active against B-cell malignancies, it has demonstrated limited benefits as monotherapy for the treatment of CLL. However, specific combinations of chemotherapy, antibodies and targeted therapies have demonstrated additive or synergistic activity in CLL cells and deliver substantial clinical benefits.

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

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.

Initial management strategies for follicular lymphoma.

Follicular lymphoma (FL) can vary markedly in its initial presentation, and no single standard approach for its initial management has been adopted. Available options for the initial management of FL include watchful waiting, radiation, single-agent rituximab and combination of rituximab and chemotherapy with strategies segregated for patients who have low and high tumor burden disease based on established criteria. However, marked debate occurs regarding the role of watchful waiting in the modern era for low tumor burden, asymptomatic patients, the optimal timing of rituximab, the selection of chemotherapy regimen to partner with rituximab in high tumor burden patients, and strategies for the management of relapsed disease.

Mobilization of hematopoietic progenitors from normal donors using the combination of granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor results in fewer plasmacytoid dendritic cells in the graft and enhanced donor T cell engraftment with Th1 polarization: results from a randomized clinical trial.

Granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) both mobilize CD34(+) stem cells into the blood when administered before apheresis but have distinct effects on dendritic cell (DC) differentiation. We previously demonstrated that the combination of GM+G-CSF results in fewer plasmacytoid DCs (pDCs) when used to mobilize peripheral blood stem cells for autologous transplantation. To test the hypothesis that the content of pDCs in an allograft can be modulated with the cytokines used for mobilization, we randomized the human leukocyte antigen-matched sibling donors of 50 patients with hematological malignancies to a mobilization regimen of either GM+G-CSF (n = 25) or G-CSF alone (n = 25).

Examining racial differences in diffuse large B-cell lymphoma presentation and survival.

We performed a retrospective cohort analysis of 701 (533 white and 144 black) patients with diffuse large B-cell lymphoma (DLBCL) treated at two referral centers in southern United States between 1981 and 2010. Median age of diagnosis for blacks was 50 years vs. 57 years for whites (p < 0.

A phase 1 dose escalation study of bortezomib combined with rituximab, cyclophosphamide, doxorubicin, modified vincristine, and prednisone for untreated follicular lymphoma and other low-grade B-cell lymphomas.

Background: Bortezomib has demonstrated efficacy in patients with relapsed B-cell non-Hodgkin lymphoma (NHL) both alone and in combination with other agents; however, limited data exist regarding its toxicity in combination with common frontline therapies for indolent NHL. A phase 1 study of bortezomib combined with rituximab, cyclophosphamide, doxorubicin, modified vincristine, and prednisone (R-CHOP) was conducted in patients with untreated follicular lymphoma (FL) and other indolent NHLs.

Methods: Nineteen patients, including 10 patients with FL, were enrolled.

A Systematic Review and Meta-Analysis of Front-line Anthracycline-Based Chemotherapy Regimens for Peripheral T-Cell Lymphoma.

Anthracycline-based chemotherapy remains standard treatment for peripheral T-cell lymphoma (PTCL) although its benefits have been questioned. We performed systematic literature review and meta-analyses examining the complete response (CR) and overall survival (OS) rates for patients with PTCL. The CR rate for PTCL patients ranged from 35.

Racial differences in the presentation and outcomes of chronic lymphocytic leukemia and variants in the United States.

Background: Chronic lymphocytic leukemia (CLL) is the most common form of adult leukemia in the United States, and prolymphocytic leukemia (PLL) is a related, rare chronic lymphoproliferative disorder.

Methods: Using the United States Surveillance, Epidemiology and End Results (SEER) data from 13 registries, we examined differences in incidence and survival for CLL, small lymphocytic lymphoma (SLL) and PLL by race. International Classification of Diseases for Oncology 3(rd) edition histology codes 9670, 9823, and 9632-34 were used to identify cases.

Hepatitis C reactivation in patients who have diffuse large B-cell lymphoma treated with rituximab: a case report and review of literature.

Background: Whether to interrupt or to continue induction therapy for lymphoma when hepatitis C virus (HCV) reactivation occurs during therapy with rituximab and chemotherapy remains a controversial question. There is limited evidence-based literature to help guide the management of patients with lymphoma in the setting of HCV reactivation. To address this issue we report an illustrative case and review the prevalence of non-Hodgkin lymphoma (NHL) in HCV-infected patients; the role of HCV in lymphomagenesis; the role of antiviral therapy in the management of HCV-associated lymphomas; as well as comparing the outcomes for NHL patients with and without HCV infection.

Racial differences in the presentation and outcomes of diffuse large B-cell lymphoma in the United States.

Background: Diffuse large B-cell lymphoma (DLBCL) is often cured with standard chemoimmunotherapy, but there is great heterogeneity in presentation and outcomes.

Methods: By using Surveillance, Epidemiology, and End Results (SEER) data from 13 registries across the United States, the authors examined differences in incidence and survival for DLBCL by race. International Classification of Diseases for Oncology, third edition histology codes 9678, 9679, 9680, and 9684 were used to identify cases.

Novel agents for diffuse large B-cell lymphoma.

Introduction: Although diffuse large B-cell lymphoma (DLBCL) is commonly considered as a cancer with a high cure rate with conventional therapies recent studies demonstrate that different biological variants of DBLCL exist, and that patients with one DLBCL variant and DLBCL patients who relapse early following rituximab-based therapy have markedly poorer outcomes with conventional management strategies. Over the last decade, there has been an increasing exploration of novel therapies derived from improved understanding of DLBCL biology and tumor-host interactions.

Areas Covered: This review examines the biological basis for novel therapeutic approaches in DLBCL and the early clinical data on compounds derived from this research.