Leukemia

he treatment of B-cell malignancies has been revolutionized by the availability of safe and effective monoclonal antibodies. The addition of rituximab to standard chemotherapy regimens prolongs the survival of patients with diffuse large B-cell lymphoma (DLBCL) and follicular non-Hodgkin lymphoma. Nevertheless, indolent and mantle cell lymphomas remain incurable, and 30% to 40% of patients with DLBCL still die from their disease. Much ongoing research has focused on optimizing monoclonal antibody use, integrating them into multiagent regimens, and developing newer antibodies. Attempts to improve on the efficacy of monoclonal antibody–based therapy have included altering the dosing schedule, optimizing patient selection, maintenance therapy, improving upon the rituximab molecule, radioimmunotherapy, as well as combinations with cytotoxic molecules and other novel agents. Preliminary data with a number of treatment regimens are promising in indolent and aggressive lymphomas. The eventual goal of targeted therapies is to individualize treatment to increase response and survival, while reducing treatment-related toxicity.

In this review, Ujjani and Cheson present a useful overview of the array of existing and developing roles for monoclonal antibodies in the management of B-cell non-Hodgkin lymphomas (NHLs). These roles may be characterized as single-agent antibody therapy, use in combination with chemotherapy and/or other antibodies, and use following an initial regimen (consolidation/maintenance). Rituximab (Rituxan), the first monoclonal antibody approved for B-cell NHL, clearly has had greatest application in each of these arenas, but it has now been joined by alemtuzumab (Campath) and ofatumumab (Arzerra) as approved single-agent therapies. Also highlighted are a number of other antibodies aimed at B-cell targets: veltuzumab, GA101, AME-133 (CD20), epratuzumab (CD22), lumiliximab (CD23), galiximab (CD80), dacetuzumab (CD40), mapatumumab, lexatumumab (TRAIL), and approaches to improve antibody therapy such as conjugation with radioisotopes or toxins.

Peripheral T-cell lymphomas, or PTCLs, represent an uncommon and biologically heterogeneous group of hematologic malignancies, accounting for less than 10% of all non-Hodgkin lymphomas worldwide, with marked geographic differences. Due to their low prevalence, variable clinical presentation and phenotypic heterogeneity, these lymphomas have historically been difficult to diagnose and categorize. Since the introduction of immunophenotyping and molecular genetic methods, as well as the development of comprehensive classification systems, there have been significant advances in diagnostic accuracy, classification, and our understanding of the biologic behavior of different PTCL subtypes. However, the molecular pathogenesis of most subtypes of PTCL remains incompletely understood, and treatment outcomes with conventional anthracycline-based chemotherapy regimens are generally significantly inferior to those in aggressive B-cell lymphomas.

Peripheral T-cell lymphomas (PTCLs) are uncommonly encountered malignancies in the United States, and hepatosplenic T-cell lymphoma (HSTCL), subcutaneous panniculitis-like T-cell lymphoma (SPTCL), and enteropathy-type T-cell lymphoma (ETTCL) are rare subtypes of PTCLs that often present with primarily extranodal disease. Despite the fact that these tumors have distinct clinical and pathologic features, they are often diagnosed after significant delay. The combination of delay in diagnosis with ineffective therapies has resulted in a poor prognosis in most cases. Techniques that identify T-cell receptor gene rearrangements and flow cytometry that can identify characteristic immunophenotypes have guided our understanding of the underlying cell of origin of these rare PTCLs. As knowledge regarding the biology of these lymphomas increases alongside the development of newer therapeutics with novel mechanisms, clinicians must accordingly improve their familiarity with the clinical settings in which these rare malignancies arise as well as the pathologic features that make them unique

NEW ORLEANS-Genentech and Biogen announced at ASH 2009 that the three-year follow-up of the CLL8 trial demonstrated that rituximab (Rituxan) plus fludarabine and cyclophosphamide (FC) chemotherapy improved overall survival in patients with previously untreated chronic lymphocytic leukemia (CLL) vs FC therapy alone.

In this issue of ONCOLOGY, Dr. Tobinai presents a thorough and thoughtful review of the current state of the art of HTLV-related adult T-cell leukemia/lymphoma (ATLL). As described, ATLL is most prevalent in Asia, where it has also been most studied, but is also seen in patients from other HTLV-endemic areas including the Caribbean, South America, and parts of Africa. ATLL is rare in North America and Europe, representing 1% to 2% of T-cell lymphomas compared to 25% in Asia.[1]

In this issue of ONCOLOGY, Tobinai reviews the management of human T-cell lymphotropic virus type 1 (HTLV-1)–associated adult T-cell leukemia/lymphoma (ATL). Although rare in the United States, an estimated 10 to 20 million people are infected with HTLV-1 worldwide and 2% to 5% will develop ATL.[1]

Sunesis Pharmaceuticals, Inc, announced that the US Food and Drug Administration has granted voreloxin orphan drug designation for the treatment of acute myeloid leukemia (AML). Sunesis is currently conducting two phase II clinical trials of voreloxin in AML: a single-agent study (REVEAL-1) in newly diagnosed elderly AML patients unlikely to benefit from standard induction chemotherapy and a study evaluating the drug in combination with cytarabine in relapsed/refractory AML.

Adult T-cell leukemia/lymphoma (ATL) is defined as a histologically or cytologically proven peripheral T-cell malignancy associated with a retrovirus, human T-cell lymphotropic virus type I (HTLV-1).[1] Southwestern Japan is the district with the highest prevalence of HTLV-1 infection and the highest incidence of ATL in the world. A high prevalence of HTLV-1 infection is also found in the Caribbean islands, tropical Africa, South America, and northern Oceania.

The purpose of this review is to familiarize oncologists with the clinical and pathologic features of this relatively rare disease spectrum. This should enable appropriate clinical management and reassurance of patients concerned about their prognosis.

Our ability to treat patients with B-cell lymphomas has improved dramatically over the past few decades. Today the majority of patients with diffuse large B-cell lymphoma are cured, the survival of patients with low-grade follicular lymphoma is improving (ie, some estimates have the average survival more than doubling), most patients with Hodgkin lymphoma (also a B-cell lymphoma) are cured, most patients with Burkitt lymphoma are cured, and our ability to diagnose and treat patients with the various marginal zone lymphomas has improved considerably.

Allos Therapeutics has received accelerated FDA approval for Folotyn (pralatrexate) as a single-agent treatment in patients with relapsed or refractory peripheral T-cell lymphoma.

One of the greatest challenges facing the physician caring for patients with chronic lymphocytic leukemia (CLL) is the heterogeneity of this disease. Over the past decade, there have been major advances in understanding the pathophysiology of CLL, and in the identification of biomarkers that are helpful to predict the clinical course for individual patients. Over the same period, the available therapeutic options have developed dramatically, exemplified by the introduction of combination therapy with purine analogs and monoclonal antibodies, resulting in significant opportunities to induce complete remission (CR) in CLL patients.

Chronic lymphocytic leukemia (CLL) is a heterogeneous disease with an extremely variable course. Survival after diagnosis can range from months to decades. As the pathogenesis of the disease is increasingly understood, we begin to unfold the molecular patterns that define the different prognostic subgroups and to develop strategies to predict the clinical course.

Chronic lymphocytic leukemia (CLL) is the most common form of adult leukemia in the Western hemisphere. Both the Rai and Binet staging systems have been important clinical tools for predicting outcomes of this heterogeneous disease.

Lymphoblastic lymphoma (LBL) is a rare disease, comprising about 2% of all non-Hodgkin lymphomas (NHLs) in adults.[1] It is a highly aggressive subtype of lymphoma, most commonly of precursor T-cell origin, occurring most frequently in adolescents and young adults, with male predominance and frequent mediastinal, bone marrow, and central nervous system (CNS) involvement.

The US Food and Drug Administration approved ofatumumab (Arzerra) for patients with chronic lymphocytic leukemia (CLL) whose cancer is no longer being controlled by other forms of chemotherapy. The product was approved under the FDA’s accelerated approval process, which allows earlier approval of drugs that meet unmet medical needs.

Lymphoblastic lymphoma (LBL) is a rare disease, most commonly of T-cell origin, that shares biologic features with acute lymphoblastic leukemia (ALL). Indeed, LBL and ALL are considered a single entity (lymphoblastic leukemia/lymphoma, T and B types) in the World Health Organization (WHO) classification of precursor lymphoid neoplasms.

The US Food and Drug Administration (FDA) has granted accelerated approval for pralatrexate injection (Folotyn) for use as a single agent for the treatment of patients with relapsed or refractory peripheral T-cell lymphoma (PTCL), which comprises a biologically diverse group of aggressive blood cancers.

Data from a pivotal phase III study demonstrate that bendamustine (Treanda) improved clinical outcomes when compared to chlorambucil (Leukeran) in patients with chronic lymphocytic leukemia (CLL).

A large, population-based study of the association between venous thromboembolism and mortality in hematologic malignancies found an increased risk of death in patients with acute lymphoblastic leukemia, but not in those with acute myelogenous leukemia. The authors had no explanation for the differential association between the two types of acute leukemia.

Patients with chronic myeloid leukemia can learn more about the disease at a new educational Web portal.

Mantle cell lymphoma (MCL) is a distinct subtype of non-Hodgkin lymphoma that occurs most commonly in older patients with advanced-stage disease.

On August 22, 2008, the US Food and Drug Administration (FDA) granted marketing approval (licensure) to romiplostim (Nplate, Amgen Inc) for the treatment of thrombocytopenia in patients with chronic immune (idiopathic) thrombocytopenic purpura (ITP) who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy.

Drs. Hernandez-Ilizaliturri and Czuczman should be complimented on their comprehensive review of management options for patients with relapsed and refractory diffuse large B-cell lymphoma (DLBCL).

A triple therapy with fludarabine, cyclophosphamide, and rituximab (Rituxan) was hailed as the new standard of care for chronic lymphocytic leukemia at ASH 2008 in San Francisco. Now a new study has deemed low-dose fludarabine and cyclophosphamide combined with high-dose rituximab (FCR-Lite) as highly effective in untreated CLL patients.

SAN FRANCISCO-While genetics has opened up new possibilities for predicting treatment response in patients with acute myeloid leukemia, there are still unanswered questions about the relationship between genetic mutations and treatment outcome, according to Bob Lowenberg, MD, PhD, who delivered the Ham-Wasserman lecture at ASH 200

SAN FRANCISCO-As a single agent, pralatrexate (PDX) shows promising clinical activity in relapsed or refractory peripheral T-cell lymphoma, producing responses in 27% of the patients enrolled in a major prospective clinical trial.

Two of the largest trials to date on the treatment of chronic lymphocytic leukemia indicate that the combination treatment of fludarabine, cyclophosphamide, and rituximab (Rituxan) should become the new standard of care for both untreated and previously treated patients.

Cephalon, Inc, announced that the US Food and Drug Administration (FDA) has approved injectable bendamustine hydrochloride (Treanda) for the treatment of patients with indolent B-cell non-Hodgkin lymphoma (NHL) that has progressed during or within 6 months of treatment with rituximab (Rituxan) or a rituximab-containing regimen. The data supporting the FDA approval show that bendamustine is effective, has a tolerable side effect profile in patients with indolent NHL, and that treatment results in a high durable response rate. In March of this year, bendamustine received approval for the treatment of patients with chronic lymphocytic leukemia, the most common form of leukemia in the United States.