Steven T. Rosen, MD

In Part 2 of this two-part series, this review covers extranodal natural killer/T-cell lymphoma, enteropathy-associated T-cell lymphoma, indolent T-cell lymphoproliferative disorder of the gastrointestinal tract, adult T-cell leukemia/lymphoma, and hepatosplenic T-cell lymphoma.

This two-part series highlights the most important aspects of PTCLs and describes current treatment options and investigative opportunities. Part 1 will cover PTCL not otherwise specified, follicular T-cell lymphoma, angioimmunoblastic T-cell lymphoma, anaplastic large-cell lymphoma (ALCL), and breast implant–associated ALCL.

An 80-year-old man presented with a disabling pruritic rash characterized by disseminated and coalescing plaques on the trunk and proximal extremities and covering 40% of his total body surface area, without peripheral lymphadenopathy.

Recent advances in mantle cell lymphoma include: (1) identification of new pathways to target, (2) novel therapeutics to treat patients with relapsed/refractory disease, and (3) monitoring of minimal residual disease and adoption of a maintenance therapy approach to prevent relapses post induction or post stem cell transplantation.

This management guide covers the risk factors, screening, diagnosis, staging, and treatment of non-Hodgkin lymphoma.

In this review we discuss adoptive cellular immunotherapies, small-molecule inhibitors, and immunomodulatory agents. We also mention other novel therapies on the horizon.

Here we review monoclonal antibodies that have received FDA approval for the treatment of NHL and CLL in the last 5 years, as well as promising agents in development.

This review will focus on newer FDA-approved targeted therapies associated with type II chemotherapy-related cardiac dysfunction, or generally reversible cardiotoxicity, and will provide the latest information on the incidence and clinical spectrum of cardiotoxicity associated with each therapy, modifiable risk factors where known, and the mechanisms of cardiotoxicity.

In this article we briefly review the labeled indications for new agents for cutaneous and peripheral T-cell lymphoma, focus on data from the last 1 to 2 years, and on data from ongoing clinical trials, with the hope that in doing so we can help elucidate difficult treatment decisions.

Ongoing studies are attempting to understand the reasons that tumor cells engage in aerobic glycolysis in lieu of oxidative phosphorylation. In this review, we discuss known benefits to tumor cells from this metabolic switch, and we highlight key enzymes that play a role in aerobic glycolysis. We also describe novel therapeutic options targeting glucose metabolism.

Today we speak with Steven T. Rosen, MD, about a couple of the projects he and his group are working on, repurposing old drugs for the treatment of multiple myeloma, that will be presented this year at ASH.

Anaplastic large cell lymphoma (ALCL) is a biologic and clinically heterogenous subtype of T-cell lymphoma. Clinically, ALCL may present as localized (primary) cutaneous disease or widespread systemic disease. These two forms of ALCL are distinct entities with different clinical and biologic features. Both types share similar histology, however, with cohesive sheets of large lymphoid cells expressing the Ki-1 (CD30) molecule. Primary cutaneous ALCL (C-ALCL) is part of the spectrum of CD30+ lymphoproliferative diseases of the skin including lymphomatoid papulosis. Using conservative measures, 5-year disease-free survival rates are>90%. The systemic ALCL type is an aggressive lymphoma that may secondarily involve the skin, in addition to other extranodal sites. Further, systemic ALCL may be divided based on the expression of anaplastic lymphoma kinase (ALK) protein, which is activated most frequently through the nonrandom t(2;5) chromosome translocation, causing the fusion of the nucleophosmin (NPM) gene located at 5q35 to 2p23 encoding the receptor tyrosine kinase ALK. Systemic ALK+ ALCLs have improved prognosis compared with ALK-negative ALCL, although both subtypes warrant treatment with polychemotherapy. Allogeneic and, to a lesser extent, autologous stem cell transplantation play a role in relapsed disease, while the benefit of upfront transplant is not clearly defined. Treatment options for relapsed patients include agents such as pralatrexate (Folotyn) and vinblastine. In addition, a multitude of novel therapeutics are being studied, including anti-CD30 antibodies, histone deacetylase inhibitors, immunomodulatory drugs, proteasome inhibitors, and inhibitors of ALK and its downstream signaling pathways. Continued clinical trial involvement by oncologists and patients is imperative to improve the outcomes for this malignancy.

The incidence rates of non-Hodgkin lymphoma (NHL) in the United States have almost doubled between 1970 and 1990, representing one of the largest increases of any cancer. Although the overall incidence rates of NHL began to stabilize in the late 1990s, the temporal trends varied by histologic subtype. Some of this increase may be artifactual, resulting from improved diagnostic techniques and access to medical care, or directly related to the development of NHL in 25- to 54-year-old men with human immunodeficiency virus (HIV) infection. However, additional factors must be responsible for this unexpected increase in frequency of NHL that has been observed throughout the United States.

A 49-year-old Caucasian man presented with progressing erythematous plaques on the face and neck in December 2007. He was treated with topical steroids, presumably for dermatitis, without improvement.

A 31-year-old man presented in May 2007 with generalized painful, ulcerated, and necrotic papules and plaques worsening for the last few months. He had been diagnosed with mycosis fungoides in October 2005. Treatments included topical corticosteroids and psoralen with ultraviolet A light therapy (PUVA), with the latter being discontinued because of the development of blisters. For the last 6 months, he had been treated with oral bexarotene (Targretin), with initial improvement of his skin lesions.

Pruritic papulo-nodular eruption

The spectrum of CD30+ lymphoproliferative diseases of the skin includes CD30+ cutaneous anaplastic large cell lymphoma, lymphomatoid papulosis, as well as borderline cases. These entities constitute the second most common group of cutaneous lymphomas according to the newly revised World Health Organization and European Organisation for Research and Treatment of Cancer consensus classification. Recent progress in immune and molecular biology, and identification of therapeutic targets have increased our understanding of these diseases and have led to novel treatment approaches. This review will provide an update on recent findings of immunologic, molecular, cytogenetic features and treatment strategies for patients with CD30+ lympho-proliferative diseases.

The past 20 years have brought significant advances in our ability to manage patients with non-Hodgkin's lymphoma. More precise classification systems, improvements in diagnosis and staging, and effective new treatments have improved outcomes and made cure a reasonable goal for many patients with these disorders.

Between 1950 and 1999, the incidence of non-Hodgkin's lymphoma (NHL)rose by 90% in the United States, representing one of the largest increases ofany cancer. Some of this increase may be artifactual, resulting from improveddiagnostic techniques and access to medical care, or directly related to thedevelopment of NHL in 25- to 54-year-old men with human immunodeficiencyvirus (HIV) infection. However, additional factors must be responsiblefor this unexpected increase in frequency of NHL that has been observedthroughout the United States.

Despite many therapeutic options for chronic lymphocytic leukemia(CLL), the disease remains incurable. Since monoclonal antibodiesand recombinant toxins that bind surface antigens expressed on themalignant lymphocytes have been developed, targeted therapy hasbecome a vital option in treating CLL. Rituximab (Rituxan), a chimerichuman-mouse anti-CD20 antibody, and alemtuzumab (Campath), ahumanized anti-CD52 monoclonal antibody, have both shown activityin CLL-as single agents and in combination with conventionalchemotherapy. The possibility of combining antibodies has beenexplored as well, with some efficacy. In this review, we discuss theclinical data on the activity of commercially available antibodies inCLL, both as monotherapy and in combination with other agents.

Drs. Girardi and Edelson provide a concise discussion of current issues surrounding the management of patients with cutaneous T-cell lymphomas. They discuss a number of current theories regarding etiology and pathogenesis and provide a

Cutaneous lymphomas comprise a spectrum of diseases characterized by infiltration of the skin by malignant lymphocytes. The clinical manifestations of cutaneous lymphomas vary, and they can mimic benign dermatoses,