Lymphoma

The article entitled “Diagnosis and Management of Mycosis Fungoides” by Shira Galper, Benjamin Smith, and Lynn Wilson is an excellent contemporary summary of the workup and management of mycosis fungoides (MF) and its leukemia variant, Sézary syndrome (SS). In their discussion of the diagnosis and staging of MF and SS, the authors include a discussion of proposed revisions by the International Society for Cutaneous Lymphoma and the European Organisation for the Research and Treatment of Cancer (ISCL/EORTC) which seek to identify prognostic subgroups. In addition, there is a complete overview of the various treatment options for management of MF and SS. This treatment overview closely parallels the 2010 National Comprehensive Cancer Network (NCCN) Practice Guidelines for MF and SS.

Galper et al. should be commended for their concise and useful review of the diagnosis and management of mycosis fungoides (MF). It is notable that all of the authors are radiation oncologists. While the reader may expect a radiation oncologist’s perspective on the management of mycosis fungoides, their review goes beyond highlighting the various radiation techniques used in the treatment of MF. It highlights the major diagnostic dilemmas when evaluating patients with skin lesions that eventually are diagnosed as MF or its leukemic counterpart, Sézary syndrome (SS). It also stresses the importance of a multidisciplinary approach in diagnosing and caring for MF patients involving dermatology, dermatopathology, radiation oncology, and hematology/oncology, and provides a concise review of the treatment options in the MF and SS armamentarium. Navigating these options requires a good understanding of the natural history of the disease, the side effects of treatment, the expected response rates of treatment, the median time to response, the patient’s comorbid conditions, and goals of care.

With better disease definition, staging, and monitoring, treatment of extranodal NK/T-cell lymphoma is becoming more rational. A large proportion of patients with localized nasal disease may enjoy prolonged disease-free survival. On the other hand, early HSCT or novel therapy may be recommended for aggressive extranasal disease.

Extranodal natural killer/T-cell lymphoma (ENKTL), nasal type, is a distinct entity of non-Hodgkin lymphoma with interesting unique biologic and clinicopathologic features. The tumor is characterized by ethnic preponderance, a consistent association with Epstein-Barr virus (EBV) infection, peculiar histopathologic findings, and a predilection to affect primarily the upper aerodigestive tract, inclusive anatomically of the nasal cavity, nasopharynx, paranasal sinuses, oral cavity, hypopharynx, and larynx. The characteristic clinical features are nasal stuffiness, relentless, nonhealing ulcers, or symptoms due to obstruction of the aforementioned areas. Distant metastasis at time of diagnosis is uncommon.

Since the creation of the World Health Organization’s nasal natural killer (NK)/T-cell lymphoma category, the attempt to further classify, describe, and improve treatment in this entity has been underway. There has been quite a bit of confusion and frustration regarding diagnosis, staging, and treatment approaches. With his article in this issue of ONCOLOGY, Dr. Au has attempted to improve our knowledge of current approaches to NK/T-cell lymphomas, providing a thorough and contemporary review of the clinical management of these difficult tumors. The following commentary reflects a deep appreciation for the author’s work and expands upon a few points not previously highlighted.

Unlike conventional radiation, Yttrium-90-ibritumomab tiuxetan (Zevalin) induces cellular damage only in the targeted tumor cells and has demonstrated activity in follicular and diffuse large B-cell non-Hodgkin’s lymphoma.

In asymptomatic disease, overall survival is often the same with immediate treatment vs watch and wait. The deciding factor may be what patients are willing to tolerate.

Multiple myeloma remains the second most common hematologic malignancy in the United States, after non-Hodgkin lymphoma.

Hematopoietic malignancies account for 6% to 8% of new cancers diagnosed annually. In the year 2009, an estimated 44,790 new cases of leukemia were diagnosed, and 21,870 deaths were attributable to leukemias of all types. The total age-adjusted incidence of leukemia, including both acute and chronic forms, is 9.6 per 100,000 population; the incidence of acute lymphoblastic leukemia (ALL) is 1.5 per 100,000 and of acute myelogenous leukemia (AML) is 2.7 per 100,000 population.

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.

In 2009 approximately 8,510 new cases of Hodgkin lymphoma (HL) will be diagnosed in the United States. Over the past 4 decades, advances in radiation therapy and the advent of combination chemotherapy have tripled the cure rate of patients with HL. In 2009, more than 80% of all newly diagnosed patients can expect a normal, disease-free life span.

Induction therapy with higher daily doses of daunorubicin improved complete response and boosted overall survival in younger patients with acute myelogenous leukemia, according to results of the phase III ECOG E1900 trial.

No branch of oncology has been more attuned to the vision of new genetically engineered targeted therapies than the field of hematopoietic malignancies. Ujjani and Cheson have produced a masterful summary of one extremely important component of the targeted therapy revolution-the realm of monoclonal antibodies directed against malignant lymphoma surface antigens.[1] The review presents a wonderful update and a glimpse of future potentially curative macromolecular cocktails. It is an attractive vision.

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 (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

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]

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.

Researchers are exploring ways to manipulate rituximab (Rituxan) when added to the current standard therapy for diffuse large B-cell lymphoma, specifically shortening the number of treatment days. Preliminary results of a phase III trial showed that rituximab plus CHOP over a 14-day cycle achieved similar response rates and comparable toxicity compared to CHOP on a 21-day cycle in newly diagnosed patients.

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.

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.

After almost a decade of research and two trials of a follicular lymphoma vaccine with negative results, a study of a personalized idiotype vaccine has achieved positive results. BiovaxID prolonged median disease-free survival by more than a year in a subset of patients who maintained complete remission after one year of chemotherapy and then received the vaccine.

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.