HIV-related non-Hodgkin's lymphoma

Non-Hodgkin's lymphoma (NHL) is the second most prevalent malignancy in patients infected with HIV. Approximately 30,000 new cases of NHL are diagnosed annually, and individuals with immunodeficiencies have a greater likelihood than the general population of developing NHL. Moreover, individuals who are seropositive for HIV have a fourfold greater risk of acquiring NHL. Most of these individuals will manifest NHL as a high-grade B-cell lymphoma with extranodal presentation. Response to standard chemotherapy and/or irradiation occurs frequently. However, because of opportunistic infections, overall survival is approximately five months. The expert nurse's role in assessment and management of symptoms associated with infection and side effects of therapy is critical.     

Classification of non-Hodgkin's lymphoma

This article provides an overview of the pathology and classification of non-Hodgkin lymphomas. Key histologic features are described for the common entities including both B-cell and T/NK-cell lineages. Additionally, details of the characteristic immunophenotypic findings, molecular genetic results, and common or clinically relevant cytogenetic alterations are described. Helpful tables are included that outline the key diagnostic features.     

Peripheral T-cell non-Hodgkin's lymphoma

T-cell non-Hodgkin's lymphoma (T-NHL) are uncommon malignancies accounting for 10% to 15% of all NHL. Geographic variation has been well documented, but the geographic variation may reflect exposure to specific pathogenic viruses, such as Epstein Barr Virus and Human T-cell leukemia virus-1 in Asian countries. The World Health Organization classification specifies 16 major subtypes of T-NHL. Each of the major subtype of peripheral T-NHL has unique characteristics and are addressed separately in this article.     

Primary pulmonary non-Hodgkin's lymphoma

BACKGROUND: Primary pulmonary non-Hodgkin's lymphoma is a very rare neoplasm. It is represented most commonly by marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type. Although there have been a few reviews of this lymphoma, clinical features, diagnostic procedure, optimal management and prognostic factors have not been well defined. METHODS: We reviewed the medical records of 24 patients who were pathologically and clinically diagnosed as primary pulmonary lymphoma between September 1995 and June 2003. RESULTS: There were 13 patients with MALT lymphoma and two with MALT lymphoma accompanied by large B-cell lymphoma, seven with diffuse large B-cell lymphoma and two with anaplastic large cell lymphoma. Half the patients were asymptomatic at presentation; 46% had respiratory symptoms and 16.7% had B-symptoms. Initial radiological findings were variable including nodules, masses, infiltrates or consolidation. The majority of patients (66.7%) needed surgical approaches (open thoracotomy or video-assisted thoracoscopy) for definite diagnosis. Bronchoscopy was performed in 83%, but only 30% showed a diagnostic yield. The 13 patients with MALT lymphoma were treated with a variety of modalities such as observation, surgery and single or combination chemotherapy, and combination chemotherapy was administered to 11 patients with non-MALT lymphoma regardless of surgery. The overall survival rate at 3 years for all 24 patients was 86% with a median follow-up of 32 months. CONCLUSION: Although this entity of lymphoma appears to have a good prognosis, further clinical experience and long-term follow-up are needed to identify prognostic factors.     

Procarbazine for non-Hodgkin's lymphoma

Procarbazine hydrochloride is an oral alkylating agent with activity against lymphoma. It is most commonly used in the treatment of Hodgkin's disease. The use of procarbazine-containing chemotherapeutic regimens in non-Hodgkin's lymphoma fell out of favor with the advent of CHOP. We report two patients with relapsed and/or refractory follicular lymphoma that achieved a complete and durable remission with a prolonged course of daily procarbazine.     

Immunotherapy for non-Hodgkin's lymphoma

The first attempt at using monoclonal antibodies in lymphoma therapy, reported in 1980, was unsuccessful. Since that time, several immunotherapeutic approaches to treating non-Hodgkin's lymphoma have been developed, with varying degrees of success. These approaches are largely based on the fact that each lymphoma is a clone of identical cells with a unique immunoglobulin on its surface. This unique portion of the immunoglobulin--the idiotype--is an ideal target for therapy. Clinical trials with antibodies have mostly targeted CD20, which is present on 95% of all B-cell lymphomas, as well as CD19 and CD22. This concept of using the idiotype to broaden the antilymphoma effect and to use it as a vaccine model has recently been evaluated. This approach would theoretically produce an active immunization with induction of humoral and cellular responses that would be longer acting than passive antibodies alone. The response is heterogeneous and polyclonal, which may be an advantage. Studies of these approaches will be outlined in this article.     

Radioimmunotherapy for non-Hodgkin's lymphoma

Radioimmunotherapy (RIT) treatment for lymphoma is a novel targeted therapeutic approach. Several years of development of radioimmunotherapeutic compounds came to fruition in February of 2002 when the US Food and Drug Administration (FDA) approved yttrium 90 ((90)Y)-ibritumomab tiuxetan ((90)Y-IT) for the treatment of relapsed or refractory, low-grade, or transformed B-cell lymphoma. (90)Y-IT uses a monoclonal anti-CD20 antibody to deliver beta-emitting (90)Y to the malignant B cells. Clinical trials have demonstrated its efficacy, which is largely independent of the intrinsic activity of the anti-CD20 antibody. A similar anti-CD20 radiotherapeutic compound, iodine 131 ((131)I)-tositumomab ((131)I-T), is also under consideration for approval. The advantages of increased efficacy compared to the native antibody are gained at the expense of myelotoxicity, which is dose-limiting but reversible. Other radioimmunoconjugates (RIC), including products for Hodgkin's lymphoma, are in earlier stages of development. Studies exploring expanded applications of RIT are under way. RIT has been shown to be an effective and clinically relevant complementary therapeutic approach for patients with lymphoma.     

原发性睾丸非霍奇金淋巴瘤

原发性睾丸非霍奇金淋巴瘤(NHL)极少见,仅占所有NHL的1%～2%,弥漫大B细胞淋巴瘤是最常见的病理类型.多发于60岁以上老年人.对侧睾丸受侵率高,易侵及中枢神经系统、皮肤等结外器官.ⅠE/ⅡE期病人睾丸切除术后综合治疗可降低复发率,提高生存率.晚期病人以化疗为主.对侧睾丸预防照射可降低其复发率,但中枢神经系统的预防性鞘内注药是否降低复发率还有争议.该病复发率高,预后差,国际预后指数与其预后相关.     

Treatment of non-Hodgkin's lymphoma.

Many of the advances in the management of non-Hodgkin's lymphomas have been based on more precise understanding of the various cell types that constitute these disorders. During the past year, we have seen some dramatic changes in the therapeutic approach to low-grade lymphomas. Until recently, the usual approach to these disorders was a purely palliative one, but a number of publications from the past year describe a more intensive approach with the goal of developing a curative modality. The use of combination chemotherapy in addition to radiation therapy for the early Ann Arbor stages as well as the use of high-dose chemotherapy with bone marrow transplantation in patients with high-risk factors has been reported recently. In the area of intermediate-grade lymphomas, most of the recent publications have described prognostic factors associated with various chemotherapy protocols. One of the most interesting recent developments is related to the dose-intensity issue. A consensus appears to be developing in regard to the correlation of dose intensity with clinical outcome. Despite the fact that new third-generation regimens have been associated with cures in 50% to 66% of the patients, a significant fraction of patients require salvage chemotherapy. Some of the new salvage regimens are discussed, as is the use of calcium channel blockers to reverse multiple-drug resistance. Finally, management of the high-grade lymphomas, specifically the small noncleaved cell type, has been associated with a cure rate in the range of 50% in two recently published studies. Patients who are human immunodeficiency virus-positive with small noncleaved cell lymphoma can be cured of their underlying malignancy, but many of them later develop complications of acquired immunodeficiency syndrome, to which they usually succumb.     

The epidemiology of non-Hodgkin's lymphoma

The incidence of non-Hodgkin's lymphoma (NHL) has doubled over the past two decades in the US and most other westernized countries. While improved cancer reporting, changes in lymphoma classification, and increases in AIDS-associated lymphomas have contributed to the startling escalation of disease incidence, these factors are estimated to account for only about 50% of the increase in observed incidence. The elucidation of etiologic factors and their mechanistic role in the pathogenesis of this malignancy are critical to advancements in disease prevention and treatment. Current evidence suggests that factors/conditions that precipitate either chronic antigenic stimulation or immunosuppression may provide a preferential milieu for development of NHL. High rates of lymphoma have been observed among individuals with autoimmune disease, organ transplants, and primary or acquired immunodeficiencies. Ultraviolet radiation, previously demonstrated to have an immunosuppressive effect, has also been suggested as a possible risk factor for NHL. Several pathogens have been linked to the risk of lymphoma, including Epstein-Barr virus, human immunodeficiency virus, human T-cell lymphotropic virus-1, Helicobacter pylori, hepatitis C, and simian virus 40. Whether these microbes are responsible for specific genetic mutations that initiate tumor growth, antigenic stimulation leading to B-cell proliferation, and increased potential of random cell replication errors, or immunosuppression, which thereby promotes tumor growth, has not been clearly delineated. Other exogenous factors which have been implicated in lymphomagenesis are chemicals and agricultural exposures, hair dyes, and blood transfusions. We must build on our current knowledge regarding the etiology of NHL in order that prevention, treatment, and ultimately, cure of this malignancy becomes a reality.     

Chemotherapy for non-Hodgkin's lymphoma.

The term non-Hodgkin's lymphoma (NHL) refers to a diverse group of illnesses that have in common a high frequency of chemotherapy sensitivity. In fact, high-grade NHL was among the first cancers to be cured with chemotherapy. Although the curability of patients with low-grade NHL remains debatable, all patients with intermediate- and high-grade NHL should be approached with curative intent, even if they present with advanced disease. Our ability to treat patients with NHL is steadily improving. There have been significant advances in our understanding of the biology of the disease and our ability to predict treatment outcome. New treatments and innovative uses of already available treatments are regularly reported. This paper reviews the highlights of the past year's literature regarding the treatment of patients with NHL.     

Immunologic markers in non-Hodgkin's lymphoma

The majority of non-Hodgkin's lymphomas (NHLs) are of B-cell lineage, with less than 20% of cases being of T-cell lineage. The B-cell NHLs phenotypically correspond to normal cells in the mid stages of normal differentiation. More specifically, by their expression of B-cell activation antigens, these tumors are the neoplastic counterparts of normal activated B cells. The follicular lymphomas--including the small cleaved, mixed small and large cell, and large cell types, as well as the small noncleaved cell (Burkitt's) lymphomas--represent malignant expansions of normal germinal center B cells by their expression of pan-B cell antigens, B-cell activation antigens, and CD10 (CALLA). The diffuse lymphomas also correspond to normal activated B cells. The small lymphocytic lymphomas express the low-affinity IL-2 receptor and CD5, both of which are induced on normal B cells following mitogen stimulation. The other diffuse B-cell NHLs similarly express activation antigens and resemble "transformed" B cells. The T-cell NHLs generally correspond to normal activated CD4+ T cells. These tumors--which include most peripheral T-cell lymphomas, cutaneous T-cell lymphomas, and HTLV-I-associated adult T-cell leukemias/lymphomas--express antigens induced on activated T cells, including IL-2 and transferrin receptors (CD25 and CD71, respectively), as well as HLA-DR. The lymphoblastic lymphomas, which are generally of T-cell lineage, phenotypically correspond to stages of intrathymic differentiation, often by their coexpression of CD4 and CD8, as well as expression of CD1. It remains controversial whether the immunophenotype of lymphoblastic lymphoma differs significantly from T-cell acute lymphoblastic leukemia. Since immunologic heterogeneity of NHL was first observed, attempts have been made to employ the data as a prognostic variable. Early studies suggested that lineage derivation or expression of markers of proliferating cells affected outcome in NHL. However, these reports were often retrospective, included various histologies, and did not treat patients uniformly. More recent prospective studies with relatively uniformly treated patients, predominantly involving DLCL, suggest that certain immunologically defined subgroups may have significantly different clinical outcomes. However, additional clinical studies will be necessary before treatment options are based upon immunologic markers.     

Second cancers following non-Hodgkin's lymphoma

The risk of second malignancies following non-Hodgkin's lymphoma (NHL) was estimated in 29,153 patients diagnosed with NHL between 1973 and 1987 in one of nine areas participating in the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. Compared with the general population, NHL patients were at a significantly increased risk of developing second cancers (observed/expected [O/E] = 1.18; O = 1231). The O/E ratio increased significantly with time to reach 1.77 in 10-year survivors. Significant excesses were noted for acute nonlymphocytic leukemia (O/E = 2.88), cancers of the bladder (O/E = 1.30), kidney (O/E = 1.47), and lung (O/E = 1.57), malignant melanoma (O/E = 2.44), and Hodgkin's disease (O/E = 4.16). Chemotherapy appeared related to subsequent acute nonlymphocytic leukemia (ANLL) and bladder cancer. Radiation therapy was associated with ANLL and possibly cancers of the lung, bladder, and bone. Malignant melanoma was not clearly related to initial NHL treatment.     

BRAF mutations in non-Hodgkin's lymphoma

Ras proteins control signalling pathways that are key regulators of several aspects of normal cell growth and malignant transformation. BRAF, which encodes an RAF family member in the downstream pathway of RAS, is somatically mutated in a number of human cancers. The activating mutation of BRAF is known to play a role in tumour development. As there have been no data on the BRAF mutation in non-Hodgkin's lymphoma (NHL), we analysed the genomic DNAs from 164 NHLs by polymerase chain reaction (PCR)-based single-strand conformation polymorphism (SSCP) for the detection of somatic mutations of BRAF (exons 11 and 15). Overall, we detected BRAF mutations in four NHLs (2.4%). Whereas most BRAF mutations in human cancers involved V599 of BRAF, all of the four BRAF mutations in the NHLs involved other amino acids (one G468A, two G468R and one D593G). To our knowledge, this is the first report on BRAF mutation in NHL, and the data indicate that BRAF is occasionally mutated in NHL, and suggest that BRAF mutation may contribute to the tumour development in some NHLs.     

Ibritumomab tiuxetan for non-Hodgkin's lymphoma

Targeted radiation therapy, or radioimmunotherapy, has been an important recent advancement in the treatment of patients with B-cell non-Hodgkin's lymphoma (NHL). 90Y ibritumomab tiuxetan comprises the murine monoclonal antibody ibritumomab, the linker chelator tiuxetan and the radiolabeled isotope 90yttrium. 90Y ibritumomab tiuxetan has been demonstrated to be efficacious in the treatment of B-cell NHL. Initial Phase I/II trials established the therapeutic dose of ibritumomab tiuxetan for low-grade NHL to be 0.4 mCi/kg, or 0.3 mCi/kg for patients with mild thrombocytopenia. Currently, there are many ongoing trials of ibritumomab tiuxetan with different dose schedules and intensities, in combination with chemotherapy and with stem cell transplantation, in an attempt to improve response rate and duration and to study its effectiveness in other B-cell lymphomas, including diffuse large B-cell lymphoma and mantle cell lymphoma. Radioimmunotherapy has great promise and the safe incorporation of 90Y ibritumomab tiuxetan into treatment will hopefully result in improved survival for patients with NHL.