Hodgkin’s lymphoma

Despite dramatic advances in the treatment of several human malignancies including Hodgkin s lymphomas and leukemias, dmg resistance remains a pressing issue in cancer chemotherapy. Acquired or induced dmg resistance afflicts practically all classes of cancer agents. It usually is manifested clinically... 

Poly(ethylene glycol) (PEG) molecules attached to adenosine deaminase (ADA) have been used in patients exhibiting symptoms of the severe combined immunodeficiency syndrome (SCID) caused by ADA deficiency. The modified enzyme has a plasma half-life of weeks as compared to the unmodified enzyme (minutes) (248). PEG-L-asparaginase has induced remissions in patients with non-Hodgkin s lymphoma (248). However, one disadvantage of PEG-enzyme treatment is its expense, ie, a year s treatment costs about 60,000 (248). 

Lomustine (2-chlorethyl-3 cyclohexyl-1 -nutrosourea, CCNU, Fig 3) is a nitrosourea for oral application. It is used for the treatment of Hodgkin s lymphomas, brain tumors and bronchial carcinomas at a dose of 3.5 mg/kg (130 mg/m2) repeated in 6-8 weeks intervals. 

Bendamustine is a useful antineoplastic drug for the treatment of non-Hodgkin s lymphomas, multiple myeloma and as a partner drug in the combination therapy of some solid tumors. The cross-resistance with other alkylating drugs is not complete. Myelosuppression and lymphocytopenia is its main dose-limiting toxicity. 

Liposomal encapsulation of DOX or DNR Preferred anthracycline delivery to the tumor Breast cancer, ovarian cancer, AIDS-related Kaposi s sarcoma, multiple myeloma (pegylated liposomal DOX). Breast cancer (uncoated liposomal DOX). AIDS-related Kaposi s sarcoma, acute mye-loblastic leukemia, multiple myeloma, non-Hodgkin s lymphomas (uncoated liposomal DNR)... 

An update of a previous study (Axelson et al. 1978), Axelson (1986) evaluated an expanded cohort of 1,424 men (levels of trichloroethylene exposure inferred from measured urinary metabolite concentrations) and found a significant increase in incidences of bladder cancer and lymphomas, and a lower than expected incidence of total cancer mortality. A further update of this work (Axelson et al. 1994) expanded the cohort to include 249 women, tracking cancer morbidity over 30 years, and found no correlation between exposure concentration or exposure time and cancer incidence at any site. The highest standardized incidence ratio noted in this study was 1.56 (95% Cl of 0.51-3.64) for 5 cases of non-Hodgkin s lymphoma observed in men. Although four of these cases occurred in persons exposed for at least 2 years, and 3 cases had a latency of 10 years or more, urinary levels of TCA showed that 4 of the 5 cases were exposed to the lowest levels of trichloroethylene (urinary levels of TCA 0-49 mg/L). The study authors mentioned that a urinary TCA level below 50 mg/L corresponds to a trichloroethylene exposure concentration of about 20 ppm. The study authors concluded that "this study provides no evidence that trichloroethylene is a human carcinogen, i.e., when the exposure is as low as for this study population."... 

Cohn P, Klotz J, Bove F, et al. 1994. Drinking water contamination and the incidence of leukemia and non-Hodgkin s lymphoma. Environ Health Perspect 102 556-561. 

Hardell L, Eriksson M, Degerman A. 1994. Exposure to phenoyacetic Acids, chlorophenols, or organic solvents in relation to histopathology, stage, and anatomical localization of non-Hodgkin s lymphoma. 

Teniposide, a topoisomerase II inhibitor, is administered as an infusion over 30 to 60 minutes to prevent hypotension. The pharmacokinetics are described by a three-compartment model, with an a half-life of 0.75 hours, a (5 half-life of 4 hours, and a terminal half-life of 20 hours. Considerable variability in clearance of teniposide in children has been reported.17 Teniposide has shown activity in the treatment of acute lymphocytic leukemia, neuroblastoma, and non-Hodgkin s lymphoma. Side effects include myelosuppression, nausea, vomiting, mucositis, and venous irritation. Hypersensitivity reactions may be life-threatening. 

This royal-blue-colored drug is an anthracenedione that inhibits DNA topoisomerase II. The pharmacokinetics of mitoxantrone may best be described by a three-compartment model, with an a half-life of 3 to 10 minutes, a 3 half life of 0.3 to 3 hours, and a median terminal half-life of 12 days. Biliary elimination appears to be the primary route of elimination, with less than 10% of the drug eliminated by the kidney.23 Mitoxantrone has shown clinical activity in the treatment of acute leukemias, breast and prostate cancer, and non-Hodgkin s lymphomas. Myelosuppression, mucositis, nausea and vomiting, and cardiac toxicity are side effects of this drug. The total cumulative dose limit is 160 mg/m2 for patients who have not received prior anthracycline or mediastinal radiation. Patients who have received prior doxorubicin or daunorubicin therapy should not receive a cumulative dose greater than 120 mg/m2 of mitoxantrone. Patients should be counseled that their urine will turn a blue-green color. 

Lomustine is an orally available nitrosurea alkylating agent. Lomustine is converted rapidly to the cis- and frans-4-hydroxy metabolites the range of half-lives of these two metabolites is 2 to 4 hours.25 Lomustine has shown clinical activity in the treatment of Hodgkin s lymphoma and melanoma. Side effects are similar to those of carmustine. Patients should receive only enough drug for one cycle at a time to prevent confusion and accidental overdose. 

While the exact mechanism of action remains unclear, dacarbazine appears to inhibit DNA, RNA, and protein synthesis. Dacarbazine disappears rapidly from the plasma, with a terminal half-life of about 40 minutes. Dacarbazine has shown clinical benefit in the treatment of melanoma, Hodgkin s lymphoma, and soft tissue sarcomas. Side effects include myelosuppression, severe nausea and vomiting, and a flulike syndrome that starts about 7 days after treatment and lasts 1 to 3 weeks. 

This hot antibody is linked to radioactive iodine and binds to the CD20 receptor present on B lymphocytes (see Rituximab above). Tositumomab has shown activity in non-Hodgkin s lymphoma. Hematologic toxicity occurs several weeks after administration and may persist for months. Since radioactive iodine may have adverse effects on the thyroid, all patients must receive thyroid-blocking agents. 

Contrast the treatment for early- and advanced-stage disease for Hodgkin s lymphoma. 

Delineate the clinical course of follicular indolent and diffuse aggressive non-Hodgkin s lymphoma and the implications for disease classification schemes and treatment goals. 

Interpret the current role for monoclonal antibody therapy in non-Hodgkin s lymphoma. 

Assess the role of autologous hematopoietic stem cell transplantation in relapsed Hodgkin s lymphoma and non-Hodgkin s lymphoma. 

Specific pathologic characteristics distinguishing Hodgkin s lymphoma from non-Hodgkin s lymphoma include morphology, cell surface antigens, and chromosomal mutations. 

The goal of treatment of Hodgkin s lymphoma is cure for all stages of disease and the first relapse. 

The recombinant monoclonal antibody rituximab is an effective treatment option for some patients with non-Hodgkin s lymphoma as a single agent and enhances the efficacy of combination chemotherapy regimens. 

The clinical course varies widely among these histologies of HL and NHL. Most lymphoma subtypes are highly proliferating tumor cells that require aggressive therapeutic intervention with chemotherapy, radiation therapy, or both. By contrast, certain subtypes of non-Hodgkin s lymphoma... 

Anaplastic large-cell lymphoma, T/null cell, primary systemic type Hodgkin s Lymphoma (Hodgkin s Disease)... 

Nodular lymphocyte-predominant Hodgkin s lymphoma Classical Hodgkin s lymphoma... 

Nodular sclerosis Hodgkin s lymphoma (grades 1 and 2) Lymphocyte-rich classical Hodgkin s lymphoma Mixed cellularity Hodgkin s lymphoma Lymphocyte depletion Hodgkin s lymphoma... 

TABLE 90-2. Negative Prognostic Factors for Hodgkin s Lymphoma and Non-Hodgkin s Lymphoma... 

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