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It is generally resistant to cancer chemotherapy drugs that are active against other lymphomas, and carries a poor prognosis.
Sirolimus has been proposed as a treatment option.
The most common chemotherapy used for non-Hodgkin lymphoma is R-CHOP.
Surgical resection is usually ineffective because of the depth of the tumour. Treatment with irradiation and corticosteroids often only produces a partial response and tumour recurs in more than 90% of patients. Median survival is 10 to 18 months in immunocompetent patients, and less in those with AIDS. The addition of IV methotrexate and folinic acid (leucovorin) may extend survival to a median of 3.5 years. If radiation is added to methotrexate, median survival time may increase beyond 4 years. However, radiation is not recommended in conjunction with methotrexate because of an increased risk of leukoencephalopathy and dementia in patients older than 60. In AIDS patients, perhaps the most important factor with respect to treatment is the use of highly active anti-retroviral therapy (HAART), which affects the CD4+ lymphocyte population and the level of immunosuppression. The optimal treatment plan for patients with PCNSL has not been determined. Combination chemotherapy and radiotherapy at least doubles survival time, but causes dementia and leukoencephalopathy in at least 50% of patients who undergo it. The most studied chemotheraputic agent in PCNSL is methotrexate (a folate analogue that interferes with DNA repair). Methotrexate therapy in patients with PCNSL typically requires hospitalization for close monitoring and intravenous fluids. Leucovorin is often given for the duration of the therapy. Standard chemotherapeutic regimens for lymphoma such as CHOP are ineffective in PCNSL, probably due to poor penetration of the agents through the blood brain barrier.
Newer treatments, such as high dose chemotherapy combined with stem cell transplant are proving to increase survival by years.
A phase 1 clinical trial of ibrutinib - an inhibitor of Bruton's tyrosine kinase - in 13 patients reported responses in 10 (77%). Five of the responses were complete.
The initial response to radiotherapy is often excellent, and may result in a complete remission. However, the duration of response with radiotherapy alone remains short, with median survival after treatment with radiotherapy just 18 months. Methotrexate based chemotherapy markedly improves survival, with some studies showing median survival after methotrexate chemotherapy reaching 48 months.
The Center for Disease Control and Prevention (CDC) included certain types of non-Hodgkin's lymphoma as AIDS-defining cancers in 1987. Immune suppression rather than HIV itself is implicated in the pathogenesis of this malignancy, with a clear correlation between the degree of immune suppression and the risk of developing NHL. Additionally, other retroviruses such as HTLV may be spread by the same mechanisms that spread HIV, leading to an increased rate of co-infection. The natural history of HIV infection has been greatly changed over time. As a consequence, rates of non-Hodgkin's lymphoma (NHL) in people infected with HIV has significantly declined in recent years.
Of all cancers involving the same class of blood cell, 2.3% of cases are Burkitt lymphoma. Epstein-Barr virus infection is strongly correlated with this cancer.
In general, the first line of treatment for Burkitt’s lymphoma is intensive chemotherapy. A few of these regimens are: the GMALL-B-ALL/NHL2002 protocol, the modified Magrath regimen (R-CODOX-M/IVAC). COPADM, hyper-CVAD, and the Cancer and Leukemia Group B (CALGB) 8811 regimen; these can be associated with rituximab. In older patients treatment may be dose-adjusted EPOCH with rituximab.
The effects of the chemotherapy, as with all cancers, depend on the time of diagnosis. With faster-growing cancers, such as Burkitt's, the cancer actually responds faster than with slower-growing cancers. This rapid response to chemotherapy can be hazardous to the patient, as a phenomenon called "tumor lysis syndrome" could occur. Close monitoring of the patient and adequate hydration is essential during the process. Since Burkitts lymphoma has high propensity to spread to the central nervous system (lymphomatous meningitis), intrathecal chemotherapy with methotrexate and/or ARA-C and/or prednisolone is given alongside with systemic chemotherapy.
Chemotherapy
- cyclophosphamide
- doxorubicin
- vincristine
- methotrexate
- cytarabine
- ifosfamide
- etoposide
- rituximab
Other treatments for Burkitt's lymphoma include immunotherapy, bone marrow transplants, stem cell transplant, surgery to remove the tumor, and radiotherapy.
Hodgkin lymphoma typically is treated with radiotherapy alone, as long as it is localized.
Advanced Hodgkin disease requires systemic chemotherapy, sometimes combined with radiotherapy. Chemotherapy used includes the ABVD regimen, which is commonly used in the United States. Other regimens used in the management of Hodgkin lymphoma include BEACOPP and Stanford V. Considerable controversy exists regarding the use of ABVD or BEACOPP. Briefly, both regimens are effective, but BEACOPP is associated with more toxicity. Encouragingly, a significant number of people who relapse after ABVD can still be salvaged by stem cell transplant.
Treatment of some other, more aggressive, forms of lymphoma can result in a cure in the majority of cases, but the prognosis for patients with a poor response to therapy is worse. Treatment for these types of lymphoma typically consists of aggressive chemotherapy, including the CHOP or R-CHOP regimen. A number of people are cured with first-line chemotherapy. Most relapses occur within the first two years, and the relapse risk drops significantly thereafter. For people who relapse, high-dose chemotherapy followed by autologous stem cell transplantation is a proven approach.
Primary cerebral lymphoma (or "primary central nervous system lymphoma") is a form of NHL. It is very rare in immunocompetent people, with an incidence of 5–30 cases per million person-years. However the incidence in immunocompromised individuals is greatly increased, up to 100 per million person-years.
Primary cerebral lymphoma is strongly associated with Epstein–Barr virus (EBV). The presence of EBV DNA in cerebrospinal fluid is highly suggestive of primary cerebral lymphoma.
Treatment of AIDS patients with antiretroviral drugs reduces the incidence of primary cerebral lymphoma.
There is no known cause for any type of Marginal Zone non-Hodgkins lymphoma, but it occurs when the body produces large amounts of abnormal lymphocytes.
Factors that may increase an individuals chance of developing nodal MZL are being over the age of 60 and having been infected with hepatitis C virus. Factors that may increase an individuals chance of developing MALT lymphoma include being over the age of 50, having an autoimmune condition (rheumatoid arthritis, Hashimoto's thyroiditis), and long lasting chronic inflammation due to infection (H.pylori, Sjogren syndrome, chlamidia infection, Borrelia infection, Campylobacter jejuni infection). Factors that increase an individuals risk of developing splenic MZL include the hepatitis C virus, Epstein-Barr virus, malaria, Sjogren syndrome, and lupus.
In order to reduce the chances of developing MZL, an individual can decrease their exposure to the possible risk factors.
Radiotherapy is the most effective treatment for local disease either as the sole treatment for low-grade lymphoma or in combination with chemotherapy for intermediate- and high-grade lymphoma. Radiotherapy dose in range of 30-45 Gy administered in fractions are advised in treating the local orbital lymphomas.
The high cure rates and long survival of many patients with Hodgkin's lymphoma has led to a high concern with late adverse effects of treatment, including cardiovascular disease and second malignancies such as acute leukemias, lymphomas, and solid tumors within the radiation therapy field. Most patients with early-stage disease are now treated with abbreviated chemotherapy and involved-field radiation therapy rather than with radiation therapy alone. Clinical research strategies are exploring reduction of the duration of chemotherapy and dose and volume of radiation therapy in an attempt to reduce late morbidity and mortality of treatment while maintaining high cure rates. Hospitals are also treating those who respond quickly to chemotherapy with no radiation.
In childhood cases of Hodgkin's lymphoma, long-term endocrine adverse effects are a major concern, mainly gonadal dysfunction and growth retardation. Gonadal dysfunction seems to be the most severe endocrine long-term effect, especially after treatment with alkylating agents or pelvic radiotherapy.
Possible options such as anthracycline-containing regimens include ABVD, BEACOPP and CHOP. Results of a trial with COPP/ABV in children suggested positive results with chemotherapy alone are possible without the need for radiation therapy. Optimal chemotherapy is a topic for debate, for example there is evidence of support for treatment with R-CHOP instead of ABVD, results showing high rates (40%) of relapse after 10 years since ABVD chemotherapy. BEACOPP has higher reported toxicity risk.
Of all cancers involving the same class of blood cell, 8% of cases are MALT lymphomas.
Lymphoma Association (UK)
Nodular Lymphocyte Predominant Hodgkin's Lymphoma (NLPHL) Facebook Group
Treatment is dependent if the lymphoma is causing issues in regards to the overall health of the individual. Since this a slow moving cancer, many patients start treatment when the symptoms appear. If the individual tests positive for hepatitis C, then anti-viral treatment is suggested since it will often get rid of the lymphoma as well. If further treatment is required the options include chemotherapy, monoclonal antibodies, and/or radiation. Radiation therapy is used for stage I and II nodal marginal zone NHL. Clinical trials show success in treatment when using drugs such as bendamustine and lenalidomida in combination with rituximab.
There is no cure for CTCL, but there are a variety of treatment options available and some CTCL patients are able to live normal lives with this cancer, although symptoms can be debilitating and painful, even in earlier stages. FDA approved treatments include the following:
- (1999) Denileukin diftitox (Ontak)
- (2000) Bexarotene (Targretin) a retinoid
- (2006) Vorinostat (Zolinza) a hydroxymate histone deacetylase (HDAC) inhibitor
- (2009) Romidepsin (Istodax) a cyclic peptide histone deacetylase (HDAC) inhibitor
Histone deacetylase (HDAC) inhibitors are shown to have antiproliferative and cytotoxic properties against CTCL.Other (off label) treatments include:
In 2010, the U.S. Food and Drug Administration granted orphan drug designation for a topical treatment for pruritus in cutaneous T-cell lymphoma to a pharmaceutical company called Elorac.
Patients with early stage disease (IA or IIA) are effectively treated with radiation therapy or chemotherapy. The choice of treatment depends on the age, sex, bulk and the histological subtype of the disease. Adding localised radiation therapy after the chemotherapy regimen may provide a longer progression-free survival compared with chemotherapy treatment alone. Patients with later disease (III, IVA, or IVB) are treated with combination chemotherapy alone. Patients of any stage with a large mass in the chest are usually treated with combined chemotherapy and radiation therapy.
It should be noted that the common non-Hodgkin's treatment, rituximab (which is a monoclonal antibody against CD20) is not routinely used to treat Hodgkin's lymphoma due to the lack of CD20 surface antigens in most cases. The use of rituximab in Hodgkin's lymphoma, including the lymphocyte predominant subtype has been recently reviewed.
Although increased age is an adverse risk factor for Hodgkin's lymphoma, in general elderly patients without major comorbidities are sufficiently fit to tolerate standard therapy, and have a treatment outcome comparable to that of younger patients. However, the disease is a different entity in older patients and different considerations enter into treatment decisions.
For Hodgkin's lymphomas, radiation oncologists typically use external beam radiation therapy (sometimes shortened to EBRT or XRT). Radiation oncologists deliver external beam radiation therapy to the lymphoma from a machine called linear accelerator which produces high energy X Rays and Electrons. Patients usually describe treatments as painless and similar to getting an X-ray. Treatments last less than 30 minutes each.
For lymphomas, there are a few different ways radiation oncologists target the cancer cells. Involved field radiation is when the radiation oncologists give radiation only to those parts of the patient's body known to have the cancer. Very often, this is combined with chemotherapy. Radiation therapy directed above the diaphragm to the neck, chest or underarms is called mantle field radiation. Radiation to below the diaphragm to the abdomen, spleen or pelvis is called inverted-Y field radiation. Total nodal irradiation is when the therapist gives radiation to all the lymph nodes in the body to destroy cells that may have spread.
The factors of poor prognosis for patients with thyroid lymphoma are advanced stage of the tumor, large size (>10 cm) as well as spreading to mediastinum. The overall survival for primary thyroid lymphoma is 50% to 70%, ranging from 80% in stage IE to less than 36% in stage IIE and IVE in 5 years.
Chemotherapy with CHOP, infusional EPOCH, hyperCVAD, and CODOX-M/IVAC is often used. The prognosis is generally poor, for example 6 to 7 months and 14 months.
Currently PTCL is treated similarly to B-cell lymphomas. However, in recent years, scientists have developed techniques to better recognize the different types of lymphomas, such as PTCL. It is now understood that PTCL behaves differently from B-cell lymphomas and therapies are being developed that specifically target these types of lymphoma. Currently, however, there are no therapies approved by the US Food and Drug Administration (FDA) specifically for PTCL. Anthracycline-containing chemotherapy regimens are commonly offered as the initial therapy. Some patients may receive a stem cell transplant. Novel approaches to the treatment of PTCL in the relapsed or refractory setting are under investigation.
Pralatrexate is one compound currently under investigations for the treatment of PTCL. For information please consult the US clinical trials database (http://www.clinicaltrials.gov).
Non-Hodgkin's lymphoma (NHL) is present in about 1%–3% of HIV seropositive people at the time of the initial diagnosis of HIV. However, it is believed that such patients have been seropositive for a prolonged period, but have simply not had their infections recognized previously. This is so because immunodysregulation must exist for an extended interval of time, in order for a lymphoproliferative process to evolve in that context.
Due to the causal relationship between "H. pylori" infection and MALT lymphoma, identification of the infection is mandatory. Histological examination of GI biopsies yields a sensitivity of 95% with five biopsies, but these should be from sites uninvolved by lymphoma and the identification of the organism may be compromised by areas of extensive intestinal metaplasia. As proton-pump inhibition can suppress infection, any treatment with this class of drug should be ceased 2 weeks prior to biopsy retrieval. Serology should be performed if histology is negative, to detect suppressed or recently treated infections. Following the recognition of the association of gastric MALT lymphoma with "H. pylori" infection, it was established that early-stage gastric disease could be cured by "H. pylori" eradication, which is now the mainstay of therapy. Fifty to 95% of cases achieve complete response (CR) with "H. pylori" treatment.
A t(11;18)(q21;q21) chromosomal translocation, giving rise to an "API2-MLT" fusion gene, is predictive of poor response to eradication therapy.
Of all cancers involving the same class of blood cell, 2% of cases are cutaneous T cell lymphomas. CTCL is more common in men and in African-American people. The incidence of CTCL in men is 1.6 times higher than in women.
There is some evidence of a relationship with human T-lymphotropic virus (HTLV) with the adult T-cell leukemia/lymphoma subtype. No definitive link between any viral infection or environmental factor has been definitely shown with other CTCL subtypes.