An example antibody for use in immunotherapy is Rituximab. Rituximab has specific use in treatment of NLPHL as it is a chimeric monoclonal antibody against the protein CD20. Studies indicate Rituximab offers potential in relapsed or refractory patients, and also in front-line treatment especially in advanced stages. Because of a tendency for relapse, maintenance treatment such as every 6 months for 2 years is suggested. Rituximab has been shown to improve patient outcomes after histological transformation.

In November 2013, ibrutinib was approved by the US FDA for treating MCL.

Other targeted agents include the proteasome inhibitor bortezomib, mTOR inhibitors such as temsirolimus, and the P110δ inhibitor GS-1101.

Current treatment typically includes R-CHOP, which consists of the traditional CHOP, to which rituximab has been added. This regimen has increased the rate of complete response for DLBCL patients, particularly in elderly patients.R-CHOP is a combination of one monoclonal antibody (rituximab), three chemotherapy agents (cyclophosphamide, doxorubicin, vincristine), and one steroid (prednisone). These drugs are administered intravenously, and the regimen is most effective when it is administered multiple times over a period of months. People often receive this type of chemotherapy through a PICC line (peripherally inserted central catheter) in their arm near the elbow or a surgically implanted venous access port. The number of cycles of chemotherapy given depends on the stage of the disease — patients with limited disease typically receive three cycles of chemotherapy, while patients with extensive disease may need to undergo six to eight cycles. A recent approach involves obtaining a PET scan after the completion of two cycles of chemotherapy, to assist the treatment team in making further decisions about the future course of treatment.Older people often have more difficulty tolerating therapy than younger people. Lower intensity regimens have been attempted in this age group.

Radiation therapy is often part of the treatment for DLBCL. It is commonly used after the completion of chemotherapy. Radiation therapy alone is not an effective treatment for this disease.

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.

Immune-based therapy is dominated by the use of the rituximab monoclonal antibody, sold under the trade name Rituxan (or as Mabthera in Europe and Australia). Rituximab may have good activity against MCL as a single agent, but it is typically given in combination with chemotherapies, which prolongs response duration. There are newer variations on monoclonal antibodies combined with radioactive molecules known as Radioimmunotherapy (RIT). These include Zevalin and Bexxar. Rituximab has also been used in small numbers of patients in combination with thalidomide with some effect. In contrast to these antibody-based 'passive' immunotherapies, the field of 'active' immunotherapy tries to activate a patient's immune system to specifically eliminate their own tumor cells. Examples of active immunotherapy include cancer vaccines, adoptive cell transfer, and immunotransplant, which combines vaccination and autologous stem cell transplant. Though no active immunotherapies are currently a standard of care, numerous clinical trials are ongoing.

There is no consensus regarding the best treatment protocol. Several considerations should be taken into account including age, stage, and prognostic scores (see International Prognostic Index). Patients with advanced disease who are asymptomatic might benefit from a watch and wait approach, as early treatment does not provide survival benefit. When patients are symptomatic, specific treatment is required, which might include various combinations of alkylators, nucleoside analogues, anthracycline-containing chemotherapy regimens (e.g., CHOP), monoclonal antibodies (e.g. rituximab),

radioimmunotherapy, autologous (self) and allogeneic (donor) hematopoietic stem cell transplantation. Follicular lymphoma is regarded as incurable, unless the disease is localized, in which case it can be cured by local irradiation. Although allogeneic stem cell transplantation may be curative, the mortality from the procedure is too high to be a first line option.

In 2010 rituximab was approved by the European Commission for first-line maintenance treatment of follicular lymphoma. Pre-clinical evidence suggests that rituximab could be also used in combination with integrin inhibitors to overcome the resistance to rituximab mediated by stromal cells . However, follicular lymphoma which is CD20 negative will not benefit from Rituximab, which targets CD20.

Trial results released in June 2012 show that bendamustine, a drug first developed in East Germany in the 1960s, more than doubled disease progression-free survival when given along with rituximab. This combination therapy also left patients with fewer side effects than the older treatment (a combination of five drugs—rituximab, cyclophosphamide (Cytoxan), doxorubicin (Adriamycin), vincristine and prednisone, collectively called R-CHOP).

There are many recent and current clinical trials for follicular lymphoma. For example, personalised idiotype vaccines have shown promise, particularly as upfront therapy, but have still to prove their efficacy in randomized clinical trials.

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.

One such development is in the delivery of doxorubicin. While it is an effective inducer of apoptosis, doxorubicin is quickly filtered out of the body. By loading a PEG-liposome with doxorubicin the circulation time and localization to tumors greatly increases. Cancerous tumors characteristically have extensive angiogenesis and leaky vasculatures, which causes the PEG-liposomes to naturally accumulate in the tumor. This also allows for patients to receive lower and fewer doses of the drug and experience fewer side effects. This is also being attempted with nanoparticles but has not been tested on FDCS. In 2008 COP plus (PEG)-liposomal doxorubicin went into a clinical trial for an FDCS patient to replace the CHOP regimen, and after 5 years the patient remains in CR.

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.

Combined modality therapy is the most common approach for the initial treatment of thyroid lymphomas. The CHOP regimen (cyclophosphamide, doxorubicin, vincristine and prednisone) has been shown high effectiveness for many types of thyroid lymphoma. However, it is suggested to perform radiation therapy only for MALT resulting a 96% complete response, with only a 30% relapse rate. Surgical treatment might be performed for patients with thyroid lymphoma in addition to chemotherapy and radiation, particularly for MALT lymphomas.

Treatment options that have been tried include zidovudine and the CHOP regimen. Pralatrexate has also been investigated. Most therapy is directed towards the cancer rather than the virus itself.

Recently, it has been reported that the traditional glucocorticoid-based chemotherapy toward ATL are largely mediated by thioredoxin binding protein-2 (TBP-2/TXNIP/VDUP1), suggesting the potential use of a TBP-2 inducer as a novel therapeutic target.

Recently, mogamulizumab, has been approved for the treatment of ATL in Japan.

At a medical conference in December 2013, researchers reported anywhere from 21-50% of ATL patients have disease expressing CD30. This suggests treatment with CD30-targeting brentuximab vedotin may be beneficial.

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.

In certain eligible patients, a conditioning regimen of high-dose chemotherapy followed by an autologous stem cell transplant may be used to extend a period of first complete remission. Likewise, a recent study suggests that high dose therapy and autologous stem cell transplantation results in favorable outcomes for elderly patients with Non-Hodgkin's Lymphoma.

Currently Aggressive NK-cell leukemia, being a subtype of 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 U.S. 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.

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).

Many low-grade lymphomas remain indolent for many years. Treatment of the nonsymptomatic patient is often avoided. In these forms of lymphoma, such as follicular lymphoma, watchful waiting is often the initial course of action. This is carried out because the harms and risks of treatment outweigh the benefits. If a low-grade lymphoma is becoming symptomatic, radiotherapy or chemotherapy are the treatments of choice; although they do not cure the lymphoma, they can alleviate the symptoms, particularly painful lymphadenopathy. Patients with these types of lymphoma can live near-normal lifespans, but the disease is incurable. Some centers advocate the use of single agent rituximab in the treatment of follicular lymphoma rather than the wait and watch approach. Watchful waiting is not a good strategy for all patients, as it leads to significant distress and anxiety in some patients. It has been equated with watch and worry.

Newer cases are also starting to be treated by taxotere and gemcitabine. Taxotere is similar to Oncovin used in CHOP; it irreversibly binds beta tubulin halting formation of microtubules. Taxotere has an added benefit though; it also phosphorylates bcl-2 to halt the anti-apoptotic pathway. The dual effect of taxotere on integral cancer pathways makes it a more potent drug than Oncovin. Gemcitabene is a nucleoside analog and when incorporated into DNA during replication leads to apoptosis; the fluorine on the 2’ carbon atom stops other nucleosides from attaching. The most important part of this combination therapy, however, is the synergism between the drugs. While researchers are not entirely sure of the mechanism, there is evidence of synergistic effects of taxotere and gemcitabine when used in combination. This allows for decreased dosages of each single agent with an increased apoptotic response.

There is no standard therapy for multicentric Castleman disease. Treatment modalities change based on HHV-8 status, so it is essential to determine HHV-8 status before beginning treatment. For HHV-8-associated MCD the following treatments have been used: rituximab, antiviral medications such as ganciclovir, and chemotherapy.

Treatment with the antiherpesvirus medication ganciclovir or the anti-CD20 B cell monoclonal antibody, rituximab, may markedly improve outcomes. These medications target and kill B cells via the B cell specific CD20 marker. Since B cells are required for the production of antibodies, the body's immune response is weakened whilst on treatment and the risk of further viral or bacterial infection is increased. Due to the uncommon nature of the condition there are not many large scale research studies from which standardized approaches to therapy may be drawn, and the extant case studies of individuals or small cohorts should be read with caution. As with many diseases, the patient's age, physical state and previous medical history with respect to infections may impact the disease progression and outcome.

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.

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.

Due to the high risk of recurrence and ensuing problems, close monitoring of dogs undergoing chemotherapy is important. The same is true for dogs that have entered remission and ceased treatment. Monitoring for disease and remission/recurrence is usually performed by palpation of peripheral lymph nodes. This procedure detects gross changes in peripheral lymph nodes. Some of the blood tests used in diagnosing lymphoma also offer greater objectivity and provide an earlier warning of an animal coming out of remission.

Complete cure is rare with lymphoma and treatment tends to be palliative, but long remission times are possible with chemotherapy. With effective protocols, average first remission times are 6 to 8 months. Second remissions are shorter and harder to accomplish. Average survival is 9 to 12 months. The most common treatment is a combination of cyclophosphamide, vincristine, prednisone, L-asparaginase, and doxorubicin. Other chemotherapy drugs such as chlorambucil, lomustine (CCNU), cytosine arabinoside, and mitoxantrone are sometimes used in the treatment of lymphoma by themselves or in substitution for other drugs. In most cases, appropriate treatment protocols cause few side effects, but white blood cell counts must be monitored.

Allogeneic and autologous stem cell transplantations (as is commonly done in humans) have recently been shown to be a possible treatment option for dogs. Most of the basic research on transplantation biology was generated in dogs. Current cure rates using stem cell therapy in dogs approximates that achieved in humans, 40-50%.

When cost is a factor, prednisone used alone can improve the symptoms dramatically, but it does not significantly affect the survival rate. The average survival times of dogs treated with prednisone and untreated dogs are both one to two months. Using prednisone alone can cause the cancer to become resistant to other chemotherapy agents, so it should only be used if more aggressive treatment is not an option.

Isotretinoin can be used to treat cutaneous lymphoma.

For HHV-8-negative MCD (idiopathic MCD), the following treatments have been used: corticosteroids, rituximab, monoclonal antibodies against IL-6 such as tocilizumab and siltuximab, and the immunomodulator thalidomide.

Prior to 1996 MCD carried a poor prognosis of about 2 years, due to autoimmune hemolytic anemia and non-Hodgkin's lymphoma which may arise as a result of proliferation of infected cells. The timing of diagnosis, with particular attention to the difficulty of determining the cause of B symptoms without a CT scan and lymph node biopsy, may have a significant impact on the prognosis and risk of death. Left untreated, MCD usually gets worse and becomes increasingly difficult and unresponsive to current treatment regimens.

Siltuximab prevents it from binding to the IL-6 receptor, was approved by the U.S. Food and Drug Administration for the treatment of multicentric Castleman disease on April 23, 2014. Preliminary data suggest that treatment siltuximab may achieve tumour and symptomatic response in 34% of patients with MCD.

Other treatments for multicentric Castleman disease include the following:

- Corticosteroids

- Chemotherapy

- Thalidomide

Diffuse large B-cell lymphomas of the stomach are primarily treated with chemotherapy with CHOP (cyclophosphamide+doxorubicine+vincristine+prednisone) with or without rituximab being a usual first choice.

Antibiotic treatment to eradicate H. pylori is indicated as first line therapy for MALT lymphomas. About 60% of MALT lymphomas completely regress with eradication therapy. Radiation treatment for H. pylori negative gastric malt lymphoma, has a high success rate, 90% or better after 5 years. Second line therapy for MALT lymphomas is usually chemotherapy with a single agent, and complete response rates of greater than 70% have been reported.

Subtotal gastrectomy, with post-operative chemotherapy is undertaken in refractory cases, or in the setting of complications, including gastric outlet obstruction.

A number of types of radiation therapy may be used including total skin electron therapy. While this therapy does not generally result in systemic toxic effects it can produce side effects involving the skin. It is only avaliable at a few institutions.