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.

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.

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.

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.

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.

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.

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.

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.

Treatment depends on the grade (I-III) but typically consist of cortisone, rituximab and chemotherapy (etoposide, vincristine, cyclophosphamide, doxorubicin). Methotrexate has been seen to induce LYG. Interferon alpha has been used by the US National Cancer Institute with varying results. In recent years hematopoietic stem cell transplantation has been performed on LYG-patients with relative good success; a 2013 study identifying 10 cases found that 8 patients survived the treatment and were disease free several years later. Two of the disease free patients later died, one from suicide and one from graft versus host disease after a second transplantation 4 years later. The remaining two patients died from sepsis after the transplantation.

Treatment with dose-adjusted EPOCH with rituximab has shown promising initial results in a small series of patients (n=17), with a 100% response rate, and 100% overall survival and progression-free survival at 28 months (median follow-up).

Some patients have no symptoms, spontaneous remission, or a relapsing/remitting course, making it difficult to decide whether therapy is needed. In 2002, authors from Sapienza University of Rome stated on the basis of a comprehensive literature review that "clinical observation without treatment is advisable when possible."

Therapeutic options include surgery, radiation therapy, and chemotherapy. Surgery is used to remove single lymph nodes, central nervous system lesions, or localized cutaneous disease. In 2014, Dalia and colleagues wrote that for patients with extensive or systemic Rosai–Dorfman disease, "a standard of care has not been established" concerning radiotherapy and chemotherapy.

Treatment with chemotherapy has been used with some success, particularly using lomustine, prednisone, doxorubicin, and cyclophosphamide. Because of the rapid progression of this aggressive disease, the prognosis is very poor.

Chemotherapy is the mainstay of treatment for lymphoma in cats. Most of the drugs used in dogs are used in cats, but the most common protocol uses cyclophosphamide, vincristine, and prednisone. Gastrointestinal lymphoma has also commonly been treated with a combination of prednisolone and high dose pulse chlorambucil with success. The white blood cell count must be monitored. Remission and survival times are comparable to dogs. Lower stage lymphoma has a better prognosis. Multicentric lymphoma has a better response to treatment than the gastrointestinal form, but infection with FeLV worsens the prognosis.

About 75% of cats treated with chemotherapy for lymphoma go into remission. Unfortunately, after an initial remission, most cats experience a relapse, after which they have a median survival of 6 months. However, about one-third of cats treated with chemotherapy will survive more than 2 years after diagnosis; a small number of these cats may be cured of their disease. Untreated, most cats with lymphoma die within 4–6 weeks. Most cats tolerate their chemotherapy well, and fewer than 5% have severe side effects. Cats do not lose their fur from chemotherapy, though loss of whiskers is possible. Other side effects include low white blood cell count, vomiting, loss of appetite, diarrhea, or fatigue. These can typically be controlled well, and most cats have a good quality of life during treatment. If a cat relapses after attaining remission, the cat can be treated with different chemotherapy drugs to try for a second remission. The chances of a second remission are much lower than the chances of obtaining a first, and the second remission is often shorter than the first.

Autologous stem-cell transplants are shown to be an effective treatment. However, this should be only considered for certain people due to toxicity concerns. It is possible that the transplant may cause problems like septic shock.

Treatment also involves central nervous system penetrating chemotherapy. Options include intrathecal, intraventricular, and systemic chemotherapy. These must penetrate the blood-brain barrier in order to be effective. Sometimes mixing multiple forms of treatment with chemotherapy seems to be the best route. For example, some significant improvement has been shown as a result of cranial radiation treatment preceding a brief course of intrathecal chemotherapy. Although this is an effective treatment to do, penetrating the blood-brain barrier can cause side effects due to the toxicity in the nervous system. These would include dizziness, confusion, and changes in mental status. Another form could be the use of pharmaceuticals, which have all shown positive results for treatment but should always be consulted with a physician to asses risks.

The current mortality is over 60% after 5 years. However, due to hematopoietic stem cell transplantation being performed only in recent years, this number could potentially be lowered in the future. In patients with CNS involvement, treatment with Interferon alpha at US National Cancer Institute resulted in complete remission in 90% of patients.

As described above, chloromas should always be considered manifestations of systemic disease, rather than isolated local phenomena, and treated as such. In the patient with newly diagnosed leukemia and an associated chloroma, systemic chemotherapy against the leukemia is typically used as the first-line treatment, unless an indication for local treatment of the chloroma (e.g. compromise of the spinal cord) emerges. Chloromas are typically quite sensitive to standard antileukemic chemotherapy. Allogeneic hematopoietic stem cell transplantation should be considered in fit patients with suitable available donor, as long term remissions have been reported.

If the chloroma is persistent after completion of induction chemotherapy, local treatment, such as surgery or radiation therapy, may be considered, although neither has an effect on survival.

Patients presenting with a primary chloroma typically receive systemic chemotherapy, as development of acute leukemia is nearly universal in the short term after detection of the chloroma.

Patients treated for acute leukemia who relapse with an isolated chloroma are typically treated with systemic therapy for relapsed leukemia. However, as with any relapsed leukemia, outcomes are unfortunately poor.

Patients with "preleukemic" conditions, such as myelodysplastic syndromes or myeloproliferative syndromes, who develop a chloroma are often treated as if they have transformed to acute leukemia.

Systemic (intravenous or oral) chemotherapy and intrathecal chemotherapy: Intrathecal therapy is when injection is done directly to the spinal cord into the sub-arachnoid space to avoid the Blood-Brain-Barrier (BBB) and gain direct access to the CSF. Intrathecal Therapy is preferred since intravenous chemotherapy do not penetrate the BBB. The most common chemicals used are liposomal cytarabine (DepoCyte) and intrathecal methotrexate (MTX).

In combination, intrathecal chemotherapy most often comprises methotrexate, cytarabine, thiotepa and steroids. Ventriculoperitoneal shunts may also be applied with chemotherapy to avoid invasive surgery to gain access to the CSF.

An example of treatment:

Intrathecal MTX injection at a dose of 15 mg/day for 5 days every other week with hydrocortisone acetate injecting IT on day one to prevent arachnoiditis, the inflammation of the arachnoid. MTX administration is continued until neurological progression or relapse occurred. Systemic chemotherapy, radiotherapy, and surgery are performed depending on the need of the patient.

Risks of treatments:

Both Chemotherapy and Radiotherapy are harmful to the body and most definitely the brain. Caution must be utilized in treating patients with NM. Another factor that makes treatment difficult is that there is no suitable method to evaluate the disease progression.

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.

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 standard treatment that has been established for NM thus treatments are almost always palliative.

Radiotherapy:

This method is used mostly for focal type of NM due to the nature of damage and success rate associated with the treatment. Radiotherapy targets and tumor and destroys the collective tissues of cancerous cells.

Large B-cell lymphoma arising in HHV8-associated multicentric Castleman's disease is a type of large B-cell lymphoma, recognized in the WHO 2008 classification. It is sometimes called the plasmablastic form of multicentric Castleman disease. It has sometimes been confused with plasmablastic lymphoma in the literature, although that is a dissimilar specific entity. It has variable CD20 expression and unmutated immunoglobulin variable region genes.

Orbital lymphoma is a common type of non-Hodgkin lymphoma that occurs near or on the eye. Common symptoms include decreased vision and uveitis. Orbital lymphoma can be diagnosed via a biopsy of the eye and is usually treated with radiotherapy or with combination with chemotherapy.

Castleman disease (CD) is a lymphoproliferative disorder of unknown cause. CD is associated with an increased risk of B-cell lymphoma.

Human herpesvirus 8 (HHV-8), also known as Kaposi sarcoma-associated herpesvirus (KSHV) has been found in some cases of multicentric Castleman disease (MCD). The HHV8 can give rise to an increased number of plasmablast cells within the mantle zone of B-cell follicles. These plasmablasts express IgM-immunoglobulin light chains, most often of lambda subtype. These plasmablasts can give rise to a spectrum of abnormalities including progression to microlymphoma (microscopic clusters of plasmablast cells) or clinical lymphoma.

This type of lymphoma is predominantly seen in acquired immunodeficiencies, including acquired immunodeficiency syndrome (AIDS) but it can also occur in immunosuppression such as with organ transplantation or the elderly. The plasmablasts do not show rearranged immunoglobulin genes, and typically lack EBV infection.

The disease predominantly affects lymph nodes and the spleen, a pattern dissimilar to plasmablastic lymphoma of the oral cavity of AIDS which is not associated with HHV-8 infection. Despite traditional chemotherapy with CHOP (cyclophosphamide, doxorubicin, prednisone, vincristine), and the possible addition of antiviral therapy and inhibition of specific cellular targets including the use of rituximab, the prognosis in this lymphoma has been poor.

This lymphoma subtype has sometimes been confused with plasmablastic lymphoma in the literature, although that is a dissimilar specific entity. Similarly, this subtype is considered distinct from other lymphomas which have a plasmablastic immunophenotype such as primary effusion lymphoma, ALK+ large B-cell lymphoma, and extracavitary HHV–8-positive lymphoma.

HHV8 is also associated with Kaposi's sarcoma and with another subtype of lymphoma, primary effusion lymphoma, previously called body cavity-based lymphoma.