The most common chemotherapy used for non-Hodgkin lymphoma is R-CHOP.

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.

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.

Nevertheless, the Working Formulation and the NHL category continue to be used by many. To this day, lymphoma statistics are compiled as Hodgkin's versus non-Hodgkin lymphomas by major cancer agencies, including the US National Cancer Institute in its SEER program, the Canadian Cancer Society and the IARC.

Lymphoma Association (UK)

Nodular Lymphocyte Predominant Hodgkin's Lymphoma (NLPHL) Facebook Group

Studies indicate that radiation therapy (radio therapy) may reduce the risk of progression in adults. In one study, stage I-II patients treated with radiation therapy showed 10-year cause-specific survival of 98%, and the rate of developing radiotherapy-related second malignancies was not increased by the treatment (1% after 10 years). A study published in 2013 on large group of patients with early-stage NLPHL indicated support for using limited-field radiation therapy as the sole treatment of early-stage disease. In a study of 1,162 NLPHL patients from the Surveillance, Epidemiology and End Results (SEER) cancer registry program, radiation therapy improved overall survival and disease specific survival.

Of all cancers involving the same class of blood cell, 8% of cases are MALT lymphomas.

"MALT lymphoma" is exquisitely immunotherapy sensitive. Chemotherapy is reserved for those uncommon patients with disseminated disease at presentation or lack of response to local treatment. Rituximab, the anti-CD20 chimeric antibody, is a key component of therapy. Responses vary from 55% to 77% with monotherapy and 100% in combination with chemotherapy. Oral alkylating agents such as cyclophosphamide or chlorambucil have been administered for a median duration of 12 months with high rates of disease control (CR up to 75%) but appear not to be active in t(11;18) disease. The purine nucleoside analogs fludarabine and cladribine also demonstrate activity, the latter conferring a CR rate of 84% (100% in those with gastric primaries) in a small study. A pivotal study of rituximab plus chlorambucil compared with chlorambucil alone (IELSG-19 study, n = 227) demonstrated a significantly higher CR rate (78% vs. 65%; p = 0.017) and 5-year EFS (68% vs. 50%; p = 0.024) over chlorambucil alone. However, 5-year OS was not improved (88% in both arms). First-line treatment of choice is generally rituximab in combination with single alkylating agents or fludarabine, or a combination of all three drugs. The final results of this study, including the later addition of a rituximab-alone arm, are pending.

Two other genetic alterations are known:

- t(1;14)(p22;q32), which deregulates BCL10, at the locus 1p22.

- t(14;18)(q32;q21), which deregulates MALT1, at the locus 18q21.

These seem to turn on the same pathway as API2-MLT (i.e., that of NF-κB). They both act upon IGH, which is at the locus 14q32.

Breast implant-associated ALCL is a recently recognized lymphoma and definitive management and therapy is under evaluation. However, it appears that removal of the implant, and resection of the capsule around the implant as well as evaluation by medical and surgical oncologists are cornerstones. Still under evaluation is the extent of capsulectomy: partial versus complete capsulectomy; similarly it is not defined the significance of replacement of the implant in the affected breast, or the removal of contralateral implant. Similarly, the value of radiation therapy and chemotherapy are under evaluation.

Currently, there is a drug, LDK378, undergoing Phase III clinical trials at Vanderbilt University that targets ALK positive small cell lung cancer, and has showed clinical promise in its previous clinical trials. Because approximately 70% of ALCL neoplasms are also ALK positive, there is hope that similar highly selective and potent ALK inhibitors may be used in the future to treat ALK positive cases of ALCL.

The lymphoma is more common in the young and in males.

A 2008 study found an increased risk of ALCL of the breast in women with silicone breast implants (protheses), although the overall risk remained exceedingly low due to the rare occurrence of the tumor.

A second regimen under evaluation is R-EPOCH (rituximab with etoposide-prednisone-vincristine-doxorubicin-cyclophosphamide), which demonstrated a 5-year progression-free survival (PFS) of 79% in a phase II trial. A phase III trial, CALGB 50303, is now comparing R-EPOCH with R-CHOP in patients with newly diagnosed DLBCL.

One area of active research is on separating patients into groups based on their prognosis and how likely they are to benefit from different drugs. Methods like gene expression profiling and next-generation sequencing may result in more effective and more personalized treatment.

Treatment with conventional immunochemotherapy is usually indicated; in younger patients, allogeneic bone marrow transplantation may be curative.

The germinal center subtype has the best prognosis,with 66.6% of treated patients surviving more than five years. The IPI score is used in prognosis in clinical practice. Lenalidomide has been recently shown to improve outcomes in the non-germinal center subtype. Ratios of immune effectors such as CD4 and CD8 to immune checkpoints such as PD-L1 and M2 macrophages are independent of and additive to the cell of origin and IPI in DLBCL, and are applicable to paraffin-embedded biopsy specimens. These findings might have potential implications for selection of patients for checkpoint blockade and/or lenalidomide within clinical trials.

For children with diffuse large B-cell lymphomas, most studies have found 5-year survival rates ranging from about 70% to more than 90%.

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.

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.

A new model of pathogenesis (lymph node changes are not “benign tumors” that secrete cytokines, but reactive changes due to excessive cytokine release from an as-yet unknown cause) and a new classification system for MCD (based on HHV-8 status) have ensued. CDCN has launched a platform for online discussion among physicians and researchers, developed a global research agenda, and launched a global patient community in partnership with EURODIS and NORD. Current strategic priorities include: 1) establishing a global patient registry, 2) empowering the global patient community to support one another and join the fight against CD, and 3) distributing high-impact research grants.

In the United States, about 500 patients are diagnosed with Richter's transformation each year.

The B-cell lymphomas are types of lymphoma affecting B cells. Lymphomas are "blood cancers" in the lymph nodes. They develop more frequently in older adults and in immunocompromised individuals.

B-cell lymphomas include both Hodgkin's lymphomas and most non-Hodgkin lymphomas. They are typically divided into low and high grade, typically corresponding to indolent (slow-growing) lymphomas and aggressive lymphomas, respectively. As a generalisation, indolent lymphomas respond to treatment and are kept under control (in remission) with long-term survival of many years, but are not cured. Aggressive lymphomas usually require intensive treatments, with some having a good prospect for a permanent cure.

Prognosis and treatment depends on the specific type of lymphoma as well as the stage and grade. Treatment includes radiation and chemotherapy. Early-stage indolent B-cell lymphomas can often be treated with radiation alone, with long-term non-recurrence. Early-stage aggressive disease is treated with chemotherapy and often radiation, with a 70-90% cure rate. Late-stage indolent lymphomas are sometimes left untreated and monitored until they progress. Late-stage aggressive disease is treated with chemotherapy, with cure rates of over 70%.

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

Most patients with T-cell prolymphocytic leukemia require immediate treatment.

T-cell prolymphocytic leukemia is difficult to treat, and it does not respond to most available chemotherapeutic drugs. Many different treatments have been attempted, with limited success in certain patients: purine analogues (pentostatin, fludarabine, cladribine), chlorambucil, and various forms of combination chemotherapy regimens, including cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP), etoposide, bleomycin (VAPEC-B).

Alemtuzumab (Campath), an anti-CD52 monoclonal antibody that attacks white blood cells, has been used in treatment with greater success than previous options. In one study of previously treated people with T-PLL, people who had a complete response to alemtuzumab survived a median of 16 months after treatment.

Some patients who successfully respond to treatment also undergo stem cell transplantation to consolidate the response.

Treatment can occasionally consist of "watchful waiting" (e.g. in CLL) or symptomatic treatment (e.g. blood transfusions in MDS). The more aggressive forms of disease require treatment with chemotherapy, radiotherapy, immunotherapy and—in some cases—a bone marrow transplant. The use of rituximab has been established for the treatment of B-cell–derived hematologic malignancies, including follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL).

T-PLL is an extremely rare aggressive disease, and patients are not expected to live normal lifespans. Before the recent introduction of better treatments, such as alemtuzumab, the median survival time was 7.5 months after diagnosis. More recently, some patients have survived five years and more, although the median survival is still low.

Additionally, some researchers separate out lymphomas that appear to result from other immune system disorders, such as AIDS-related lymphoma.

Classic Hodgkin's lymphoma and nodular lymphocyte predominant Hodgkin's lymphoma are now considered forms of B-cell lymphoma.