Diffuse Large B-Cell Lymphoma (DLBCL)

Overview
Diffuse large B-cell lymphoma (DLBCL) is the most common form of NHL, accounting for more than 30 percent of newly diagnosed cases. DLBCL is an aggressive (fast-growing) lymphoma. It can arise in lymph nodes or outside of the lymphatic system, in the gastrointestinal tract, testes, thyroid, skin, breast, bone, or brain. Although DLBCL is the most common form of NHL, there are several subtypes that may affect the prognosis (how well patients will do with standard treatment) and treatment. For example, DLBCL that only affects the brain is called “primary central nervous system lymphoma” and is treated differently than DLBCL that affects areas outside of the brain. Another example is “primary mediastinal B-cell lymphoma” which often occurs in younger patients and grows rapidly in the chest (mediastinum) Often, the first sign of DLBCL is a painless rapid swelling in the neck, armpit, or groin, which is caused by enlarged lymph nodes. For some patients, the swelling may be painful. Other symptoms include night sweats, unexplained fevers, and weight loss. Most patients with DLBCL are adults, although this lymphoma is sometimes seen in children.

Diagnosis and staging is done by biopsy from the affected lymph node or affected organ/ site, PET-CT scan of whole body and a bone marrow test

Treatment Options for 1st line

• Immediate treatment is necessary.
• Most important aspect of therapy is anti CD20 antibody, the Rituximab, which is a kind of immunotherapy or targeted therapy and attacks the CD20 antigen on the cancer cells.
• Rituximab should be combined with the chemotherapy for more efficient cancer cell kill. Commonly used chemotherapeutic agents are known as CHOP regime for up to 6 cycles.
• Radiation may be advised for special situations like having a large mass of lymphoma at the time of diagnosis

The first line treatment can cure up to 90% of patients in early stage of disease and upto 40% of patients in advanced stages of disease. Some patients may not respond to chemotherapy at all while few patients respond initially but later on relapse. The patient who relapse or who does not respond to initial treatment, require more intensive treatment.

Treatment options for relapse or refractory patients:

• Salvage chemotherapy (Rituximab with intensive chemotherapy like ICE or DHAP regime) for 2-3 cycles followed by autologous stem cell transplantation
• Salvage chemotherapy followed by allogeneic stem cell transplantation. Allogeneic stem cell transplantation should be considered for refractory disease or for very early relapsing disease.
• Investigational therapies or clinical trials: Various investigational drugs are Bortezomib (Velcade), Brentuximab vedotin (Adcetris), Everolimus (Afinitor), Lenalidomide (Revlimid), Panobinostat, Vorinostat (Zolinza)

Follicular Lymphoma

Overview
Follicular lymphoma (FL), a B-cell lymphoma, is the most common indolent (slow-growing) form of NHL, accounting for approximately 20 percent to 30 percent of all NHLs. Common signs of disease include enlargement of the lymph nodes in the neck, underarm, stomach, or groin. More often, people with FL have no obvious symptoms of the disease at diagnosis. Few patients can have symptoms like fatigue, shortness of breath, night sweats, and weight loss and pain in affected organ/ site. Approximately 30-40 % of patients with FL will eventually transform to a more aggressive form of lymphoma like Diffuse Large B Cell Lymphoma and may require intensive chemotherapy followed by autologous stem cell transplantation.

Diagnosis depends on biopsy from affected node or organ, PET-CT scan of whole body or a CT scan of whole body and a bone marrow test
Treatment Options

• Watchful waiting/ no treatment: for patients who are asymptomatic or not having any difficulty because the disease may be kept under observation without any active treatment
• Radiation therapy is good enough for a patient who is having an early stage disease/ localized disease (stage-1) and having some symptoms because of it. FL is generally very responsive to radiation. Radiation can provide a cure in some patients with limited disease.
• Multiagent chemotherapy + immunotherapy should be reserved for patients who are having advanced stages of disease and having symptoms/ difficulties related to it.
• Common combination regimens include: Rituximab with CVP regime (R-CVP), R-CHOP, R-Bendamustine.
• Maintenance therapy: Rituximab is also recommended as maintenance therapy for 2 years.
• After treatment, many patients will have a remission that lasts for years; however, the disease does return in most patients. For these patients, following additional therapies are often successful in providing another remission.
• Radioimmunotherapy (RIT) alone or in combination with chemotherapy: Two radioimmunotherapy drugs are commercially available: Iodine 131 tositumomab (Bexxar) and Y90 ibritumomab tiuxetan (Zevalin). Both produce similar clinical results with durable remissions for appropriate patients.
• High-dose chemotherapy and an autologous stem cell transplant or an allogeneic stem cell transplant may provide a prolonged disease-free interval.
• Investigational therapy: Bortezomib (Velcade), Everolimus (Afinitor), Idelalisib (GS-1101, formerly CAL-101), Ibrutinib (PCI-32765), Lenalidomide (Revlimid), Ofatumumab (Arzerra), Panobinostat

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)

Overview
Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are B-cell lymphomas. CLL and SLL are essentially the same disease, the only difference being where the cancer primarily occurs. When most of the cancer cells are located in the bloodstream and the bone marrow, the disease is referred to as CLL, although the lymph nodes and spleen are often involved. When the cancer cells are located mostly in the lymph nodes, the disease is called SLL. CLL/SLL tends to be an indolent (slow-growing) cancer; however, over time, it can progress to a more aggressive type of lymphoma. Common signs of disease include a swelling of the liver and spleen and enlargement of the lymph nodes in the neck, underarm, stomach, or groin. Other symptoms of CLL/SLL can include fatigue, shortness of breath, anemia, bruising, night sweats, weight loss, and frequent infections. Sometimes patients with CLL may have autoimmune destruction of their own red blood cells or platelets. Often, people with CLL/SLL have no obvious symptoms of the disease at diagnosis. Approximately one-third of all CLL/SLL patients will live for years without symptoms. Diagnosis of CLL/ SLL depends on flow cytometry on peripheral blood or biopsy from affected node. Stages of CLL/ SLL are somewhat different than other lymphomas. CLL/ SLL can be divided into 5 stages depending on presence/ absence of lymph node enlargement, liver/ spleen enlargement or low Hb/ low platelets.

Treatment Options

• Watchful waiting (no treatment given) for stage 0, 1 and 2 patients with no symptoms related to disease. The patient is closely monitored to look for any sign of progression and need of treatment.
• hemo-immunotherapy: Rituximab which is anti CD20 monoclonal antibody, which can specifically attack lymphoma/ CLL cells along with chemotherapy like fludarabine/ cyclophosphamide (FCR regime) or with bendamustine (BR regime)
• Allogeneic stem cell transplantation for patients with relapsed/ refractory disease or with some other certain high risk features.
• Occasionally, a patient with CLL may have autoimmune phenomena leading to destruction of their own red cells and platelets leading to AIHA or ITP. These patients require treatment with steroids or IVIg to combat these autoimmune cytopenias.
• Chlorambucil, Cyclophosphamide monotherapy
• Investigational agents: Lenalidomide, Ibrutinib (A BTK kinase inhibitor), Idelalisib, Ofatumumab (another monoclonal antibody for CD20)

Mantle Cell Lymphoma

Overview
Mantle cell lymphoma (MCL) is a rare, B-cell NHL that most often affects men over the age of 60. The disease may be aggressive (fast growing) but it can also behave in a more indolent (slow growing) fashion in some patients. MCL comprises about five percent of all NHLs. The disease is called “mantle cell lymphoma” because the tumor cells originally come from the “mantle zone” of the lymph node. MCL is usually diagnosed as a advanced stage disease that has typically spread to the gastrointestinal tract and bone marrow. A diagnosis of MCL requires a biopsy from affected node or tissue. A blood test may also be necessary to measure the white blood cell count and certain proteins, which help to diagnose MCL. Other tests, such as a bone marrow biopsy and a computed axial tomography (CAT) scan may be used to confirm a diagnosis and to determine the stage. Endoscopy of the intestines is usually done particularly in mantle cell lymphoma because of high rates of gastro-intestinal involvement. Overproduction of a protein called Cyclin D1 is found in more than 90 percent of patients with MCL. Identification of excess Cyclin D1 from a biopsy is considered a very sensitive tool for diagnosing MCL.
Treatment Options

• Watchful waiting: For the subset of patients who do not yet have symptoms and who have a relatively small amount of slow growing disease. This is a rare scenario in mantle cell lymphoma.
• MCL is usually diagnosed once it has spread throughout the body, and the majority of these patients will require treatment.
• Combination chemotherapy (CHOP or DHAP regime or bendamustine), typically in combination with the monoclonal antibody rituximab (anti CD20), as first-line treatment, followed by autologous stem cell transplant should be recommended for majority of the patients.
• HyperCVAD (cyclophosphamide, vincristine, doxorubicin, dexamethasone alternating with methotrexate and cytarabine) plus rituximab are recommended as aggressive induction therapy and are associated with durable remissions in newly diagnosed patients.
• For older patients, who are not fit for Autologous stem cell transplantation, chemotherapy followed by a prolonged course of rituximab alone, known as maintenance, is often recommended.
• Allogeneic stem cell transplantation should be considered for refractory or relapsed disease
• Bortezomib (Velcade) in combination with conventional chemotherapy.
• Lenalidomide (Revlimid) for the treatment of patients with mantle cell lymphoma (MCL) whose disease has relapsed or progressed after two prior therapies.
• Investigational agents: Idelalisib (GS-1101, formerly CAL-101), vorinostat (Zolinza), ofatumumab (Arzerra), everolimus (Afinitor), panobinostat, and temsirolimus (Torisel).

Marginal Zone Lymphoma

Overview
Marginal zone lymphomas are a group of indolent (slow-growing) NHL B-cell lymphomas, which account for approximately 12 percent of all B-cell lymphomas. The median age for diagnosis is 65 years.

There are three types of marginal zone lymphoma:
Extranodal marginal zone lymphoma or mucosa-associated lymphoid tissue (MALT)
is the most common form of marginal zone lymphoma. It occurs outside the lymph nodes, in places such as the stomach, small intestine, salivary gland, thyroid, eyes, and lungs. MALT lymphoma is divided into two categories: gastric, which develops in the stomach, and non-gastric, which develops outside of the stomach. This form of lymphoma makes up about nine percent of all B-cell lymphomas.

In many cases of MALT lymphoma, there is a previous medical history of inflammation or autoimmune disorders. For example, Helicobacter pylori (H. pylori), a microbial pathogen linked to chronic gastritis, has been associated with a significant portion of patients with gastric MALT lymphoma.

Nodal marginal zone lymphoma
(sometimes called monocytoid B-cell lymphoma)occurs within the lymph nodes and accounts for about two percent of all B-cell lymphomas.
Splenic marginal zone lymphoma
occurs most often in the spleen and blood. It has been associated with Hepatitis C. This form of lymphoma makes up about one percent of all B-cell lymphomas.
Treatment Options
The type of treatment selected for a marginal zone lymphoma patient depends on the stage of disease, the age of the patient, the patient’s overall health, any signs or symptoms related to the lymphoma, and the location of the disease.

Treatment Options for Gastric MALT

• Initial treatment is antibiotic therapy, which is typically given for two weeks. Approximately 70 percent to 90 percent of patients respond to antibiotic therapy, and approximately half of the patients require no further treatment.
• If the lymphoma relapses after antibiotic therapy, there are many additional treatment options available, including: Rituximab, chemotherapy with CVP or CHOP regime, Bendamustine, Bortezomib, Radiation (low dose), Surgical excision

Treatment Options for Non-gastric MALT

• Non-gastric MALT can appear in a variety of areas throughout the body. Therefore, treatment is usually based on the exact location and extent of spread.
• Surgery for certain sites (lung, breast) or radiation therapy with or without chemotherapy.
• More advanced disease usually includes immunoradiotherapy with chemotherapy.
• Among the common first-line treatments are bendamustine plus rituximab and CHOP regime with rituximab.
• Antibiotic therapy such as doxycycline for marginal zone lymphoma that affects the area around the eye (“ocular adnexal marginal zone lymphoma”)

Treatment Options for Nodal Marginal Zone Lymphoma

• watch and wait” or “watchful waiting until symptoms appear
• When treatment is necessary, options include radiation therapy, chemotherapy (CVP/ CHOP/ Bendamustine) in combination with rituximab.

Treatment Options for Splenic Marginal Zone Lymphoma:

• Splenectomy is usually curative in many patients
• Rituximab as sole first line therapy is also curative in many patients
• Splenectomy followed by rituximab is now a days preferred due to very high response rates and low rates of relapses.
• Chemotherapy (CVP/ CHOP/ Bendamustine) in combination of rituximab may be used in first line or as salvage therapy

Peripheral T-Cell Lymphoma (PTCL)

Overview T-cell lymphomas account for approximately 15 percent of all NHLs. A similar lymphocyte called a natural killer (NK) cell shares many features with T-cells. When NK cells become cancerous, the cancer is called NK or NK/T-cell lymphoma and is generally grouped with other T-cell lymphomas. There are many different forms of T-cell lymphomas, some of which are extremely rare. T-cell lymphomas can be aggressive (fast-growing) more commonly or indolent (slow-growing). Common types of T cell lymphomas are described below.
Anaplastic Large Cell Lymphoma Anaplastic large cell lymphoma (ALCL) is a T-cell lymphoma. ALCL comprises about three percent of all NHLs and 10 percent to 30 percent of all NHLs in children. Initial symptoms of ALCL can include painless swelling of lymph nodes, rapid weight loss, and tiredness. ALCL can initially appear either in the skin, in lymph nodes, or in organs throughout the body. ALCL that appears in the skin is called primary cutaneous ALCL. The characteristic features of primary cutaneous ALCL include the appearance of solitary or multiple raised red skin lesions that do not go away, have a tendency to ulcerate, and may itch. These ALCL lesions are tumors, and they can appear on any part of the body, often grow very slowly, and may be present for a long time before being diagnosed. Approximately 10 percent of the time, primary cutaneous ALCL extends beyond the skin to lymph nodes or organs. If this occurs, it is usually treated like the systemic forms of ALCL. Patients with systemic ALCL are divided into two groups, depending on whether or not their cells have an abnormal form of a protein on their surface called “anaplastic lymphoma kinase” (ALK). Although both lymphomas are treated as aggressive (fast-growing) lymphomas, the disease course is different in patients who have ALK-positive (have the abnormal protein) or ALK-negative (do not have the abnormal protein) ALCL. ALK-positive ALCL responds well to standard chemotherapy treatments, putting most patients in long-term remission. Most people with ALK-negative ALCL initially respond to treatment, but many people will relapse within five years. Because of this, ALK-negative patients are sometimes treated more aggressively, often with a stem cell transplant after remission.
Treatment Options

• Local radiation therapy for a localized/ solitary skin lesion
• Chemotherapy for multiple skin lesions
• Chemotherapy for systemic ALCL-ALK positive
• Chemotherapy followed by Autologous stem cell transplantation for systemic ALCL-ALK negative
• Chemotherapy followed by Autologous stem cell transplantation for relapsed ALCL
• Chemotherapy followed by Allogeneic stem cell transplantation for refractory ALCL
• Newer drugs/ clinical trials/ palliation for refractory disease

Although newly diagnosed systemic ALCL patients respond well to common first-line chemotherapy, long-term disease outcome varies depending on the subtype. Patients with ALK-positive disease usually respond very well to chemotherapy, with a long-term disease-free survival rate of over 70 percent. In contrast, patients with ALK-negative disease have less than a 30 percent long-term disease-free survival rate with similar treatments and require stem cell transplantation to improve the outcome.
Angioimmunoblastic T-Cell Lymphoma
Angioimmunoblastic T-cell lymphoma (AITL) is a rare, aggressive (fast-growing) form of T-cell lymphoma. Symptoms of AITL include high fever, night sweats, skin rash, and autoimmune disorders, as a result of which, the body’s immune system does not recognize, and consequently destroys, its own cells and tissues, such as red blood cells (in the case of AIHA) or platelets (in the case of ITP). The majority of patients with AITL are diagnosed with advanced-stage disease. These patients respond well to chemotherapy initially but relapse rate is very high and overall, after 5 years, the survival ranges from 10-30%. To prevent the relapses and to improve the results, autologous stem cell transplantation should be done in all patients who respond to chemotherapy. While for some patients, who does not get a good response to chemotherapy or who relapses, the allogeneic stem cell transplantation should be considered.

Treatment Options

• Multiagent chemotherapy followed by autologous stem cell transplantation is the first line treatment in all cases.
• Allogeneic stem cell transplantation in refractory or relapsed cases
• Investigational therapy/ clinical trials or palliation for relapsed/ refractory cases after stem cell transplantation fails

Peripheral T-cell Lymphoma Not Otherwise Specified (PTCL NOS)
refers to a group of diseases that do not fit into any of the other subtypes of PTCL. PTCL-NOS is the most common PTCL subtype, making up about one quarter of all PTCLs. It is also the most common of all the T-cell lymphomas. The term PTCL can be confusing as it can refer to the entire spectrum of mature T-cell lymphomas, but it can also refer to the specific PTCL-NOS subtype. Although most patients with PTCL-NOS are diagnosed with their disease confined to the lymph nodes, sites outside the lymph nodes, such as the liver, bone marrow, gastrointestinal tract, and skin, may also be involved. This group of PTCLs is aggressive and requires combination chemotherapy upon diagnosis. Diagnosis depends on biopsy from affected node or organ and a whole body PET-CT and a bone marrow test.

Treatment options:

• Patients usually respond well to chemotherapy but the problem is that many of the patients relapses sooner or later after completion of chemotherapy.
• Multiagent chemotherapy commonly recommended is CHOP regime with addition of Etoposide (CHOEP) for 6 cycles.
• To prevent relapses and to improve the chances of long term disease free survival, high dose chemotherapy coupled with Autologous stem cell transplantation should be done in first go itself.
• Patients with relapsed or refractory disease should be treated with salvage chemotherapy followed by autologous stem cell transplantation or allogeneic stem cell transplantation
• Investigational therapy or palliation: for patients with relapsed/ refractory disease even after stem cell transplantation

Hodgkin Lymphoma (HL)

HL, also known as Hodgkin disease, is not as common as NHL. HL can occur in both children and adults. HL is characterized by the presence of very large cells called Reed-Sternberg (RS) cells, although other abnormal cell types may be present. HL usually starts in the lymph nodes; however, it often spreads from one lymph node to another and can also spread to other organs.
Common signs and symptoms of HL include swelling of the lymph nodes (which is often but not always painless), fever, night sweats, unexplained weight loss, and lack of energy. While most people who have these complaints will not have HL, anyone with persistent symptoms should be seen by a physician to make sure that lymphoma is not present.

Common Types of HL
HL has been divided into two main classifications: classical HL (CHL), which accounts for 90 to 95 percent of cases, and nodular lymphocyte predominant HL. Classical Hodgkin Lymphoma can further subdivided into 4 subclasses depending upon its morphology (microscopic) features and prognosis: Nodular Sclerosis, Mixed Cellularity, Lymphocyte-Depletion, Lymphocyte-Rich. Lymphocyte Predominant Hodgkin Lymphoma HL accounts for 5 to 10 percent of all HL cases. This subtype is usually diagnosed at an early stage and is not very aggressive. Diagnosis and staging depends on biopsy from affected node or organ and a whole body PET-CT scan. A bone marrow aspiration and biopsy is also required.

Treatment Options
Over 80 percent of patients with HL survive for five years, and many are cured. Most patients treated for HL will receive some form of chemotherapy, and sometimes radiation therapy, as their first treatment. The recommended treatment for HL are

• ABVD regime (adriamycin, bleomycin, vinblastine, and dacarbazine)
• MOPP (mechlorethamine, vincristine, prednisone, and procarbazine)
• BEACOPP and Escalated BEACOPP regimes, which includes bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone
• Stem cell transplantation is typically used in the relapsed or refractory (disease does not respond to treatment) setting.
• Brentuximab vedotin (Adcetris) is a monoclonal antibody for CD30. It is recommended for the treatment of relapsed/ refractory HL after stem cell transplantation or after failure of two previous chemotherapy regimens

Other uncommon/ rare types of non Hodgkin lymphomas
Adult T-Cell Leukemia/Lymphoma
Adult T-cell leukemia/lymphoma (ATLL) is a rare and often aggressive (fast-growing) T-cell lymphoma that can be found in the blood (leukemia), lymph nodes (lymphoma), skin, or multiple areas of the body. ATLL has been linked to infection by the human T-cell lymphotropic virus type 1 (HTLV-1) which is common in parts of Japan, the Caribbean, and some areas of South and Central America and West Africa. Patients with ATLL are severely immune-compromized and at very high risk of serious infections.
Subtypes of ATLL
There are four subtypes of ATLL: 1.) acute, 2.) lymphomatous, 3.) chronic, and 4.) smoldering. Acute and lymphomatous are fast-growing forms of ATLL, whereas chronic and smoldering are less aggressive:
Treatment Options
a.Observation without treatment, called “watch and wait” or “watchful waiting,” may be appropriate for some people who have one of the slower-growing subtypes of ATLL with mild or no symptoms, although follow-up monitoring is required.
b.Antiretroviral therapy for some indolent and aggressive forms of ATLL

• Chemotherapy along with antiretroviral therapy for aggressive forms of ATLL
• In some patients, bone marrow transplantation may be appropriate following remission.

Cutaneous B-Cell Lymphoma (CBCL)
When lymphomas originate in the skin (5% of all NHLs), and there is no evidence of disease outside of the skin, they are called primary cutaneous lymphomas. Primary cutaneous B-cell lymphomas (CBCLs) occur when the lymphoma cells originate in B-cells. These are usually indolent (slow-growing). They may appear on the skin as a reddish rash, lump, or nodule. The disease tends to recur on the skin, but will rarely develop into a systemic (throughout the body) lymphoma. Prognosis is usually very good, although it can relapse in skin. Two common types of Cutaneous B-Cell Lymphoma are Primary Cutaneous Follicle Center Lymphoma and Primary Cutaneous Marginal Zone B-cell Lymphoma. Other less common types of Cutaneous B cell lymphoma are Primary Cutaneous Diffuse Large B-cell Lymphoma-Leg-type, intravascular large B-cell lymphoma, T-cell rich large B-cell lymphoma, plasmablastic lymphoma, and anaplastic B-cell lymphoma. These are more aggressive (fast-growing), almost always systemic lymphomas with cutaneous symptoms.

Treatment Options

• Observation (no treatment)
• Radiation or surgery to remove the lesion
• Rituximab either alone or in combination with chemotherapy
• Treatments Under Investigation: panobinostat, lenalidomide

Cutaneous T-Cell Lymphoma (CTCL)

The T-cell lymphomas that involve the skin are called cutaneous T cell lymphomas. Cutaneous T-Cell Lymphoma (CTCL) also can involve the blood, the lymph nodes and other internal organs in its advanced stages. Symptoms can include dry skin, itching (which can be severe), a red rash, nodular lesions over skin and enlarged lymph nodes. The disease affects men more often than women and usually occurs in men in their 50s and 60s.

Mycosis fungoides is the most common type of CTCL. The disease looks different in each patient, with skin symptoms that can appear as patches, plaques (thicker, raised, usually itchy lesions), or tumors (raised bumps, which may or may not ulcerate). Patches or plaques are often mistaken for eczema, psoriasis, or dermatitis.

A medical history, physical exam, and skin biopsy are essential for diagnosis. In addition, a series of imaging tests may be needed to determine if the cancer has spread to the lymph nodes or other organs (although that uncommonly occurs). These tests may include a CT scan, PET scan or MRI. A bone marrow biopsy may also be done. Mycosis fungoides can be difficult to diagnose in its early stages because the symptoms and skin biopsy findings are similar to those of other skin conditions.

Sezary syndrome is an advanced, variant form of mycosis fungoides, which is characterized by the presence of lymphoma cells in the blood along with extensive skin involvement.

Treatment Options
Treatment selection for CTCL depends on the extent of skin involvement, the type of skin lesion, and whether the cancer has spread to the lymph nodes or other internal organs. The treatment is either directed at the skin or the entire body (systemic). Many patients live normal lives while they treat their disease, and some are able to remain in remission for long periods of time.

Skin-directed therapies include topical corticosteroids, retinoids, or imiquimod (which activates immune cells), topical chemotherapy, local radiation, methotrexate, extracorporeal photo-pheresis, ultraviolet light (phototherapy) with psoralen, mechlorethamine gel.

Systemic therapies for more advanced disease are usually deferred until patients have not responded well to topical therapies. More advanced disease is commonly treated with radiation, chemotherapy, and/or therapies such as: Bortezomib (Velcade), Denileukin diftitox (Ontak), Pralatrexate (Folotyn), Romidepsin (Istodax), Vorinostat (Zolinza). Combination chemotherapy regimens are generally reserved for when patients have not responded well to several single-agent therapies. Options for refractory disease (disease that no longer responds to the initial therapy) include alemtuzumab (Campath), liposomal doxorubicin, and gemcitabine.

Treatments Under Investigation: Everolimus, lenalidomide (Revlimid), brentuximab vedotin (Adcetris), panobinostat, forodesine.

Blastic NK-cell Lymphoma
is a very rare cancer, affecting only a few people (usually adults) each year. This lymphoma was previously thought to arise from a T- or NK-cell. However, newer studies indicate that it may arise from another type of white blood cell called a plasma, or dendritic, cell. This lymphoma is fast-growing and can be difficult to treat. It can arise anywhere in the body. Dark red or purple skin lesions are a common feature.
Enteropathy-type T-cell lymphoma
is an extremely rare subtype of T-cell lymphoma that appears in the intestines and is strongly associated with celiac disease. Treatment is with chemotherapy and stem cell transplantatyion.
Hematosplenic gamma-delta T-cell Lymphoma
is an extremely rare and aggressive disease that starts in the liver or spleen. This lymphoma may occur in those with inflammatory bowel disease who are immunosuppressed (that is, their immune system was suppressed as part of treatment). Treatment is with intensive chemotherapy and stem cell transplantation.
Nasal NK/T-cell Lymphomas
are relatively rare in the United States, but common in Asia and parts of Latin America. It is a fast-growing lymphoma that typically originates in the lining of the nose or upper airway. It is treated with radiation and various combinations of chemotherapy in early stages of disease and intensive chemotherapy followed by stem cell transplantation for advanced stages of disease0.
Treatment-related lymphomas
sometimes appear after solid organ or bone marrow transplantation. The immune system suppression that is required to transplant patients can put them at risk for developing these lymphomas. Treatment-related lymphomas may require therapy that differs from the standard treatments normally used to treat these conditions.
Lymphoma in Children and Adolescents Lymphoma is the third most common cancer in children. Half of these children have Hodgkin lymphoma (HL) and are often treated with simple combinations of chemotherapy and radiation. The other 50% have non-Hodgkin lymphoma (NHL), which usually requires more complicated regimens of chemotherapy. The NHLs in children are more commonly high grade/aggressive ones and require more intensive chemotherapy.
Presentation/ symptoms

• Swelling of the lymph nodes, which may or may not be painless
• Chills, Fever
• Night sweats
• Unexplained weight loss
• Lack of energy
• Itchiness

While most children with these complaints do not have lymphoma, anyone with persistent symptoms should see their doctor to be certain lymphoma is not present. Although the causes of lymphoma remain unknown, the following may increase the risk of childhood or adolescent lymphomas:

• Family history (though no hereditary pattern has been firmly established)
• Autoimmune disease
• Receipt of an organ transplant
• Exposure to chemicals such as pesticides, fertilizers or solvents
• Infection with viruses such as Epstein-Barr, human T-lymphotropic virus type 1, HIV, hepatitis C, or certain bacteria such as Helicobacter pylori

Diagnosis:
An excision biopsy or trucut from lymph node or involved tissue is mandatory. Other tests for supporting the diagnosis and staging include CT scans or PET-CT scan, bone marrow biopsy.
Treatment:
The NHLs in children are more commonly high grade/aggressive ones and require more intensive chemotherapy.

• Rituximab should be used depending upon CD20 expression on lymphoma cells
• Chemotherapies: usually high intensity combination chemotherapy blocks. Several protocols used are LMB, BFM protocols

Prognosis of childhood aggressive lymphomas, treated with intensive chemo, is generally good.
Follow-up
Patients in remission should have regular visits with a physician who is familiar with their medical history as well as with the treatments they have received. Medical tests, such as blood tests and computed axial tomography (CAT) scans, may be required at various times during remission to evaluate the need for additional treatment. Some treatments can cause long-term effects or late effects, which can vary based on duration and frequency of treatments, age, gender, and overall health at the time of treatment. Doctors will also check for these effects during follow-up care. Survivors and their caregivers are encouraged to keep copies of all medical records and test results as well as information on the types, amounts, and duration of all treatments received.