Non-Hodgkin lymphoma (NHL) represents a monoclonal proliferation of lymphoid cells of B-cell (90%) or T-cell (10%) origin. The incidence of these tumors increases with age, to 62.8/million population per annum at age 75 years, and the overall rate is increasing at about 3% per year. Previous classifications were based principally on histological appearances. The current WHO classification stratifies according to cell lineage (T or B cells) and incorporates clinical features, histology, chromosomal abnormalities and concepts related to the biology of the lymphoma. Clinically, the most important factor is grade, which is a reflection of proliferation rate. High-grade NHL has high proliferation rates, rapidly produces symptoms, is fatal if untreated, but is potentially curable. Of all cases of NHL in the developed world, over two-thirds are either diffuse large B-cell NHL (high-grade) or follicular NHL (low-grade). Other forms of NHL, including Burkitt lymphoma, mantle cell lymphoma, mucosa-associated lymphoid tissue (MALT) lymphomas and T-cell lymphomas, are less common.¹

INCIDENCE

• 12 new cases/ 100 000 people/year

Gender ratio

• Slight male excess

Age

• Median age 65–70 years

AETIOLOGY¹

• No single causative abnormality described
• Lymphoma is a late manifestation of HIV infection
• Specific lymphoma types are associated with viruses: e.g. Epstein–Barr virus (EBV) with post-transplant NHL, human herpes virus 8 (HHV 8) with a primary effusion lymphoma, and human T-cell lymphotropic virus (HTLV-1) with adult T-cellleukemia lymphoma
• Gastric lymphoma can be associated with Helicobacter pylori infection
• Some lymphomas are associated with specific chromosomal translocations:

The t (14; 18) in follicular lymphoma results in the dysregulatedexpression of the BCL-2 gene product,      which inhibits apoptotic cell death

The t (8; 14) found in Burkitt lymphoma and the t (11; 14) in mantle cell lymphoma alter function of c-myc and cyclin D1, respectively, resulting in malignant proliferation

• Lymphoma occurs in congenital immune deficiency states and in immune suppressed patients after organ transplantation

CLINICAL FEATURES

Unlike Hodgkin lymphoma, NHL is often widely disseminated at presentation, including in extra nodal sites. Patients present with lymph node enlargement, which may be associated with systemic upset: weight loss, sweats, fever and itching. Hepatosplenomegaly may be present. Sites of extra nodal involvement include the bone marrow, gut, thyroid, lung, skin, testis, brain and, more rarely, bone. Bone marrow involvement is more common in low-grade (50–60%) than high-grade (10%) disease. Compression syndromes may occur, including gut obstruction, ascites, superior vena cava obstruction and spinal cord compression. The same staging system is used for both HL and NHL, but NHL is more likely to be stage III or IV atpresentation.¹

INVESTIGATIONS¹

• Bone marrow aspiration and trephine to identify bone marrow involvement.
• Immuno phenotyping of surface antigens to distinguishT-cell from B-cell tumors. This may be done on blood, marrow or nodal material.
• Cytogenetic analysis to detect chromosomal translocation and molecular testing for T-cell receptor or immuno globulin gene rearrangements.
• Immunoglobulin determination. Some lymphomas are associated with IgG or IgM par proteins, which serve as markers for treatment response.
• Measurement of uric acid levels. Some very aggressive high-grade NHLs are associated with very high urate levels, which can precipitate renal failure when treatment is started.
• HIV testing. HIV is a risk factor for some lymphomas and affects treatment decisions.
• Hepatitis B and C testing. This should be done prior to therapy with rituximab.

MANAGEMENT

Low-grade grade Non-Hodgkin Lymphoma

The majority of patients (80%) present with advanced stage disease and will run a relapsing and remitting course over several years. Asymptomatic patients may not require therapy and are managed by ‘watching and waiting’. Indications for treatment include marked systemic symptoms, lymphadenopathy causing discomfort or disfigurement, bone marrow failure or compression syndromes. In follicular lymphoma, the options are:

• Radiotherapy: This can be used for localized stage I disease, which is rare.¹
• Chemotherapy: Most patients will respond to oral therapy with chlorambucil, which is well tolerated but not curative. More intensive intravenous chemotherapy in younger patients is said to produce better quality of life but no survival benefit.¹
• Monoclonal antibody therapy: Humanized monoclonal antibodies can be used to target surface antigens on tumor cells and to induce tumor cell apoptosis directly.¹
• Kinase inhibitors: It is said to be useful for poor-prognosis lymphoma withlow-grade histology but aggressive clinical behavior. These targeted therapies are likely to become more widelyused in low-grade lymphomas in the near future.¹
• Transplantation: Younger patients withshort first or second remissions or who relapse duringrituximab maintenance should be considered.¹

High-grade Non-Hodgkin Lymphoma

Patients with diffuse large B-cell NHL need treatment at initial presentation:

• Chemotherapy: The majority (>90%) are treated within travenous combination chemotherapy.¹
• Monoclonal antibody therapy: When combined with CHOP chemotherapy, rituximab (R) increases the complete response rates and improves overall survival. R-CHOP iscurrently recommended as first-line therapy for those with stage II or higher diffuse large B-cell lymphoma.¹
• Radiotherapy or HSCT: chosen as per case requirement.¹

PROGNOSIS

Low-grade NHL runs an indolent remitting and relapsing course, with an overall median survival of 12 years. Transformation to a high-grade NHL occurs in 3% per annum and is associated with poor survival. In diffuse large B-cell NHL treated with R-CHOP, some 75%of patients overall respond initially to therapy and 50% will have disease-free survival at 5 years. The prognosis for patients with NHL is further refined according to the international prognostic index (IPI). For high-grade NHL, 5-year survival ranges from over 75% in those with low-risk scores (age <60 years, stage I or II, one or fewer extra nodal sites, normal LDH and good performance status) to 25% in those with high-risk scores (increasing age, advanced stage, concomitant disease and a raised LDH). Relapse is associated with a poor response to further chemotherapy (<10% 5-year survival), but in patients under 65 years HSCT improves survival.¹

DIETARY SUGGESTIONS

• Plenty of fruit and vegetables.
• Enough carbohydrates (starchy) foods.
• Some meat, fish, eggs, and pulses.
• Some milk and other dairy foods or dairy
• Small amounts of foods high in fatand sugar.

Homeopathic Management of Non-Hodgkin Lymphoma

Role of homeopathy in NHL is symptomatic management and improving the overall life condition of the patient. Homeopathy can help improve the life condition and prolonging the life. Some reports have been there where homeopathy has been said to be curative, but such reports need more evidence and more detailed and long term follow up records. Homeopathy if used as an adjunct can definitely play an important role in improving the condition of the NHL. Some symptomatically beneficially medicines are discussed below but need to be taken in recommendation with a registered homeopathic practitioner only.

HOMEOPATHIC MEDICINES

Ferrum Phos– Anemia with hemorrhage and general debility and constipation. Chlorosis in young girls with delayed menses.

Calcarea Flour – in durations of tissues, glands, tumors, stony hard.

Calcaria Carb– indicated for lymphoma and especially indicated when the lymphatic glands especially cervical glands are involved. Exhaustive sweat and perspiration.

Ceanonthus– lymphoma where it’s useful for cases with enlargement of spleen.

China – when the periodicity of fever and chill with enlargement of spleen is marked. Bowels disturbed and the skin is hot and dry.

Phosphorous –Palpitation of heart and shortness of breath on; least exertion. Loose and offensive stools with complete exhaustion thereafter.

Natrum Mur– very well marked medicine for lymphoma treatment where the complexion is pale, earthy; skin greasy; anemia with chilliness, cold feet and chills down the back.

Thuja – warts, growths tumors.

Reference

1. Ralston S.H., Penman I.D., Strachan M.W.J., Hobson R.P. Davidson’s, Principles and Practice of Medicine. 23^rded. Edinburgh; Churchill Livingstone/Elsevier; 2018. 1417p.
2. Schroyens F, Synthesis Treasure Edition 2009, accessed through RADAR Software