Non Hodgkin’s lymphoma Rakesh Biswas MD, Professor, Department of Medicine, People's College of Medical Sciences, Bhanpur, Bhopal, India

Staging Stage I : Involvement of single LN region (I) or extra lymphatic site (IAE ) Stage II : Two or more LN regions involved (II) or an extra lymphatic site and lymph node regions on the same side of diaphragm Stage III : Involvement of lymph node regions on both sides of diaphragm, with (IIIE) or without (III) localized extra lymphatic involvement or involvement of the spleen (IIS) or both (IISE) Stage IV : Involvement outside LN areas (Liver, bone marrow) A : Absence of ‘B’ symptoms B : B symptoms present

Non Hodgkin’s lymphoma Incidence is increasing NHL>HD Median age of presentation is 65-70 yrs M>F More often clinically disseminated at diagnosis B-cell-70% ; T-cell-30%

Clinical features Widely disseminated at presentation Nodal involvement: Painless lymphadenopathy, often cervical region is the most common presentation Hepatospleenomegaly Extranodal : Intestinal lymphoma ( abdominal pain, anemia, dysphagia); CNS ( headache, cranial nerve palsies, spinal cord compression) ; Skin, Testis; Thyroid; Lung Bone marrow (low grade): Pancytopenia

Clinical features contd Systemic symptoms Sweating, weight loss, itching Metabolic complications: hyperuricemia, hypercalcemia, renal failure Compression syndrome: Gut obstruction Ascites SVC obstruction S/C Compression

Classification REAL Clinical / Working Formulation Low grade Intermediate grade High grade

Classification Low grade Proliferation: Low Course: Indolent Symptoms: -ve Treatment: Not curable High grade High Rapid, fatal(un-Rx) +ve Potentially Curable

Etiology Cannot be attributed a single cause Chromosomal translocations: t (14, 18) Infection: Virus:EBV, HTLV,HHV-8, HIV Bacteria: H.Pylori - Gastric lymphoma Immunology: Congenital immunodeficiency, Immunocompromised patients - HIV, organ transplantation

Management Low grade: Asymptomatic : No treatment ; Radiotherapy for localised disease (Stage 1); Chemotherapy: mainstay is Chlorambucil; Initial response good , but repeated relapses, median survival 6-10 yrs; Newer: Fludarabine, 2-CdA (Chlorodeoxyadenosine) Monoclonal antibody: Rituximab SCT/BMT All cells have protein markers on their surface, known as antigens. Monoclonal antibodies are designed in the laboratory to specifically recognise particular protein markers on the surface of some cancer cells. The monoclonal antibody then 'locks' onto this protein. This either triggers the cell to destroy itself or signals to the body's immune system to attack and kill the cancer cell. For example, rituximab, the monoclonal antibody that is used in the treatment of non-Hodgkin's lymphoma, recognises a protein marker known as CD20. CD20 is found on the surface of the abnormal B cells that are found in some of the most common types of non-Hodgkin's lymphoma. When rituximab locks onto CD20 on the surface of a B cell, the cell may be destroyed directly, but also the body's natural defences are alerted. Rituximab effectively targets the lymphoma cells for destruction by the body's immune system, which can now kill the cancer cells. CD20 is also found on the surface of normal B cells, one of the types of white blood cells that circulate in the body. This means that these normal B cells, too, may be destroyed when rituximab is used. However, the stem cells in the bone marrow that develop into B cells do not have CD20 on their surface. Stem cells are therefore not destroyed by rituximab and can go on to replenish the body with healthy B cells. Although the number of mature, normal B cells is temporarily reduced by the treatment, they return to previous levels after the treatment.

Aggressive ( high / intermediate grade): Chemotherapy: mainstay CHOP -every 3 weeks, at least 6 cycles Cyclophosphamide, Doxorubicin Hydrochloride, Vincristine, Prednisolone

High risk cases with poor prognostic factors or relapse : High dose chemotherapy combined with autologous BMT / SCT Monoclonal antibody With CNS involvement / leukemic relapse : Similar to ALL

Prognosis Low grade : Median survival –10 yrs High Grade: Increasing age, advanced stage, concomitant disease, raised LDH,T- cell phenotype : Poor prognosis