Hodgkin’s Lymphoma

RVS Chaitanya Koppala

Lymphoma (?) accounts for approximately 3% of new cases of cancer reported in the UK each year.

The primary cancerous cell of origin is the lymphocyte; as a result, there is often considerable overlap between lymphomas and lymphoid

leukaemias.

Lymphomas are subdivided into two main categories: Hodgkin's lymphoma (HL) Non-Hodgkin's lymphoma (NHL).

Both HL and NHL can be further classified based on histology. The site of malignancy is usually a lymph node.

Extranodal disease, most frequently of the stomach, skin, oral cavity and pharynx, small intestine and CNS, can occur and is more common in NHL than HL.

Hodgkin's lymphoma

Hodgkin's disease, now known as HL, was first described by Thomas Hodgkin in 1832.

HL accounts for 30% of all lymphomas and has an incidence in the UK of 2.2 /100,000/women and 3.3/100,000/men.

It is predominantly a disease of young adults, having a peak incidence between the ages of 15 and 35 years.

AetiologyThe cause of HL is unknown

Epstein–Barr (glandular fever) virus has been identified in 50% of HL cases.

Certain associations like genetic link with HL ; for example, same-sex siblings of patients with HL have a 10 times higher risk of developing the disease.

Patients with reduced immunity, for example, AIDS

PathologyThe diagnosis is made by histological examination of an excised

lymph node biopsy.

The characteristic pathological finding in HL is the identification of a large, abnormal bi-nucleate lymphocyte called a Reed-Sternberg cell.

HL as classified by the World Health Organization (WHO) has two distinct entities: Classic HL Nodular lymphocyte-predominant Hodgkin's lymphoma (NLPHL).

Classic Hodgkin's is further subdivided into four histological types:

Nodular sclerosis: this is the most common type in the UK, predominant in young adults and females, and has an excellent prognosis

Mixed cellularity: this is second most common type of classic HL and more common in males (70% male)

Lymphocyte depleted: this carries a poor prognosis and is more common in HIV-positive individuals

Lymphocyte rich: this is a rare type of classic HL

NLPHL accounts for 5% of HL cases and is more common in men.

Signs and symptoms:Painless enlargement of lymph nodesAbout 40% of patients will present with fever, night sweats and/or weight loss. MalaiseItching (25%)Pain at the site of enlarged nodes.Bone pain (skeletal involvement)Primary involvement of the gut, central nervous system or bone marrow is rare. Breathlessness. Viral and fungal infections.

Laboratory findings

NormochromicNormocytic anaemiaRaised ESREosinophilia. Leucocytosis due to an increase in neutrophils. Advanced disease is associated with lymphopenia (lymphocytes <0.6

× 109 L−1). Plasma lactate dehydrogenase (LDH) is raised in 30–40% of patients

at diagnosis and has been associated with a poor prognosis.

Investigations and staging Once the diagnosis has been made on biopsy

Further investigations are needed to Assess disease activity and the Extent of its spread through the lymphoid system.

staging is essential for assessing prognosis, with cure rates for localised tumours (stage I or II) being much higher than those for widespread disease (stage IV).

The tests required to establish the stage include a

Complete historyPhysical examination FBCUrea and electrolytes (U and Es)Chest X-ray and computed tomography (CT)Erythrocyte sedimentation rate (ESR)Serum LDH Liver function tests (LFTs)Positron emission tomography (PET) can be used to detect active residual

disease.

Management

HL is potentially curable and, in general, sensitive to both chemotherapy and radiotherapy

The two main goals of treatment are to Maximize the likelihood of cure Minimizing the risk of late toxicity such as infertility.

Stage of disease is the biggest factor in treatment choice and outcome.

The management determined by the stage of the disease Localised NLPHL frequently involves one isolated lymph node and tends

to be indolent (slow growing). If there are no risk factors, it can be treated with IFRT alone; all other

types are treated as advanced (stage III or IV) classic HL. In Europe, the treatment of classic HL is determined by whether the

disease is staged as Early favourable disease, Early unfavourable disease, Advanced disease or Relapsed

Early-stage (favourable) disease

The cure rate for patients with stages I and IIA disease is greater than 90%.

Patients with stages I and IIA disease may be cured with radiotherapy alone

However, due to radiation-related late effects, cardiac toxicity and secondary malignancy and the incidence of relapse (25–30%),

Most receive combined modality treatment (chemotherapy and radiotherapy).

This usually consists of two to four cycles of ABVD (Adriamycin (doxorubicin), bleomycin, vinblastine, dacarbazine) chemotherapy followed by IFRT of 20–30 Gy

The aim of chemotherapy is to destroy subclinical disease outside the field of radiotherapy.

Early-stage (unfavourable) disease

Patients with stage I or II presenting with bulky disease, B symptoms or with more than two sites of disease are considered to be poor risk if treated with radiotherapy alone.

B symptoms are any of the following symptoms: unexplained loss of weight, unexplained fever, drenching night sweats.

These patients are treated with four to six cycles of combination chemotherapy, for example, ABVD, and radiotherapy (20–30 Gy) to sites of bulky disease.

Advanced diseasePatients with advanced disease (stages III and IV) are treated with

combination chemotherapy.

The first widely used combination chemotherapy regimen was MOPP (mechlorethamine, vincristine (Oncovin), procarbazine and prednisolone)

The above produced a response rate of 80% and long-term disease-free survival of approximately 50%.

ABVD has replaced MOPP chemotherapy ( less fertility, haematological toxicity, acute leukaemia and myelodysplasia)

Management

If the Hodgkin disease was in the upper body, (?) given to the mantle field, which included lymph node areas in the neck, chest, and under the arms.

If the Hodgkin disease occurs below the diaphragam inverted Y field (?) therapy included the lymph nodes in the upper abdomen, the spleen, and the lymph nodes in the pelvis

Combination chemotherapy regimens effective in the treatment of Hodgkin's lymphoma

Salvage therapy for relapsed disease

Relapsed disease refers to disease progression after completion of primary treatment which resulted in a complete remission.

Depending on previous treatment, options include Salvage radiotherapy, Salvage chemotherapy High-dose chemotherapy with autologous stem cell support.

In this procedure, stem cells are collected from the patient and returned following high-dose chemotherapy.

Patients who relapse after initial radiotherapy alone have a good chance of cure with combination chemotherapy, at least equal to that of patients initially treated with chemotherapy for advanced disease.

Occasionally, radiotherapy is used if the disease is localised and previously non-irradiated..

Salvage chemotherapy regimens effective in thetreatment of lymphoma

New agents• Antibody rituximab (Anti-CD20 ) has shown remission in 80% of cases

of NLPHL• Anti - CD30 (expressed in the majority of classic HL) • Immunotoxin conjugate SGN-35 (most promising )• Panobinostat (histone deacetylases inhibitor), has been granted orphan

drug designation for the treatment of HL. • Gemcitabine has shown activity in relapsed classic HL with response

rates up to 79%• Bortezomib and lenalidomide for relapsed HL(licensed for myeloma)