1. NIAZY B HUSSAM Ph.D. Clinical Pharmacy1
Lymphoma
NIAZY B HUSSAM
Ph.D. Clinical Pharmacy

2. Lymphoma is cancer of the lymphatic system and 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 leukemia.

3. Lymphomas are subdivided into two main categories:
1. Hodgkin's lymphoma (HL) and
2. 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.

4. Hodgkin lymphoma (HL) There are six types of HL, an uncommon form of lymphoma that involves the Reed-Sternberg cells.
Non-Hodgkin lymphoma (NHL) There are more than 61 types of NHL, some of which are more common than others. Any lymphoma that does not involve Reed-Sternberg cells is classified as non-Hodgkin lymphoma.

5. Hodgkin lymphoma (HL) There are six types of HL, an uncommon form of lymphoma that involves the Reed-Sternberg cells.
Non-Hodgkin lymphoma (NHL) There are more than 61 types of NHL, some of which are more common than others. Any lymphoma that does not involve Reed-Sternberg cells is classified as non-Hodgkin lymphoma.

6. Hodgkin's lymphoma

7. Aetiology
The cause of HL is unknown, but a number of risk factors have been identified.
Epstein–Barr (glandular fever) virus has been identified in 50% of HL cases.
Patients with reduced immunity, for example, AIDS or those taking immunosuppressants, may have an increased risk of developing HL.

8. Pathology
The characteristic pathological finding in HL is the identification of a large, abnormal binucleate lymphocyte called a Reed-Sternberg cell.
HL has two distinct entities:
1. Classic HL
2. 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

9. Pathology
The characteristic pathological finding in HL is the identification of a large, abnormal binucleate lymphocyte called a Reed-Sternberg cell.
HL has two distinct entities:
1. Classic HL
2. 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

10. Pathology
The characteristic pathological finding in HL is the identification of a large, abnormal binucleate lymphocyte called a Reed-Sternberg cell.
HL has two distinct entities:
1. Classic HL
2. 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

11. HL usually presents with (B symptoms)
Signs and symptoms
HL usually presents with (B symptoms)
1. Painless enlargement of lymph nodes, often in the neck.
2. About 40% of patients will present with fever,
3. Night sweats and/or weight loss.
4. Malaise,
5. Itching (25%)
6. Pain at the site of enlarged nodes after drinking alcohol.
7. Bone pain may result from skeletal involvement.
If lymph nodes in the chest are involved,
8. Patients may present with breathlessness.
9. Disturbance of immune function due to a progressive loss of immunologically competent T-lymphocytes, with patients becoming particularly prone to viral and fungal infections.

12. Laboratory findings Laboratory findings include 1
Laboratory findings Laboratory findings include 1. Norm chromic, normocytic anaemia, 2. A raised erythrocyte sedimentation rate 3. Eosinophilia. 4. Leucocytosis due to an increase in neutrophils. 5. Advanced disease is associated with lymphopenia 6. Plasma lactate dehydrogenase (LDH) is raised in 30–40% of patients at diagnosis and has been associated with a poor prognosis.

13. Investigations and staging

17. Management lly curable and, in
HL is potential general, sensitive to both cheomotherapy and radiotherapy
Stage of disease is the biggest factor in treatment choice and outcome. The management of classic HL is determined by the stage of the disease box 1.

18. Box 1 Disease staging for Hodgkin's lymphoma
Early stage
European Organisation for Research and Treatment of Cancer (EORTC) risk factors in localised disease  
A. Favourable (patients must have all features)
1. Clinical stage 1 or 2 2. Maximum of three nodal areas involved 3. Age less than 50 years of age 4. ESR< 50 mm/h 5. Mediastinal/thoracic mass ratio < 0.33 at D5/6  
B. Unfavourable
Clinical stage 2 with 4 or more nodal areas involved
Age >50 years of age
ESR >50 mm/h without B symptoms or >30 mm/h with
B symptoms (fever, night sweats, weight loss)
Mediastinal/thoracic ratio >0.33 at D5/6a  
Advanced stage
Hasenclever score
1. Age >45 years of age 2. male gender 3. Serum albumin <40 g/L 4. Hb <10.5 g/dL
5. Stage 4 disease 6. Leucocytosis, that is, WCC >15 × 109 L−1 7. Lymphopenia, that is, <0.6 × 109 L−1 or <8% of total WCC  

19. Early-stage (favorable) disease: 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 radiotherapy

20. Early-stage (unfavourable) disease These patients are treated with four to six cycles of combination chemotherapy, for example, ABVD, and radiotherapy to sites of bulky disease.

21. Advanced disease Patients with advanced disease (stages III and IV) are treated with combination chemotherapy. 1. MOPP (mechlorethamine, vincristine (Oncovin), procarbazine and prednisolone) 2. ABVD. Six to eight cycles of ABVD is considered the current standard treatment for advanced disease. 3. BEACOPP (bleomycin, etoposide, Adriamycin (doxorubicin), cyclophosphamide, vincristine, procarbazine, prednisolone)

23. Non-Hodgkin's lymphoma
The NHLs are a heterogeneous group of lymphoid malignancies
ranging from indolent, slow-growing tumors to aggressive, rapidly fatal disease.
The disease is rare in subjects under 30 years of age
the incidence steadily increases with increasing age;
NHL is slightly more common in men than in women

24. Aetiology The aetiology is unclear Following organ transplantation
Viruses have been implicated in the pathogenesis of NHL; for example, Burkitt's lymphoma is one of the most common neoplasms to develop in HIV-related immunosuppressed patients, human T-lymphotrophic virus type 1 (HTLV-1), Epstein–Barr Virus (EBV) is associated with post-transplant lymphoproliferative disorder (PTLD).
3. Exposure to certain chemicals such as pesticides and solvents
4. There is an increased incidence of gastro-intestinal lymphomas in patients with Crohn's disease.

25. Signs and symptoms
painless lymph- adenopathy, frequently in the neck area
Signs and symptoms of infection, anaemia or thrombocytopenia may be present in patients with bone marrow involvement.
Hepatosplenomegaly
B symptoms
Unexplained loss of weight,
Unexplained fever,
Drenching night sweats.

26. Laboratory findings
Anemia,
Raised erythrocyte sedimentation rate and a
Raised serum LDH level.
Reduction in circulating immunoglobulins,
The immune disruption caused by the disease may also result in an increased susceptibility to viral infection or autoimmune haemolytic anaemia or thrombocytopenia.

27. Diagnosis
Diagnosis is based on a thorough history, physical examination and investigation of a lymph node.
Peripheral blood lymphocytosis (increased lymphocytes)
A bone marrow aspirate is required to exclude leukemia
CT scans of the chest; abdomen and pelvis are required to assess the extent of the disease
Lumbar punctures should be performed for patients at high risk of CNS involvement, for example, Burkitt's lymphoma.
Erythrocyte sedimentation rate, LDH and serum β2-microglobulin levels may indicate disease activity and can be of prognostic importance.

28. Staging NHL is defined as stage I, II, III or IV, Stage I being disease limited to a single lymph node and stage IV being advanced disease, with involvement of extralymphatic sites.

29. Treatment Indolent non-Hodgkin's lymphoma
For the minority of patients presenting with limited- stage disease (stage I), radiotherapy to the involved field is generally used.
Rituximab, cyclophosphamide, vincristine, pred- nisolone (R-CVP) is used as the first-line treatment for advanced (stage III or IV)
R-CHOP (rituximab, cyclophos- phamide, doxorubicin, vincristine, prednisolone) can also be used as first-line treatment for young patients with aggressive disease and is an option in relapsed disease.

30. Relapsed indolent non-Hodgkin's lymphoma
If the time to relapse post-rituximab is greater than 6 months, re-treated with rituximab
If the time to relapse is less than 6 months, ibritumomab tiuxetan (Zevalin®) may be considered.
Radiotherapy may be an option in this situation and this is being evaluated through an ongoing clinical trial.

31. Aggressive non-Hodgkin's lymphoma The treatment for advanced-stage aggressive NHL is six cycles of the combination of R-CHOP chemotherapy

32. Relapsed aggressive non-Hodgkin's lymphoma
To induce a remission in patients with aggressive lymphoma and relapsed disease, it may be reasonable to use the same or similar regimen used for front-line chemotherapy.
There are several salvage regimens in use and they generally have response rates of between 40% and 70%. Examples of salvage regimens are
ICE (ifosfamide, carboplatin, etoposide),
ESHAP (etoposide, methylprednisolone, cytarabine, cisplatin) and
DHAP (cisplatin, cytarabine, dexamethasone)

34. Adverse effects associated with chemotherapy regimens used in the lymphomas
Bone marrow suppression
nausea and vomiting Mucositis
Alopecia
Impaired gonadal function
Neuropathy
Constipation
Cardiomyopathy
Lung fibrosis