Australian Doctor 14th July Issue 14JULY2023 issue | Page 37

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PAGE 35 development of the neoplastic lymphocyte . B-cell lymphomas can be divided into two broad groups based on their biological behaviour and treatment approaches : 8 aggressive B-cell non-Hodgkin ’ s lymphoma ( the prototypical example is diffuse large B-cell lymphoma [ DLBCL ]) presents with more proliferative disease and in many cases is considered curable with a defined course of treatment , while indolent lymphomas ( the most common is follicular lymphoma , see figure 6 ) are slow growing and may require treatment multiple times over many years . B-cell non-Hodgkin ’ s lymphomas can involve lymph nodes as well as almost any organ in the body , including the bone marrow .

Cancers primarily of the lymphoid cells in the bone marrow are known as leukaemias , though there may be overlap with lymphomas with predominantly lymph node involvement . Chronic lymphocytic leukaemia ( CLL ) is a slow-growing cancer of mature B lymphocytes that presents with a high white cell count and / or diffuse lymphadenopathy . 9 T-cell lymphomas comprise about 10-15 % of non-Hodgkin ’ s lymphomas and occur more frequently in Asian and South American populations . 10 They can behave aggressively and have poorer outcomes than their B-cell counterparts . Some may exclusively involve the skin — cutaneous T-cell lymphoma ( see figure 7 ) — and exhibit a spectrum of clinical behaviour , from indolent to more aggressive forms . Natural killer cell lymphomas are rare and display a range of behaviour from indolent to aggressive .

MANAGEMENT

AN individualised approach to treatment encompassing patient and disease factors is crucial to achieve the best clinical outcome .

The patient ’ s age , comorbidities and preferences will guide the intensity of treatment and specific drug choices . 11 For example , drug dosing will often need to be reduced to account for liver or renal impairment , and certain chemotherapy regimens are too toxic to deliver safely above a certain age threshold or in frail patients .

Important disease factors are the histopathological subtype of lymphoma , and the risk stratification using grade , stage , serum biomarkers and imaging . Cytogenetic analysis ( the lymphoma cell ’ s chromosomes or ‘ karyotype ’) can both define certain lymphoma subtypes and provide important prognostic information . New technologies that provide comprehensive genetic analysis play an increasing role in diagnosis and treatment decisions . Patients with aggressive lymphomas will generally require treatment soon after diagnosis , while patients with more indolent lymphomas may undergo a period of observation (‘ watch and wait ’) until they develop a clinical indication that requires treatment . During initial therapy , there is close clinical monitoring of response , and often also interim PET scanning to confirm response . 12 After treatment , if the lymphoma has responded well to therapy then the patient has achieved ‘ remission ,’ which may be partial or complete depending on the degree of response . If the lymphoma returns after initial treatment (‘ relapse ’), patients may receive additional courses of therapy (‘ salvage

Innate immunity ( rapid response )

Natural killer cell

Macrophage

Complement protein

Figure 1 . Adaptive and innate immune systems .

Figure 2 . Preauricular swelling with differential diagnosis of parotid swelling or lymphadenopathy .

Box 1 . Investigation of lymphoma

chemotherapy ’). Occasionally , the patient may not respond to therapy at all (‘ refractory ’), and these lymphomas are generally very difficult to treat .

Discussion of new patient cases at a multidisciplinary team meeting is the standard of care in modern practice . 13 This allows peer review and specialised input from radiology , anatomical pathology and radiation oncology colleagues that is crucial for accurate

Dendritic cell

Basophil

Eosinophil

Neutrophil

Mast cell

Granulocytes

• Blood tests :

— FBC ( elevated lymphocyte count can indicate circulating lymphoma cells , anaemia and thrombocytopenia can indicate bone marrow infiltration ; a normal FBC does not exclude lymphoma ). — Kidney and liver function . — Lactate dehydrogenase ( a marker of cell turnover and can be seen in lymphoma , though non-specific ).

• Biopsy : — Preferably excision or core biopsy sent for flow cytometry and histopathology .

• Imaging : — CT or PET scan ( staging at diagnosis and can guide site of biopsy , see figures 3 and 4 ).

• Bone marrow biopsy ( see figure 5 ): — For staging and / or diagnostic purposes , through not routinely done in all cases .

diagnosis , subclassification and monitoring of response to therapy .

Team-based care is crucial for achieving the best outcomes for patients , and support from nurse practitioners , dietetics , physiotherapy and psychology services is essential for holistic patient centred care .

Chemotherapy

The advent of multiagent chemotherapy markedly improved γδ T-cell

Natural killer T-cell

B-cell

Antibodies

Shutterstock outcomes in lymphoma , and it remains the mainstay of most modern treatment regimens , even in the age of novel therapies . Most patients with lymphoma will enter remission after treatment with upfront chemotherapy regimens , and salvage chemotherapy or stem cell transplantation may be offered if there is return of the lymphoma .

Chemotherapy drugs cause cell death through a variety of mechanisms , though these drugs are not specific enough to avoid damage to normal cells . 14 They are usually given in combinations that utilise different mechanisms of action , and in specified doses that maximise response , while minimising toxicity . They may be combined with immunotherapies and other newer agents . Common regimens include R-CHOP ( rituximab , cyclophosphamide , hydroxydaunorubicin hydrochloride [ doxorubicin hydrochloride ], vincristine [ Oncovin ] and prednisone ) for DLBCL , and ABVD ( doxorubicin hydrochloride [ Adriamycin ], bleomycin sulfate , vinblastine sulfate and dacarbazine ) for Hodgkin ’ s lymphoma . Chemotherapy treatments are usually given IV ; they are now

Adaptive immunity ( slow response )

CD4 + T-cell

T-cell

CD8 + T-cell

increasingly delivered in the outpatient setting rather than in hospital .

TOXICITY AND SUPPORTIVE CARE The toxicities of chemotherapy are related to damage of normal tissue , particularly those that are rapidly dividing . The most common side effects are nausea and vomiting , hair loss , and suppression of the immune system through a transient decrease in bone marrow production . 14 The most important white cell line affected is the neutrophil , with fever and neutropenia (‘ febrile neutropenia ’) particularly important because of the body ’ s inability to mount a defence . 15 Patients are counselled to present promptly for assessment and treatment if they develop a fever during chemotherapy . Other consequences of bone marrow suppression may be decreased red cells , necessitating blood transfusions , and low platelets which may predispose to bleeding .

Modern supportive care has improved the tolerability and safety of chemotherapy . 16 A range of antiemetic agents are given prophylactically and can prevent significant nausea for most patients . The availability of the white cell boosting recombinant granulocyte colony-stimulating factor , including a long acting pegylated formulation , to reduce the period of neutropenia and the risk of infection is also routine for more intensive treatment regimens . Certain chemotherapy regimens and novel therapies may predispose patients to more opportunistic infections that require prophylaxis in the appropriate clinical context ( see table 1 ).

COVID-19 and lymphoma

Patients with lymphoma are vulnerable to severe outcomes with COVID- 19 , both because of their disease and the use of B-cell depleting treatments . A full course of vaccination , including booster vaccination where indicated , is essential . However , a subset of patients may have inadequate immune response to vaccination , and strategies such as pre-exposure prophylaxis with long-lasting monoclonal