lymphoma and cancer treatments Flashcards
(37 cards)
what is it?
- Malignant tumours derived from cells of the immune system
- Many different forms with variable clinical course and prognosis
- Diagnosis based on clinical, histological, immunophenotypic and genetic studies
how does it present?
A ‘lump’: lymphadenopathy – rubbery, soft, non-tender
Itch without rash, alcohol-induced pain
Relevant to compression, infiltration/extranodal disease: renal failure, superior vena cava obstruction, effusions, marrow failure (some, not all)
B symptoms
- fever
- night sweats
- weight loss
how is it diagnosed?
Accurate diagnosis and classification needs specific characterisation of cell types by morphology, immunophenotype and genetics
Ensures accurate diagnosis and classification that is the basis for treatment decisions
If lymphoma or other malignancy is suspected-request a surgeon to biopsy.
o Fine needle aspirate is almost always insufficient.
o A core biopsy is often insufficient.
o Need a big sample to assess architecture of the lesion
how is it investigated?
CT and PET imaging
Ann Arbor staging system
lactate dehydrogenase (LDH) - prognostic not diagnostic
steroids in treating lymphoma
- Lymphocytes are normally sensitive to steroid therapy and some lymphomas are exquisitely sensitive
- Steroids are an integral part of multiagent chemotherapy regimens for the routine treatment of lymphoma
- Steroids can be used in the emergency management of suspected lymphoma but starting steroid before biopsy can cause cell necrosis and distort cellular and tissue architecture to confuse the diagnosis
what is non-hodgkin’s lymphoma?
most common form of lymphoma
diverse group of diseases
what are the differences in B and T cell NHL?
B cell lymphomas
o Most common form of NHL
o Low grade forms
o High grade forms
T cell lymphomas (high grade)
o Less common
o More complex classification
- Diffuse large B cell lymphoma is a common high-grade NHL
- Extra-nodal disease particularly with T cell NHL, Burkitt lymphoma
what is the basis of NHL treatment?
Multi-agent chemotherapy +/- radiotherapy –risks of neutropenia, cardiotoxicity (also in Hodgkin lymphoma)
o Increase the doses in those who need it for cure and accept increased side effects.
o Reduce chemotherapy or miss out radiotherapy in those who don’t need it to avoid long-term side effects.
what forms of NHL can be cured?
High-grade NHL is potentially curable, low-grade is incurable but many patients may not need treatment
what is the plan B treatment for NHL patients where chemo fails?
High-dose therapy with autologous stem cell rescue or CAR-T therapy
what is supportive therapy?
to go with chemotherapy and prevent death from side effects
what are the things done in supportive therapy?
o Prompt treatment of neutropenic fever/ infection
o Red cell and platelet transfusion
o Growth factors (GCSF)
o Prophylactic antibiotics and antifungals to prevent infection occurring in the first place eg itraconazole or posaconazole
what are the benefits of monoclonal antibody therapy + chemo?
o More effective than chemotherapy alone
o Monoclonal antibodies – Immune treatment, affect only cells which possess target protein, avoid side effects but with chemo so same risks
what are the monoclonal antibodies used in NHL treatment?
Rituximab (CD20) in B cell NHL
Brentuximab (CD30) in T cell NHL
what are biological agents?
o Not chemo don’t affect cells as they divide
o Variety of modes of action
o Not targeted to malignant cells so side effects
what are proteosome inhibitors and IMIDs?
Biological agents
Proteosome – dustbin for old proteins inside cells, breaks into amino acids for recycling. Blocking allows accumulation of toxic proteins in cell causing apoptosis
IMIDs – thalidomide, lenaliodomide and pomalidomide – less side effects like neuropathy. Poorly understood mode of action (immunomodulatory,
anti-angiogenic) used mainly for treatment of myeloma and other plasma cell disorders
what are molecularly targeted treatments?
o Ideally – target pathway specific to the cancer cell, avoid side effects, more effective than chemotherapy
what do tyrosine kinase inhibitors treat?
chronic myeloid leukaemia
what are the properties of tyrosine kinase inhibitors as a molecularly targeted treatment?
Imatinib, nilotinib, dasatinib, bosutinib and ponatinib.
Generally well tolerated
Achieve haematological, cytogenetic and molecular remissions in the majority of patients
Some patients can stop treatment without relapsing (treatment free remission leading to cure)
Only curative treatment option prior to TKIs was allogeneic bone marrow transplantation – very rarely indicated now
immune therapy as a cancer treatment?
o Allogenic bone marrow transplant (from a matched donor) is immune therapy
o T cells from donor cause immune attack on cancer. Graft versus Leukaemia or lymphoma Effect (GvL) but also have immune attack of normal cells. Very toxic. Graft versus Host Disease (GVHD).
what is the principle of adoptive immunotherapy?
Make patients own immune cells recognise the cancer as foreign and attack it, avoids toxicity of graft versus host disease. Most promising is CAR-T cell therapy (Chimeric Antigen Receptor (CAR) T cells)
What is CAR-T therapy used for in the NHS?
- relapsed/refractory diffuse large B cell lymphoma and primary mediastinal B cell lymphoma (types of high grade B cell non-Hodgkin’s lymphoma)
- relapsed/refractory B cell acute lymphoblastic leukaemia in people aged up to 25 years
what is burkitt lymphoma and how is it managed?
- Fastest growing human tumour
- Endemic type (EBV link) vs sporadic
- HIV association
- Chromosomal translocations involving c-myc
- High cure rates in high income countries – beware of tumour lysis at the start
what is hodgkin’s lymphoma?
- Less common than NHL
- Usually very good prognosis
- Peak incidence in third decade
- Spread to lymph node groups is orderly
