Overview of transformed lymphoma (TL)
Transformed lymphoma can occur in patients with Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL).
A transformed lymphoma is a lymphoma that was initially diagnosed as indolent (slow growing) but has transformed into an aggressive (fast growing) disease. Indolent lymphomas are typically made up of small, slow growing cells. If the proportion of larger, faster-growing cells increases, the lymphoma begins to act like an aggressive lymphoma such as diffuse large B-cell lymphoma (DLBCL). This is a process known as transformation’.
Although indolent (slow growing) B-cell lymphomas are most commonly associated with transforming to aggressive disease, indolent T-cell lymphomas can also progress to aggressive disease.
The cause of transformation may be that the genes in the indolent lymphoma cells become damaged over time and cause the cells to grow more rapidly.
Who is affected by transformed lymphoma?
Transformed lymphoma can happen in any type of low-grade lymphoma, however it is rare for this to happen and only occurs in about 1 to 3 percent of patients per year. The average onset of transformation is 3-6 years from diagnosis but after 15 years the chances of transformation is very rare.
A risk factor associated with transformed lymphoma is bulky disease (a large tumour) at the time of diagnosis.
Symptoms that may indicate the lymphoma has transformed
- A rapid increase in size of lymph nodes
- Rapid swelling of the liver or the spleen
- Blood tests (elevated lactate dehydrogenase (LDH) or calcium
B symptoms is the term that doctors call the following symptoms:
- Night sweats (drenching sleep wear & bedding at night)
- Unexplained weight loss
- Persistent fevers (especially at night > 38C)
Types of lymphoma that can transform
|Indolent lymphoma||Transformed lymphoma|
|Chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL)||Transforms to Diffuse large B-cell lymphoma (DLBCL) – this transformation is called Richter syndrome|
|Follicular lymphoma||Most common transformation is to Diffuse Large B-cell lymphoma (DLBCL) Aggressive B-cell lymphoma, with features intermediate between DLBCL and Burkitt lymphoma|
|Lymphoplasmacytic lymphoma (Waldenstrom’s macroglobulinemia)||Diffuse Large B-cell lymphoma (DLBCL)|
|Mantle cell lymphoma (MCL)||Blastic (or blastoid) MCL|
|Marginal zone lymphomas (MZL)||Diffuse Large B-cell lymphoma (DLBCL)|
|Mucosa-associated lymphoid tissue lymphoma (MALT)||Diffuse Large B-cell lymphoma (DLBCL)|
|Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL)||Diffuse Large B-cell lymphoma (DLBCL)|
|Cutaneous T-cell lymphoma (CTCL)||Large cell lymphoma|
Diagnosis of transformed lymphoma (TL)
If transformed lymphoma is suspected, another biopsy is always required to confirm that the lymphoma, has transformed. A biopsyis a surgical procedure to remove part of or all of an affected lymph node or other tissue that is send to a pathologist. The biopsy can be done under local or a general anaesthetic depending on what part of the body is being biopsied. The biopsy can be one of three ways:
- Fine needle aspirate
- Core needle biopsy
- Excisional node biopsy
An excisional node biopsy is the best investigative option, as it collects the most adequate amount of tissue to be able to do the necessary testing for a diagnosis.
Waiting for test results can be a difficult time. It may help to talk to family, friends or a specialist cancer nurse.
Staging of lymphoma
Once a diagnosis of transformed lymphoma is made, there are further tests that are required to see where else in the body the lymphoma has affected or is located. This is called staging. The staging of your lymphoma helps your doctor to know the best treatment management for you.
There are four stages from stage 1 (lymphoma in one area) through to stage 4 (lymphoma that is widespread).
- Early stage means stage 1 and some stage 2 lymphoma. This can also be referred to as ‘localised’. Stage 1 or 2 means that the lymphoma is found in one area or a few areas close together.
- Advanced stage means the lymphoma is stage 3 and stage 4, and it is widespread lymphoma. In most cases, the lymphoma has spread to parts of the body that are far from each other.
Staging scans and tests
The scans and tests needed for staging and before treatment can start may include:
- Positron emission tomography (PET) scan
- Computed tomography (CT) scan
- Bone marrow biopsy
- Lumbar puncture & magnetic resonance imaging (MRI) – If lymphoma is suspected in the brain or spinal cord
Patients may also undergo a number of baseline tests prior to any treatment commencing to check organ functions. These are often repeated during and after the treatment has completed to assess whether the treatment has affected the functioning of organs. Sometimes the treatment and follow-up care may need to be adjusted to help manage side effects. These may include:
- Physical examination
- Vital observations (blood pressure, temperature, & pulse rate)
- Heart scan
- Kidney scan
- Breathing tests
- Blood tests
It may take some time for all the necessary biopsies and tests to be done (an average of 1-3 weeks), but it is important for the doctors to have a complete picture of the lymphoma and the general health of the patient in order to make the best treatment decisions
Many of the staging and organ function tests are done again after treatment to check whether the lymphoma treatment has worked and the effect this has had on the body.
Prognosis of transformed lymphoma (TL)
The prognosis of the transformed lymphoma will depend on which lymphoma the indolent lymphoma has transformed into and a number of other factors that are specific to each patient.
Once all of the results from the biopsy and the staging scans have been completed, the doctor will review these to decide the best possible treatment for a patient. At some cancer centres, the doctor will also meet with a team of specialists to discuss the best treatment and this is called a multidisciplinary team (MDT) meeting.
Doctors take into consideration many factors about the lymphoma and the patient’s general health to decide when and what treatment is required. This is based on:
- The stage of lymphoma
- Symptoms (including the size and location of the lymphoma)
- How the lymphoma is affecting the body
- Past medical history & general health
- Current physical and mental wellbeing
- Patient preferences
Transformed lymphoma needs to be treated in the same way as an aggressive lymphoma. Treatment can include:
- Combination chemotherapy
- Autologous stem cell transplant (if healthy enough)
- Radiotherapy (usually with chemotherapy)
- CAR T-cell therapy (Chimeric antigen receptor T-cell therapy – after 2 prior therapies)
- Ofatumumab for Richter’s syndrome (Transformation of B-cell CLL)
- Nivolumab for Richter’s syndrome (Transformation of B-cell CLL)
- Ibrutinib for Richter’s syndrome (Transformation of B-cell CLL)
- Clinical trial participation