Follicular lymphoma (FL) is a common type of non-Hodgkin lymphoma, characterized by its slow-growing nature. This indolent cancer originates from B-cells, a type of white blood cell, and often presents with enlarged lymph nodes that may fluctuate in size. “Transformation” refers to a change from this slower-growing form to a more aggressive lymphoma, which necessitates a different treatment approach.
Understanding Follicular Lymphoma Transformation
Follicular lymphoma transformation involves a fundamental shift at the cellular level, where FL cells acquire genetic changes that drive aggressive growth. This process is defined by a histological demonstration of an increase in the proportion of large cells infiltrating the lymph nodes diffusely, leading to the effacement of the follicular architecture. These genetic alterations can include changes like c-MYC rearrangement, and inactivation of TP53 and cyclin D1.
The most common form of transformation is into diffuse large B-cell lymphoma (DLBCL), a more aggressive subtype. Other less common transformations can include Burkitt lymphoma, other high-grade B-cell lymphomas, or even Hodgkin lymphoma. This transformation can occur at any point during the disease course, with a median time from diagnosis to transformation ranging from 40 to 66 months in reported series. Occasionally, FL may have already transformed at initial diagnosis, presenting as a mixture of high-grade and low-grade lymphoma.
The risk of transformation is estimated to affect around 2 to 3 in every 100 people with follicular lymphoma each year. Over a 10-year period, transformation may occur in up to a third of individuals diagnosed with FL. The exact reasons for transformation are not fully understood, but it involves the accumulation of genetic alterations within the lymphoma cells. Scientists are actively researching these cellular changes to better understand and predict transformation.
Recognizing the Signs of Transformation
Recognizing follicular lymphoma transformation involves new or worsening clinical signs and symptoms. A rapid growth of lymph nodes or other masses is a common indicator, suggesting a shift from FL’s slow-growing nature. Patients may also experience new or exacerbated B symptoms, which include unexplained fevers, drenching night sweats, and significant unintentional weight loss. The appearance of new pain or discomfort can also signal transformation.
Elevated levels of lactate dehydrogenase (LDH) in blood tests can also point towards transformation, as this enzyme is often higher in more aggressive lymphomas. For a conclusive diagnosis, a new biopsy of the suspicious lesion is considered the gold standard. This biopsy allows detailed examination of cells to confirm histological changes consistent with aggressive lymphoma.
Imaging techniques, particularly PET/CT scans, play an important role in identifying areas of increased metabolic activity within the body. These “hot spots” indicate rapidly growing cells, guiding the medical team in selecting the most appropriate biopsy site. Clinical suspicion, elevated biomarkers, and targeted imaging help identify potential transformation, but biopsy remains the definitive diagnostic step.
Treatment Approaches for Transformed Lymphoma
Once follicular lymphoma has transformed, it is typically treated as an aggressive lymphoma, most commonly diffuse large B-cell lymphoma (DLBCL). Treatment aims to aggressively target the faster-growing cancer cells. This usually involves multi-agent chemotherapy regimens.
These chemotherapy regimens are often combined with immunotherapy, such as rituximab, which targets a protein found on the surface of B-cells. A common regimen is R-CHOP, which includes rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone. The specific combination and duration of treatment are determined by the patient’s overall health, the extent of the transformed lymphoma, and individual characteristics.
For select patients, stem cell transplantation may be considered. This can be either an autologous stem cell transplant, using the patient’s own stem cells, or an allogeneic stem cell transplant, using donor stem cells. These treatments deliver higher doses of chemotherapy, followed by the rescue of blood-forming cells, to eradicate the transformed lymphoma.
Prognosis and Follow-up Care
Follicular lymphoma transformation is a serious event, but treatment advancements have improved outcomes for many patients. Prognosis varies depending on the type of aggressive lymphoma and the patient’s response to treatment. Many patients achieve remission and experience extended periods of disease control.
Ongoing monitoring and regular follow-up appointments are important for post-treatment care. These appointments typically include physical examinations, blood tests, and surveillance imaging, such as PET/CT scans, to detect any signs of recurrence or new issues. The frequency and type of follow-up tests are tailored to each patient’s specific situation and risk factors.
Supportive care measures are also integrated into the long-term management plan to address any potential long-term side effects of treatment. This may include managing fatigue, neuropathy, or other treatment-related complications to improve the patient’s quality of life. The medical team works closely with patients to ensure continued surveillance and address any emerging concerns.