Amyloidosis describes a group of rare conditions characterized by the buildup of abnormal protein deposits, called amyloid, within organs and tissues. While “amyloid cancer” is a term sometimes used, amyloidosis is not a form of cancer. Instead, it refers to situations where it is linked to or caused by an underlying cancerous or pre-cancerous condition, particularly those affecting the blood and bone marrow.
What is Amyloid and Its Connection to Cancer
Amyloid refers to misfolded proteins that aggregate into insoluble fibrils, depositing in various organs and tissues. These deposits can interfere with organ function, potentially leading to damage or failure. Over 20 types of amyloidosis exist, each named for the specific misfolded protein.
The most common form of systemic amyloidosis, AL (Light Chain) amyloidosis, is directly caused by disorders of plasma cells. Plasma cells are white blood cells in the bone marrow that produce antibodies.
In AL amyloidosis, abnormal plasma cells, often part of conditions like multiple myeloma, produce faulty immunoglobulin light chain proteins. These light chains misfold and aggregate, forming amyloid fibrils that deposit in organs such as the heart, kidneys, liver, spleen, nervous system, and gastrointestinal tract. This accumulation progressively damages tissues and impairs organ function.
AL amyloidosis is the most prevalent type linked to blood cancers. The severity of the disease depends on which organs are affected and the extent of amyloid accumulation.
Identifying the Signs and Diagnosis
The symptoms of amyloidosis are often non-specific and can vary widely depending on which organs are affected by amyloid deposits. Common symptoms may include fatigue, swelling in various body parts, shortness of breath, unexpected weight loss, numbness or tingling sensations, and easy bruising. Since these signs can mimic other more common conditions, diagnosing amyloidosis can be challenging and often involves visiting multiple doctors.
Diagnosis typically begins with clinical suspicion based on symptoms, followed by initial blood and urine tests for abnormal proteins. If these tests indicate protein presence, a tissue biopsy is usually the next step. Biopsies can be taken from accessible sites like the abdominal fat pad or bone marrow, or from an affected organ like the heart, liver, or kidney if specific organ involvement is suspected.
After a biopsy, the tissue sample is stained with Congo Red, which binds to amyloid proteins. Under polarized light, these deposits show a characteristic apple-green birefringence, confirming amyloidosis. The specific protein type is then determined using techniques like mass spectrometry. Identifying the protein type, such as AL amyloid, helps determine if the amyloidosis is related to an underlying cancer.
Once amyloidosis is confirmed and typed, further tests are conducted to identify the underlying cancer, particularly in cases of AL amyloidosis. These tests include a bone marrow biopsy to assess for abnormal plasma cells, and specialized blood and urine tests such as serum free light chain assays and protein electrophoresis, which detect abnormal proteins produced by plasma cell disorders.
Treatment Approaches
Treatment for cancer-related amyloidosis primarily focuses on stopping the production of the amyloid-forming protein by targeting the underlying cancerous cells. For AL amyloidosis, which originates from abnormal plasma cells, treatment strategies are often similar to those used for multiple myeloma, a related plasma cell cancer.
Common approaches involve chemotherapy regimens to destroy abnormal plasma cells, including drugs like cyclophosphamide, bortezomib, and dexamethasone, often used in combination. Immunomodulatory drugs and proteasome inhibitors are also employed to suppress abnormal plasma cell activity.
For eligible patients, autologous stem cell transplantation (ASCT) may be considered. This procedure involves collecting the patient’s own healthy stem cells, administering high-dose chemotherapy to eliminate the abnormal plasma cells, and then reinfusing the collected stem cells to help the bone marrow recover. While ASCT can lead to deep and durable suppression of the plasma cell clone, patient selection is careful due to the intensity of the treatment.
Beyond targeting the underlying cause, supportive care is an important component of managing amyloidosis to alleviate symptoms and preserve organ function. This can include diuretics to manage fluid retention and swelling, medications to control heart rate or blood thinners for cardiac involvement, and pain management for neuropathy. These supportive measures aim to improve the patient’s quality of life while waiting for the primary treatment to reduce amyloid production and allow for organ recovery.
Ongoing Research and Outlook
Current research efforts are focused on improving the understanding, diagnosis, and treatment of amyloidosis, particularly its connection with cancer. Scientists are exploring novel drugs designed to directly target the amyloid proteins themselves. This includes developing amyloid-fibril disrupting agents and antibodies that can bind to and clear existing amyloid deposits from organs.
Another area of active investigation involves improving early diagnostic techniques to identify amyloidosis before significant organ damage occurs. Researchers are also working to better understand the complex mechanisms of amyloid formation and how these deposits lead to organ dysfunction. Advances in personalized medicine approaches are also being explored, aiming to tailor treatments more specifically to individual patients based on their unique disease characteristics.
The outlook for patients with cancer-related amyloidosis continues to improve with these ongoing advancements. The development of more effective therapies to control the underlying plasma cell disorders and the emergence of potential therapies to remove deposited amyloid offer hope for improved outcomes, including longer remissions and enhanced quality of life for those affected by this complex condition.