Amyloidosis

Clinical Description

Amyloidosis is a disease caused by abnormal proteins that misfold and aggregate and deposit in organs such as the kidney, heart, liver, blood vessels and peripheral nerves. The abnormal proteins that can cause amyloidosis are dubbed ‘precursor’ proteins; the misfolded forms are intermediate protein species; and the deposits are a mixture of fibrils composed of the aggregated misfolded proteins and other constituents that accumulate with the fibrils and inhibit inflammation, such as vitronectin, apolipoprotein E and serum amyloid P protein. The intermediate species are toxic and cause organ dysfunction, illness and symptoms.   

There are four forms of amyloidosis. 
  1. The most common form of amyloidosis is called immunoglobulin light chain  or AL amyloidosis. In patients with AL, clonal plasma cells in the bone marrow produce part of an antibody, an immunoglobulin light-chain protein, that causes disease. Treatment for AL includes combination chemotherapy and stem cell transplantation. The median age at diagnosis is 63.
  2. Familial or hereditary amyloidosis develops among people who inherit a specific genetic abnormality. In the most common type, the liver produces an abnormal or mutated form of a protein called transthyretin; treatment for this form of amyloidosis (ATTRm) is liver transplantation, although newer therapies are in clinical trials.
  3. Age-related amyloidosis is also caused by the transthyretin protein but in this instance the protein is normal or ‘wildtype’ in sequence, not mutated. The vast majority of cases of age-related amyloidosis (ATTRwt) occur in men over the age of 70 and involve symptoms of progressive heart failure. Survival with ATTRwt can be in the 3 to 5 year range and new therapies are needed.
  4. Secondary amyloidosis (AA), very rare in the developed world, is caused by inflammation resulting from either infectious chronic diseases (tuberculosis, bronchiectasis, osteomyelitis, leprosy) or inflammatory chronic diseases (rheumatoid arthritis, granulomatous ileitis). Treatment involves eliminating the source of inflammation.

Symptoms of Amyloidosis

Symptoms can include fatigue, loss of libido and weight loss, and may also include a feeling of fullness in the stomach, limiting the size of meals one can eat comfortably; numbness, tingling, burning or bursts of pain in the lower extremities; cough and breathing problems when lying flat, shortness of breath on climbing stairs or an incline, and dizziness on standing, swelling of the legs, swallowing difficulties, bleeding into the skin, enlarged tongue, joint pain, and hoarseness.

Half of patients with AL have kidney involvement and lose a significant amount of normal protein in their urine. Half have symptoms of heart involvement – inability to lie flat without cough or breathing difficulties and shortness of breath when they exert themselves. In a quarter of patients with AL, the liver becomes enlarged and uncomfortable, and the gastrointestinal tract is involved also, causing stomach discomfort on the right side, abdominal swelling, weight loss, early fullness with eating, diarrhea or constipation.

Risk Factors of Amyloidosis

Risk factors for different types of diseases are those traits that increase the likelihood that an individual will develop the disease. The cause of AL amyloidosis is unknown, and therefore there are no known risk factors for the disease. The ATTRm form of hereditary amyloidosis is genetic and should be suspected if patients present with symptoms of amyloidosis and they have a first degree family member who has had the disease; a type of ATTRm, the I122V form of TTR, is also prevalent in blacks. Genetic testing for the known types of hereditary amyloidosis is performed at Tufts Medical Center. The ATTRwt form that occurs in elderly men is not associated with any known risk factors; it can be diagnosed with a simple scan – the PYP scan – in patients in whom amyloidosis is suspected. The primary risk factor for AA amyloidosis is the presence of a chronic inflammatory condition. 

How Amyloidosis is Diagnosed

To diagnose amyloidosis, physicians use a number of tests including blood and urine studies, bone marrow studies, and a biopsy taken from an affected organ or a site rich in blood vessels (such as abdominal fat). In over 95 percent of patients with AL, a free monoclonal light-chain is found in the blood. The diagnosis starts with a detailed clinical medical history and physical exam. 

Once amyloidosis is suspected, multiple tests are often required to make a final diagnosis, including a tissue biopsy as noted above. Other tests obtained evaluate kidney, liver and heart function. Cardiac testing is very important in order to characterize the patient’s need for treatment and the type of therapy that may work best. For AL, the bone marrow is usually the site where the factory for light chains exists and therefore bone marrow aspiration and biopsy are important studies. Of particular importance are genetic tests of the abnormal plasma cells themselves – at Tufts we select these abnormal cells for  studies that can help us decide what treatments to use. In addition, serum immunoglobulin levels, free light chains, and protein electrophoresis are obtained to check for abnormal proteins in the blood. There are many other studies that are required as part of the diagnostic process for amyloidosis, including electrocardiogram, echocardiogram, breathing tests, and 24-hour urine collection.  

Treatment Options for Amyloidosis at Tufts Medical Center

Treatment for patients with newly diagnosed AL amyloidosis usually involves combination chemotherapy or stem cell transplantation to eliminate the abnormal plasma cells that make the immunoglobulin light chains causing the disease. For patients who cannot undergo stem cell transplantation, combination chemotherapy with bortezomib (Velcade) and other drugs such as the steroid dexamethasone, or oral therapy with melphalan and dexamethasone, can be easily administered. For patients who undergo stem cell transplantation, a safe and effective therapy, additional chemotherapy after transplant, called consolidation, is provided to reduce the risk of relapse. In addition, at Tufts, we have protocol options that allow for ‘minimal residual disease’ testing on bone marrow aspirates obtained annually after patients achieve complete responses. These studies will help us to understand the risk of relapse in patients whose disease is undetectable by standard testing. 

For AL patients whose disease has relapsed, we have numerous options including new drugs on clinical trials. Furthermore, for AL patients whose plasma cells have been eliminated but whose kidneys or heart still show signs of amyloid disease, there are new therapies as well available on clinical trials.

Tufts investigators have identified a number of unique aspects of amyloidosis, including the role that various genes play in the disease and the frequency with which patients have two different proteins that can cause amyloidosis. We have an active research program seeking to understand the genes in the abnormal plasma cells that cause AL amyloidosis. By studying the plasma cells that produce the abnormal light chains we hope to unlock important secrets of this devastating illness, and to develop new therapies, over the coming years. 

If you are a patient here, the team of doctors at Tufts will include your hematologist as well as a cardiologist, nephrologist and neurologist. Our Cancer Center offers treatment with medical therapy and autologous stem cell transplant.  Autologous stem cell transplant is a process by which a patient’s own blood stem cells are collected, cryopreserved in the stem cell laboratory, and then infused into the patient after he or she has received a high dose of chemotherapy. 

Organ transplant, including kidney and heart transplant, is an option for only a limited number of patients with amyloidosis. At Tufts we perform kidney and heart transplants for young AL patients who are found eligible. 

Programs + Services


Hematologic Malignancies Program

Tufts Medical Center's Hematologic Malignancies Program in Boston uses the latest techniques to pinpoint your cancer type and provide you with the most effective treatment.
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John C. Davis Myeloma and Amyloid Program

The John C. Davis Myeloma and Amyloid Program at Tufts Medical Center in Boston is home to some of the world’s top experts in plasma cell disease.
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Kidney and Blood Pressure Center

The Tufts MC Kidney and Blood Pressure Center provides both one-time consultations and ongoing care for chronic or acute kidney disease and high blood pressure.
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Doctors + Care Team

Ronald D. Perrone, MD

Ronald D. Perrone, MD

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Accepting New Patients

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Title(s): Scientific Director, Clinical and Translational Research Center; Professor, Tufts University School of Medicine
Department(s): Medicine, Nephrology, Clinical and Translational Research Center (CTRC)
Appt. Phone: 617-636-5866
Fax #: 617-636-2369

Polycystic kidney disease (PKD)

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Mark J. Sarnak, MD, MS

Mark J. Sarnak, MD, MS

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Accepting New Patients

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Title(s): Chief, Division of Nephrology; Director, Research Training Program; Professor, Tufts University School of Medicine
Department(s): Medicine, Nephrology
Appt. Phone: 617-636-5866
Fax #: 617-636-2369

Dialysis, general nephrology, chronic kidney disease (CKD), diabetic kidney disease, glomerular disease, vasculitis, hypertension, cardiovascular disease in patients with kidney disease, acute kidney disease, acute kidney injury and kidney stones

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Raymond L. Comenzo, MD

Raymond L. Comenzo, MD

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Accepting New Patients

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Title(s): Director, Transfusion Services; Director, John C. Davis Myeloma and Amyloid Program; Professor, Tufts University School of Medicine
Department(s): Medicine, Pathology and Laboratory Medicine, Hematology/Oncology
Appt. Phone: 617-636-6454
Fax #: 617-636-3175

Myeloma, amyloidosis, stem cell transplant, transfusion medicine

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Scott J. Gilbert, MD

Scott J. Gilbert, MD

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Title(s): Director, Fellowship Training Program; Professor, Tufts University School of Medicine
Department(s): Medicine, Nephrology
Appt. Phone: 617-636-5866
Fax #: 617-636-2369

Kidney transplantation, systemic lupus erythematosus, dialysis, general nephrology, chronic kidney disease (CKD), diabetic kidney disease, glomerular disease, vasculitis, hypertension, cardiovascular disease in patients with kidney disease, acute kidney disease, acute kidney injury and kidney stones

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Lesley A.  Inker, MD, MS

Lesley A. Inker, MD, MS

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Title(s): Director, Kidney and Blood Pressure Center; Director, Kidney Function and Evaluation Center; Director, Quality Improvement; Professor, Tufts University School of Medicine
Department(s): Medicine, Nephrology
Appt. Phone: 617-636-5866
Fax #: 617-636-2369

Geriatric nephrology, pregnancy, HIV-associated kidney disease, kidney transplantation, kidney donor evaluation, medical treatment for kidney failure without dialysis, kidney function evaluation (GFR), general nephrology, chronic kidney disease (CKD), diabetic kidney disease, glomerular disease, vasculitis, hypertension, cardiovascular disease in patients with kidney disease, acute kidney disease, acute kidney injury and kidney stones

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Andreas K. Klein, MD

Andreas K. Klein, MD

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Title(s): Associate Chief, Division of Hematology Oncology; Director, Hematologic Malignancies Program; Director, Bone Marrow and Hematopoietic Cell Transplant Program; Regulatory Affairs Director, CTSI; Associate Professor, Tufts University School of Medicine
Department(s): Medicine, Hematology/Oncology
Appt. Phone: 617-636-6227
Fax #: 617-636-8538

Lymphoma, myeloma, bone marrow transplantation (BMT), immune reconstitution after BMT

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Amy Kuhlik, MD

Amy Kuhlik, MD

Accepting New Patients

Title(s): Nephrologist; Dean for Student Affairs and Assistant Professor, Tufts University School of Medicine
Department(s): Medicine, Nephrology
Appt. Phone: 617-636-5866
Fax #: 617-636-2369

Pregnancy, general nephrology, chronic kidney disease (CKD), diabetic kidney disease, glomerular disease, vasculitis, hypertension, cardiovascular disease in patients with kidney disease, acute kidney disease, acute kidney injury and kidney stones

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Andrew S. Levey, MD

Andrew S. Levey, MD

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Title(s): Chief Emeritus, Division of Nephrology; Professor of Medicine, Tufts University School of Medicine; Dr. Gerald J and Dorothy R. Friedman Professor Emeritus, Tufts University School of Medicine
Department(s): Medicine, Nephrology
Appt. Phone: 617-636-5866
Fax #: 617-636-2369

Kidney function evaluation (GFR), chronic kidney disease (CKD), diabetic kidney disease, glomerular disease, systemic lupus erythematosus, vasculitis, hypertension, cardiovascular disease in patients with kidney disease, acute kidney disease, acute kidney injury and kidney stones

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Klemens B. Meyer, MD

Klemens B. Meyer, MD

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Title(s): Medical Director, Dialysis Clinic, Inc., Boston and Walden Pond, Concord, MA; Director Dialysis Services, Tufts Medical Center; Medical Director for Home Dialysis, Dialysis Clinics, Inc, Somerville, MA; Professor, Tufts University School of Medicine
Department(s): Medicine, Nephrology
Appt. Phone: 617-636-5866
Fax #: 617-636-5539

Dialysis, home dialysis, medical treatment for kidney failure without dialysis, general nephrology, chronic kidney disease (CKD), diabetic kidney disease, glomerular disease, vasculitis, hypertension, cardiovascular disease in patients with kidney disease, acute kidney disease, acute kidney injury and kidney stones

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Dana C. Miskulin, MD, MS

Dana C. Miskulin, MD, MS

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Title(s): Nephrologist; Associate Professor, Tufts University School of Medicine
Department(s): Medicine, Nephrology
Appt. Phone: 617-636-5866
Fax #: 617-636-2369

Polycystic kidney disease (PKD), dialysis, home dialysis, general nephrology, chronic kidney disease (CKD), diabetic kidney disease, glomerular disease, vasculitis, hypertension, cardiovascular disease in patients with kidney disease, acute kidney disease, acute kidney injury and kidney stones

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Monika Pilichowska, MD, PhD

Monika Pilichowska, MD, PhD

Title(s): Director, Clinical Hematology and Hematopathology; Director, Hematopathology Fellowship Program; Associate Professor, Tufts University School of Medicine
Department(s): Pathology and Laboratory Medicine
Appt. Phone: 617-636-7216
Fax #: 617-636-7128

Hematology and hematopathology, flow cytometry, surgical pathology and cytology, renal pathology (medical renal disease)

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Research + Clinical Trials


A Phase 2, Multicohort Study of Daratumumab-Based Therapies in Participants with Amyloid Light Chain (AL) Amyloidosis

The purpose of this study is to characterize cardiac safety of Daratumumab, Cyclophosphamide, Bortezomib, and Dexamethasone (D-VCd) treatment regimens (Arm A: immediate daratumumab + VCd treatment and Arm B: daratumumab + deferred VCd) in newly diagnosed systemic amyloid light chain (AL) amyloidosis with cardiac involvement and to identify potential mitigation strategies for cardiac toxicity (cohort 1); to characterize the pharmacokinetics of subcutaneous (SC) daratumumab, among racial and ethnic minorities, including Black or African American, with newly diagnosed AL amyloidosis treated with D-VCd (cohort 2).
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