Diagnosis and treatment of AL amyloidosis.
AL (amyloid light-chain) amyloidosis is a plasma cell disorder in which depositions of amyloid light-chain protein cause progressive organ failure. Virtually all patients with AL amyloidosis have a monoclonal protein in the serum or urine or a monoclonal population of plasma cells in the bone marrow. The most common target organ is the kidney and renal amyloidosis manifests as proteinuria or nephrotic syndrome in 3/4 of the patients. The median survival is one to two years. It is important to recognize that the amyloidosis is a dynamic process, and chemotherapy induced reduction of the activity of the plasma cell clone reduces the supply of the amyloid precursor protein and can result in a major regression of the deposits. Amyloid-related nephrotic syndrome and renal failure are potentially reversible. Conventional-dose melphalan as standard treatment can prolong the median duration of survival about 10 months, but the clinical response rates with improvement of impaired organ function are low with a slow response. Upfront high-dose chemotherapy with autologous peripheral blood stem cell transplantation is much more effective and can result in a major improvement of the patient's clinical condition, but the treatment-related toxicity can be relevant due to impaired organ function. The initial use of a conventional-dose chemotherapy consisting of vincristine, doxorubicin and dexamethasone (VAD) to achieve a remission and subsequent high-dose chemotherapy is the concept of a German trial. The improvement of the condition of the patient by this approach may increase the tolerability of high-dose chemotherapy and reduce transplantation-related problems.
Sezer
O
O
Universitätsklinikum Charité, Campus Mitte, Medizinische Klinik, Humboldt Universität, Berlin, Germany.
Eucker
J
J
Jakob
C
C
Possinger
K
K
D000682:Amyloid / Q000737:chemistry*; D000686:Amyloidosis / Q000150:complications / Q000175:diagnosis* / Q000628:therapy*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D004317:Doxorubicin / Q000031:analogs & derivatives / Q000627:therapeutic use; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D009404:Nephrotic Syndrome / Q000209:etiology*; D011379:Prognosis; D011507:Proteinuria / Q000209:etiology*
D000682:Amyloid; D000970:Antineoplastic Agents; C053044:4'-deoxy-4'-iododoxorubicin; D004317:Doxorubicin