Immunoglobulin light chain amyloidosis: 2014 update on diagnosis, prognosis, and treatment

Abstract

Disease Overview: Immunoglobulin light chain amyloidosis is a clonal, nonproliferative plasma cell disorder in which fragments of immunoglobulin light chain are deposited in tissues. Clinical features depend on organs involved but can include restrictive cardiomyopathy, nephrotic syndrome, hepatic failure, peripheral/autonomic neuropathy, and atypical multiple myeloma. Diagnosis: Tissue biopsy stained with Congo red demonstrating amyloid deposits with apple‐green birefringence is required for diagnosis. Invasive organ biopsy is not required because amyloid deposits can be found in bone marrow biopsy or subcutaneous fat aspirate in 85% of patients. Verification that amyloid is composed of immunoglobulin light chains is mandatory. Prognosis: N‐terminal pro‐brain natriuretic peptide (NT‐proBNP), serum troponin T, and difference between involved and uninvolved immunoglobulin free light chain values are used to classify patients into four groups of similar size; median survivals are 94.1, 40.3, 14.0, and 5.8 months. Therapy: All patients with a systemic amyloid syndrome require therapy to prevent deposition of amyloid in other organs and prevent progressive organ failure of involved sites. Stem cell transplant (SCT) is preferred, but only 20% of patients are eligible. Requirements for safe SCT include NT‐proBNP <5,000 ng/mL, troponin T <0.06 ng/mL, age <70 years, <3 organs involved, and serum creatinine ≤1.7 mg/dL. Nontransplant candidates can be offered melphalan–dexamethasone or cyclophosphamide–bortezomib–dexamethasone. Other combinations of chemotherapy with agents such as cyclophosphamide–thalidomide (or lenalidomide)–dexamethasone, bortezomib–dexamethasone, and melphalan–prednisone–lenalidomide have documented activity. Future Challenges: Late diagnosis remains a major obstacle to initiating effective therapy. Recognizing the presenting syndromes is necessary for improving survival.Am. J. Hematol. 89:1133–1140, 2014. © 2014 Wiley Periodicals, Inc.

Induction therapy pre‐autologous stem cell transplantation in immunoglobulin light chain amyloidosis: a retrospective evaluation

“…Survival outcomes were estimated using the Kaplan-Meier method, and survival curves were compared between groups using the log-rank test. Risk ratios were estimated based on the univariate and multivariable Cox proportional hazard models, the latter of which was performed in a stepwise 7 fashion. Variables tested in risk modeling included age, gender, year of diagnosis, interval from diagnosis to ASCT, whether or not induction therapy was administered, number of induction regimens, attenuated conditioning melphalan dose, BMPC >10% at diagnosis, AL amyloid staging, serum creatinine, and albumin less than 3.5 g/dL.…”

“…[1] Left untreated, the ongoing tissue deposition of amyloid fibrils will result in progressive system and organ failure, leading to a shorter survival of 10 -14 months. [2] Treatment with melphalan, [3][4][5] bortezomib [6,7] or autologous stem cell transplant (ASCT) has been proven to be an effective therapy to improve survival outcome. [8][9][10] Data from a tertiary center reported a high hematological response rate of 76% with ASCT and 39% of CR rate.…”

Amyloid cardiomyopathy

“…Valvular defects (mitral and tricuspid insufficiency) are relatively frequent with infiltration of the valvular and suspensory system. Chronic refractory cardiac failure and sudden death due to electromechanical dissociation or arrhythmogenic states are among the most frequent causes of death 7,8,[16][17][18][19][20][21][22][23] . A thorough physical examination may indicate the possible presence of amyloidosis.…”

Prognosztikai tényezők könnyűlánc-amyloidosisban

“…A monoklonális plazmasejt-populáció jelenléte megállapítható szérum-, illetve vizeletelektroforézissel, immunfi xációval és a szérum szabad KL menynyiségi meghatározásával [5,6]. A végső diagnózishoz nélkülözhetetlen a monoklonális protein jelenlétének igazolása az amyloiddepozitumból is [7,8].…”