A European collaborative study of treatment outcomes in 346 patients with cardiac stage III AL amyloidosis

National Amyloidosis Centre, University College London Medical School, London, United Kingdom
Blood (Impact Factor: 10.45). 03/2013; 121(17). DOI: 10.1182/blood-2012-12-473066
Source: PubMed


Treatment outcomes of patients with cardiac stage III light chain (AL) amyloidosis remain poorly studied. Such cases have been excluded from most clinical studies due to perceived dismal prognosis. We report treatment outcomes of 346 patients with stage III AL amyloidosis from the United Kingdom, Italy, Germany, and Greece. Median overall survival (OS) was 7 months with OS at 3, 6, 12, and 24 months of 73%, 55%, 46%, and 29%, respectively; 42% died before first response evaluation. On an intention-to-treat basis, the overall hematologic response rate was 33%, including a complete response rate of 12%. OS rates at 12 and 24 months, respectively, for 201 response evaluable patients were 88% and 85% for complete responders, 74% and 53% for partial responders, and 39% and 22% for nonresponders. Forty-five percent of responders achieved an organ response. Amino-terminal fragment of brain-type natriuretic peptide (NT-proBNP) >8500 ng/L and systolic blood pressure (SBP) <100 mm Hg were the only factors that independently impacted OS and identified an especially poor prognosis subgroup of patients with a median OS of only 3 months. Outcome and organ function of stage III AL amyloidosis without very elevated NT-proBNP and low SBP is improved by a very good hematologic response to chemotherapy.

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    • "High-sensitivity troponin T has also been shown to have independent prognostic significance[54,77]. Additional prognostic factors that have been described include: multiorgan involvement[78,79]; ≥ 10% BMPCs[8]; abnormal cytogenetics [t(11; 14) and trisomies][80]; systolic blood pressure <100 mm Hg[81]; performance status (ECOG >2)[82]; serum uric acid >8 mg/dl[83,84]; body mass index (BMI) <22, and unintentional weight loss >10% in 6 months[85]. Emerging prognostic biomarkers in AL amyloidosis include: osteopontin, a potential biomarker of cardiac injury and biomechanical strain[86]; soluble suppression of tumorigenicity 2, a marker of cardiac remodeling and fibrosis[87], and human placental growth factor, a marker for endothelial dysfunction[88]. "
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    ABSTRACT: Immunoglobulin amyloid light-chain (AL) amyloidosis is the most common form of systemic amyloidosis, where the culprit amyloidogenic protein is immunoglobulin light chains produced by marrow clonal plasma cells. AL amyloidosis is an infrequent disease, and since presentation is variable and often nonspecific, diagnosis is often delayed. This results in cumulative organ damage and has a negative prognostic effect. AL amyloidosis can also be challenging on the diagnostic level, especially when demonstration of Congo red-positive tissue is not readily obtained. Since as many as 31 known amyloidogenic proteins have been identified to date, determination of the amyloid type is required. While several typing methods are available, mass spectrometry has become the gold standard for amyloid typing. Upon confirming the diagnosis of amyloidosis, a pursuit for organ involvement is essential, with a focus on heart involvement, even in the absence of suggestive symptoms for involvement, as this has both prognostic and treatment implications. Details regarding initial treatment options, including stem cell transplantation, are provided in this review. AL amyloidosis management requires a multidisciplinary approach with careful patient monitoring, as organ impairment has a major effect on morbidity and treatment tolerability until a response to treatment is achieved and recovery emerges.
    Full-text · Article · Jan 2016 · Acta Haematologica
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    • "According to the revised prognostic staging system for AL amyloidosis, the present patient is categorized to stage 3 (NT-ProBNP ≥1800 pg/mL, and FLC-diff ≥18 mg/dL).5 Both studies indicated that the survival curves of these most advanced stage III patients had dropped steeply at first 6 months after diagnosis.4,5 Therefore, the risk of developing lethal arrhythmia due to cardiac amyloidosis is estimated to be extremely high in the present patient. "
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    ABSTRACT: A 64-year-old female was diagnosed with systemic amyloidosis associated with multiple myeloma. Bortezomib and dexamethasone-therapy was initiated; however, she developed lethal ventricular fibrillation (VF) and cardiac arrest after 84 hours of therapy. Cardiopulmonary resuscitation using direct current shocks with epinephrine and amiodarone was initiated but failed to receive cardiac function. Although her arterial pulsations recovered immediately after the injection of vasopressin, she died of heart failure 8 hours after the onset of VF. Cardiac amyloidosis was verified by autopsy. Although the direct association of bortezomib with lethal VF remained to be clarified in our patient, the current report emphasizes on bortezomib as a substantial risk factor for cardiomyocyte damage. The potential risk of lethal events associated with cardiac amyloidosis should be carefully considered during bortezomib treatment for patients with AL amyloidosis.
    Full-text · Article · Sep 2013 · Hematology Reports
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    ABSTRACT: AL amyloidosis patients with multi-organ and particularly cardiac involvement have historically been considered to have a bad prognosis. The introduction of autologous stem cell transplantation was associated with unacceptable toxicity in high-risk patients, but responding patients have prolonged overall survival. Toxicities can be decreased by careful patient selection, but this reduces the applicability of this treatment modality to a limited number of patients. Efforts are therefore needed to design novel more effective regimens, with the use of new medications, such as thalidomide, lenalidomide and bortezomib, next generation immunomodulatory drugs and proteasome inhibitors. Their combination with dexamethasone and alkylating agents show promising results, allowing a high percentage of remission and subsequent event-free and overall survival, even in a significant proportion of high risk, poor prognosis populations. This review includes the state-of-the-art treatment for AL amyloidosis patients as of 2012, in light of the progress in management of this disease during recent years.
    No preview · Article · Jan 2013 · British Journal of Haematology
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