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Q1. Please select the CORRECT description(s) about systemic AL amyloidosis:

(1) Autologous stem cell transplantation has survival benefit. (2) Third fourths of AL patients have monoclonal gammopathy of free κ light chain. (3) Cardiac involvement is a factor associated with worse outcome. (4) Acquired factor XI deficiency is an uncommon but well-document complication.

  • (A) 1
  • (B) 1+3
  • (C) 2+4
  • (D) 1+2+3
  • (E) 1+2+3+4
點此顯示正解

(B) 1+3

詳解

Answer Explanation

The correct answer is (B) "1+3 correct" because statements 1 and 3 are true while statements 2 and 4 contain factual errors.

Why Statement (1) is Correct: Autologous stem cell transplantation (ASCT) does provide survival benefit in carefully selected AL amyloidosis patients. The key qualifier is patient selection—ASCT is reserved for patients with adequate organ function, particularly cardiac function, who can tolerate the procedure. Patients with advanced cardiac involvement (Mayo stage III-IV) are generally excluded due to high treatment-related mortality12.

Why Statement (3) is Correct: Cardiac involvement is definitively associated with worse outcomes in AL amyloidosis. The Mayo cardiac biomarker staging systems (2004, 2012, and European modification) use cardiac troponin and NT-proBNP to stratify patients into prognostic groups23. The Mayo 2004 staging system classifies patients based on cardiac troponin T (<0.035 μg/L) and NT-proBNP (<332 ng/L) thresholds, with stage III patients (both markers elevated) having median survival of only 3.5-4.1 months compared to 26.4-27.2 months for stage I25. The Mayo 2012 staging system added the difference in free light chains (dFLC) and shows median survival ranging from 94.1 months for stage I to 5.8 months for stage IV4. Cardiac involvement is present in approximately 75% of AL amyloidosis cases and is the main driver of morbidity and mortality1[^10].

Figure 2: Survival of Patients With Amyloidosis Based on Staging

Why Statement (2) is Wrong: This statement incorrectly identifies kappa (κ) light chain as predominant. In reality, lambda (λ) light chain predominates in AL amyloidosis by approximately 3:1 over kappa. This is the opposite of what occurs in multiple myeloma, where kappa is more common. The lambda predominance is a characteristic feature of AL amyloidosis.

Why Statement (4) is Wrong: The statement incorrectly identifies factor XI deficiency. The actual coagulation abnormality in AL amyloidosis is acquired factor X deficiency, not factor XI. Factor X deficiency occurs due to adsorption of factor X to amyloid fibrils[10][12]. Studies show factor X deficiency occurs in 8.7% to 62.3% of AL amyloidosis patients depending on the cohort and definition used[11][12][^13]. The Choufani study found 8.7% of 368 consecutive AL amyloidosis patients had factor X levels below 50% of normal, with bleeding complications occurring in 56% of those affected[^12]. Factor X deficiency is associated with prolonged prothrombin time (PT) and partial thromboplastin time (PTT), higher Mayo stage, multi-organ involvement, and inferior survival outcomes[10][11]. Importantly, factor X levels can improve with effective treatment of the underlying plasma cell dyscrasia through chemotherapy or stem cell transplantation[12][13].

詳解 · 中文翻譯

答案解釋

正確答案是 (B)「1+3 正確」，因為陳述 1 和 3 真實，而陳述 2 和 4 包含事實錯誤。

為何陳述 (1) 正確： 自體幹細胞移植（ASCT）確實在 精心選擇的 AL 澱粉樣變患者中提供生存益處。關鍵限定符是患者選擇——ASCT 保留用於具有充分器官功能、特別是心臟功能能夠耐受該程序的患者。具有晚期心臟受累（Mayo 第 III-IV 期）的患者通常被排除，因為治療相關死亡率高12。

為何陳述 (3) 正確： 心臟受累在 AL 澱粉樣變中明確與較差的預後相關。Mayo 心臟生物標誌物分期系統（2004、2012 和歐洲修改）使用心臟肌鈣蛋白和 NT-proBNP 將患者分層為預後組23。Mayo 2004 分期系統根據心臟肌鈣蛋白 T（<0.035 μg/L）和 NT-proBNP（<332 ng/L）閾值分類患者，第 III 期患者（兩個標誌物升高）中位生存僅 3.5-4.1 個月，相比第 I 期的 26.4-27.2 個月25。Mayo 2012 分期系統增加了遊離輕鏈差異（dFLC），中位生存範圍從第 I 期的 94.1 個月到第 IV 期的 5.8 個月4。心臟受累出現於約 75% 的 AL 澱粉樣變病例，是發病率和死亡率的主要驅動1[^10]。

為何陳述 (2) 錯誤： 此陳述錯誤地將 kappa（κ）輕鏈識別為主導。實際上，lambda（λ）輕鏈在 AL 澱粉樣變中以約 3:1 相對於 kappa 佔主導。這與多發性骨髓瘤相反，其中 kappa 更常見。Lambda 優勢是 AL 澱粉樣變的特徵性特徵。

為何陳述 (4) 錯誤： 陳述錯誤地識別 第 XI 因子 缺乏。AL 澱粉樣變中的實際凝血異常是 獲得性第 X 因子缺乏症，而非第 XI 因子。第 X 因子缺乏症發生於 第 X 因子對澱粉樣纖維的吸附[10][12]。研究顯示第 X 因子缺乏症發生於 8.7% 到 62.3% 的 AL 澱粉樣變患者，取決於隊列和所用定義[11][12][^13]。Choufani 研究發現 368 個連續 AL 澱粉樣變患者中的 8.7% 有第 X 因子水平低於正常 50%，其中 56% 的受影響者發生出血併發症[^12]。第 X 因子缺乏症與凝血酶原時間（PT）和部分促凝血激酶時間（PTT）延長、更高的 Mayo 期、多器官受累和較低的生存預後相關[10][11]。重要地是，通過化療或幹細胞移植有效治療潛在漿細胞惡性腫瘤，第 X 因子水平可以改善[12][13]。

參考文獻 (AMA)

  1. Sanchorawala V. Systemic Light Chain Amyloidosis. The New England Journal of Medicine. 2024;390(24):2295-2307. doi:10.1056/NEJMra2304088. PMID:38924733. ↩↩↩↩

  2. Gertz MA, Dispenzieri A. Systemic Amyloidosis Recognition, Prognosis, and Therapy: A Systematic Review. Jama. 2020;324(1):79-89. doi:10.1001/jama.2020.5493. PMID:32633805. ↩↩↩↩↩↩

  3. Kittleson MM, Ruberg FL, Ambardekar AV, et al. 2023 ACC Expert Consensus Decision Pathway on Comprehensive Multidisciplinary Care for the Patient With Cardiac Amyloidosis: A Report of the American College of Cardiology Solution Set Oversight Committee. Journal of the American College of Cardiology. 2023;81(11):1076-1126. doi:10.1016/j.jacc.2022.11.022. PMID:36697326. ↩↩

  4. Zaha VG, Hayek SS, Alexander KM, et al. Future Perspectives of Cardiovascular Biomarker Utilization in Cancer Survivors: A Scientific Statement From the American Heart Association. Circulation. 2021;144(25):e551-e563. doi:10.1161/CIR.0000000000001032. PMID:34753300. ↩↩

  5. Pregenzer-Wenzler A, Abraham J, Barrell K, Kovacsovics T, Nativi-Nicolau J. Utility of Biomarkers in Cardiac Amyloidosis. JACC. Heart Failure. 2020;8(9):701-711. doi:10.1016/j.jchf.2020.03.007. PMID:32653441. ↩↩

  6. Choufani EB, Sanchorawala V, Ernst T, et al. Acquired Factor X Deficiency in Patients With Amyloid Light-Chain Amyloidosis: Incidence, Bleeding Manifestations, and Response to High-Dose Chemotherapy. Blood. 2001;97(6):1885-7. doi:10.1182/blood.v97.6.1885. PMID:11238135. ↩

  7. Abdallah N, Muchtar E, Dispenzieri A, et al. Coagulation Abnormalities in Light Chain Amyloidosis. Mayo Clinic Proceedings. 2021;96(2):377-387. doi:10.1016/j.mayocp.2020.06.061. PMID:33549257. ↩

  8. Gao YJ, Shen KN, Chang L, et al. Prevalence, Clinical Characteristics and Treatment Outcome of Factor X Deficiency in a Consecutive Cohort of Primary Light-Chain Amyloidosis. Leukemia Research. 2022;120:106917. doi:10.1016/j.leukres.2022.106917. PMID:35849875. ↩

Slide annotations

Factor X deficiency is the most common coagulation factor deficiency amongst patients with AL amyloidosis

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