跳轉到

Q1. Please select all CORRECT descriptions about daratumumab? (1) Daratumumab is a monoclonal anti-CD38 IgG kappa antibody. (2) Patients treated with daratumumab may have false positive indirect Coombs’ test (IAT). (3) Pretreatment with dithiothreitol removes CD38 on red blood cell and reduce the interference of daratumuab in IAT. (4) Kell antigen on RBC is also removed by dithiothreitol and all patients should be transfused with K+k- RBCs.

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

(D) 1+2+3

詳解

The correct answer is (D) 1+2+3 correct. Statements (1), (2), and (3) are accurate descriptions of daratumumab and its interference with blood bank testing, while statement (4) contains a critical error regarding transfusion practice.

Analysis of Each Statement:

(1) TRUE: Daratumumab is a monoclonal anti-CD38 IgG kappa antibody

Daratumumab is a human IgG1-kappa monoclonal antibody that targets CD3814. This is correctly stated in the FDA prescribing information and all major references on the drug.

(2) TRUE: Patients treated with daratumumab may have false positive indirect Coombs test (IAT)

Daratumumab binds to CD38 expressed on red blood cells, causing panagglutination in the indirect antiglobulin test (IAT)145. All patients receiving daratumumab show positive IATs due to this interference, which can mask the presence of clinically significant alloantibodies47. This creates a major challenge for pretransfusion compatibility testing.

Figure 3: Resolving interference of daratumumab in the indirect antiglobulin test ( IAT ). (A, B) Daratumumab in the patient's serum binds to the test RBC s. After adding the anti‐IgG reagent, RBC agglutination is observed, thereby generating a false‐positive result (A) or masking the presence of irregular antibodies (B). (C, D) Daratumumab‐specific anti‐idiotype antibodies are added to the patient's serum and bind to daratumumab (1). Alternatively, test RBC s are treated with DTT , resulting in denaturation of CD 38 and loss of daratumumab binding (2). If the patient has no irregular antibodies, binding of daratumumab to RBC s is blocked generating a negative IAT test result. However, if the serum contains irregular antibodies, binding of these antibodies to RBC will result in a true positive IAT test result.

(3) TRUE: Pretreatment with dithiothreitol removes CD38 on RBCs and reduces daratumumab interference in IAT

Treatment of reagent red blood cells with dithiothreitol (DTT) is a validated method to mitigate daratumumab interference147. DTT is a reducing agent that disrupts disulfide bonds in the extracellular domain of CD38, resulting in denaturation of the CD38 protein and abolishing daratumumab binding47. The standard AABB procedure uses 0.2 M DTT, though lower concentrations (0.01 M) have also been studied[^9].

(4) FALSE: Kell antigen on RBC is also removed by DTT and all patients should be transfused with K+k- RBCs

This statement contains multiple errors:

First error - The phenotype designation: The question originally stated "K+k-" but the author's correction notes this should be "K-/k+" (Kell-negative, Cellano-positive), which is the common phenotype found in approximately 91% of the population. However, this correction doesn't salvage the statement.

Second and critical error - "All patients should be transfused": The statement incorrectly suggests that all patients require a specific Kell phenotype. The actual recommendation is more nuanced:

  • DTT treatment denatures Kell antigens, preventing detection of anti-Kell antibodies when using DTT-treated reagent cells147
  • The FDA label states: "supply K-negative units after ruling out or identifying alloantibodies using DTT-treated RBCs"1
  • This means providing K-negative blood (not K+k-) when DTT-treated cells are used for antibody screening, to prevent sensitization to Kell antigens that cannot be detected47[^8]
  • However, not all patients require this approach. Best practice includes:
  • Phenotyping or genotyping patients before starting daratumumab for ABO, Rh, and Kell antigens[8][10][^11]
  • If pre-existing anti-Kell is ruled out and the patient's Kell status is known, phenotype-matched units can be provided
  • Some institutions use D and K matching only rather than extended phenotyping, given the low alloimmunization rates observed in daratumumab-treated patients[^8]
  • Recent data suggest alloimmunization rates are very low in daratumumab patients, possibly due to the drug's immunosuppressive effects[8][10]

The statement's use of "all patients" is incorrect because transfusion strategy should be individualized based on pre-treatment phenotyping/genotyping and antibody screening results, not a blanket policy for all patients[8][10][^11].

詳解 · 中文翻譯

正確答案是 (D) 1+2+3 正確。敘述 (1)、(2) 及 (3) 是關於 daratumumab 及其對輸血檢測的干擾的精確描述，而敘述 (4) 包含關於輸血實踐的關鍵誤差。

每個敘述的分析：

(1) 正確：Daratumumab 是一種單克隆 anti-CD38 IgG kappa 抗體

Daratumumab 是一種 人類 IgG1-kappa 單克隆抗體，靶點 CD3814。這在 FDA 處方資訊及所有關於此藥物的主要文獻中被正確陳述。

(2) 正確：用 daratumumab 治療的患者可能有假陽性間接 Coombs 試驗（IAT）

Daratumumab 結合至 在紅血球上表達的 CD38，導致 在間接抗人球素試驗（IAT）中的泛聚集145。所有接收 daratumumab 的患者因此干擾顯示 IAT 陽性，這可能掩蓋臨床顯著同種異體抗體的存在47。這為輸血前相容性檢驗創造重大挑戰。

圖 3：解決 daratumumab 在間接抗人球素試驗 (IAT) 中的干擾。(A, B) 患者血清中的 Daratumumab 結合至測試 RBCs。加入 anti-IgG 試劑後，觀察 RBC 聚集，因此產生假陽性結果 (A) 或掩蓋不規則抗體的存在 (B)。(C, D) Daratumumab 特異性 anti-idiotype 抗體被加入患者血清並結合至 daratumumab (1)。或者，測試 RBCs 用 DTT 處理，導致 CD38 變性及 daratumumab 結合喪失 (2)。若患者無不規則抗體，daratumumab 到 RBCs 的結合被阻斷，產生負 IAT 試驗結果。然而，若血清含不規則抗體，這些抗體到 RBC 的結合將導致真陽性 IAT 試驗結果。

(3) 正確：用二硫蘇糖醇（DTT）前處理移除 RBCs 上的 CD38 及減少 daratumumab 在 IAT 中的干擾

用 二硫蘇糖醇（DTT） 處理試劑紅血球是被驗證的方法以減輕 daratumumab 干擾147。DTT 是一種還原劑，破壞 CD38 細胞外域中的二硫鍵，導致 CD38 蛋白變性及消除 daratumumab 結合47。標準 AABB 程序使用 0.2 M DTT，雖然較低濃度（0.01 M）也被研究[^9]。

(4) 錯誤：RBC 上的 Kell 抗原也被 DTT 移除，所有患者應該輸注 K+k- RBCs

此敘述包含 多個誤差：

第一誤差 - 表型指定：題目原始陳述「K+k-」但作者的更正注釋指出這應該是「K-/k+」（Kell 陰性、Cellano 陽性），為在約 91% 人口中發現的常見表型。然而，此更正不救敘述。

第二及關鍵誤差 - 「所有患者應該被輸注」：敘述錯誤地提議 所有患者需要特定 Kell 表型。實際建議更細緻：

  • DTT 處理 變性 Kell 抗原，當使用 DTT 處理試劑細胞時防止 anti-Kell 抗體偵測147
  • FDA 標籤狀態：「在使用 DTT 處理 RBCs 排除或識別同種異體抗體後供給 K 陰性血單位」1
  • 這表示提供 K 陰性血液（不是 K+k-）當 DTT 處理細胞用於抗體篩選時，以防止對無法偵測的 Kell 抗原的敏感化47[^8]
  • 然而，不是所有患者需要此方法。最佳實踐包括：
  • 在開始 daratumumab 之前患者的表型或基因型分析針對 ABO、Rh 及 Kell 抗原[8][10][^11]
  • 若先前存在的 anti-Kell 被排除且患者的 Kell 狀態已知，可提供表型匹配血單位
  • 某些醫療機構僅使用 D 及 K 匹配而非擴展表型分析，鑑於在 daratumumab 治療患者中所見的低同種異體免疫率[^8]
  • 最近資料提示同種異體免疫率在 daratumumab 患者中非常低，可能由於藥物的免疫抑制效應[8][10]

敘述對「所有患者」的使用是錯誤的，因為輸血策略應基於前期治療表型/基因型分析及抗體篩選結果個體化，不是對所有患者的籠統政策[8][10][^11]。

參考文獻 (AMA)

  1. Food and Drug Administration. DARZALEX. 2025. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a4d0efe9-5e54-467e-9eb4-56fa7d53b60b. ↩↩↩↩↩↩↩↩↩↩

  2. van de Donk NW, Janmaat ML, Mutis T, et al. Monoclonal Antibodies Targeting CD38 in Hematological Malignancies and Beyond. Immunological Reviews. 2016;270(1):95-112. doi:10.1111/imr.12389. PMID:26864107. ↩

  3. Lancman G, Arinsburg S, Jhang J, et al. Blood Transfusion Management for Patients Treated With Anti-Cd38 Monoclonal Antibodies. Frontiers in Immunology. 2018;9:2616. doi:10.3389/fimmu.2018.02616. PMID:30498492. ↩

  4. Hosokawa M, Kashiwagi H, Nakayama K, et al. Distinct Effects of Daratumumab on Indirect and Direct Antiglobulin Tests: A New Method Employing 0.01 Mol/L Dithiothreitol for Negating the Daratumumab Interference With Preserving K Antigenicity (Osaka Method). Transfusion. 2018;58(12):3003-3013. doi:10.1111/trf.14900. PMID:30267414. ↩↩↩↩↩↩↩↩↩↩↩↩↩↩

  5. Phou S, Costello C, Kopko PM, Allen ES. Optimizing Transfusion Management of Multiple Myeloma Patients Receiving Daratumumab-Based Regimens. Transfusion. 2021;61(7):2054-2063. doi:10.1111/trf.16425. PMID:33960433. ↩↩

  6. Eritzpokhoff L, Talegón De La Fuente E, Carril Barcia A, et al. Absence of Red Blood Cell Alloimmunization in Transfused Patients Receiving Daratumumab: Experience From a Single Center. Journal of Clinical Medicine. 2025;14(16):5754. doi:10.3390/jcm14165754. PMID:40869587. ↩

  7. Murphy MF, Rajbhandary S, Carayiannis S, Cohn CS. How Do Transfusion Services Manage Patients Taking Therapies Such as Anti-Cd38 and Anti-Cd47 Known to Interfere With Red Blood Cell Compatibility Testing?. Transfusion. 2024;64(7):1217-1222. doi:10.1111/trf.17880. PMID:38767410. ↩↩↩↩↩↩↩↩↩↩

Slide correction

K-/k+

Figures