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Evaluating Rabbit ATG as First-Line Therapy for Pediatric Aplastic Anemia

This presentation by Dr. Seiji Kojima of Nagoya University discusses the use of rabbit ATG in treating severe aplastic anemia (SAA) in children. It explores the efficacy of rabbit ATG compared to horse ATG, and the impact of different matching donor types on long-term outcomes. The data includes patient demographics, response rates after six months, and overall survival metrics from a comprehensive review of pediatric cases. The results indicate that rabbit ATG is a feasible first-line treatment without matched donors and emphasizes bone marrow transplantation as a primary option.

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Evaluating Rabbit ATG as First-Line Therapy for Pediatric Aplastic Anemia

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  1. 再生长再性贫血一线移植策略 Seiji Kojima MD. PhD. Department of Pediatrics Nagoya University Graduate School of Medicine Chairman of the Severe Aplastic Anemia Working Party Asia-Pacific Blood and Marrow Transplantation Group

  2. #2 #1 Yes No Yes #3 No Yes No APHCON Treatment Guideline for SAA

  3. 今天的主题 • 应用兔ATG 能作为一线治疗吗? • 比较结果可以期待 MRD 和1MMD? • 如无何时供者，第二次应用ATG + CSA 是适应症吗?

  4. 兔ATG治疗SAA经验 长期结果马或兔ATG治疗儿童AA Nagoya大学应用兔ATG 的经验

  5. 马vs 兔 ATG n= 33 n= 29 n= 22 n= 69 n= 32 n= 79 n= 46 n= 35 n= 105 n= 24 n= 29 n= 42 n= 60 n= 60

  6. Seiji Kojima MD Department of Pediatrics Nagoya University Graduate School of Medicine

  7. 患者特征

  8. 6个月反应 NE NR PR CR horse ATG rabbit ATG

  9. 6个月反应的预测因素

  10. 总生存 horse ATG 92% rabbit ATG 84%

  11. 死亡原因

  12. 免疫抑制治疗 Japan AA 97 Horse ATG: 15 mg /kg/day x 5 days CSA: 6 mg/kg/day adjusted to blood level G-CSF: Only when ANC < 0.2 x 109/L Nagoya Univ in Thymoglobulin era ( 2009 Aug ~ Now ) Rabbit ATG: 3.75 mg /kg/day x 5 days CSA: 6 mg/kg/day adjusted to blood level G-CSF: Only when ANC < 0.2 x 109/L

  13. ‘中性粒细胞减少’在兔ATG治疗后 Rabbit ATG CyA WBC Neutr

  14. EBV 再激活患者的临床过程 180,000 Rituximab 375 mg/m2 140,000 EBV copy number [copies / mL (whole blood)] 100,000 60,000 20,000 0 0 7 14 21 28 35 45 49 56 Days after administration of rabbit ATG

  15. 副作用

  16. COLON

  17. 日本免疫抑制剂后的EBV –LPD

  18. 今天的主题 • 应用兔ATG 能作为一线治疗吗? • 比较结果可以期待 MRD 和1MMD? • 如无何时供者，第二次应用ATG + CSA 是适应症吗?

  19. 患者(N = 578) Matched unrelated Donor (MUD) (n=213) 1MMRD @HLA Class I (n =32) MMRD (n=53) 1MMRD @HLA class II (n=12) Matched related donor (MRD) (n=312) 2-3 MMRD (n=9) Grouped by SEROLOGICAL HLA typing data (A, B, and DR) • 578 children (0-19 y) with AA • Received BMT between 1990-2009 • Available for serological HLA data (A, B, and DR) • Registered to The Japan Society for Hematopoietic Cell Transplantation

  20. 患者特征

  21. 5年总生存 MRD (n=312) 91.4 +/- 1.5% Class-I 1MMRD (n=32) 91.7 +/- 4.6% Class-II 1MMRD (n=12) 91.7 +/- 8.0% 1.00 0.75 MUD (n=213) 79.0 +/- 2.9% 2-3 MMRD (n=9) 66.7 +/- 12.2% probability of surivival 0.50 0.25 0.00 0 2000 4000 6000 8000 days after transplantation

  22. OS的多因素分析结果 HR (95% CI) P-value

  23. 急性GVHD (III – IV级) 1.00 MRD 5.2 +/- 1.4 % 1MMRD (class I) 32.9 +/- 10.1% p < .001 1MMRD (class II) 18.5 +/- 11.9% p = .03 2-3 MMRD 0.0% p = NS MUD 16.2 +/- 2.9% p < .001 0.75 0.50 1MMRD (Class I) 0.25 1MMRD (Class II) MUD MRD 2-3 MMRD 0.00 0 20 40 60 80 100 Days after transplantation

  24. 慢性GVHD (广泛性) 1.00 0.75 MRD 9.0 +/- 1.7 % 1MMRD (class I) 10.0 +/- 5.5% 1MMRD (class II) 0.0 % 2-3 MMRD 12.5 +/- 11% MUD 14.3 +/- 2.8% 0.50 0.25 0.00 0 2000 4000 6000 8000 Days after transplantation P= Not significant

  25. 儿童AA治疗步骤 BMT from MRD/1MMRD BMT from MUD Newly diagnosed AA MRD/1MMRD(+) MUD(+) MRD/1MMRD(-) NR MUD(-) IST 2nd IST or HAPLO / CBT CR/PR FIRST LINE THERAPY SECOND LINE THERAPY

  26. 今天的主题 • 应用兔ATG 能作为一线治疗吗? • 比较结果可以期待 MRD 和1MMD? • 如无何时供者，第二次应用ATG + CSA 是适应症吗?

  27. day–7–6–5–4–3–2–10+1+2+3+4+5+6 BMT PBSCT Flu(30mg/ m2 ×４) 　　　○ 　 ○ 　 ○ ○ ATG (2.5mg/kg ×４) 　　　　　　　 ○ ○　○ ○ 　　 (5mg/kg ×１) ○ L-PAM(70mg/m2 ×２)○　○ TBI(2.5Gy ×２)○ 半相合供者的预处理方案 • GVHD Prophylaxis：FK506+sMTX Nagoya University

  28. 患者特征

  29. 结果

  30. 结论 当没有马ATG时，应用兔ATG 作为一线治疗是可行的. 当1MMD 存在时, 骨髓移植是儿童SAA的一线选择. 对免疫抑制剂无效者当没有HLA-相合的无关供者时，半相合移植是可行的.

  31. 致谢 • Asian Pacific Blood and Marrow Transplantation Group : Childhood Aplastic Anemia Study Group Dao Chul Jeong, Xiao Fan Zhu • The Japan Society for Hematopoietic Cell Transplantation Childhood Aplastic Anemia Working Group Hideki Muramatsu, Hiromasa Yabe, Akira Kikuchi, Ryoji Kobayashi • Japan Childhood Aplastic Anemia Study Group Nao Yoshida, Yoshiyuki Takahashi, Akira Ohara

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