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Upfront Transplant Strategies in Aplastic Anemia

Upfront Transplant Strategies in Aplastic Anemia. 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. #1. Yes. No. Yes. #3. No.

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Upfront Transplant Strategies in Aplastic Anemia

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  1. Upfront Transplant Strategies in Aplastic Anemia 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. Today’s Topics Use of rabbit ATG can be justified as a front-line therapy? Comparable outcome can be expected between MRD and 1MMD? Second course of ATG + CSA should be indicated if no alternative donor is available?

  4. Experience of rabbit ATG for SAA Long term outcome of AA children treated with horse ATG or rabbit ATG Rabbit ATG experience in Nagoya University

  5. horse vs rabbit 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. Patient Characteristics

  8. Response at 6M NE NR PR CR horse ATG rabbit ATG

  9. Predictive factor for response at 6months

  10. OS horse ATG 92% rabbit ATG 84%

  11. Causes of death

  12. Immunosuppressive Therapy 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. ‘Neutrophil dip’ after rabbit ATG Rabbit ATG CyA WBC Neutr

  14. EBV Reactivated Patient’sClinical Course 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. Side effects

  16. COLON

  17. EBV –LPD after immunosuppressive therapy in Japan

  18. Today’s Topics Use of rabbit ATG can be justified as a front-line therapy? Comparable outcome can be expected between MRD and 1MMD? Second course of ATG + CSA should be indicated if no alternative donor is available?

  19. PATIENTS (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. PATIENT CHARACTERISTICS

  21. 5-year OVERALL SURVIVAL 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. MULTIVARIATE ANALYSIS OF OS HR (95% CI) P-value

  23. ACUTE GVHD (grade III – IV) 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. CHRONIC GVHD (Extensive) 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. TREATMENT ALGORISM FOR CHILDREN WITH AA 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. Today’s Topics Use of rabbit ATG can be justified as a front-line therapy? Comparable outcome can be expected between MRD and 1MMD? Second course of ATG + CSA should be indicated if no alternative donor is available?

  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)○ Preconditioning Regimen from Haploidentical Donor • GVHD Prophylaxis：FK506+sMTX Nagoya University

  28. Patient Characteristics

  29. Outcome

  30. Conclusion Use of rabbit ATG as a front-line therapy is justified when horse ATG is not available. When 1MMD donor is available, bone marrow transplantation is the first choice of treatment for SAA children. Haploidentical transplantation can be indicated if HLA-mached unrelated donor is not found for non-responder to immunosuppressive therapy.

  31. Acknowledgement • 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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