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Experience of Hematopoietic Stem Cell Transplantation in NTUH, 1983-2012

Experience of Hematopoietic Stem Cell Transplantation in NTUH, 1983-2012. 唐季祿 醫師 台大醫院 , 內科部血液科 , 骨髓移植病房 台灣大學台成幹細胞治療中心 . HSCT Center Advancement in NTUH. *HEPA: high-efficient particle absorbing. Largest HSCT center in Taiwan, 14 beds, >100 cases/year. Cumulative numbers of HSCT, 1983-2011 .

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Experience of Hematopoietic Stem Cell Transplantation in NTUH, 1983-2012

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  1. Experience of Hematopoietic Stem Cell Transplantation in NTUH, 1983-2012 唐季祿 醫師 台大醫院,內科部血液科,骨髓移植病房 台灣大學台成幹細胞治療中心

  2. HSCT Center Advancement in NTUH *HEPA: high-efficient particle absorbing Largest HSCT center in Taiwan, 14 beds, >100 cases/year

  3. Cumulative numbers of HSCT, 1983-2011 Allo-BMT 501 -PBSCT 611 -BM+PB 4 -PB+UCB 1 Auto-PBSCT 360 -BMT 36 -BM+PB 10 CBT 24 Total 1547 N 175101111 1191333 28474957535663 64 81 7972777077 7483104 151 151

  4. Annual Numbers of HSCT, 1983-2011 N=1547

  5. Types of Donor, 1983-2011 N=1547

  6. 5PW BMT ward Clean and safe environments Anteroom Pressure / Humidity Central monitor

  7. Friendly and comfortable patient support HEPA-class 10,000 room Toilet- dry/wet separated

  8. HEPA-room (class 10,000) Pressure-releasing facilities Toilet- dry/wet separated Family communication window Anti-mold painting

  9. Autologous Stem Cell Sources by Recipient Age, 1983-2011 Age≦20 yrs Age >20 yrs

  10. Allogeneic Stem Cell Sources by Recipient Age, 1983-2011 Age≦20 yrs Age >20 yrs

  11. Trends in Transplantation by Recipient Age, 1983-2011 N=84 N=322 N=380 N=761 % 8% 12% 32% > 50 y < 50 y Autologous Allogeneic

  12. Allogeneic transplantations by conditioning regimen intensity and age, 2000-2011

  13. 69 y, AML, CR2, s/p MUD-RIST, D+17,轉出隔離病房,D+24出院

  14. Transplant outcome for age older than 55 years of AML or high-risk MDS at NTUH (median age 58 y, 55 - 69) 3-yr overall survival 56.9% 2006 – 2012, unpublished

  15. Unrelated Donor Stem Cell Sources by Recipient Age, 1994-2011 Age >20 yrs Age≦20 yrs

  16. Indications of HSCT, 1983-2011 N=1547 %

  17. Reasons to do HSCT twice or more, 1983-2011 N=113 35 remains alive

  18. Numbers of 2nd Malignancy N=57 20 remains alive

  19. Overall Survival,1983-2011 Disease free survival, 1983-2011 692 dead, 719 alive, 242 remains alive more than 10 years

  20. Overall survival, by transplant eras, 1983-2011

  21. Main cause of death N=692

  22. Main cause of death – by Donor type Autologous Unrelated donor Matched sibling donor

  23. Overall survival after HLA-matched sibling donor transplantation for AML, by risk group and cell sources, 1984-2011

  24. Overall survival after HLA-matched sibling donor transplantation for ALL, by risk group and cell sources, 1984-2011

  25. Overall survival after HLA-matched sibling transplantation for CML, by risk group and transplant year, 1984-2011

  26. Overall survival after autologous transplantation for Lymphoma, by risk group, 1983-2011

  27. Overall survival for Lymphoma, by transplant type, 1983-2011

  28. Overall survival after allogeneic transplantation for MDS/MPD, 1986-2011

  29. Overall survival after allogeneic transplantation for Anemia, by age group, 1984-2011

  30. 108 / kg BW 106 / kg BW 18 18 Total cells 15 15 CD 34+ cells 12 12 9 p = 0.01 9 p < 0.001 6 6 3 3 0 0 BMT PBSCT (n= 55) (n- 34) BMT PBSCT (n= 55) (n- 34) Results of Stem Cell Yields in Allo-HSCT (Median and 95% C.I.)

  31. 1.0 0.8 0.6 0.4 0.2 0 Probability of Acute GVHD grade 2-4 in HLA-matched Allo-HSCT NTUH 1993-2008.07 P = 0.020 Probability PBSCT 27% (n =174) Allo-BMT 14% (n =180) 0 20 40 60 80 100 120 Time (Days)

  32. 1.0 0.8 0.6 0.4 0.2 0 Probability of chronic cGVHD in HLA-Identical Allo-HSCT NTUH 1993-2008.07 All type cGVHD Extensive cGVHD PBSCT 70% (n =142) PBSCT 48% (n =142) Probability P < 0.0001 P < 0.0001 BMT 25% (n =162) BMT 10% (n =162) 0 6 12 18 24 0 6 12 18 24 months months

  33. GVHD can improve 5-year Leukemia-free survival GVHD (+) 78% No GVHD 61% P =0.006

  34. 19M Stem Cell Donors Worldwide

  35. Allogeneic Transplants for Age > 20yrs,Registered with the CIBMTR 1992-2009- by Donor Type and Graft Source - Number of Transplants * * Data incomplete Slide 11 SUM-WW11_11.ppt

  36. 1.0 0.8 HLA-Matched sibling donor P = 0.05 0.6 0.4 Allo-PBSCT (n =34) 0.2 Allo-BMT (n =55) 0 0 60 120 Time (Days) First Taiwan UD-BMT Outcome Report (Shaw CK et al, BMT 23:727, 1999) • 1994~1997 Total 48 Taiwan patients analyzed Engraftment rate 83.3% Acute GVHD 80% ≧ grade 2 67.5% grade 3-4 37.5%  Similar to NMDP data but higher than that from JMDP, Japan

  37. Grade 3-4 acute GVHD 1.0 1.0 CsA + MTX 73% (12/22) 0.8 0.8 P < 0.0001 0.6 0.6 0.4 0.4 ATG + MMF/MTX 5% (1/35) FK-506 + MTX +Steroid 0% (0/17) 0.2 0.2 0 0 Post-HSCT days 0 20 40 60 80 100 Impact of GVHD Prophylaxis on Acute GVHD after URD-HSCT, NTUH 1994-2005 Grade 2-4 acute GVHD CsA + MTX 84% (18/22) P < 0.0001 ATG + MMF/MTX 47% (14/35) FK-506 + MTX 36% (4/17) 0 20 40 60 80 100 Post-HSCT days

  38. Improving 3y-OS after URD-HSCT in leukemia since 2004 in NTUH (n=254) SR + IR HR 2004-2012 52% (n=102) 2004-2012 50% (n=39) 1994-2003 24% (n=41) 1994-2003 8% (n=12) P < 0.001 P < 0.001

  39. Protocol for Allo-HSCT with PMRD F F F F F Fludarabine 30 mg/m2/d x 5d C C Cyclophosphamide 60 mg/Kg/d x 2d Fractional TBI total 1200 cGy or Busulfan 16 mg/Kg PBSCT D-8 D-7 D-6 D-5 D-4 D-3 D-2 D-1 D 0 D+1 D+2 D+3 D+4 Donor : G-CSF 10 ug/Kg/d x 5d A A A (rabbit) ATG 2.5 mg/Kg/d x 3d GVHD prophylaxis : CsA 3 mg/Kg/d, D-1~D+30 then taper Methotrexate

  40. Haploidentical HSCT ─ Results • All engrafted with 100% donor chimerism (FISH or STR) • Acute GVHD: 9% (1/11, grade 1) • Chronic GVHD: 100% (5/5, 2 extensive) • CMV infection: 73% (8/11), EBV-PTLD: 18% (2/11)

  41. Parental donor vs. URD HSCTNTUH 2001-2011

  42. AML: significant advancement in the past decades

  43. Intensity of Consolidation correlated with adult AML Survival (NTUH, 1985-1999) BMT (n=41) BMT (n=41) Standard C/T (n=182) Standard C/T (n=139) Low-dose or no C/T (n=24) Low-dose or no C/T (n=36) All patients (n=259) Patients age 50 years or less (n=204)

  44. HSCT for AML (NTUH, 1984-2011) • 425 HSCT, 54 received twice, total 479 • Auto-HSCT 33 (8%), allo-HSCT 392 (92%) • Sex (M: F) 213 : 212 • Median age (range) 32 y/o (1-69) • Disease status at HSCT • CR1 (SR) 176 (42%) • CR2 (IR) 143 (34%) • Relapsed/refractory (HR) 103 (24%)

  45. Comparable outcome of Auto- vs Allo-HSCT for AML in CR1 Overall Survival Relapse risk At 5 years, 62% vs. 64%, p=0.602 At 5 years, 33% vs. 29%, p=0.770 Allo-HSCT (n=155) Auto-HSCT (n=21) Auto-HSCT (n=21) Allo-HSCT (n=155)

  46. Poor outcome after auto-HSCT in AML >CR1 Overall Survival Relapse risk Auto-HSCT (n=9) 100% vs. 54%, p=0.003 At 5 years, 0% vs. 30%, p=0.196 Allo-HSCT (n=237) Allo-HSCT (n=237) Auto-HSCT (n=9) • Auto: 8 at CR2, 1 at CR3, all died, 8 relapse, 1 TRM

  47. Independent risk factors for OS in 325 AML Multivariate Cox regression analysis for OS

  48. Post-HSCT 5 year OS Post-HSCT 5 year RFS CEBPA double mutation 88% (n=9) CEBPA double mutation CEBPA double mutation 78% (n=9) Other genotypes 46% (n=91) Other genotypes 38% (n=91) P=0.045 P=0.045 CEBPA double mutation had better OS and RFS

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