Frontline alternative donor SCT versus IST for children with SAA who lack matched related donor Hyoung Jin Kang
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1 Frontline alternative donor SCT versus IST for children with SAA who lack matched related donor Hyoung Jin Kang Department of Pediatrics, Cancer Research Institute, Seoul National University College of Medicine, Seoul National University Children s Hospital, Seoul, Republic of Korea
2 Korean Society of Hematology COI disclosure Name of author : Hyoung Jin Kang I have no personal or financial interests to declare: I have no financial support from an industry source at the curre nt presentation.
3 Treatment of choice for Young SAA patient with Matched related donor
4 Classic Treatment Strategy for SAA Blood. 2012;120:1185
5 BM > PB (IBMTR) cgvhd OS
6 BM > PB (EBMT)
7 BM > PB (EBMT)
8 Treatment of choice for SAA patient with Matched related donor BMT > PBSCT
9 Radiation and Solid tumor Risk factor for solid tumor after BMT 1. Age (RR = 1.11 per year) 2. Radiation (RR = 9.56)
10 Radiation increase Tumor
11 Treatment of choice for SAA patient with Matched related donor BMT without RT
12 CyATG = Cy (IBMTR)
13 Death with cgvhd after 5 years
14 ATG for cgvhd prophylaxis: unrelated setting (ATG-F Group)
15 ATG for cgvhd prophylaxis: related setting (Alberta, Canada)
16 ATG for cgvhd prophylaxis: related setting (Hamburg, Germany)
17 Treatment of choice for SAA patient with Matched related donor BMT with Cy ± ATG (No RT)
18 CsA+MTX vs CsA
19 Treatment of choice for SAA If Matched Sibling Donor (+) HSCT with Bone Marrow Conditioning regimen: Cy ± ATG (No RT) GVHD prophylaxis: CsA + MTX
20 Treatment of choice for SAA patient without Matched related donor
21 Classic Treatment Strategy for SAA Blood. 2012;120:1185
22 Unrelated SCT for SAA Optimal conditioning in SAA for BMT with matched related donor CPM + ATG with MTX + CsA GVHD prophylaxis: survival about 90% Optimal conditioning for unrelated donor transplantation Not determined Conditioning Survival (%) CPM + ATGAM 20% (Seattle, 1996) 2-6 Gy TBI + CPM + ATGAM 58% (NMDP, 2001) TBI/LFI + CPM ATG 56% (JMDP, 2002)
23 SAA retrospective study by KSPHO Jeong DC. J Pediatr Hematol Oncol. 2011;33:172.
24 IST vs USCT after 1 st IST failure Year 2008 Failure Free S 2 nd line after IST USCT
25 Treatment of choice for SAA patient without Matched related donor IST USCT after IST failure
26 Results of unrelated SCT Blood. 2012;120:1185 Survival: 51-94%
27 Unrelated SCT for SAA (CMC) SR 75%
28 Unrelated SCT for SAA (CMC) SR 88%
29 Unrelated SCT for SAA (JCAASG) Recommended conditioning regimen CY 120 mg/kg Rabbit ATG 10 mg/kg TBI 10 Gy OS: 93% or CY 3000 mg/m^2 Rabbit ATG 10 mg/kg Fludarabine 100 mg/m^2 Local field irradiation 3 Gy
30 Unrelated SCT for SAA (BMTCTN) Conditioning regimen CY study dose Rabbit ATG 9 mg/kg Fludarabine 120 mg/m^2 TBI 2 Gy
31 Development of unrelated SCT
32 Unrelated SCT for SAA (EBMT) No RT
33 2 Prospective SAA USCT study by Korean Society of Ped HO
34 Background of KSPHO SAA study First fludarabine based conditioning for SAA MD Anderson, 2 unrelated + 3 familial mismatched (BMT, 2001) variable combinations of Fluda + CPM + ATGAM good engraftment but severe GVHD Thymoglobulin potent than other ATG in preventing GVHD and rejection of solid organ transplants 1. To avoid TBI toxicity for children: fludarabine 2. To allow good engraftment and reduce GVHD: thymoglobulin Fluda + CPM + thymoglobulin conditioning for UD transplant in SAA
35 Pilot Study of USCT Day CPM 50 mg/kg Fluda 30 mg/m 2 ratg 2.5 mg/kg ubmt/pbsct Kang HJ. Bone Marrow Transplant Results 5 patients: full engraftment in all 1 TRM: adenoma rupture 1 st Muticenter Prospective Study
36 1 st Prospective Study ( ) Kang HJ. Biol Blood Marrow Transplant Results Engraftment: 100% TRM: 9/28 Thrombotic microangiopathy (N=2) Pneumonia (N=1) Myocardiac infarction (N=1) PTLD (N=3) cgvhd-associated complications (N=2)
37 2 nd Study: reduced toxicity conditioning Study 1 Day CPM 50 mg/kg Fluda 30 mg/m 2 ratg 2.5 mg/kg ubmt/pbsct CPM 200 mg/kg 120 mg/kg Fluda 120 mg/m mg/m 2 Study 2 Day CPM 60 mg/kg Fluda 40 mg/m 2 ratg 2.5 mg/kg ubmt/pbsct GVHD prophylaxis (Allow institutional protocol)
38 2 nd Prospective Study ( ) Kang HJ. Biol Blood Marrow Transplant Results TRM: 1/29 Pneumonia (N=1)
39 MRD = Alternative donor (Texas Children s Hospital, Houston, USA)
40 MRD = UD Long term outcome (National Univ. Hosp. Copenhagen, Denmark) OS Related (N=25) 96% Unrelated (N=26) 89%
41 Upfront USCT = MSD SCT (UK, EBMT) Upfront USCT = MSD SCT
42 Upfront USCT vs IST OS: Upfront USCT = IST EFS: Upfront USCT > IST
43 Upfront USCT vs Post-IST USCT OS: Upfront USCT > Post-IST USCT EFS: Upfront USCT > Post-IST USCT
44 Upfront USCT vs IST (Samsung Medical Center, Seoul, Korea) OS: Upfront USCT = IST EFS: Upfront USCT > IST
45 Upfront USCT vs Post-IST USCT EFS: Upfront USCT > Post-IST USCT
46 Sub-analysis KSPHO study Upfront USCT > Post-IST USCT History of IST was a risk factor of overall survival Upfront: 89.2% > Post-IST: 70%
47 Treatment Strategy for SAA 2012 Blood. 2012;120:1185
48 For children, outcomes after UD HSCT are similar to those of matched sibling donor HSCT, resulting in the move to consider UD HSCT as first-line therapy for SAA in the absence of a matched sibling donor. (2013 ASH) Hematology Am Soc Hematol Educ Program. 2013;2013:82
49 Treatment Strategy for SAA 2017 Blood. 2017;129:1428
50 Korean Guideline for SAA 2016
51 IST horse ATG > rabbit ATG (Western)
52 IST horse ATG > rabbit ATG (East Asian)
53 IST (horse ATG)+TPO for Age 2yrs Improved Response rates Historical cohort: 66% vs IST+TPO: 87% Outcomes of USCT should be compared with recently improved IST.
54 Conclusions 1. SAA with MRD & Age < 40 yrs BMT, CyATG, CsA+MTX standard tx. 2. SAA without MRD & Age < 20 yrs Front line SCT with MUD c non-radiation conditioning vs IST with Horse ATG+TPO No direct evidence yet. Time for prospective randomization study.
55 Thank You Esp. to Members of Korean Society of Pediatric Hematology-Oncology
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