1. Jacek Wachowiak HEMOTOPOIETIC STEM CELL TRANSPLANTAION IN CHILDREN 2006/2007

3. ANNUAL NUMBERS OF BLOOD AND MARROW TRANSPLANTS WORLDWIDE 1970-2000
5,000
10,000
15,000
20,000
25,000
30,000
35,000
40,000
Autologous
NUMBER OF TRANSPLANTS
Allogeneic
1970
1975
1980
1985
1990
1995
2000
YEAR
MDM01_21.ppt

4. ALLOGENEIC STEM CELL SOURCES BY AGE
100
Bone Marrow
Peripheral Blood
Cord Blood 80 60
% OF TRANSPLANTS 40 20
Age £20 yrs
Age >20 yrs
SUM02_27.ppt

5. AUTOLOGOUS STEM CELL SOURCES BY AGE
100
Bone Marrow (BM)
Peripheral Blood (PB)
BM + PB 80 60
% OF TRANSPLANTS 40 20
Age £20 yrs
Age >20 yrs
SUM02_28.ppt

8. INDICATIONS FOR BLOOD AND MARROW TRANSPLANTATION (IBMTR / ABMTR, 2002)
4,500
Allogeneic (Total N = 6,700)
Autologous (Total N = 11,000)
4,000
3,500
3,000
2,500
TRANSPLANTS
2,000
1,500
1,000
500
Non-Hodgkin Lymphoma
AML
Breast Cancer
Hodgkin Disease
Other Cancer
CML
ALL
MDS/Other Leukemia
CLL
Ovarian Cancer
Multiple Myeloma
Non-Malignant Disease
SUM02_45.ppt

10. INDICATIONS FOR 552 ALLOGENEIC HSct IN POLISH CHILDREN 1989-2005

11. INDICATIONS FOR HSCT IN CHILDREN WITH HAEMATOLOGICAL MALIGNANCIES AND NON-MALIGNANT DISEASE
Allogeneic HSCT Autologous HSCT
Diagnosis Disease phase HLA matched alternative sibling donors 1   ALL I CR ( VHR )   II CR   > II CR   AML I CR ( HR )   II CR   MDS   CML chronic phase   accel. /blastic crisis   NHL I CR   II CR   Hodgkin’s disease I CR   II CR   SAA   Fanconi anemia   Blackfana-Diamonda anemia   Congenital immunodeficiences   Inborn errors of metabolism  

13. McCann SR, Lawler M Monitoring outcome: MRD, chimaerism and relapse In : The EBMT Handbook 2004, Eds. J Apperley, E Carreras, E Gluckman, A Gratwohl, T Masszi

15. CAUSES OF DEATH AFTER TRANSPLANTS DONE IN 1996-2000
AUTO
Infection (5%)
Other (7%)
Organ toxicity
(7%)
Relapse (78%)
IPn (3%)
CAUSES OF DEATH AFTER TRANSPLANTS DONE IN
(ABMTR / IBMTR)
HLA-ID SIB
Infection
(17%)
Other
(12%)
Organ toxicity
(14%)
Relapse (34%)
IPn (8%)
GVHD (15%)
UNRELATED
Infection (21%)
Other
(17%)
Organ toxicity
15%)
Relapse (23%)
IPn (9%)
GVHD
(15%)

16. TREATMENT OF ALL IN CHILDREN

17. Transplantation groups
INDICATIONS FOR ALLO-HSCT IN CHILDREN WITH HR-ALL W I CR (acc. to ALL SCT I-BMF 2006)
Criteria for allogeneic HSCT in CR1
Transplantation groups
MSD MD
MMD
MRD (timepoint 2, day 77) >10-3 +
MRD (timepoint 2, day 77) =10-3 -
NRd33
PPR
t(9;22)
t(4;11) #
pro-B-ALL
(+)$
T-ALL
M3-BM on day 15 *
initial WBC  /µL *
PGR

18. pEFS in children with VHR-ALL treated according to protocol BFM-95  MSD-BMT

20. Typ dawcy komórek krwiotwórczych Lokalizacja wznowy i poziom MRD
INDICATIONS FOR ALLO-HSCT IN CHILDREN WITH ALL  CR2 (ACC. ALL SCT I-BMF 2006)
Kryteria kwalifikujące do allogenicznej HSCT
Typ dawcy komórek krwiotwórczych CR
Grupa ryzyka
Lokalizacja wznowy i poziom MRD
(po bloku F2 lub przed
Prot II-IDA lub R2)
Podgrupa
MSD MD
MMD
CR2
S2 BM
MRD <10-3 A -
B/C +
Bez wyniku MRD
MRD ≥10-3
A/B/C
S2 IEM
CNS, jedno jądro D
Obustronne zajęcie jąder S3 S4
>CR2
S2 BM S2 z zajęciem szpiku kostnego S2 IEM S2 z izolowaną wznową pozaszpikową MRD Minimal Residual Disease

21. __ __ SCT: n = 73; CCR = 28; pEFS = .37  .06
pEFS in children with ALL in relapse type S3 or S4 according to treatment option (CHT vs CHT + HSCT) (BFM Study 95/96)
__ __ SCT: n = 73; CCR = 28; pEFS = .37  .06
______ no SCT: n = 33; CCR = 5; pEFS = .00  .00
p < 0.001

22. Woolfrey, A. E. et al. Blood 2002; 99: 2002-2008
Figure 1.
Woolfrey, A. E. et al. Blood 2002; 99:
Copyright ©2002 American Society of Hematology. Copyright restrictions may apply.

24. AIE1 SR HR HAM AI haM HAE AI1 haM1 R Radioterapia
Leczenie podtrzymujące
1 rok
Cytarabina ith 1, 2
Allogeniczne przeszczepienie komórek krwiotwórczych szpiku kostnego od zgodnego dawcy rodzinnego
Indukcja Indukcja Konsolidacja Intensyfikacja
▼ ▼ ▼ ▼ ▼ ▼ ▼
Dzień ~ ~140
MRD MRD MRD MRD MRD MRDa MRDa
a – u pacjentów z obecnym markerem molekularnym
1 – inne postępowanie dla dzieci z AML w zespole Downa i dla dzieci z AML M3
2 – jeden raz w tygodniu, przez 4 tygodnie od rozpoczęcia leczenia podtrzymującego
A: cytarabina HAE: wysokie dawki cytarabina/ etopozyd
I: idarubicyna R: randomizacja
E: etopozyd SR: grupa standardowego ryzyka
HA: cytarabina wysokodawkowana HR: grupa wysokiego ryzyka
M: mitoksantron MRD: minimalna choroba resztkowa

25. TYPE OF HSCT I TYPE OF DONOR IN CHILDREN
WITH DE NOVO AML RESISTANT TO TREATMENT AND IN CHILDREN WITH AML IN CR2
(WG AML SCT BFM-2005)
TyPE OF DONOR
MSD MD
MMD
De novo AML treated acc. to AML-BFM-2005 Interim
- no CR after Induction 2 or
- aplastic BM after 6 weeks from Induction 2 +
CR2 - CR1 < 18 months
CR2 - CR1 > 18 months
or auto-HSCT
CR3

27. PROBABILITY OF SURVIVAL AFTER HLA-IDENTICAL SIBLING TRANSPLANTS FOR AML BY REMISSION STATUS AND AGE,
100 80
CR1, <20y (N = 839) 60
CR1, ³20y (N = 2,449)
PROBABILITY, %
CR2+, ³20y (N = 653) 40
CR2+, <20y (N = 184) 20
P = 1 2 3 4 5 6
YEARS
SUM02_5.ppt

28. PROBABILITY OF SURVIVAL AFTER ALLOGENEIC TRANSPLANTS FOR AML BY DONOR TYPE AND REMISSION STATUS,
100 80
HLA-identical sibling, CR1 (N = 3,298) 60
PROBABILITY, %
HLA-identical sibling, CR2+ (N = 837) 40
Unrelated, CR2+ (N = 567) 20
Unrelated, CR1 (N = 424)
P = 1 2 3 4 5 6
YEARS
SUM02_4.ppt

29. PROBABILITY OF SURVIVAL AFTER AUTOTRANSPLANTS FOR AML AGE £20 YEARS, 1994-1999
100 80 60
CR1 (N = 209)
PROBABILITY, % 40
CR2+ (N = 64) 20
Not in remission (N = 29)
P = 1 2 3 4 5 6
YEARS
SUM02_8.ppt

30. TREATMENT OF CMLIN CP
(wg CML-paed II )

31. TREATMENT OF CML IN CP
(wg CML-paed II )

32. TREATMENT OF CML IN AP
(wg CML-paed II )

33. PROBABILITY OF SURVIVAL AFTER ALLOGENEIC TRANSPLANTS FOR CML IN CHRONIC PHASE BY DONOR TYPE AND DISEASE DURATION,
100 80
HLA-identical sibling, <1y (N = 2,876) 60
HLA-identical sibling, ³1y (N = 1,391)
PROBABILITY, %
Unrelated, <1y (N = 613) 40
Unrelated, ³1y (N = 936) 20
P = 1 2 3 4 5 6
YEARS
SUM02_3.ppt

34. JMML Event-Free Survival by Donor
YEARS AFTER TRANSPLANTATION
PROBABILITY (95%CI)
MFD: N = 48; E = 21
UD: N = 52; E = 26
P = N.S.
MFD = 55% (41-70)
UD = 49% (35-63) 1 2 3 4 5 . 6 8
Locatelli F et al. Blood 2005

35. SCT in RC Bu Cy (Mel): EFS and TRM by Donor1 .
MFD: 0.86, SE=0.08 . 8
UD: 0.83, SE=0.08
MFD: N = 23
UD: N = 24 . 6
Bu Cy Mel N = 37
Bu Cy + other N = 4
Bu Cy only N = 6
CUMULATIVE INCIDENCE . 4
UD: 0.17, SE=0.08 . 2
MFD: 0.14, SE=0.08
Log Rank: p=n.s. . 1 2 3 4 5
YEARS AFTER TRANSPLANTATION
EWOG-MDS, Interim Analysis, August 2004

36. EFS High Grade MDS by Donor
H MDS 2
EFS High Grade MDS by Donor 1 . . 8
MFD = 67% (53-81) . 6
P = 0.02
PROBABILITY (95% CI)
UD = 45% (31-58) . 4 . 2
MFD: N = 50; events = 15
UD: N = 61; events = 31 . 1 2 3 4 5
YEARS FROM HSCT
4 / 2003

37. A comparison of allogeneic and autologous bone marrow transplantation for lymphoblastic lymphoma Levine JE, Harris RE, Loberiza FR et al. on behalf of IBMTR i ABMTR Blood 2003; 101:

38. INDICATIONS FOR HSCT IN CHILDREN WITH ALCL (wg EICNHL 2004)

39. INDICATIONS FOR HSCT IN SOLID TUMORS IN CHILDREN
Allo Auto
Diagnosis Disease stage HLA matched alternative sibling donors   ALL I CR ( VHR )   II CR   > II CR   AML I CR ( HR )   II CR   MDS   CML CP I   AP / BP   NHL I CR   II CR   Choroba Hodgkina I CR   II CR Neuroblastoma   CNS tumors   Ewinga’s tumor Soft tissue sarcoma   Nephroblastoma   

40. RESULTS OF AUTOLOGOUS HSCT IN CHILDREN WITH SOLID TUMORS
AUTHOR
NUMBER
OF CHILDREN
DIAGNOSIS & DISEASE STAGE
pDFS (%)
Matthay, 1999
379
High risk neuroblastoma in I CR 43
Graham, 1997
Dunkel, 1998
Guruangan, 1999 23 49 20
CNS tumors
<10 – 50%
Ladenstein, 1995 63
Ewing’s sarcoma
21%
Grupa Robocza ds.
Guzów Litych przy
EBMT 52
Soft tissue sarcoma 30
Kremens, 2002 25
Nephroblastoma 51

41. PROBABILITY OF SURVIVAL AFTER AUTOTRANSPLANTS FOR NEUROBLASTOMA 1994-1999
100 80 60
Remission (N = 412)
PROBABILITY, % 40
Not in remission (N = 327) 20
P = NS 1 2 3 4 5 6
YEARS
SUM02_26.ppt

42. INDICATIONS FOR HSCT IN CHILDREN WITH HAEMATOLOGICAL MALIGNANCIES AND NON-MALIGNANT DISEASE
Allogeneic HSCT Autologous HSCT
Diagnosis Disease phase HLA matched alternative sibling donors 1   ALL I CR ( VHR )   II CR   > II CR   AML I CR ( HR )   II CR   MDS   CML chronic phase   accel. /blastic crisis   NHL I CR   II CR   Hodgkin’s disease I CR   II CR   SAA   Fanconi anemia   Blackfana-Diamonda anemia   Congenital immunodeficiences   Inborn errors of metabolism  

43. PROBABILITY OF SURVIVAL AFTER ALLOGENEIC TRANSPLANTS FOR SEVERE APLASTIC ANEMIA BY DONOR TYPE AND AGE,
100 80
HLA-identical sibling, £20y (N = 844) 60
HLA-identical sibling, >20y (N = 845)
PROBABILITY, %
Unrelated, £20y (N = 244) 40
Unrelated, >20y (N = 114) 20
P = 1 2 3 4 5 6
YEARS
SUM02_14.ppt

44. PROBABILITY OF SURVIVAL AFTER ALLOGENEIC TRANSPLANTS FOR FANCONI ANEMIA BY DONOR TYPE AND AGE,
100
HLA-identical sibling, £10y (N = 109) 80
HLA-identical sibling, >10y (N = 100) 60
PROBABILITY, % 40
Unrelated, £10y (N = 36) 20
P =
Unrelated, >10y (N = 58) 1 2 3 4 5 6
YEARS
SUM02_15.ppt