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

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Presentation on theme: "Jacek Wachowiak HEMOTOPOIETIC STEM CELL TRANSPLANTAION IN CHILDREN 2006/2007."— Presentation transcript:

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

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3 ANNUAL NUMBERS OF BLOOD AND MARROW TRANSPLANTS WORLDWIDE 1970-2000 MDM01_21.ppt NUMBER OF TRANSPLANTS YEAR 197019751980198519901995 0 5,000 10,000 15,000 20,000 25,000 30,000 35,000 40,000 Autologous Allogeneic 2000

4 ALLOGENEIC STEM CELL SOURCES BY AGE 1995-2000 % OF TRANSPLANTS SUM02_27.ppt 100 0 20 40 60 80 1995-19971998-20001995-19971998-2000 Bone Marrow Peripheral Blood Cord Blood Age 20 yrs

5 AUTOLOGOUS STEM CELL SOURCES BY AGE 1995-2000 SUM02_28.ppt % OF TRANSPLANTS 100 0 20 40 60 80 1995-19971998-20001995-19971998-2000 Bone Marrow (BM) Peripheral Blood (PB) BM + PB Age 20 yrs

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8 INDICATIONS FOR BLOOD AND MARROW TRANSPLANTATION (IBMTR / ABMTR, 2002) SUM02_45.ppt TRANSPLANTS 4,500 0 500 1,000 1,500 2,000 Non-Hodgkin Lymphoma AML CMLHodgkin Disease Ovarian Cancer Allogeneic (Total N = 6,700) Autologous (Total N = 11,000) 2,500 3,000 4,000 3,500 Multiple Myeloma Breast Cancer ALLMDS/Other Leukemia Other Cancer Non-Malignant Disease CLL

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

11 DiagnosisDisease phase HLA matchedalternative sibling donors 1 ALLI CR ( VHR ) 2 + II CR + + > II CR + + AMLI CR ( HR ) 3 ++ II CR + + MDS + + CMLchronic phase + + accel. /blastic crisis + + NHLI CR 4 + II CR + ++ Hodgkins diseaseI CR 5 + II CR 6 + SAA + + 7 Fanconi anemia + + Blackfana-Diamonda anemia + 8 + 8 Congenital immunodeficiences + + Inborn errors of metabolism + + Allogeneic HSCT Autologous HSCT INDICATIONS FOR HSCT IN CHILDREN WITH HAEMATOLOGICAL MALIGNANCIES AND NON-MALIGNANT DISEASE

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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

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

16 TREATMENT OF ALL IN CHILDREN

17 INDICATIONS FOR ALLO-HSCT IN CHILDREN WITH HR-ALL W I CR (acc. to ALL SCT I-BMF 2006) Criteria for allogeneic HSCT in CR1Transplantation groups MSDMDMMD MRD (timepoint 2, day 77) >10 -3 +++ MRD (timepoint 2, day 77) =10 -3 ++- NRd33+++ PPR +t(9;22)+++ PPR +t(4;11) #++- PPR +pro-B-ALL+(+)$- PPR +T-ALL(+)$ - PPR +M3-BM on day 15 *+(+)$- PPR + initial WBC 100.000/µL * +(+)$- PGR +t(9;22)++- PGR +t(4;11) #+--

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

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20 Kryteria kwalifikujące do allogenicznej HSCTTyp dawcy komórek krwiotwórczych CRGrupa ryzyka Lokalizacja wznowy i poziom MRD (po bloku F2 lub przed Prot II-IDA lub R2) PodgrupaMSDMDMMD CR2S2 BM MRD <10 -3 A--- B/C+-- Bez wyniku MRDA+-- B/C++- MRD 10 -3 A/B/C++- S2 IEM CNS, jedno jądroD--- Obustronne zajęcie jąder D++- S3 +++ S4 +++ >CR2 +++ S2 BMS2 z zajęciem szpiku kostnego S2 IEMS2 z izolowaną wznową pozaszpikową MRDMinimal Residual Disease INDICATIONS FOR ALLO-HSCT IN CHILDREN WITH ALL CR2 (ACC. ALL SCT I-BMF 2006)

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

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24 AIE 1 SR HR HAMAIhaMHAE AI 1 haM 1 HAE R Radioterapia Leczenie podtrzymujące 1 rok Cytarabina ith 1, 2 Allogeniczne przeszczepienie kom ó rek krwiotw ó rczych szpiku kostnego od zgodnego dawcy rodzinnego Indukcja 1 Indukcja 2 Konsolidacja Intensyfikacja Dzień 11521-28 42-5688 ~112 ~140 MRDMRD MRD MRDMRD 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:cytarabinaHAE:wysokie dawki cytarabina/ etopozyd I:idarubicynaR:randomizacja E:etopozydSR:grupa standardowego ryzyka HA:cytarabina wysokodawkowanaHR:grupa wysokiego ryzyka M:mitoksantronMRD:minimalna choroba resztkowa

25 TyPE OF DONOR MSDMDMMD 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++ + or auto-HSCT 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)

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27 PROBABILITY OF SURVIVAL AFTER HLA-IDENTICAL SIBLING TRANSPLANTS FOR AML BY REMISSION STATUS AND AGE, 1994-1999 PROBABILITY, % 100 0 20 40 60 80 0 YEARS SUM02_5.ppt P = 0.0001 CR2+, 20y (N = 184) CR1, 20y (N = 839) CR2+, 20y (N = 653) CR1, 20y (N = 2,449) 123 465

28 PROBABILITY OF SURVIVAL AFTER ALLOGENEIC TRANSPLANTS FOR AML BY DONOR TYPE AND REMISSION STATUS, 1994-1999 PROBABILITY, % 100 0 20 40 60 80 0 YEARS SUM02_4.ppt P = 0.0001 HLA-identical sibling, CR1 (N = 3,298) HLA-identical sibling, CR2+ (N = 837) Unrelated, CR1 (N = 424) Unrelated, CR2+ (N = 567) 123 465

29 PROBABILITY OF SURVIVAL AFTER AUTOTRANSPLANTS FOR AML AGE 20 YEARS, 1994-1999 PROBABILITY, % 100 0 20 40 60 80 0 YEARS SUM02_8.ppt P = 0.0001 123 465 CR1 (N = 209) CR2+ (N = 64) Not in remission (N = 29)

30 TREATMENT OF CMLIN CP (wg CML-paed II - 2006)

31 TREATMENT OF CML IN CP (wg CML-paed II - 2006)

32 TREATMENT OF CML IN AP (wg CML-paed II - 2006)

33 PROBABILITY OF SURVIVAL AFTER ALLOGENEIC TRANSPLANTS FOR CML IN CHRONIC PHASE BY DONOR TYPE AND DISEASE DURATION, 1994-1999 PROBABILITY, % 100 0 20 40 60 80 0 YEARS 123 46 SUM02_3.ppt P = 0.0001 HLA-identical sibling, 1y (N = 2,876) HLA-identical sibling, 1y (N = 1,391) Unrelated, 1y (N = 613) Unrelated, 1y (N = 936) 5

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) 012345 0.0 0.2 0.4 0.6 0.8 1.0 Locatelli F et al. Blood 2005

35 012345 YEARS AFTER TRANSPLANTATION 0.0 0.2 0.4 0.6 0.8 1.0 MFD: 0.14, SE=0.08 UD: 0.17, SE=0.08 MFD:N = 23 UD:N = 24 CUMULATIVE INCIDENCE Log Rank: p=n.s. Bu Cy Mel N = 37 Bu Cy + other N = 4 Bu Cy only N = 6 MFD: 0.86, SE=0.08 UD: 0.83, SE=0.08 SCT in RC Bu Cy (Mel): EFS and TRM by Donor EWOG-MDS, Interim Analysis, August 2004

36 012345 YEARS FROM HSCT 0.0 0.2 0.4 0.6 0.8 1.0 PROBABILITY (95% CI) UD = 45% (31-58) MFD = 67% (53-81) P = 0.02 MFD:N = 50; events = 15 UD:N = 61; events = 31 H MDS 2 EFS High Grade MDS by Donor 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: 2476-2482

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

39 DiagnosisDisease stage HLA matchedalternative sibling donors ALLI CR ( VHR ) + II CR + ++ > II CR + + AMLI CR ( HR ) ++ II CR + ++ MDS + + CMLCP I + + AP / BP + + NHLI CR + II CR + ++ Choroba HodgkinaI CR + II CR + Neuroblastoma + CNS tumors + Ewingas tumor + Soft tissue sarcoma + Nephroblastoma + AlloAuto INDICATIONS FOR HSCT IN SOLID TUMORS IN CHILDREN

40 RESULTS OF AUTOLOGOUS HSCT IN CHILDREN WITH SOLID TUMORS AUTHORNUMBER OF CHILDREN DIAGNOSIS & DISEASE STAGE pDFS (%) Matthay, 1999379 High risk neuroblastoma in I CR 43 Graham, 1997 Dunkel, 1998 Guruangan, 1999 23 49 20 CNS tumors<10 – 50% Ladenstein, 199563Ewings sarcoma21% Grupa Robocza ds. Guzów Litych przy EBMT 52Soft tissue sarcoma30 Kremens, 200225Nephroblastoma51

41 PROBABILITY OF SURVIVAL AFTER AUTOTRANSPLANTS FOR NEUROBLASTOMA 1994-1999 PROBABILITY, % 100 0 20 40 60 80 0 YEARS 123 46 SUM02_26.ppt P = NS 5 Remission (N = 412) Not in remission (N = 327)

42 DiagnosisDisease phase HLA matchedalternative sibling donors 1 ALLI CR ( VHR ) 2 + II CR + + > II CR + + AMLI CR ( HR ) 3 ++ II CR + + MDS + + CMLchronic phase + + accel. /blastic crisis + + NHLI CR 4 + II CR + ++ Hodgkins diseaseI CR 5 + II CR 6 + SAA + + 7 Fanconi anemia + + Blackfana-Diamonda anemia + 8 + 8 Congenital immunodeficiences + + Inborn errors of metabolism + + Allogeneic HSCT Autologous HSCT INDICATIONS FOR HSCT IN CHILDREN WITH HAEMATOLOGICAL MALIGNANCIES AND NON-MALIGNANT DISEASE

43 PROBABILITY OF SURVIVAL AFTER ALLOGENEIC TRANSPLANTS FOR SEVERE APLASTIC ANEMIA BY DONOR TYPE AND AGE, 1994-1999 PROBABILITY, % 100 0 20 40 60 80 0 YEARS 123 46 SUM02_14.ppt P = 0.0001 5 HLA-identical sibling, 20y (N = 845) HLA-identical sibling, 20y (N = 844) Unrelated, 20y (N = 114) Unrelated, 20y (N = 244)

44 PROBABILITY OF SURVIVAL AFTER ALLOGENEIC TRANSPLANTS FOR FANCONI ANEMIA BY DONOR TYPE AND AGE, 1994-1999 PROBABILITY, % 100 0 20 40 60 80 0 YEARS 123 46 SUM02_15.ppt P = 0.0001 5 HLA-identical sibling, 10y (N = 109) Unrelated, 10y (N = 36) HLA-identical sibling, 10y (N = 100) Unrelated, 10y (N = 58)


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