Aplasia Midollare

Transcript

1 Aplasia Midollare

2 Anemia aplastica acquisita (SAA) E una malattia immunomediata Organo specifica (come il diabete I) Ha come effetto la distruzione delle Cellule Staminali Emopoietiche (CSE)

3 Citopenia Blasti Midollari?? Sì AL, MDS citogenetica NO Clonale (-7,-5,+8) DEB pos Normale MDS,AL Fanconi Anticorpi Sì Citop. periferica GPI No Clone GPI- AA/ EPN No acquired AA

4 AA patients treated with IS or BMT (n=2479) (EBMT) A % Overall Survival p< A= <16yy n=914 77% B= >=16yy n= % B 0 days from BMT Locasciulli et al,2007 Haematologica

5 BMT Issues Conditioning Stem Cell Source GvHD prophylaxis Donor Type

6 Survival after HLA identical sibling BMT according to age 0-20yr 0 20yr (n (n = 192) = 192) 20-30yr 30yr (n (n = 171) = 171) 30-40yr 40yr (n (n = 93) = 93) > > 40yr (n (n = 123) = 123) Years

7 100 AA patients treated BMT Match Sibling Donor A 75 % Overall Survival p< A= <16yy n=461 85% B= >=16yy n=814 71% B 0 Figure 1a days from BMT

8 HLA identical sibling BMT Cyclophosphamide + ATG Overall survival 80-90% Critical barriers Graft failure: 4-14% Acute GVHD: 12-30% Chronic GVHD: 30-40% Prior treatment with ATG Total abdominal irradiation Older age (> 40 yr) Age > 16 years (1) Prior immunosuppression (1) TAI (2) Kahl 2005, Ades 2004, Champlin 2006 update of 2004

9 BMT HLA id siblings # age effect # CY 200 +ALG= best regimen # GvHD proph CsA+MTX

10 100 AA patients treated BMT Alternative Donor % Overall Survival p=0.3 A= <16yy n=146 62% B= >=16yy n=146 50% A B 0 Figure 1b days from BMT

11 100 AA patients treated BMT Alternative Donor patients<16yy % Overall Survival B p=0.001 A= n=62 48% B= n=84 75% A 0 Figure 2b days from BMT

12 100 AA patients treated BMT Alternative Donor patients >=16yy % Overall Survival B p=0.01 A= n=48 38% B= n=98 63% A 0 Figure 3b days from BMT

13 MUD transplants for SAA: FLU+CY+TBI 2Gy+ATG n=19 79% % Overall Survival Median age 31 (7-46) Interval Dx-Tx 543 dd ( ) Number IS treatm pre-bmt= 2 Rejection 2 = 11% GvHD II+= 1 (5%) days from BMT

14 BMT Unrelate donors # age effect # UD Tx : results improving In children and adults # HLA typing

15 How do we solve the age effect # change SC source # change conditioning

16 Acquired Aplastic Anemia ; HLA id. siblings; transplanted BM PBSC EBMT/IBMTR PBSC study BM P< p < 0.01

17 PB Tx in SAA # more chronic GvHD # more late TRM # decreased Quality of Life

18 Consensus & Recommendation SAA Kyoto 2004: HLA id BMT Transplant protocol : HLA id siblings OLDER (>30) 1. CY ATG 8 2. Combination of CY+FLU or CY BU low dose Combination of CY + TBI 2

19 EBMT WPSAA protocol Conditioning regimens for patients aged 30+ HLA id sibs FLU 30 mg/m^2x4 CY 300 mg/m^2x4 ATG (thymo) 3.75 mg/kg x2 aiming at a mortality of <40%

20 IS therapy Data from EBMT WPSAA A.Locasciulli

21 SAA nsaa <1985 vsaa =>1995

22 ALG+CsA Resta la combinazione di prima scelta ALG H : gone ATG rabbit

23 AAA patients treated with IS A % Overall Survival A= <16yy n=304 79% B= >=16yy n=582 61% B p= Figure 5 days from IS

24 AAA patients treated with IS vsaa : PMN < A % Overall Survival A= <16yy n=175 83% B= >=16yy n=140 62% B p= Figure 6 days from IS

25 AAA patients treated with IS SAA nsaa PMN > A % Overall Survival A= <16yy n=129 74% B= >=16yy n=442 61% B p= Figure 7 days from IS

26 Should we use G-CSF together with ALG+CsA?? 1. Chugai trial (GCSF vs contr) BJH GITMO trial (5 vs 10 ug) Haematol 2004

27 % of Failure Free Survival Effect of WBC increase during GCSF treatment and survi GITMO trial WBC >14x10^9/l n= % 57% WBC 5-14x10^9/l n= % P= WBC<5x10^9/ n= Months from treatment

28 GITMO trial % of Survival Fig.4 P= Effect of age on survival Age <20 n=38 Age n=21 Age >40 n= Months from treatment 81% 80% 34%

29 Clonal Evolution after ATG All % AML/MDS Years after ALG Tichelli 1988

30 Clonal abnormalities afteralg+csa+gcsf % of clonal abnormalities non resp PR CR

31 AAA patients treated with IS PMN <200 AGE < >=1990 n=119 85% % Overall Survival p< <1990 n=66 51% 0 days from IS

32 Aree di ricerca: # trapianto prot elderly (>30yy) prot UD (FLU CY TBI) # IS random +/- GCSF random H vs R ATG (nsaa) phase II CAMPATH

33 M. Podestà, A. Pitto, G. Piaggio, MT Valle, F Frassoni MT Van Lint. Ematologia 2, S.Martino Genova E. Zocchi, S. Bruzzone, L. Franco, L. Guida, A. De Flore Biochimica Univ. Genova. GITMO Italia (pavia, cagliari, bolzano, vicenza, palermo, catania, napoli, ancona, bergamo, cuneo, torino) J Passweg, H Schrezenmeier e A Locasciulli WPSAA EBMT

34 Donna 64 anni, con Plt Blasti Midollari citogenetica NO Normale 2,4 gg sur Sì Citop. periferica TERAPIA: steroidi (1999); risposta Recidiva; splenectomia (2001); risposta Recidiva (2002)

35 Donna 64 anni, con Plt 5.000, splenectomizzata Nel 2002 Recidiva e ipoplasia midollare: talidomide risposta recidiva Nel 2002 Linfociti 40%-60% oligoclone gamma/delta Nel Ciclosporina ; risposta; recidiva Nel 2005 LDH Nel 2006 clone GPI- (CD14 20%, CD16 40%) Nel 2007 Hb 12; GB 9.000, L 73%, Pt MMF, CyA, pred

36 Donna nata 1934 Diagnosi? 1. AITP 2. MDS 3. EPN 4. Malattia linfoproliferativa