1. Il trapianto allogenico da donatore alternativo dopo condizionamento a ridotta intensità
Alessandro Rambaldi

2. The role of the conditioning regimen and
Is the donor type (related or unrelated) still an issue in the setting of RIC allograft?
The role of the conditioning regimen and
GVHD prophylaxis

3. Perez-Simon et al: Blood. 2002;100:3121-3127
Nonmyeloablative transplantation with or without alemtuzumab: comparison between 2 prospective studies in patients with lymphoproliferative disorders
Perez-Simon et al: Blood. 2002;100:
Transplantation-related mortality

4. Perez-Simon et al: Blood. 2002;100:3121-3127
Nonmyeloablative transplantation with or without alemtuzumab: comparison between 2 prospective studies in patients with lymphoproliferative disorders
Perez-Simon et al: Blood. 2002;100:
The conditioning regimen
fludarabine 150 mg/m2 +
melphalan 140 mg/m2
Event Free Survival

5. Perez-Simon et al.: BBMT 14:664-671 (2008)
Reduced-Intensity Conditioning Allogeneic Transplantation from Unrelated Donors: Evaluation of Mycophenolate Mofetil Plus Cyclosporin A as Graft versus- Host Disease Prophylaxis
Two RIC regimens
The lymphoid RIC regimen
fludarabine 150 mg/m2 and melphalan 70 mg/m2
2) The myeloid RIC regimen
fludarabine 150 mg/m2 and busulfan 1 mg/kg for 10 doses (days-6 to-4) total 10 mg/kg
Perez-Simon et al.: BBMT 14: (2008)

6. Perez-Simon et al.: BBMT 14:664-671 (2008)
Reduced-Intensity Conditioning Allogeneic Transplantation from Unrelated Donors: Evaluation of Mycophenolate Mofetil Plus Cyclosporin A as Graft versus- Host Disease Prophylaxis
Perez-Simon et al.: BBMT 14: (2008)

7. Perez-Simon et al.: BBMT 14:664-671 (2008)
Reduced-Intensity Conditioning Allogeneic Transplantation from Unrelated Donors: Evaluation of Mycophenolate Mofetil Plus Cyclosporin A as Graft versus- Host Disease Prophylaxis
Perez-Simon et al.: BBMT 14: (2008)

8. OS for patients over age 50 after nonmyeloablative or myeloablative transplantation
Alyea, E. P. et al. Blood 2005;105:
Copyright ©2005 American Society of Hematology. Copyright restrictions may apply.

9. Factors having an impact on PFS
Alyea, E. P. et al. Blood 2005;105:
Copyright ©2005 American Society of Hematology. Copyright restrictions may apply.

10. Cumulative incidence of TRM and risk of relapse after nonmyeloablative or myeloablative transplantation for patients over the age of 50
Myeloablative TRM
Nonmyeloablative relapse
Nonmyeloablative TRM
Myeloablative relapse
Myeloablative relapse
Alyea, E. P. et al. Blood 2005;105:
Copyright ©2005 American Society of Hematology. Copyright restrictions may apply.

11. Eight-year experience with allogeneic stem cell transplantation for relapsed follicular lymphoma after nonmyeloablative conditioning with fludarabine, cyclophosphamide, and rituximab Khouri IF et al. Blood. 2008;111:

12. Unrelated hematopoietic stem cell transplantation with reduced intensity regimens in high-risk patients for age or disease: results from two independent prospective GITMO studies
for Gruppo Italiano Trapianti di Midollo Osseo (GITMO)
and Italian Bone Marrow Donor Registry (IBMDR)

13. Patients who activated an UD search N = 326
Patients who underwent a UD allograft
N = 121 (37%)
Patients who stopped the UD search
N = 171 (53%)
Death, N=90 (28%)
Another protocol, N=33 (10%)
No longer eligible, N=33 (10%)
Donor not available, N=9 (3%)
Withdrawn consent, N=6 (2%)
Patients who still have an ongoing search
N = 34 (10%)

14. Patients characteristics by treatment strategy
Univariate analyses.*Non parametric test for the medians; § Fisher exact test

15. Results of 121 patients actually allografted

16. Clinical results of allografted patients
Program A: TBI+Alemtuzumab+Fludarabine+Melphalan; Program B: Thiotepa+Cyclophamide+ATG
* Risk status at transplant defined as standard for 1st and 2nd CR or CML in Chronic Phase. High risk for 3rd CR or more, PR, refractory relapse, active disease, chemotherapy resistant
† Defined as PMN > 500x109/L

17. Clinical results of allografted patients
Program A: TBI+Alemtuzumab+Fludarabine+Melphalan; Program B: Thiotepa+Cyclophamide+ATG

18. OS OS EFS EFS OS OS EFS EFS
All patients (N=121) Acute Leukemias (N=27) OS OS
EFS
EFS A B
Non Hodgkin Lymphoma (N=30) Hodgkin Disease (N=41) OS OS
EFS
EFS C D

19. TRM TRM RR RR A B TRM TRM RR RR C D
All patients (N=121) Acute Leukemias (N=27)
TRM
TRM RR RR A B
Non Hodgkin Lymphoma (N=30) Hodgkin Disease (N=41)
TRM
TRM RR RR C D

20. Incidence of Acute and Chronic Graft versus Host Disease.2 .4 .6 .8 1 50
100
150
200
Days from transplant
Grades 2-4: 44%
Grades 3-4: 20% .2 .4 .6 .8 1
100
200
300
400
500
Days from transplant
Acute GVHD
Chronic GVHD
Chronic GVHD: 25%
Extensive GVHD: 9% A B

21. Impact of allogeneic transplant on Overall Survival by diagnosis (1)
Multivariable Cox proportional hazard models.
* Time-dependent covariate

22. Impact of allogeneic transplant on Overall Survival by diagnosis (2)
Multivariable Cox proportional hazard models.
* Time-dependent covariate

23. Prognostic factors for the prediction of Overall Survival
Multivariable Cox proportional hazard model.
* Time-dependent covariate

24. Protocollo GlobAl
Confronto randomizzato tra regimi di condizionamento a ridotta intensità contenenti rispettivamente Globulina Anti Linfocitaria verso Alemtuzumab nel trapianto allogenico da donatore non familiare
Sponsorizzato dal GITMO
Gruppo Italiano Trapianto Midollo Osseo

25. Curve di reclutamento
Il protocollo prevede l’arruolamento di pazienti.
I risultati della analisi ad interim saranno disponibili a metà Novembre e permetteranno di prendere una decisione sulla opportunità di chiudere la fase di reclutamento.

26. Decessi
Follow-up post trapianto (mediana 6.0 mesi [0.4 – 25.7])

27. Conclusions The conditioning regimen The GVHD prophylaxis
The patients you are selecting for the allograft