Il trapianto allogenico da donatore alternativo dopo condizionamento
- Slides: 27
Il trapianto allogenico da donatore alternativo dopo condizionamento a ridotta intensità Alessandro Rambaldi
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
Nonmyeloablative transplantation with or without alemtuzumab: comparison between 2 prospective studies in patients with lymphoproliferative disorders Perez-Simon et al: Blood. 2002; 100: 3121 -3127 Transplantation-related mortality
Nonmyeloablative transplantation with or without alemtuzumab: comparison between 2 prospective studies in patients with lymphoproliferative disorders Perez-Simon et al: Blood. 2002; 100: 3121 -3127 The conditioning regimen fludarabine 150 mg/m 2 + melphalan 140 mg/m 2 Event Free Survival
Reduced-Intensity Conditioning Allogeneic Transplantation from Unrelated Donors: Evaluation of Mycophenolate Mofetil Plus Cyclosporin A as Graft versus- Host Disease Prophylaxis Two RIC regimens 1) The lymphoid RIC regimen fludarabine 150 mg/m 2 and melphalan 70 mg/m 2 2) The myeloid RIC regimen fludarabine 150 mg/m 2 and busulfan 1 mg/kg for 10 doses (days-6 to-4) total 10 mg/kg 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: 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: 664 -671 (2008)
OS for patients over age 50 after nonmyeloablative or myeloablative transplantation Alyea, E. P. et al. Blood 2005; 105: 1810 -1814 Copyright © 2005 American Society of Hematology. Copyright restrictions may apply.
Factors having an impact on PFS Alyea, E. P. et al. Blood 2005; 105: 1810 -1814 Copyright © 2005 American Society of Hematology. Copyright restrictions may apply.
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 Copyright © 2005 American Society of Hematology. Copyright restrictions may apply. Alyea, E. P. et al. Blood 2005; 105: 1810 -1814
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: 5530 -5536
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)
Patients who activated an UD search N = 326 Patients who underwent a UD allograft Patients who stopped the UD search Patients who still have an ongoing search N = 171 (53%) N = 121 (37%) 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%) N = 34 (10%)
Patients characteristics by treatment strategy Univariate analyses. *Non parametric test for the medians; § Fisher exact test
Results of 121 patients actually allografted
Clinical results of allografted patients Program A: TBI+Alemtuzumab+Fludarabine+Melphalan; Program B: Thiotepa+Cyclophamide+ATG * Risk status at transplant defined as standard for 1 st and 2 nd CR or CML in Chronic Phase. High risk for 3 rd CR or more, PR, refractory relapse, active disease, chemotherapy resistant † Defined as PMN > 500 x 109/L
Clinical results of allografted patients Program A: TBI+Alemtuzumab+Fludarabine+Melphalan; Program B: Thiotepa+Cyclophamide+ATG
All patients (N=121) Acute Leukemias (N=27) OS OS EFS A B Non Hodgkin Lymphoma (N=30) Hodgkin Disease (N=41) OS OS EFS C D
All patients (N=121) Acute Leukemias (N=27) TRM RR RR A B Non Hodgkin Lymphoma (N=30) Hodgkin Disease (N=41) TRM RR C RR D
1 1 Incidence of Acute and Chronic Graft versus Host Disease Chronic GVHD . 6 . 8 Acute GVHD . 4 Grades 2 -4: 44% Chronic GVHD: 25%. 2 Grades 3 -4: 20% 0 0 Extensive GVHD: 9% 0 A 50 100 Days from transplant 150 200 100 B 200 300 Days from transplant 400 500
Impact of allogeneic transplant on Overall Survival by diagnosis (1) Multivariable Cox proportional hazard models. * Time-dependent covariate
Impact of allogeneic transplant on Overall Survival by diagnosis (2) Multivariable Cox proportional hazard models. * Time-dependent covariate
Prognostic factors for the prediction of Overall Survival Multivariable Cox proportional hazard model. * Time-dependent covariate
Protocollo Glob. Al 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
Curve di reclutamento 250 Randomisation (N=103) Registration (N=215) Il protocollo prevede l’arruolamento di 100 -150 pazienti. 150 I risultati della analisi ad interim saranno disponibili a metà Novembre e permetteranno di prendere una 100 decisione sulla opportunità di chiudere la fase di reclutamento. 50 ar m -05 ay -0 ju 5 lse 05 pno 05 v 0 ja 5 nm 06 ar m -06 ay -0 ju 6 lse 06 pno 06 v 0 ja 6 nm 07 ar m -07 ay -0 ju 7 lse 07 pno 07 v 0 ja 7 nm 08 ar m -08 ay -0 ju 8 lse 08 p 08 0 m Number of patients 200 Months
Decessi Follow-up post trapianto (mediana 6. 0 mesi [0. 4 – 25. 7])
Conclusions • The conditioning regimen • The GVHD prophylaxis • The patients you are selecting for the allograft
- Alessandro rambaldi
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- Avanti e dopo cristo
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- Linea del tempo medioevo
- Diarrea dopo gelato artigianale
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- Chi è lo storico
- Que es un modelo alternativo
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- Progetto alternativo alla religione cattolica
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- 選択的スプライシング
- Que es un modelo alternativo