Conclusion de l’atelier
1) Notre travail se limite aux indications classiques excluant les greffes pour hémoglobinopathies et autres pathologies constitutionnelles.
2) Nous encourageons les centres à privilégier les essais cliniques.
3) Il est possible de limiter le nombre de conditionnements :
a) MAC : 3 conditionnements (exemples : Cy-ICT (8-12 Gys); Cy-BU et Flu-BU4)
b) Séquentiel: 1 conditionnement (exemple: KOLB)
c) Atténué : (RIC) un conditionnement (Slavin=Flu-BU2-SAL2); (NMA) un conditionnement (exemple : Seattle= ICT2+/-Flu)
d) AM: deux conditionnements (exemples, géno : Cy-SAL; phéno : Cy-Flu-ICT2-SAL.
e) Cordon: deux conditionnements (exemples, MAC: Fluda-ICT12-Cy; RIC: Fluda-ICT2-Cy)
4) Pour les greffes à conditionnement atténué où la source de cellules est la moelle, le risque de rejet justifie la modification du conditionnement.
5) Si greffes non apparenté et CSP (9-10/10) ou Mo (9/10), le conditionnement doit comporter du SAL.
Recommandations
En tenant compte des données ci-dessus, chaque centre devrait pouvoir choisir une ou deux types de conditionnement par intensité. Le tableau 1 peut être rempli avec les choix du centre en fonction des modalités de la greffe à proposer et l’indication. Le tableau 2 représente un exemple pour un centre donné.
Questions résiduelles à explorer
1) Place réelle de l’ICT dans le conditionnement myéloablatif des LAL.
2) RIC/MAC et LAM RC1 ?
3) Faut-il rajouter du SAL si greffon médullaire (MO) à partir d’un donneur non apparenté 10/10?
4) Quel RIC si greffon MO pour éviter le risque de rejet?
Références
1. Bacigalupo A, Ballen K, Rizzo D, et al: Defining the intensity of conditioning regimens: working definitions. Biol Blood Marrow Transplant 15:1628-33, 2009
2. Schmid C, Schleuning M, Schwerdtfeger R, et al: Long-term survival in refractory acute myeloid leukemia after sequential treatment with chemotherapy and reduced-intensity conditioning for allogeneic stem cell transplantation. Blood 108:1092-9, 2006
3. Thomas E, Storb R, Clift RA, et al: Bone-marrow transplantation (first of two parts). N Engl J Med 292:832-43, 1975
4. Thomas ED, Storb R, Clift RA, et al: Bone-marrow transplantation (second of two parts). N Engl J Med 292:895-902, 1975
5. Bunin N, Aplenc R, Kamani N, et al: Randomized trial of busulfan vs total body irradiation containing conditioning regimens for children with acute lymphoblastic leukemia: a Pediatric Blood and Marrow Transplant Consortium study. Bone Marrow Transplant 32:543-8, 2003
6. Ringden O, Ruutu T, Remberger M, et al: A randomized trial comparing busulfan with total body irradiation as conditioning in allogeneic marrow transplant recipients with leukemia: a report from the Nordic Bone Marrow Transplantation Group. Blood 83:2723-30, 1994
7. Davies FE, Rawstron AC, Pratt G, et al: Positive and negative selection to reduce tumour contamination in peripheral blood stem cell harvests. Hematol Oncol 18:111-20, 2000
8. Ringden O, Potter MN, Oakhill A, et al: Transplantation of peripheral blood progenitor cells from unrelated donors. Bone Marrow Transplant 17 Suppl 2:S62-4, 1996
9. Cantoni N, Gerull S, Heim D, et al: Order of application and liver toxicity in patients given BU and CY containing conditioning regimens for allogeneic hematopoietic SCT. Bone Marrow Transplant 46:344-9, 2010
10. Kerbauy FR, Tirapelli B, Akabane H, et al: The effect of administration order of BU and CY on toxicity in hematopoietic SCT in humans. Bone Marrow Transplant 43:883-5, 2009
11. Nilsson C, Forsman J, Hassan Z, et al: Effect of altering administration order of busulphan and cyclophosphamide on the myeloablative and immunosuppressive properties of the conditioning regimen in mice. Exp Hematol 33:380-7, 2005
12. Ringden O, Labopin M, Tura S, et al: A comparison of busulphan versus total body irradiation combined with cyclophosphamide as conditioning for autograft or allograft bone marrow transplantation in patients with acute leukaemia. Acute Leukaemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT). Br J Haematol 93:637-45, 1996
13. Slattery JT, Kalhorn TF, McDonald GB, et al: Conditioning regimen-dependent disposition of cyclophosphamide and hydroxycyclophosphamide in human marrow transplantation patients. J Clin Oncol 14:1484-94, 1996
14. Michel G, Valteau-Couanet D, Gentet JC, et al: Weight-based strategy of dose administration in children using intravenous busulfan: Clinical and pharmacokinetic results. Pediatr Blood Cancer, 2011
15. Nguyen L, Leger F, Lennon S, et al: Intravenous busulfan in adults prior to haematopoietic stem cell transplantation: a population pharmacokinetic study. Cancer Chemother Pharmacol 57:191-8, 2006
16. Kiehl MG, Kraut L, Schwerdtfeger R, et al: Outcome of allogeneic hematopoietic stem-cell transplantation in adult patients with acute lymphoblastic leukemia: no difference in related compared with unrelated transplant in first complete remission. J Clin Oncol 22:2816-25, 2004
17. Marks DI, Wang T, Perez WS, et al: The outcome of full-intensity and reduced-intensity conditioning matched sibling or unrelated donor transplantation in adults with Philadelphia chromosome-negative acute lymphoblastic leukemia in first and second complete remission. Blood 116:366-74, 2010
18. Mohty M, Labopin M, Volin L, et al: Reduced-intensity versus conventional myeloablative conditioning allogeneic stem cell transplantation for patients with acute lymphoblastic leukemia: a retrospective study from the European Group for Blood and Marrow Transplantation. Blood 116:4439-43, 2010
19. Bernard F, Bordigoni P, Simeoni MC, et al: Height growth during adolescence and final height after haematopoietic SCT for childhood acute leukaemia: the impact of a conditioning regimen with BU or TBI. Bone Marrow Transplant 43:637-42, 2009
20. Bresters D, van Gils IC, Kollen WJ, et al: High burden of late effects after haematopoietic stem cell transplantation in childhood: a single-centre study. Bone Marrow Transplant 45:79-85, 2009
21. Rizzo JD, Curtis RE, Socie G, et al: Solid cancers after allogeneic hematopoietic cell transplantation. Blood 113:1175-83, 2009
22. Chemaitilly W, Boulad F, Oeffinger KC, et al: Disorders of glucose homeostasis in young adults treated with total body irradiation during childhood: a pilot study. Bone Marrow Transplant 44:339-43, 2009
23. Oudin C, Simeoni MC, Sirvent N, et al: Prevalence and risk factors of the metabolic syndrome in adult survivors of childhood leukemia. Blood 117:4442-8, 2011
24. Pui CH, Cheng C, Leung W, et al: Extended follow-up of long-term survivors of childhood acute lymphoblastic leukemia. N Engl J Med 349:640-9, 2003
25. Schrezenmeier H, Passweg JR, Marsh JC, et al: Worse outcome and more chronic GVHD with peripheral blood progenitor cells than bone marrow in HLA-matched sibling donor transplants for young patients with severe acquired aplastic anemia. Blood 110:1397-400, 2007
26. Eapen M, Le Rademacher J, Antin JH, et al: Effect of stem cell source on outcomes after unrelated donor transplantation in severe aplastic anemia. Blood 118:2618-21, 2011
27. Bacigalupo A, Lamparelli T, Barisione G, et al: Thymoglobulin prevents chronic graft-versus-host disease, chronic lung dysfunction, and late transplant-related mortality: long-term follow-up of a randomized trial in patients undergoing unrelated donor transplantation. Biol Blood Marrow Transplant 12:560-5, 2006
28. Finke J, Bethge WA, Schmoor C, et al: Standard graft-versus-host disease prophylaxis with or without anti-T-cell globulin in haematopoietic cell transplantation from matched unrelated donors: a randomised, open-label, multicentre phase 3 trial. Lancet Oncol 10:855-64, 2009
29. Socie G, Schmoor C, Bethge WA, et al: Chronic graft-versus-host disease: long-term results from a randomized trial on graft-versus-host disease prophylaxis with or without anti-T-cell globulin ATG-Fresenius. Blood 117:6375-82, 2011
30. Mohty M, Labopin M, Balere ML, et al: Antithymocyte globulins and chronic graft-vs-host disease after myeloablative allogeneic stem cell transplantation from HLA-matched unrelated donors: a report from the Societe Francaise de Greffe de Moelle et de Therapie Cellulaire. Leukemia 24:1867-74, 2010
31. Barker JN, Weisdorf DJ, DeFor TE, et al: Rapid and complete donor chimerism in adult recipients of unrelated donor umbilical cord blood transplantation after reduced-intensity conditioning. Blood 102:1915-9, 2003