Matched Sibling Allogenic Stem Cell Transplantation With Adoptive Immunotherapy With Regulatory And Conventional T Cells For High Risk Acute Myeloid Leukemia

The study is a multicentric, interventional study that evaluates the efficacy of allogeneic HLA-matched allo-HSCT consisting of myeloablative conditioning coupled with donor Treg/Tcon adoptive immunotherapy for high-risk AML patients.

Sex

All

Minimum age

18 Years

Maximum age

70 Years

Inclusion Criteria:

* Diagnosis of AML with adverse genetic mutations in Complete Remission (CR) or incomplete (i) CR according to ELN 2022 recommendations with or without MRD positivity at the time of the HSCT procedure;
* Diagnosis of AML with intermediate genetic mutations in Complete remission (CR) or incomplete (i) CR according to ELN 2022 with MRD positivity at the time of the transplant;
* Fitness to undergo allo-HCT with myeloablative conditioning regimens according to center policy;
* Availability of a family HLA-matched hematopoietic stem cell donor suitable to be treated with G-CSF (10 mcg/kg/die) for a maximum of 7 days and able to tolerate 2 or more leukaphereses.
* Age ≥ 18 and ≤ 70 years
* ECOG ≤ 2
* HCT-CI ≤ 4
* Signature of the informed consent

Exclusion Criteria:

* Prior allo-HSCT
* AML with favorable genetic abnormalities
* AML with intermediate genetic risk with MRD negativity
* Active disease at transplant (\> 5% bone marrow infiltration)
* Availability of a haploidentical or matched unrelated donor (MUD)
* Age \< 18 years or \> 70 years
* ECOG \> 2
* Unacceptable lung, liver, kidney, and/or heart function and presence of relevant psychiatric diseases according to clinical judgment
* Uncontrolled bacterial, viral, or fungal infections at time of enrollment
* Pregnancy
* No signature of the informed consent

• BACKGROUNDPierini A, Ruggeri L, Carotti A, Falzetti F, Saldi S, Terenzi A, Zucchetti C, Ingrosso G, Zei T, Iacucci Ostini R, Piccinelli S, Bonato S, Tricarico S, Mancusi A, Ciardelli S, Limongello R, Merluzzi M, Di Ianni M, Tognellini R, Minelli O, Mecucci C, Martelli MP, Falini B, Martelli MF, Aristei C, Velardi A. Haploidentical age-adapted myeloablative transplant and regulatory and effector T cells for acute myeloid leukemia. Blood Adv. 2021 Mar 9;5(5):1199-1208. doi: 10.1182/bloodadvances.2020003739. PMID 33646302
• BACKGROUNDMartelli MF, Di Ianni M, Ruggeri L, Falzetti F, Carotti A, Terenzi A, Pierini A, Massei MS, Amico L, Urbani E, Del Papa B, Zei T, Iacucci Ostini R, Cecchini D, Tognellini R, Reisner Y, Aversa F, Falini B, Velardi A. HLA-haploidentical transplantation with regulatory and conventional T-cell adoptive immunotherapy prevents acute leukemia relapse. Blood. 2014 Jul 24;124(4):638-44. doi: 10.1182/blood-2014-03-564401. Epub 2014 Jun 12. PMID 24923299
• BACKGROUNDDi Ianni M, Falzetti F, Carotti A, Terenzi A, Castellino F, Bonifacio E, Del Papa B, Zei T, Ostini RI, Cecchini D, Aloisi T, Perruccio K, Ruggeri L, Balucani C, Pierini A, Sportoletti P, Aristei C, Falini B, Reisner Y, Velardi A, Aversa F, Martelli MF. Tregs prevent GVHD and promote immune reconstitution in HLA-haploidentical transplantation. Blood. 2011 Apr 7;117(14):3921-8. doi: 10.1182/blood-2010-10-311894. Epub 2011 Feb 3. PMID 21292771
• BACKGROUNDNguyen VH, Zeiser R, Dasilva DL, Chang DS, Beilhack A, Contag CH, Negrin RS. In vivo dynamics of regulatory T-cell trafficking and survival predict effective strategies to control graft-versus-host disease following allogeneic transplantation. Blood. 2007 Mar 15;109(6):2649-56. doi: 10.1182/blood-2006-08-044529. Epub 2006 Nov 9. PMID 17095616