Safely Delivered Targeted High-dose Irradiation Followed by Adoptive Immunotherapy with Regulatory and Conventional T Cells to Increase Potency of Hematopoietic Stem Cell Transplantation in High-risk Acute Leukemia

The study is a monocentric, interventional study that evaluates the efficacy of allogeneic HLA-matched or haploidentical transplantation consisting of an irradiation-based conditioning regimen coupled with donor Treg/Tcon adoptive immunotherapy for high-risk acute leukemia patients.

Sex

All

Minimum age

18 Years

Maximum age

65 Years

Inclusion Criteria:

* AML patients

  * Diagnosis of AML with indication to allogeneic hematopoietic cell transplantation.
  * Diagnosis of adverse genetic risk leukemia or presence of MRD or active disease (bone marrow infiltration 5-30%) at the time of the transplant procedure.
  * Availability of a hematopoietic stem cell donor (family or unrelated HLA-matched or HLA-haploidentical with the patient) 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 ≤ 65 years
  * ECOG ≤ 2
  * HCT-CI ≤ 4 (51,52)
  * Absence of relevant psychiatric diseases
  * Signature of the informed consent

ALL patients

* Diagnosis of ALL, either T or B (Philadelphia negative) or mixed phenotype with indication to allogeneic transplant
* Presence of MRD or active disease (bone marrow infiltration 5-30%) or patient with ≥ 2nd complete hematologic remission at the time of the transplant procedure.
* Availability of a hematopoietic stem cell family donor (family or unrelated HLA-matched or HLA-haploidentical with the patient) 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 ≤ 65 years
* ECOG ≤ 2
* HCT-CI ≤ 4
* Absence of relevant psychiatric diseases
* Signature of the informed consent

Exclusion Criteria:

* AML patients

  * AML in CR MRD-
  * AML with \> 5% peripheral blasts or bone marrow infiltration ≥ 30%
  * Age \< 18 years or \> 65 years
  * ECOG \> 2
  * Unacceptable lung, liver, kidney, and/or heart function and presence of relevant psychiatric diseases according to clinical judgment
  * Pregnancy
  * No signature of the informed consent
* ALL patients

  * ALL with \> 5% peripheral blasts or bone marrow infiltration ≥30%
  * Philadelphia positive ALL
  * Age \< 18 years or \> 65 years
  * ECOG \> 2
  * Unacceptable lung, liver, kidney, and/or heart function and presence of relevant psychiatric diseases according to clinical judgment
  * Pregnancy
  * No signature of the informed consent

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• BACKGROUNDChistolini P, Cossu G, De Luca M, Marazzi M, Mavilio F, Migliaccio G, et al. LINEE GUIDA PER L'INGEGNERIA DEI TESSUTI E LA TERAPIA CELLULARE. Not DellIstituto Super Sanità. 1999 May 1;Vol. 12:1-8
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• BACKGROUNDRuggeri L, Capanni M, Urbani E, Perruccio K, Shlomchik WD, Tosti A, Posati S, Rogaia D, Frassoni F, Aversa F, Martelli MF, Velardi A. Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science. 2002 Mar 15;295(5562):2097-100. doi: 10.1126/science.1068440. PMID 11896281
• Ciurea SO, Cao K, Fernandez-Vina M, Kongtim P, Malki MA, Fuchs E, Luznik L, Huang XJ, Ciceri F, Locatelli F, Aversa F, Castagna L, Bacigalupo A, Martelli M, Blaise D, Handgretinger R, Roy DC, O'Donnell P, Bashey A, Lazarus HM, Ballen K, Savani BN, Mohty M, Nagler A. The European Society for Blood and Marrow Transplantation (EBMT) Consensus Guidelines for the Detection and Treatment of Donor-specific Anti-HLA Antibodies (DSA) in Haploidentical Hematopoietic Cell Transplantation. Bone Marrow Transplant. 2018 May;53(5):521-534. doi: 10.1038/s41409-017-0062-8. Epub 2018 Jan 15.