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

Summary

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.

Eligibility

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

Conditions5

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