Suicide Gene Therapy for Donor Lymphocytes Infusion After Allogeneic Hematopoietic Stem Cell Transplantation

The main complications of allogeneic hematopoietic stem cell transplantation (HSCT) include graft-versus-host disease (GVHD) and poor immune reconstitution leading to severe infections and leukemia relapse. Mature donor T-cells present in the transplant facilitate T-cell reconstitution but also induce GVHD, which itself impairs immune reconstitution. We have developed a strategy of alloreactive T-cell depletion, using T-cells expressing the Herpes simplex thymidine kinase (TK) suicide gene combined with a ganciclovir (GCV) treatment. This system permits the selective elimination of dividing TK+ T-cells in vivo. To test this hypothesis in preclinical settings, we have previously developed several experimental models of GVHD using TK+ T-cells in mice. The demonstration that a preventive treatment with GCV administered close to the time of HSCT could control GVHD brought the proof of concept. We now propose a clinical trial to test whether donor lymphocytes infusion (DLI) using TK-transduced cells permits to induce a graft-versus-tumor (GVT) effect for treatment of relapse after HSCT, while GVHD can be controlled by GCV treatment.

Sex

All

Minimum age

18 Years

Maximum age

70 Years

Inclusion Criteria:

* Hematological malignancy.
* Previous allogeneic hematopoietic stem cell transplantation.
* Relapse diagnosed at the molecular, cytogenetic, or cytological level.
* Failure of a previous stdILD or inclusion in first intention without previous stdDLI.
* Age \> 18 years and \< 70 years at the time of inclusion. For patients between 15 and 18 years of age, a case-per case inclusion will be studied.
* Performance status considered on the score Eastern Cooperative Oncology Group (ECOG) \< 2.
* Life expectation 1-month-old superior.
* Signed written informed consent.
* Negative human chorionic gonadotropin (HCG) in the 7 days preceding the inclusion for women in age of procreation.
* Membership of the French national insurance.

Exclusion Criteria:

* Grade \>II acute GVHD or chronic extensive GVHD at the time of inclusion.
* Patient receiving an immunosuppressive treatment for GVHD treatment at the time of inclusion.
* Dysfunction of liver (alanine aminotransferase / aspartate transaminase (ALAT/ASAT) \> 5 N, or bilirubin \> 50 µM), or of the renal function (creatinine clearance \< 30 ml / min).