Since the discovery that Treg suppress anti-tumor immune responses, inhibiting their function has become a major challenge for the development of efficient immunotherapy for cancer. In humans, we previously reported the positive results of a first clinical trial using Treg depletion for anti-tumor response amplification in the field of allogeneic hematopoietic stem cell transplantation (HSCT). The present project aims at developing this anti-tumor immunotherapeutic strategy in the same setting, i.e. donor lymphocyte infusion (DLI) for relapsing hematological malignancies after HSCT, using a new selection marker: CD127. The choice of this new strategy is supported by our results of a retrospective clinical study and pre-clinical data. Using human cells, this studies demonstrated, in vitro and in vivo in animal murine models, that Treg depletion through CD127 positive selection is much more efficient to improve allogeneic immune responses of donor T-cells as compared to the previous strategy using the CD25 marker.
Adult patient (older than 18 years old without upper limit of age) diagnosed with leukemia, myelodysplasia, myeloproliferative disorder or lymphoproliferative disorder (CLL, myeloma, lymphoma)
Previous allogeneic HSCT from a matched sibling, haplo-identical or unrelated donor (any type of conditioning regimen)
Haematological relapse (molecular, cytogenetic or cytological) after HSCT
Patient refractory (no or partial response) to one or several previous standard unmanipulated DLI
Acute grade ≥ II or moderate/severe chronic GVHD at the time of inclusion
Patient receiving immunosuppressive treatment for GVHD or any other reason
Creatinine clearance< 50 ml/min
Serum aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) or alanine transaminase (ALT)/serum glutamate pyruvate transaminase (SGPT) > 5.0 x upper limit of normal (ULN)
Single group
T-reg depleted DLI
DrugTreg depleted Donor Lymphocytes Infusion
cumulative incidence of GVHD in its acute grade ≥ II and/or severe chronic form (according Glucksberg-Thomas and NIH scales, respectively), and uncontrolled after a 14-day immunosuppressive course including steroids.
Composite criteria. In this evaluation, death from non-GVHD cause will be taken as a competitive event
Incidence of acute and/or chronic GVHD, with corresponding grades according to NIH and Glucksberg-Thomas scales
Date of putative relapse/progression for estimation of cumulative incidence (taking into account the competitive risk of death not related to relapse)
Date of putative relapse/progression for estimation disease-free survival
Number, causes and date of deaths
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