Graft-versus-host disease (GVHD) is a major complication of allogeneic hematopoietic stem cell transplantation (allo-CSH).
Recently, in the context of semi-identical (=haploidentical) HLA donors, but also of compatible HLA donors, the use of cyclophosphamide (CY) administered in high doses at early post-transplant (PT) (=PTCY) (Days +3 and +4 or +5) has shown excellent control of acute and chronic GVH, even enabling the discontinuation of other immunosuppressive drugs administered after allo-CSH (ciclosporin, mycophenolate mofetyl (MMF) or Cellcept).
This step has already been taken in the context of allo-CSH with myeloablative conditioning (MAC), which is a minoritary conditioning in adults.
However, in the context of allo-CSH with reduced-intensity conditioning (RIC), which predominates in adults, this strategy seems insufficient to prevent the risk of GVHD.
The idea of reducing the use of immunosuppressants in the context of RIC/HLA-compatible transplants seems, however, still relevant, in order to reduce their adverse effects, improve patients' quality of life and enhance the reconstitution of the post-transplant immune system.
Age: ≥ 18 and ≤ 70 years old
Patient with hematologic malignancy
Indication for HSC allograft with attenuated conditioning
Pluripotent stem cell (PSC) engraftment
History of allograft
Patient eligible for myeloablative conditioning (MAC)
Bone marrow transplant
Other progressive cancerous disease, or antecedent of cancer in the last five years, with the exception of a carcinoma of the skin or a carcinoma in situ of the uterine cole treated and in remission.
Parallel
Methotrexate
Drug15 mg/m² on Day+1 after graft (=Day0) 10 mg/m² 3 days on Day+4/Day+6/Day+11 after graft (=Day0)
Post-Transplant Cyclophosphamide
Drug50 mg/kg intravenous 2 days on Day+3/Day+5 after graft (=Day0)
Fludarabine
DrugConditioning regimen: 30 mg/m² Intravenous 5 days from Day-6 to Day-2 (Day-6/Day-5-/Day-4/Day-3/Day-2 before graft (=Day0)
Cycophosphamide
DrugConditioning regimen: 14.5 mg/kg intravenous 2 days on Day-6/Day-5 before graft (=Day0)
Anti-Thymoglobulin
DrugConditioning regimen: 2.5 mg/kg intravenous on Day-2 before graft (=Day0)
total body irradiation
Radiation2 grays on Day-1 before graft (=Day0)
hematopoietic stem cells
Other interventionHigh dose of hematopoietic stem cells derived from peripheral blood on transplantation day (=Day0 graft)
Graft nuclear cells
Other interventionGraft nuclear cells CD3+ cells if needed after transplantation
Donor Lymphocytes Injection
Other interventionDLI with CD3+ if relapse after transplantation or in prevention of relapse
Clofarabine
DrugConditioning regimen: 30 mg/m² Intravenous 5 days from Day-6 to Day-2 (Day-6/Day-5-/Day-4/Day-3/Day-2 before graft (=Day0)
Thiotepa
DrugConditioning regimen: 5 mg/kg Intravenous at Day-6 before graft (=Day0)
Busulfan
DrugConditioning regimen: 3.2 mg/kg Intravenous 2 days at Day-2 and Day-1 before graft (=Day0)
Fludarabine
DrugConditioning regimen: 40 mg/m² intravenous 4 days on Day-5/Day-4/Day-3/Day-2 before graft (=Day0)
Incidence of grade 3-4 acute GVHD following allo-CSH for all patients and for each conditioning group (Baltimore and TBF).
Estimation of the incidence of grade 3 and 4 acute GVHD following allo-CSH (excluding post-DLI\* acute GVHD) according to Mount Sinai criteria.
Incidence of engraftment
Engraftment assessed on hematological reconstitution (number of days of aplasia with PNN \<0.5 G/L and platelets \< 20 G/L, number of platelet and red cell concentrate transfusions)
Overall survival (OS)
survival between day 0 of transplantation and date of death or last follow-up
Disease-free survival (DFS)
survival between day 0 of transplantation and date of relapse, death or last follow-up
GVHD and relapse-free survival (GRFS)
relapse-free survival without grade 3-4 acute GVHD or chronic GVHD requiring systemic treatment
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