Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only treatment option with a significant chance of healing in lymphoid hematological refractory or multiple relapses after chemotherapy. However, all patients with an indication of allo-HSC can not benefit because of two limitations: the toxicity of the treatment and graft shortage available. For patients refractory or in relapses with an indication of allo-HSC, used the combinaison of an SET followed by the reduced-intensity allo-HSC (RIC) has shown some interesting results. A post-transplant immune modulation with prophylactic injections of donor lymphocytes (PDLI) showed its effectiveness to decrease the risk of relapse while having a lower toxicity than chemotherapy
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
OTHER
Masking
NONE
Enrollment
40
Sequential chemotherapy: - Thiotepa 5 mg/kg/day for 1 day (D-13) -Cyclophosphamide 400 mg/m²/day for 4 days (J-12 to J-9)- Etoposide 100 mg/m²/day for 4 days (J-12 to J-9) Repos days J-8 and J-6 Reduced-intensity conditioning (RIC)-Fludarabine 30 mg/m²/day for 5 days (J-5 to D-1)- Busulfan IV 3.2 mg/kg/day for 2 days (J-5 and J-4)- Anti-lymphocyte serum (Thymoglobuline) 2.5 mg / kg / day for 2 days (J-3 and J-2)
Graft of peripheral stem cells is preferred at DO
* Cyclophosphamide 50mg/ kg/day on days D + 3 and D + 5 - Cyclosporine A (CSA; 3 mg / kg / day IV from D+6) * Mycophenolate mofetil (MMF; 30 mg/kg/ day, maximum x2 1g / day from day J+6)
According to the protocols of each center
According to the protocols of each center. In the absence of clinical indication against-disease (GVHD), phasing MMF between days D + 35 and D + 56, then phasing APF between D + 62 and D + 90 \- PDLI: 3 injections from the D + 120 patients who discontinued immunosuppressive therapy for ≥ 1 month and having no active GVHD or history of acute GVHD grade\> II.
Service d'hématologie clinique Hôpital Saint Antoine
Paris, France
Overall survival (OS)
Describe efficacy and safety of the combination of an SET followed by the RIC with post-transplant immune modulation by PDLI in patients with refractory or relaps lymphoid hematological refractory or multiple relapses lymphoid hematological disorders
Time frame: 2 years after transplantation
Partial or complete remission rate by standard criteria relapse incidence and death related to the disease and free survival
Describe the efficacy of this therapeutic strategy in terms of remission of disease, incidence of relapse and relapse-free survival
Time frame: 90 days and then 6, 12 and 24 months after transplantation
Cumulative incidence of death not related to relapse
Describe not related to relapse mortality
Time frame: 90 days and then 12 and 24 months after transplantation
Cumulative incidence of acute and chronic graft against host disease (GVHD)
Describe the incidence of acute and chronic graft against host disease (GVHD)
Time frame: 100 days and then 12 and 24 months after transplantation
Number of patients for whom PDLI was possible and number PDLI / patient ; incidence, severity and treatment of possible secondary GVHD in these patients
Describe the feasibility of prophylactic injections of donor lymphocytes (PDLI)
Time frame: 2 years after transplantation
Immune reconstitution post-transplantation in the peripheral blood
Immune reconstitution will be determined by CD4 lymphocyte, CD8, T regulators, Natural Killer cells and B cells levels in the peripheral blood
Time frame: 30, 90 and 180 days after transplantation
Tolerance of this therapeutic strategy
The tolerance will be evaluated by: 1. The cumulative incidence of death not related to relapse at 90 days, 1 year and 2 years after transplantation 2. The cumulative incidence of acute and chronic graft against host disease (GVHD) 3. The incidence of advert events
Time frame: 90 days and the 6, 12 and 24 month after transplantation
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