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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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Relapsed or refractory lymphoid hematological disorders | Other | Patients in refractory or relapses with an indication of allo-HSC used the combination of an SET followed by the RIC with the PDLI |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sequential Packaging (SET) | Drug | 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) |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 2 years after transplantation |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 90 days and then 6, 12 and 24 months after transplantation |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Service d'hématologie clinique Hôpital Saint Antoine | Paris | France |
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Patients with refractory or relaps lymphoid hematological disorders
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| Transfusion graft | Drug | Graft of peripheral stem cells is preferred at DO |
|
| Prevention of GVHD | Drug |
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| Care supports | Drug | According to the protocols of each center |
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| Lymphocyte injection of prophylactic donor (PDLI) | Drug | 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. |
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| Cumulative incidence of death not related to relapse |
Describe not related to relapse mortality |
| 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) | 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) | 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 | 30, 90 and 180 days after transplantation |
| Tolerance of this therapeutic strategy | The tolerance will be evaluated by:
| 90 days and the 6, 12 and 24 month after transplantation |