Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Myelodysplastic Syndromes, Hodgkin Lymphoma, Non-hodgkin Lymphoma
Conditions
Keywords
posttransplant cyclophosphamide, ATG, calcineurin-free GVHD prophylaxis, graft-versus-host disease
Brief summary
Hematopoietic stem cell transplantation is a curative treatment for a number of benign and malignant hematologic diseases. One of the key parts of hematopoietic stem cell transplantation is the prophylaxis of graft-versus-host disease. Since the end of the 1970s, with the introduction of cyclosporine, calcineurin inhibitors (cyclosporine and tacrolimus) have become part of almost all prophylactic regimens, even though they are a group of drugs with a poor toxicity profile that requires monitoring. constant serum level. Since 2008, post-transplant cyclophosphamide has been introduced with great success, associated with a calcineurin inhibitor and mycophenolate, in the prophylaxis of graft-versus-host disease in haploidentical transplantation (50% matched). Since then, in view of this enormous success, efforts have been made to incorporate post-transplant cyclophosphamide in matched related and unrelated transplants, or with a mismatch. This is a prospective, 2-arm, non-randomized study. Arm 1, with related donors, and arm 2, with unrelated donors. Patients will be allocated in these arms according to donor availability (patients with a matched-sibling donor will receive a matched-sibling transplant; patients with no related donors but with unrelated donors, an unrelated transplant). Patients who are ready for transplantation with matched-sibling or unrelated donors will be recruited to participate in the study. The stem cell collection target will be 5E6 CD34/kg recipient weight for peripheral source. If a quantity greater than this is collected, the remainder will be cryopreserved according to the institutional protocol. Graft-versus-host disease prophylaxis will be performed on D+3 and D+4 with cyclophosphamide and with ATG on D-3 and D-2 for matched-sibling or unrelated donors transplants.
Interventions
DRUGATG 5.0
ATG 2.5 mg/kg on days -3 and -2
Cyclophosphamide 50 mg/kg on days +3 and +4
DRUGATG 4.0
ATG 2.5 mg/kg on day -2 + 1.5 mg/kg on day -3
Sponsors
Instituto Nacional de Cancer, Brazil
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Intervention model description
Patients with a matched sibling donor will be assigned to the PTCy+ATG4.l0 arm, while patients with a matched unrelated donor will be assigned to the PTCy+ATG5.0 arm
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Patient with (1) acute leukemia in first or second remission; (2) myelodysplasia with less than 20% blasts; (3) Hodgkin's or non-Hodgkin's lymphoma, in partial remission after salvage therapy * Who will receive a related or unrelated, HLA-compatible transplant; * Who is a transplant candidate with FluMel, FluTBI, CyTBI, BuCy or BuFlu conditioning; * Peripheral blood source; * Age between 18 and 60 years.
Exclusion criteria
\- Hepatic dysfunction (transaminases x2 the normal value)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative incidence of grades III-IV acute GVHD by the MAGIC criteria | 6 months | Cumulative incidence of acute graft-versus-host disease, grades III-IV by the MAGIC criteria |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative incidence of steroid-refractory acute GVHD as defined by Mohty et al PMID 32756949 | 6 months | Cumulative incidence of steroid-refractory graft-versus-host disease |
| Cumulative incidence of chronic GVHD as defined by the NIH criteria | 3 years | Cumulative incidence of chronic graft-versus-host disease |
| Cumulative incidence of steroid-requiring chronic GVHD as defined by the NIH criteria | 3 years | Cumulative incidence of steroid-requiring chronic graft versus host disease |
| Cumulative incidence of non-relapse mortality, i.e., death not following disease relapse | 3 years | Cumulative incidence of death not caused by primary malignant disease or following relapse |
| Cumulative incidence of relapse, defined as > 5% blasts in bone marrow or 1% blasts in peripheral blood (acute leukemias/myelodysplasia) or biopsy proven relapse or positve PET-CT (lymphoma) | 3 years | Cumulative incidence of relapse of primary malignant disease |
| Cumulative incidence of grades II-IV acute GVHD by the MAGIC criteria | 6 months | Cumulative incidence of acute graft-versus-host disease, grades II-IV by the MAGIC criteria |
| Rate of disease-free survival (death or relapse) | 3 years | Composite outcome of death or primary disease relapse |
| Cumulative incidence of clinically significant CMV reactivation (which led to antiviral treatment) | 3 year | Incidence of cytomegalovirus reactivation |
| Cumulative incidence of posttransplant lymphoproliferative disorder (biopsy-proven or positive EBV PCR combined with clinical symptoms) | 3 years | Incidence of posttransplant lymphoproliferative disorder |
| Cumulative incidence CMV disease (biopsy-proven CMV disease OR suggestive CMV+ BAL) | 3 years | Cumulative incidence of cytomegalovirus disease |
| Measuremnt of quality of life using the FACT-BMT scale | 2 years | Measurement quality of life |
| Rate of overall survival | 3 years | Death by any cause |
Countries
Brazil
Contacts
Primary ContactLeonardo J Arcuri, MD, PhD
Outcome results
None listed