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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Matched-sibling donor transplants | Experimental | Matched sibling transplants will receive PTCy + ATG4.0 |
|
| Matched unrelated donor transplants | Experimental | Unrelated transplants will receive PTCy + ATG5.0 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ATG 5.0 | Drug | ATG 2.5 mg/kg on days -3 and -2 |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Cumulative incidence of grades III-IV acute GVHD by the MAGIC criteria | Cumulative incidence of acute graft-versus-host disease, grades III-IV by the MAGIC criteria | 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| Cumulative incidence of grades II-IV acute GVHD by the MAGIC criteria | Cumulative incidence of acute graft-versus-host disease, grades II-IV by the MAGIC criteria | 6 months |
| Cumulative incidence of steroid-refractory acute GVHD as defined by Mohty et al PMID 32756949 |
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Inclusion Criteria:
Exclusion Criteria:
- Hepatic dysfunction (transaminases x2 the normal value)
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Leonardo J Arcuri, MD, PhD | Contact | +5521981334715 | leonardojavier@gmail.com |
| Name | Affiliation | Role |
|---|---|---|
| Leonardo J Arcuri, MD, PhD | Instituto Nacional de Cancer | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Instituto Nacional de Cancer | Recruiting | Rio de Janeiro | Rio de Janeiro | 20230-130 | Brazil |
Upon finalization of the study, data will be shared on reasonable requests.
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| ID | Term |
|---|---|
| D015470 | Leukemia, Myeloid, Acute |
| D054198 | Precursor Cell Lymphoblastic Leukemia-Lymphoma |
| D009190 | Myelodysplastic Syndromes |
| D006689 | Hodgkin Disease |
| D008228 | Lymphoma, Non-Hodgkin |
| D006086 | Graft vs Host Disease |
| ID | Term |
|---|---|
| D007951 | Leukemia, Myeloid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| D003520 | Cyclophosphamide |
| ID | Term |
|---|---|
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
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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
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| Cyclophosphamide injection |
| Drug |
Cyclophosphamide 50 mg/kg on days +3 and +4 |
|
| ATG 4.0 | Drug | ATG 2.5 mg/kg on day -2 + 1.5 mg/kg on day -3 |
|
Cumulative incidence of steroid-refractory graft-versus-host disease |
| 6 months |
| Cumulative incidence of chronic GVHD as defined by the NIH criteria | Cumulative incidence of chronic graft-versus-host disease | 3 years |
| Cumulative incidence of steroid-requiring chronic GVHD as defined by the NIH criteria | Cumulative incidence of steroid-requiring chronic graft versus host disease | 3 years |
| Cumulative incidence of non-relapse mortality, i.e., death not following disease relapse | Cumulative incidence of death not caused by primary malignant disease or following relapse | 3 years |
| 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) | Cumulative incidence of relapse of primary malignant disease | 3 years |
| Rate of overall survival | Death by any cause | 3 years |
| Rate of disease-free survival (death or relapse) | Composite outcome of death or primary disease relapse | 3 years |
| Cumulative incidence of clinically significant CMV reactivation (which led to antiviral treatment) | Incidence of cytomegalovirus reactivation | 3 year |
| Cumulative incidence of posttransplant lymphoproliferative disorder (biopsy-proven or positive EBV PCR combined with clinical symptoms) | Incidence of posttransplant lymphoproliferative disorder | 3 years |
| Cumulative incidence CMV disease (biopsy-proven CMV disease OR suggestive CMV+ BAL) | Cumulative incidence of cytomegalovirus disease | 3 years |
| Measuremnt of quality of life using the FACT-BMT scale | Measurement quality of life | 2 years |
| D006402 |
| Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007945 | Leukemia, Lymphoid |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D001855 | Bone Marrow Diseases |
| D008223 | Lymphoma |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |