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there was almost no patient would enroll in this study.
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Allogeneic stem cell transplantation (SCT) remains a powerful therapeutic modality for patients with acute myeloid leukemia (AML).The superior clinical outcomes of allogeneic human SCT versus chemotherapy alone as post-remission treatment could be related to the graft-versus-leukemia (GVL) effects of recovered donor T cells. Our previous study investigated both the association of MRD status with transplant outcomes in haplo-SCT and matched sibling donor transplantation(MSDT), and also possible differences in the transplant outcomes of patients with positive pre-MRD (as determined by MFC) who underwent haplo-SCT versus MSDT. It provided new evidence that unmanipulated haplo-SCT is superior to matched sibling donor transplantation in eradicating pre-transplantation MRD, indicating that unmanipulated haploidentical allografts have stronger GVL effects.As to the AML patients in standard-risk, who have a positive MRD before MSDT, whether these patients should be given any relapse prevention is the question to be answered in this study. Interferon α-2b exerts a relatively strong immunomodulatory effect. It can kill AL cells by regulating T-cell and/or natural killer cell functions.Consequently, interferon α-2b may have potential value for high-risk AL patients after transplantation. The study hypothesis: Using interferon α-2b following hematopoietic stem cell transplantation in patients with standard-risk AML can further reduce relapse rate and improve leukemia-free survival.
The standard-risk AML patients (18-60 years) receiving HLA-identical allogeneic stem cell transplantation in Peking University Institute of Hematology will be enrolled in this study if their MRD were positive before SCT, in CR1/CR2, remain in CR and MRD negative in the first two months after transplantation. The patients in this study will be treated with interferon-alpha injection twice a week (3 million units / time, iH) since the third month posttransplant. If the patients were well tolerated, the interferon-alpha treatment will continue 6 months. All the enrolled patients will undergo MRD monitoring after SCT as the same as the routine procedure. Bone marrow examination will be performed at the regular time points (+1, 2,3, 4, 5, 6, 9, 12 month) and 8-colour flow cytometry and RQ-PCR-based WT1 examination will be empolyed to evaluate MRD and disease status. Based on the statistical calculation, in order to reduce the incidence of relapse from 40% (previous data) to 15% (the cumulative incidence of relapse in pre-MRD- AML patients), total 29 patients will be enrolled. The main side effects might related to interferon-alpha include induction of severe GVHD, hematological toxicity and Flu - like symptoms. If the patients met the following criteria, they will withdraw from the trial: 1)met the combined criteria for positive MRD (MRDco+) which was defined as 2 consecutive FCM+ or WT1+ results or both FCM+ and WT1+ in a single sample within 1 year after transplantation; 2)hematological relapse; 3) grade III or IV acute GVHD, or moderate/ severe chronic GVHD; 4) severe infection; 5) grade IV hematological toxicity; 6) organ failure; 7) death; 8) patients refuse to continue the interferon-alpha treatment. The main end point of the study is one-year cumulative incidence of relapse. the second end points include OS, NRM, DFS, MRD, GVHD, infection and hematological toxicity.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Interferon alpha group | Experimental | The patients in arm will be receive interferon alpha injection (3 million U/time)twice a week, as the intervention since the third month after HLA-identical transplantation. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Interferon-alpha | Drug | patients in Interferon-alpha group will receive Interferon-alpha injection since the third month after transplantation for six months. |
|
| Measure | Description | Time Frame |
|---|---|---|
| cumulative incidence of relapse | the cumulative incidence of relapse | within the first year after transplantation |
| Measure | Description | Time Frame |
|---|---|---|
| OS | overall survival | within the first year after transplantation |
| NRM | non-relapse motality | within the first year after transplantation |
| Measure | Description | Time Frame |
|---|---|---|
| Hematologic toxicity | any decrease of blood cells including white, red blood cells and platelet | within the first year after transplantation |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Xiaojun Huang, Dr. | Peking University Institute of Hematology | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Peking University People's Hospital | Beijing | 100044 | China |
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| ID | Term |
|---|---|
| D012008 | Recurrence |
| D015470 | Leukemia, Myeloid, Acute |
| ID | Term |
|---|---|
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D007951 | Leukemia, Myeloid |
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| ID | Term |
|---|---|
| D016898 | Interferon-alpha |
| ID | Term |
|---|---|
| D007370 | Interferon Type I |
| D007372 | Interferons |
| D016207 | Cytokines |
| D036341 | Intercellular Signaling Peptides and Proteins |
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Single Group Assignment
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| DFS | disease-free survival | within the first year after transplantation |
| MRD | cumulative incidence of MRD+ | within the first year after transplantation |
| acute GVHD | acute graft-versus-host disease | within 100 days after transplantation |
| chronic GVHD | chronic graft-versus-host disease | within the first year after transplantation |
| infection | bacteria, fungal, virus, etc. | within the first year after transplantation |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D010455 |
| Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D011506 | Proteins |
| D001685 | Biological Factors |