Leukemia is one of the common malignant tumors that threaten human health. Although the efficacy of AML treatment has improved significantly in recent years, it remains one of the major diseases threatening human health. Current research on AML treatment mainly has two directions. One is the addition of new targeted therapy drugs, and the other research direction is to enhance the intensity of AML chemotherapy, including the use of large doses of anthracycline drugs or the use of high-dose cytarabine treatment.
Since the 1990s, induction remission has been achieved by using anthracyclines in combination with high-dose cytarabine. The ECOG (Eastern Cooperative Oncology Group) contends that high-dose induction chemotherapy fails to enhance the bone marrow remission rate but elevates the chemotherapy-related mortality rate. Bradstock and the Australian Group also noted that although it does not increase the bone marrow remission rate, it can result in longer survival time and disease-free survival time. The clinical study from EORTC-GIMEMA AML-12 discovered that AML patients under the age of 45 could benefit from induction therapy incorporating high-dose cytarabine. In our previous randomized controlled clinical trials, it was found that the HAD and DA regimens containing intermediate-dose cytarabine could enhance the complete remission rate and improve the overall survival of adult AML. However, the degree of benefit varies among different AML subgroups.
The abnormalities of RUNX1-RUNX1T1 and CBFβ-MYH11 respectively involve a subunit of CBF (core binding factor), thus the two are collectively called CBF leukemia. Previous retrospective studies show that this type of leukemia benefits from intensified treatment regimens such as FLAG. However, at present, there is a lack of prospective randomized controlled clinical studies to confirm this. Therefore, in this study, we intend to further verify through a prospective randomized controlled clinical trial whether the induction treatment regimen containing intermediate-dose cytarabine can improve the long-term efficacy of adult RUNX1-RUNX1T1 acute myeloid leukemia.
AML conforming to WHO (2022) or ICC standards
Possessing the RUNX1::RUNX1T1 fusion gene
Age ranging from 14 to 60 years old, regardless of gender.
The performance status assessment of the Eastern Cooperative Oncology Group (ECOG-PS) being 0 - 2.
Acute promyelocytic leukemia accompanied by PML-RARA fusion gene.
Acute myeloid leukemia featuring BCR-ABL fusion gene.
Patients undergoing retreatment (but can receive cytoreductive therapy with hydroxyurea and cytarabine).
Individuals concurrently having malignant tumors in other organs (requiring treatment).
Parallel
cytarabine
DrugCytarabine combined with daunorubicin was used for induction therapy. According to the different doses of cytarabine, it was divided into standard dose group and intermediate dose group.In addition, high doses of cytarabine are also used for post-remission treatment.
daunorubicin
Drugcombined with cytarabine and used for induction therapy
idarubicin
Drugcombined with cytarabine and cyclophosphamide and used for post-remission treatment
cyclophosphamide
Drugcombined with cytarabine and idarubicin and used for post-remission treatment
overall survival
Used to evaluate all patients who enter clinical trials. From the date of entry into the trial until the date of patient death (including any cause) or last survival follow-up.
Complete remission (CR)/CR with partial hematologic recovery (CRh)/CR with incomplete hematologic recovery (CRi) rate after induction therapy
The ratio of patients achieved CR/CRh/CRi after induction therapy.
RUNX1::RUNX1T1 minimal residual disease (MRD) reduction >3 logs after 2 courses
RUNX1::RUNX1T1 MRD is measured by real-time PCR.
RUNX1::RUNX1T1 molecular MRD undectable rate
MRD levels monitored by polymerase chain reaction are associated with outcomes in acute myeloid leukemia with RUNX1-RUNX1T1.
Relapse-free survival (RFS)
Defined only for patients achieving CRc; measured from the date of achievement of remission until the date of hematologic relapse or death from any cause; patients not known to have relapsed or died at last follow-up are censored on the date they were last known to be alive
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