The Gut Microbiome and Sorafenib Maintenance Therapy in FLT3-ITD Positive AML After Allo-HSCT

The Gut Microbiome and Sorafenib Maintenance Therapy in FMS-like Tyrosine Kinase 3 (FLT3)/Internal Tandem Duplication (ITD) Positive Acute Myeloid Leukemia (AML) Patients After Allogeneic Hematopoietic Stem Cell Transplantation (Allo-HSCT)

This prospective trial investigates the effect of sorafenib maintenance therapy in FLT3-ITD positive AML patients after allo-HSCT in terms of gut microbiome.

Hematopoietic stem cell transplantation (HSCT) is used as a potentially curative therapy for patients with hematopoietic malignancies. Sorafenib, an inhibitor of multiple kinases including FLT3, has shown promising activity in FLT3-ITD-positive AML. Our previous studies demonstrated that sorafenib maintenance post-transplantation could improve the outcomes of FLT3-ITD-positive AML patients, which is associated with sorafenib enhancing the graft-versus-leukemia (GVL) effect. Some studies show that gut microbiome is associated with graft-versus-host-disease (GVHD) and GVL. However, the effect of gut microbiome on sorafenib maintenance after allo-HSCT remains unknown.

Inclusion Criteria:

• FLT3-ITD Positive AML
• Allo-HSCT Recipients

Exclusion Criteria:

• intolerance to sorafenib pretransplantation
• Cardiac dysfunction (particularly congestive heart failure)
• Hepatic abnormalities (bilirubin ≥ 3 mg/dL, aminotransferase> 2 times the upper limit of normal)
• Renal dysfunction (creatinine clearance rate < 30 mL/min)
• Any abnormality in a vital sign (e.g., heart rate, respiratory rate, or blood pressure)
• Patients with any conditions not suitable for the trial (according to the investigators' decision)