Editor’s Note: Since 2008, the World Health Organization (WHO) has recognized t(6;9)(p22;q34)/DEK-NUP214 fusion gene-positive acute myeloid leukemia (AML) as a distinct subtype. This type of AML is characterized by a low incidence rate, high malignancy, a high risk of relapse after chemotherapy, and very poor prognosis. Hematopoietic stem cell transplantation can significantly improve these poor outcomes, although the relapse rate after transplantation remains high. From April 14 to 17, 2024, the 50th European Society for Blood and Marrow Transplantation (EBMT) annual meeting took place in Glasgow, UK. At this conference, a study by Dr. He Hai from the team of Professor Ruijuan Sun at Hebei Yanda Lu Daopei Hospital in China was presented as a poster. The study revealed that strengthening the pre-treatment regimen in allo-HSCT for treating AML patients with t(6;9)/DEK-NUP214 could effectively reduce the post-transplant relapse rate. This journal has specially invited Dr. He Hai to share the research findings and their clinical significance with peers immediately.
Research Background
Previous studies have shown that hematopoietic stem cell transplantation can significantly improve the poor prognosis of acute myeloid leukemia (AML) with the t(6;9)(p22;q34)/DEK-NUP214 fusion gene, yet the rate of relapse after transplantation remains high. Currently, there are no studies focusing on reducing the relapse rate in this subtype of leukemia post-transplantation. Our center has achieved good therapeutic effects by implementing an enhanced pre-treatment regimen in allo-HSCT for this type of AML.
Research Methods
A retrospective analysis was conducted on 28 patients with t(6;9)/DEK-NUP214 AML who underwent allo-HSCT at our center from 2015 to 2022, using SPSS 25.0 for statistical analysis. Observational endpoints included overall survival (OS), relapse-free survival (RFS), cumulative incidence of relapse (CIR), transplant-related mortality (TRM), and both acute and chronic GVHD. All outcomes were measured starting from the time of stem cell infusion. Pre-treatment regimen: All patients received an enhanced pre-treatment regimen based on standard intensity busulfan (Bu) or total body irradiation (TBI) combined with cyclophosphamide (Cy), with additional decitabine 20 mg/m²·day for 5 days, purine nucleoside analogs (cladribine 5 mg/m²·day for 5 days or fludarabine 30 mg/m²·day for 5 days), and idarubicin 6-10 mg/m²·day for 3 days. The total dose of TBI was 1000-1200cGy administered over 3 days. Patients were divided into groups based on the enhanced regimen: decitabine group (10 patients), purine nucleoside analogs group (11 patients), and idarubicin group (7 patients).
Research Results
The median follow-up period for the 28 patients was 42 months (range 3-100 months). All patients successfully underwent transplantation, with median engraftment times for white blood cells and platelets at 13 days (range 10-20 days) and 12 days (range 6-29 days), respectively. The 3-year OS rate post-allo-HSCT was 85.9%, the RFS rate was 81.6%, the CIR was 3.4%, and the TRM was 10.7%. Among the patients who achieved complete remission (CR) at the time of transplantation (22 patients), the 3-year OS was 87% and RFS was 82.6%. In patients not in remission (NR) at transplantation (6 patients), the 3-year OS was 83% and RFS was 83%, with no statistically significant difference in survival between the two groups (P=0.666).
By the end of the follow-up, there was one case of hematologic relapse, who underwent a second allo-HSCT. Three patients died, with a median OS of 8 months (range 3-15 months), all due to transplant-related deaths (two from intracranial infections and one from multi-organ failure). None of the 28 patients experienced hepatic veno-occlusive disease or grade III or higher hemorrhagic cystitis during pre-treatment. Fifteen patients experienced fevers during pre-treatment, with two cases of bacterial sepsis, one of fungal pneumonia, seven with liver damage, and nine with diarrhea, all of which were controlled after anti-infection and liver protection treatment. Three patients developed post-transplant thrombotic microangiopathy, which improved after treatment. Eight patients developed CMV viremia and one developed EBV viremia, all of whom became virus-negative after antiviral treatment. Post-transplant, 11 patients (39%) developed grade II-IV acute GVHD, 4 patients (14%) developed grade III-IV acute GVHD, and 14 patients (50%) developed chronic GVHD, mainly involving the skin, oral cavity, and lungs in one case.
Research Conclusions
Allogeneic hematopoietic stem cell transplantation is an effective treatment for AML with t(6;9)/DEK-NUP214. The use of an enhanced pre-treatment regimen in allo-HSCT is safe and effective, significantly reducing the relapse rate and improving the relapse-free survival rate in these patients.
Researcher’s Comments
t(6;9)/DEK-NUP214 AML is a high-risk acute myeloid leukemia with a low incidence rate. Classified by WHO and the European LeukemiaNet as having a poor prognosis, patients receiving only chemotherapy have a 3-year OS of 23-54%, RFS of 7-18%, and a high 3-year CIR of up to 62%, indicating poor prognosis. Therefore, allo-HSCT is recommended as a first-line treatment option. Literature reports on the overall effectiveness of allo-HSCT show a 3-year OS of 38-53%; even with transplantation, outcomes remain suboptimal. This study used three different enhanced pre-treatment regimens for allo-HSCT in treating this subtype of AML, effectively reducing post-transplant relapse rates and improving relapse-free survival rates, with results superior to current domestic and international research.
Dr. He Hai’s Poster Presentation at EBMT 2024
Expert Profile
Dr. He Hai, Attending Physician
Hebei Yanda Lu Daopei Hospital
Graduated from the Medical Department of Hebei University in 2011
Began working at the Lu Daopei Medical Group in 2012, serving as an attending physician in the bone marrow transplantation department
Engages in clinical treatment and research in hematology chemotherapy and hematopoietic stem cell transplantation
Specializes in various hematologic bone marrow transplants and complication management
Expert Profile
Ruijuan Sun
Member of the Organ and Cell Disease Professional Committee of the Hematology Physicians Branch of the Chinese Medical Doctor Association
Member of the Umbilical Cord Blood Application Committee of the China Maternal and Child Health Association
Member of the Langfang City Anti-Cancer Association in Hebei Province
Has been engaged in clinical work related to hematopoietic stem cell transplantation for over 20 years. Successfully completed over a thousand cases of allogeneic hematopoietic stem cell transplantation, treating patients ranging from 7 months to 69 years old. Proficient in treating various types of benign and malignant blood tumors, acute and chronic GVHD, severe infections, and various complications post-transplantation, particularly experienced in using immunotherapy to prevent relapse post-transplantation. Successfully participated in the first autologous umbilical cord blood treatment for severe aplastic anemia in children in China. Involved in the first transplantation for XIAP-related hemophagocytic syndrome in China and successfully completed multiple stem cell transplants for congenital ichthyosis. Frequently shares her expertise at international bone marrow transplant conferences such as APBMT, EBMT, and TCT.
