Improved Survival Rates with Bu/Cy+Melphalan and Bu/Cy+Thiotepa Regimens in Haploidentical Stem Cell Transplantation for Non-Down Syndrome Acute Megakaryoblastic Leukemia (AMKL)
At the 66th Annual Meeting of the American Society of Hematology (ASH) held in San Diego from December 7-10, 2024, Dr. Zhi-Jie Wei, Director of the Hematology Department at Lu Daopei Hospital, presented groundbreaking research on the treatment of Non-Down Syndrome Acute Megakaryoblastic Leukemia (Non-DS-AMKL). His team’s study, titled “Improved Outcomes with Bu/Cy+Melphalan and Bu/Cy+Thiotepa Regimens in Haploidentical Hematopoietic Stem Cell Transplantation for Non-Down Syndrome Acute Megakaryoblastic Leukemia,” was featured in Abstract 3492 and marks a significant advancement in AMKL treatment.
Non-DS-AMKL, a rare and aggressive form of leukemia, accounts for a small percentage of both pediatric and adult acute myeloid leukemia (AML) cases. While DS-AMKL often has a better prognosis, Non-DS-AMKL has a poor prognosis with a three-year overall survival (OS) rate of less than 40%. Haploidentical hematopoietic stem cell transplantation (haplo HCT) is currently the only curative treatment available for these patients.
The study focused on the use of modified Bu/Cy-based regimens in conjunction with either Melphalan (MEL) or Thiotepa (TT) to improve survival rates and reduce complications in patients undergoing haploidentical stem cell transplantation. The results were promising, showing a significant improvement in overall survival (OS) among complete remission (CR) patients. The OS for CR patients was 68.2%, compared to 16.7% for patients who did not achieve CR (PR/NR), highlighting the critical role of achieving CR in improving survival outcomes.
The study included 59 Non-DS-AMKL pediatric patients with a median age of 2 years. After treatment, all patients achieved successful engraftment, with a median time of 13 days for neutrophil engraftment and 9 days for platelet engraftment. Notably, the Bu/Cy+MEL and Bu/Cy+TT regimens resulted in a 100% OS rate for patients in the Bu/Cy+TT group, although there were no significant differences in OS between the Bu/Cy and Bu/Cy+MEL groups.
In terms of complications, the modified regimens showed a reduction in the incidence of Grade III-IV acute graft-versus-host disease (aGVHD) and transplant-related mortality (TRM), further underscoring the safety of the new protocols. The incidence of severe aGVHD was significantly lower in the Bu/Cy+TT group, with a reduction in both acute and chronic GVHD compared to the traditional Bu/Cy regimen.
Dr. Wei emphasized the potential of these modified regimens in improving the outcomes of Non-DS-AMKL patients, particularly in those achieving complete remission. The study provides valuable insights into optimizing treatment protocols for AMKL and sets the stage for further clinical exploration. While the results for partial remission and non-remission patients were less promising, the approach offers hope for better treatment strategies in the future.
With continued research and data collection, the Lu Daopei Hospital team aims to refine these regimens to provide lasting solutions for Non-DS-AMKL patients, potentially changing the landscape of treatment for this challenging leukemia subtype.