The 29th Annual Meeting of the European Hematology Association (EHA) was grandly held in Madrid, Spain, from June 13 to 16, 2024. The EHA conference featured numerous captivating presentations, particularly in the area of non-remission acute myeloid leukemia (NR-AML), which attracted significant attention. A study by Professor Zhijie Wei's team from Beijing Lu Daopei Hospital, targeting NR-AML patients undergoing salvage haploidentical hematopoietic stem cell transplantation (haplo-HCT) (Abstract No.: P1324), was included in the conference abstracts. This study aimed to retrospectively analyze clinical and follow-up data of NR-AML patients treated with haplo-HCT at the hospital, summarizing the impact of adding unrelated cord blood infusion on patient survival and the incidence of severe (grade III-IV) graft-versus-host disease (GVHD). To provide a deeper understanding of this study, Professor Zhijie Wei was invited to give a detailed introduction, which is summarized below.

Background

Haplo-HCT is an effective treatment for relapsed/refractory acute myeloid leukemia (R/R-AML), particularly for patients who fail to achieve minimal residual disease (MRD) negativity or complete remission after prolonged chemotherapy. While haplo-HCT benefits from a strong graft-versus-leukemia (GVL) effect, severe acute GVHD (aGVHD) remains one of the major causes of failure post-transplantation. Reducing the incidence of severe aGVHD and improving long-term survival are key goals of haplo-HCT.

Previously, our team discovered that haploidentical allogeneic hematopoietic stem cell transplantation combined with third-party unrelated cord blood infusion significantly reduced the incidence of severe GVHD and improved overall survival (OS) in pediatric AML patients in CR1 (EBMT Abstract No.: 998). Building on this, our study further explores these effects in NR-AML patients.

Methods

This study included NR-AML patients who received their first haplo-HCT treatment at Beijing Lu Daopei Hospital and Hebei Yanda Lu Daopei Hospital from October 2014 to June 2023. The experimental group (haplo-cord HCT group) received haplo-HCT combined with an infusion of HLA-matched (≥4/6) single unrelated cord blood unit, with a total nucleated cell (TNC) count of 0.5*10^7/kg. The control group (haplo-HCT group) underwent haplo-HCT without unrelated cord blood infusion. All patients received myeloablative conditioning regimens based on Bu/CY or TBI/FLU, and GVHD prophylaxis with CsA+MMF+sMTX+ATG.

Results

A total of 79 patients were included in the study, with 68 in the haplo-cord HCT group and 11 in the haplo-HCT group (details in Table 1). Seventy-five patients received Bu/CY-based myeloablative conditioning, and 4 received TBI/CY-based conditioning. All patients were followed up until December 27, 2023, with a median follow-up time of 48 (1-106) months. Thirty-nine patients died, with transplant-related mortality (TRM) rates of 20/68 (29.4%) in the haplo-cord HCT group and 6/11 (54.5%) in the haplo-HCT group. The detailed causes of death are listed in Table 2. The 4-year OS in the haplo-cord HCT group was significantly higher than in the haplo-HCT group (56.7% vs. 20%, P=0.002, Figure 1), and the incidence of grade III-IV aGVHD was significantly lower (14.7% vs. 45.5%, P=0.046, Figure 2). In terms of viral infections, the haplo-cord HCT group had higher but not statistically significant rates of post-transplant CMV viremia and EBV viremia compared to the haplo-HCT group (72.1% vs. 45.5%, P=0.158, Figure 3; 14.7% vs. 9.1%, P=0.976, Figure 4). There was no significant difference in post-transplant relapse rates between the two groups (14.7% vs. 27.3%, P=0.545, Figure 5).

Conclusion

Salvage haplo-HCT combined with unrelated cord blood infusion significantly improves long-term survival and reduces the incidence of grade III-IV aGVHD in non-remission acute myeloid leukemia patients compared to haplo-HCT without cord blood infusion, ultimately benefiting patients. There was no significant difference between the two groups regarding viral infections and post-transplant relapse rates.

However, this study has limitations, including being single-center with a small sample size. Our team will continue to expand the sample size to validate these findings. We hope to identify more effective treatment pathways for this most challenging group of myeloid leukemia patients, ultimately saving more lives.