AL-06. Impact of pre allo-HSCT MRD status on relapse prophylaxis in high-risk acute myeloid leukemia in children

Summary

Relapse of acute myeloid leukemia (AML) remains one of the main causes of mortality and, therefore, lower long-term survival in children after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The relapse incidence reaches 40% depending on cytogenetic and molecular biological risk factors, the remission status at the time of allo-HSCT. The role of the level of minimal residual disease (MRD) is being studied. It is known that MRD(+) status after allo-HSCT requires preventive therapy. The predictive value of MRD (±) before allo-HSCT in children with AML in the need for prophylactic therapy after allo-HSCT has not been determined.

Aim

To study the effect of prophylactic therapy after allo-HSCT on the overall and relapse free survival of children with high risk AML, depending on the MRD (±) status before allo-HSCT. Patients and methods. Data of 57 children with high risk AML who underwent allo-HSCT at R. M. Gorbacheva Research Institute between 2003 and 2020, age – from 0.5 to 18 years (the median age – 9 years) were analyzed. The retrospective analysis included patients (pts) who were in MRD(+) or MRD(-) in AML remission at the time of allo-HSCT, and during the entire follow-up period after transplantation they had MRD-negative status and complete donor chimerism. Patients with primary graft failure, relapse within 2 months after allo-HSCT, graft-versus-host disease (GVHD) 2-4 grade who didn’t allow performing prophylaxis of disease recurrence were excluded from analysis. Depending on the post-transplant prophylaxis, the pts were divided into 2 groups (Table 1).

Results

Median follow-up of pts after allo-HSCT is 68 months. Overall survival (OS) in the group of children with AML who received post-transplant disease prophylaxis after allo-HSCT is 87.5%, in pts without prophylactic therapy – 90% (p=0.727). Relapse free survival (RFS) – 93.8% and 75.6%, respectively (p=0.130). Graft-versus-host/relapse-free-survival (GRFS) is 62% vs 56.1%, respectively (p=0.655). Post-transplant disease prophylaxis in MRD (+) pts prior to allo-HSCT increased RFS compared to MRD (+) pts before allo-HSCT who did not receive therapy – 100% vs 36.4%, respectively (p=0.008), which did not affect on OS – 87.5% vs 92%, respectively (p=0.268). In high risk AML pts with MRD(-) status before transplantation, post-transplant prophylaxis of relapse had no effect on OS – 88.7% vs 100% (p=0.083) and RFS – 87.5% vs 92 % (p=0.671), respectively.

Conclusion

Post-transplant prophylaxis of relapse is advisable in a cohort of children with high risk AML with MRD(+) status before allo-HSCT. An increase in OS in this group should be considered in the structure of other complications (GVHD, infections).

Keywords

Allogeneic hematopoietic stem cell transplantation, acute myeloid leukemia, post-transplant prophylaxis of acute myeloid leukemia relapse, minimal residual disease.