Combining Melphalan or Thiotepa with an Intensive Conditioning Regimen Significantly Reduces Relapse Rates in Minimal Residual Disease-Positive (MRD+) Pediatric Acute Myeloid Leukemia Patients Post Haploidentical Hematopoietic Stem Cell Transplantation

Introduction

Acute myeloid leukemia (AML) is the second most common hematological malignancy in children, representing 15% to 20% of childhood leukemia cases. Minimal residual disease (MRD) status before transplantation is a key prognostic factor in pediatric AML. MRD positivity (MRD+) is linked to lower survival rates and higher relapse rates.

Methods

We retrospectively analyzed 18 pediatric AML patients with MRD+ who underwent haploidentical hematopoietic stem cell transplantation (haplo-HSCT) at our hospital from January 2020 to November 2023. Among them, 8 had the RUNX1::RUNX1T1 fusion gene, 1 had KMT2A::MLLT3, 1 had KMT2A::MLLT6, and 1 had KMT2A::ENL. MRD was assessed by flow cytometry. The median age was 7.5 years (range: 2 to 17 years) with a male-to-female ratio of 11:7. The median pre-transplant MRD was 2.26% (range: 0.01% to 89.9%). There were 7 cases in first complete remission (CR1), 3 in second complete remission (CR2), 1 in partial remission (PR), and 7 with no remission (NR). All received myeloablative conditioning with melphalan or thiotepa: 14 with Busulfan/Cyclophosphamide (Bu/Cy), 3 with Busulfan/Fludarabine (Bu/Flu), 10 with melphalan, and 8 with thiotepa. Melphalan was given at 110 mg/m² and thiotepa at 5-7.5 mg/kg, both on days -3 and -2. The median follow-up was 37.11 months (range: 4.19 to 53.71 months).

Results

All patients achieved 100% white blood cell engraftment with a median time of 15 days (range: 10 to 19 days) and platelet engraftment with a median of 10 days (range: 7 to 21 days). At one month post-transplant, all had negative bone marrow MRD. No relapse occurred, but 3 patients died (2 from pneumonia and 1 from grade III acute graft-versus-host disease [aGVHD]). All 3 were in NR status pre-transplant. The estimated 4-year overall survival (OS) rate was 83.3%. Grade III-IV aGVHD occurred in 11.11% of patients, and extensive chronic graft-versus-host disease (cGVHD) in 16.67%. Mucositis was noted in 4 patients, with only 1 case being moderate to severe. Cytomegalovirus (CMV) reactivation occurred in 66.67% and Epstein-Barr virus (EBV) in 33.33% of patients, with median onset times of 28 and 32 days, respectively.

Conclusions

In pediatric AML patients with MRD+, haplo-HSCT using a conditioning regimen that includes melphalan or thiotepa resulted in 100% engraftment of white blood cells and platelets without an increased incidence of mucositis. No relapse of the primary disease was observed during the follow-up period, and the estimated 4-year OS rate was 83.3%. The rates of CMV and EBV reactivation, as well as the incidence of GVHD did not increase. These findings suggest that this regimen can effectively reduce the risk of post-transplant relapse and improve survival outcomes.

No relevant conflicts of interest to declare.