# Disease Burden at the Time of Transplantation Is a Primary Predictor of Outcomes in Pediatric MDS: A Single-Center Experience

## TL;DR

This study finds that children with fewer abnormal blood cells at the time of transplant have better survival rates in a rare blood disease called pediatric MDS.

## Contribution

The study identifies blast burden at transplantation as a primary predictor of outcomes in pediatric MDS, offering new insights for treatment strategies.

## Key findings

- Children with less than 5% blasts in bone marrow at transplant had an 87% two-year survival rate.
- Patients with ≥5% blasts had a significantly lower two-year survival rate of 54%.
- Higher blast burden led to increased relapse rates but not higher transplant-related mortality.

## Abstract

Myelodysplastic syndrome is a rare and serious blood disease in children that can lead to leukemia. A stem cell transplant is often the only chance for a cure, but it is difficult to predict which children will respond well to this treatment. This study analyzed 36 patients who received transplants at a single center to better understand how disease features affect outcomes. Children with fewer abnormal cells, referred to as blasts, in their bone marrow at the time of transplant had significantly improved survival rates. Chemotherapy given before transplant helped lower disease levels but did not always prevent relapse, especially in patients with more aggressive disease. These high-risk patients had a two-year survival rate of just over 50%, compared to over nearly 90% in other children. This suggests that current treatments may not be sufficient to overcome aggressive disease. More effective and less toxic approaches are urgently needed, both before and after transplant, to improve outcomes. Developing targeted therapies and understanding the unique genetic characteristics in pediatric patients will be key to making progress. This study highlights the importance of continuing research to help more children survive, particularly those with the highest risk disease.

Background: Hematopoietic cell transplantation (HCT) remains the only curative therapy for pediatric myelodysplastic syndrome (MDS) in all but rare cases. While HCT outcomes for pediatric MDS are similar across the largest registry and single-center trials, factors identified as contributing to inferior outcomes vary from study to study. We performed an analysis to provide more clarity on the prognostic implications of disease characteristics, including blast burden and cytogenetic abnormalities, in the current era. Methods: We conducted a retrospective analysis of 36 consecutive children (<18 years of age at HCT) who underwent allogeneic HCT for MDS between June 2000 and October 2019 at the Fred Hutchinson Cancer Center. Results: Overall survival (OS) was 77% (95% CI 64–92%) and relapse-free survival (RFS) was 71% (95% CI 57–88%) at 2 years post-HCT. Patients with <5% blasts by morphology in the bone marrow at the time of HCT showed superior 2-year OS at 87% (95% CI 74–100%) as compared to 54% (95% CI 32–93%) in patients with ≥5% blasts, consistent with an HR of 4.6 (CI 1.14–18.7, p = 0.03). The inferior outcomes in patients with ≥5% blasts were due to increased relapse incidence (HR 7.6, CI 1.5–39.3) with no difference in NRM or acute GVHD. Conclusions: OS and RFS were comparable to what has been observed in other large, single-center studies (OS 77%, RFS 71% at 2 years) and compared favorably to outcomes from the largest multi-center retrospective analyses.