Clonal Myeloproliferative Disorders in Patients with Down Syndrome-Treatment and Outcome Results from an Institution...

Area of Science:

• Pediatric Hematology Oncology
• Genetics and Genomics
• Clinical Trial Design

Background:

• Children with Down syndrome (DS) exhibit an elevated risk for clonal myeloproliferative disorders.
• The optimal balance between treatment intensity and toxicity in DS patients with these disorders remains undefined.
• Understanding risk factors and treatment strategies is crucial for improving outcomes in this vulnerable population.

Purpose of the Study:

• To analyze risk factors and identify optimal treatment strategies for children with Down syndrome and myeloproliferative disorders.
• To compare outcomes between classical Myeloid Leukemia associated with DS (ML-DS) and sporadic DS-Acute Myeloblastic Leukemia (DS-AML).
• To evaluate the impact of treatment intensity, specifically high-dose ARA-C (HDARA-C), on the outcomes of ML-DS patients.

Main Methods:

• Retrospective analysis of 78 pediatric patients (<16 years) with Down syndrome and myeloproliferative disorders.
• Categorization into Transient Abnormal Myelopoiesis (TAM) and DS-Acute Myeloblastic Leukemia (DS-AML), including classical ML-DS with megakaryoblastic immunophenotype (AMKL) and sporadic DS-AML (non-AMKL).
• Patients with DS-AML were treated according to four BFM-based protocols; outcomes were analyzed based on immunophenotype and treatment intensity.

Main Results:

• Transient Abnormal Myelopoiesis (TAM) rarely required treatment, with a 5-year Event-Free Survival probability (EFSp) of 74.4%.
• DS-Acute Myeloblastic Leukemia (DS-AML) had a 5-year EFSp of 60.6%, with infections being the primary cause of treatment-related deaths.
• Megakaryoblastic immunophenotype (AMKL) was identified as the strongest favorable prognostic factor (p = 0.000). ML-DS showed better outcomes and lower relapse rates compared to non-DS-AMKL (p = 0.0002). No significant difference in 5-year EFSp was observed with or without high-dose ARA-C (HDARA-C) (p = 0.172), though a trend towards higher relapse rates without HDARA-C was noted.

Conclusions:

• Transient Abnormal Myelopoiesis (TAM) in Down syndrome generally requires minimal intervention, with early treatment effective for severe cases.
• The megakaryoblastic immunophenotype is a key indicator of favorable prognosis in DS-AML, associated with reduced relapse rates.
• While treatment-related mortality remains a concern, current data do not support omitting high-dose ARA-C (HDARA-C) in ML-DS due to a potential increase in relapse rates.