Survival outcomes of children with relapsed or refractory myeloid leukemia associated with Down syndrome

Authors

• Nikhil Raghuram
• Daisuke Hasegawa
• Kentaro Nakashima
• Syaza Rahman
• Evangelia Antoniou
• Torjus Skajaa
• Pietro Merli
• Anupam Verma
• Karen R. Rabin
• Catherine Aftandilian
• Rishi S. Kotecha
• Daniel Cheuk
• Kirsi Jahnukainen
• Alexandra Kolenova
• Walentyna Balwierz
• Alice Norton
• Maureen O'Brien
• Sonia Cellot
• Ashley Chopek
• Nira Arad-Cohen
• Bianca Goemans
• Marta Rojas-Vasquez
• Hany AriffinFollow
• Jack Bartram
• E. Anders Kolb
• Franco Locatelli
• Jan-Henning Klusmann
• Henrik Hasle
• Bryan Mcguire
• Afia Hasnain

Document Type

Article

Publication Date

11-1-2023

Abstract

Children with Down syndrome (DS) are at a significantly higher risk of developing acute myeloid leukemia, also termed myeloid leukemia associated with DS (ML-DS). In contrast to the highly favorable prognosis of primary ML-DS, the limited data that are available for children who relapse or who have refractory ML-DS (r/r ML-DS) suggest a dismal prognosis. There are few clinical trials and no standardized treatment approach for this population. We conducted a retrospective analysis of international study groups and pediatric oncology centers and identified 62 patients who received treatment with curative intent for r/r ML-DS between year 2000 to 2021. Median time from diagnosis to relapse was 6.8 (range, 1.1-45.5) months. Three-year event-free survival (EFS) and overall survival (OS) were 20.9 +/- 5.3% and 22.1 +/- 5.4%, respectively. Survival was associated with receipt of hematopoietic stem cell transplantation (HSCT) (hazard ratio HR], 0.28), duration of first complete remission (CR1) (HR, 0.31 for > 12 months) and attainment of remission after relapse (HR, 4.03). Patients who achieved complete remission (CR) before HSCT, had an improved OS and EFS of 56.0 +/- 11.8% and 50.5 +/- 11.9%, respectively compared to those who underwent HSCT without CR (3-year OS and EFS of 10.0 +/- 9.5%). Treatment failure after HSCT was predominantly because of disease recurrence (52%) followed by treatment-related mortality (10%). The prognosis of r/r ML-DS remains dismal even in the current treatment period and serve as a reference point for current prognostication and future interventional studies. Clinical trials aimed at improving the survival of patients with r/r ML-DS are needed.

Publication Title

Blood Advances

Recommended Citation

Raghuram, Nikhil; Hasegawa, Daisuke; Nakashima, Kentaro; Rahman, Syaza; Antoniou, Evangelia; Skajaa, Torjus; Merli, Pietro; Verma, Anupam; Rabin, Karen R.; Aftandilian, Catherine; Kotecha, Rishi S.; Cheuk, Daniel; Jahnukainen, Kirsi; Kolenova, Alexandra; Balwierz, Walentyna; Norton, Alice; O'Brien, Maureen; Cellot, Sonia; Chopek, Ashley; Arad-Cohen, Nira; Goemans, Bianca; Rojas-Vasquez, Marta; Ariffin, Hany; Bartram, Jack; Kolb, E. Anders; Locatelli, Franco; Klusmann, Jan-Henning; Hasle, Henrik; Mcguire, Bryan; and Hasnain, Afia, "Survival outcomes of children with relapsed or refractory myeloid leukemia associated with Down syndrome" (2023). Research Publications (2021 to 2025). 3657.
https://knova.um.edu.my/research_publications_2021_2025/3657

Divisions

ummc

Funders

International Berlin-Frankfurt-Muenster AML Study Group

Volume

7

Issue

21

Publisher

Elsevier

Publisher Location

RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS