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

Raghuram N 1 , Hasegawa D 2 , Nakashima K 3 , Rahman S 4 , Antoniou E 5 , Skajaa T 6 Show all authors , Merli P 7 , Verma A 8 , Rabin KR 9 , Aftandilian C 10 , Kotecha RS 11 , Cheuk D 12 , Jahnukainen K 13 , Kolenova A 14 , Balwierz W 15 , Norton A 16 , O'Brien M 17 , Cellot S 18 , Chopek A 19 , Arad-Cohen N 20 , Goemans B 21 , Rojas-Vasquez M 22 , Ariffin H 4 , Bartram J 6 , Kolb EA 23 , Locatelli F 7 , Klusmann JH 24 , Hasle H 25 , McGuire B 1 , Hasnain A 26 , Sung L 1 , Hitzler J 1

Affiliations 

  • 1 Division of Hematology/Oncology, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada
  • 2 Department of Pediatrics, St. Luke's International Hospital, 9-1, Akashi-cho, Chuo-ku, Tokyo, 104-8560, Japan
  • 3 Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
  • 4 Division of Paediatric Haematology-Oncology and BM Transplantation, University of Malaya Medical Centre, Kuala Lumpur, Malaysia
  • 5 Department of Pediatric Hematology and Oncology, University Children's Hospital Essen, University of Duisburg-Essen, Essen, Germany
  • 6 Department of Haematology, Great Ormond Street Hospital for Children, London, United Kingdom
  • 7 Department of Pediatric Hematology/Oncology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ospedale Pediatrico Bambino Gesù, Sapienza University of Rome, Rome, Italy
  • 8 Division of Hematology/Oncology, Department of Pediatrics, University of Utah and Primary Children's Hospital, Salt Lake City, UT
  • 9 Pediatric Hematology-Oncology, Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX
  • 10 Division of Hematology, Oncology, Stem Cell Transplantation and Regenerative Medicine, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA
  • 11 Department of Clinical Haematology, Oncology, Blood and Marrow Transplantation, Perth Children's Hospital, Perth, WA, Australia
  • 12 Department of Paediatrics and Adolescent Medicine, the University of Hong Kong and Hong Kong Children's Hospital, Hong Kong, China
  • 13 Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
  • 14 Comenius University Children's Hospital Limbova 1, Bratislava, Slovakia
  • 15 Department of Pediatric Oncology and Hematology, Institute of Pediatrics, Jagiellonian University Medical College, Krakow, Poland
  • 16 Department of Haematology, Birmingham Women's and Children's NHS Foundation Trust, Birmingham, United Kingdom
  • 17 Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH
  • 18 Division of Hematology, Department of Pediatrics, Ste-Justine Hospital, Montréal, Université de Montréal, Montréal, QC, Canada
  • 19 Pediatric Blood and Marrow Transplant Program, Cancer Care Manitoba, University of Manitoba, Winnipeg, MB, Canada
  • 20 Pediatric Hematology-Oncology Department, Ruth Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel
  • 21 Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands
  • 22 Department of Pediatric Hematology-Oncology, Stollery Children's Hospital, University of Alberta, Edmonton, Canada
  • 23 Nemours Center for Cancer and Blood Disorders/Alfred I. DuPont Hospital for Children, Wilmington, DE
  • 24 Goethe University Frankfurt, Frankfurt, Germany
  • 25 Department of Paediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark
  • 26 Division of Genome Diagnostics, Department of Pediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, ON, Canada
Blood Adv, 2023 Nov 14;7(21):6532-6539.
PMID: 36735769 DOI: 10.1182/bloodadvances.2022009381

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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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