Characteristics and outcomes of children with acute myeloid leukemia and Down syndrome who are ineligible for clinical trials due to severe comorbidities

Pediatr Blood Cancer. 2019 Nov;66(11):e27942. doi: 10.1002/pbc.27942. Epub 2019 Aug 18.

Abstract

Background: High survival rates of 80-90% have been reported in recent clinical trials of reduced-intensity chemotherapies for children with acute myeloid leukemia and Down syndrome (AML-DS). However, a certain number of children with AML-DS have complicating comorbidities, including congenital heart disease (CHD), and are therefore ineligible for enrolment in clinical trials.

Methods: We retrospectively analyzed the clinical characteristics and outcomes of children with AML-DS who were excluded from Japanese clinical trials conducted between 2000 and 2015.

Results: Twelve children (six males and six females) were identified and were ineligible for CHD (n = 8) and other comorbidities, including hyperleukocytosis complicated with coagulopathy, severe hemophagocytosis, pulmonary fibrosis, and hypoxic-ischemic encephalopathy (n = 1 each). The median age at the diagnosis was 14 months (range, 5 months to 11.5 years). Among all cases, 11 patients were treated with curative intent. Four patients were considered intolerant to intensive chemotherapy and received only low-dose cytarabine-based chemotherapy: three failed to achieve remission and died of disease, while one successfully achieved remission but eventually died of infection. Seven cases underwent regular-intensive chemotherapy for AML-DS: six were alive and in remission; one had relapsed disease. One patient who received the best supportive care died of disease. Finally, six patients remained in continuous complete remission, while six died. The 5-year overall survival rate was 51%.

Conclusions: The prognosis of AML-DS patients who received insufficient treatment due to severe complication was poor. The optimal dose intensity of curative chemotherapy for such cases should be explored.

Keywords: Down syndrome; acute myeloid leukemia; clinical trial; comorbidity; congenital heart disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Child
  • Child, Preschool
  • Clinical Trials as Topic / standards
  • Comorbidity
  • Down Syndrome / epidemiology*
  • Female
  • Genetic Predisposition to Disease
  • Heart Defects, Congenital / epidemiology
  • Heart Defects, Congenital / genetics
  • Humans
  • Hypoxia-Ischemia, Brain / epidemiology
  • Infant
  • Kaplan-Meier Estimate
  • Leukemia, Myeloid, Acute / drug therapy
  • Leukemia, Myeloid, Acute / epidemiology*
  • Leukemia, Myeloid, Acute / etiology
  • Leukemia, Myeloid, Acute / genetics
  • Lymphohistiocytosis, Hemophagocytic / epidemiology
  • Male
  • Patient Selection
  • Pulmonary Fibrosis / epidemiology
  • Retrospective Studies
  • Treatment Failure