Comparison of long-term outcomes between children with aplastic anemia and refractory cytopenia of childhood who received immunosuppressive therapy with antithymocyte globulin and cyclosporine

Haematologica. 2015 Nov;100(11):1426-33. doi: 10.3324/haematol.2015.128553. Epub 2015 Aug 13.

Abstract

The 2008 World Health Organization classification proposed a new entity in childhood myelodysplastic syndrome, refractory cytopenia of childhood. However, it is unclear whether this morphological classification reflects clinical outcomes. We retrospectively reviewed bone marrow morphology in 186 children (median age 8 years; range 1-16 years) who were enrolled in the prospective study and received horse antithymocyte globulin and cyclosporine between July 1999 and November 2008. The median follow-up period was 87 months (range 1-146 months). Out of 186 patients, 62 (33%) were classified with aplastic anemia, 94 (49%) with refractory cytopenia of childhood, and 34 (18%) with refractory cytopenia with multilineage dysplasia. Aplastic anemia patients received granulocyte colony-stimulating factor more frequently and for longer durations than other patients (P<0.01). After six months, response rates to immunosuppressive therapy were not significantly different among the 3 groups. Acquisition of chromosomal abnormalities was observed in 5 patients with aplastic anemia, 4 patients with refractory cytopenia of childhood, and 3 patients with refractory cytopenia with multilineage dysplasia. Although the cumulative incidence of total clonal evolution at ten years was not significantly different among the 3 groups, the cumulative incidence of monosomy 7 development was significantly higher in aplastic anemia than in the other groups (P=0.02). Multivariate analysis revealed that only granulocyte colony-stimulating factor administration duration of 40 days or more was a significant risk factor for monosomy 7 development (P=0.02). These findings suggest that even the introduction of a strict morphological distinction from hypoplastic myelodysplastic syndrome cannot eradicate clonal evolution in children with aplastic anemia.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study

MeSH terms

  • Anemia, Aplastic* / blood
  • Anemia, Aplastic* / complications
  • Anemia, Aplastic* / drug therapy
  • Anemia, Aplastic* / pathology
  • Antilymphocyte Serum / administration & dosage*
  • Child
  • Child, Preschool
  • Chromosome Deletion*
  • Chromosome Disorders* / blood
  • Chromosome Disorders* / etiology
  • Chromosome Disorders* / pathology
  • Chromosomes, Human, Pair 7
  • Cyclosporine / administration & dosage*
  • Female
  • Follow-Up Studies
  • Granulocyte Colony-Stimulating Factor / administration & dosage*
  • Humans
  • Infant
  • Leukemia, Myeloid, Acute* / blood
  • Leukemia, Myeloid, Acute* / etiology
  • Leukemia, Myeloid, Acute* / pathology
  • Male
  • Myelodysplastic Syndromes* / blood
  • Myelodysplastic Syndromes* / etiology
  • Myelodysplastic Syndromes* / pathology
  • Prospective Studies

Substances

  • Antilymphocyte Serum
  • Granulocyte Colony-Stimulating Factor
  • Cyclosporine

Supplementary concepts

  • Monosomy 7 of Bone Marrow