Control of thrombotic thrombocytopenic purpura by sirolimus in a child with juvenile myelomonocytic leukemia and somatic N-RAS mutation

Pediatr Blood Cancer. 2014 Oct;61(10):1871-3. doi: 10.1002/pbc.25013. Epub 2014 Mar 3.

Abstract

We describe an infant who developed juvenile myelomonocytic leukemia (JMML) at the age of 6 months. Myeloproliferation was effectively controlled by low-dose cytosine arabinoside and 13-cis retinoic acid therapy. Two years after therapy for JMML was stopped, at the age of 5 years, the patient developed autoimmune thrombotic thrombocytopenic purpura (TTP). TTP was transiently controlled by plasma exchange, prednisolone, rituximab, and cyclophosphamide, but relapsed within a short time. Long-term control of TTP was established by sirolimus. Somatic N-RAS G38A→Gly13Asp substitution was restricted to hematopoietic cells. The somatic N-RAS mutation may link myeloproliferation and autoimmunity.

Keywords: autoimmune lymphoproliferative syndrome; juvenile myelomonocytic leukemia; sirolimus; thrombotic thrombopenic purpura.

Publication types

  • Case Reports

MeSH terms

  • Age of Onset
  • Antibiotics, Antineoplastic / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Child, Preschool
  • Cytarabine / administration & dosage
  • Genes, ras*
  • Humans
  • Infant
  • Isotretinoin / administration & dosage
  • Leukemia, Myelomonocytic, Juvenile / complications
  • Leukemia, Myelomonocytic, Juvenile / drug therapy
  • Leukemia, Myelomonocytic, Juvenile / genetics*
  • Mutation*
  • Purpura, Thrombotic Thrombocytopenic / complications
  • Purpura, Thrombotic Thrombocytopenic / drug therapy*
  • Purpura, Thrombotic Thrombocytopenic / genetics*
  • Sirolimus / therapeutic use*

Substances

  • Antibiotics, Antineoplastic
  • Cytarabine
  • Isotretinoin
  • Sirolimus