title: Control of thrombotic thrombocytopenic purpura by sirolimus in a child with juvenile myelomonocytic leukemia and somatic N-RAS mutation.
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.
authors.affiliation: Federal Research Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russia.
authors.forename: Michael
authors.initials: M
authors.lastname: Maschan
authors.forename: Vlasta
authors.initials: V
authors.lastname: Bobrynina
authors.forename: Lili
authors.initials: L
authors.lastname: Khachatryan
authors.forename: Irina
authors.initials: I
authors.lastname: Kalinina
authors.forename: Galina
authors.initials: G
authors.lastname: Solopova
authors.forename: Pavel
authors.initials: P
authors.lastname: Avdonin
authors.forename: Tatiana
authors.initials: T
authors.lastname: Nasedkina
authors.forename: Galina
authors.initials: G
authors.lastname: Novichkova
authors.forename: Alexei
authors.initials: A
authors.lastname: Maschan
mesh_terms: D017668:Age of Onset; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002675:Child, Preschool; D003561:Cytarabine / Q000008:administration & dosage; D011905:Genes, ras; D006801:Humans; D007223:Infant; D015474:Isotretinoin / Q000008:administration & dosage; D054429:Leukemia, Myelomonocytic, Juvenile / Q000150:complications / Q000188:drug therapy / Q000235:genetics*; D009154:Mutation; D011697:Purpura, Thrombotic Thrombocytopenic / Q000150:complications / Q000188:drug therapy* / Q000235:genetics*; D020123:Sirolimus / Q000627:therapeutic use*
chemical_list: D000903:Antibiotics, Antineoplastic; D003561:Cytarabine; D015474:Isotretinoin; D020123:Sirolimus
keywords: autoimmune lymphoproliferative syndrome; juvenile myelomonocytic leukemia; sirolimus; thrombotic thrombopenic purpura