title: Hematologic abnormalities and acute myeloid leukemia in children and adolescents administered intensified chemotherapy for the Ewing sarcoma family of tumors.
abstract: OBJECTIVE
  Current treatment of the Ewing sarcoma family of tumors (ESFT) includes intensive multiagent chemotherapy with topoisomerase II inhibitors, alkylating agents, and granulocyte colony-stimulating factor (G-CSF). This treatment approach has been associated with myelodysplasia and acute myeloid leukemia. Because macrocytosis and thrombocytopenia are distinctive features of myelodysplasia, the authors evaluated a cohort of patients treated for ESFT to determine the degree and duration of macrocytosis and thrombocytopenia and their relation with the development of therapy-related hematologic malignancies.
  
  
  METHODS
  The study group consisted of 73 patients with ESFT treated on two consecutive protocols (EW92 and EW87). Both chemotherapy regimens incorporated the same agents but differed in cumulative drug dose, dose per course, and the use of G-CSF. Platelet counts and the mean corpuscular volume (MCV) of erythrocytes were determined at diagnosis and during follow-up visits after completion of treatment.
  
  
  RESULTS
  Patients in the EW92 group had significantly greater MCVs after treatment than did the less intensively treated EW87 group. These changes persisted throughout the 40-month observation period. Patients in the EW92 group also had lesser mean platelet counts after treatment than those in the EW87 group. MCV differences (from baseline) were inversely related to platelet counts. The cumulative incidence of treatment-related acute myeloid leukemia was 7.8%+/-4.7% at 4 years in the EW92 group and zero in the EW87 group.
  
  
  CONCLUSIONS
  Patients treated for ESFT with intensive chemotherapy that includes large doses of alkylators, topoisomerase II inhibitors, and G-CSF characteristically have persistently elevated MCVs and decreased platelet counts after completion of therapy. These hematologic abnormalities may represent stem cell damage, predisposing patients to myelodysplasia and acute myeloid leukemia, but further study is needed to establish this relation.
authors.affiliation: Department of Hematology-Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
authors.forename: C
authors.initials: C
authors.lastname: Rodriguez-Galindo
authors.forename: C A
authors.initials: CA
authors.lastname: Poquette
authors.forename: N M
authors.initials: NM
authors.lastname: Marina
authors.forename: D R
authors.initials: DR
authors.lastname: Head
authors.forename: A
authors.initials: A
authors.lastname: Cain
authors.forename: W H
authors.initials: WH
authors.lastname: Meyer
authors.forename: V M
authors.initials: VM
authors.lastname: Santana
authors.forename: A S
authors.initials: AS
authors.lastname: Pappo
mesh_terms: D000293:Adolescent; D000328:Adult; D000748:Anemia, Macrocytic / Q000097:blood / Q000139:chemically induced*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000097:blood* / Q000188:drug therapy; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004909:Erythrocyte Indices / Q000187:drug effects; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D007951:Leukemia, Myeloid / Q000097:blood / Q000139:chemically induced*; D008297:Male; D009190:Myelodysplastic Syndromes / Q000139:chemically induced; D016609:Neoplasms, Second Primary / Q000097:blood / Q000139:chemically induced*; D010976:Platelet Count / Q000187:drug effects; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D012512:Sarcoma, Ewing / Q000097:blood* / Q000188:drug therapy; D013921:Thrombocytopenia / Q000097:blood / Q000139:chemically induced*