title: Incidence and clinical outcome of children with BCR/ABL-positive acute lymphoblastic leukemia (ALL). A prospective RT-PCR study based on 673 patients enrolled in the German pediatric multicenter therapy trials ALL-BFM-90 and CoALL-05-92.
abstract: A variety of oncogenes are activated by specific chromosomal translocations, which are associated with distinct subtypes of leukemia. The identification of these rearrangements provides critical diagnostic and prognostic information, which may contribute to the selection of specific anti-leukemic therapy. The translocation t(9;22), the equivalent of the BCR/ABL rearrangement, is associated with a poor prognosis. We therefore used RT-PCR to detect this molecular event in a prospective study including 890 children. 673 of them suffered from acute lymphoblastic leukemia (ALL) at primary diagnosis and a transcription of the chimeric gene was detected in 21 of 648 with a successful analysis (3.2%). All children were treated by one of the two German multicenter childhood ALL therapy studies ALL-BFM-90 or COALL-05-92, respectively. Comparison of clinical features between BCR/ABL-positive and -negative children showed no significant differences regarding WBC, percentage of blasts, splenomegaly, hepatomegaly and age. Immunophenotypic studies at diagnosis in 21 BCR/ABL-positive children identified common ALL in 16 patients (76.2%), pre-B-ALL in four (19.0%), and an early T-lineage ALL in one (4.8%). Coexpression of myeloid antigens (CD13 and/or CD33) was observed in six of 16 common ALL patients as well as in the one child with early T-lineage ALL phenotype. The type of breakpoint (m-BCR/ABL: n = 14; M-BCR/ABL: n = 7) showed no correlation with clinical parameters. A comparison of cytogenetic and molecular data was performed in 16 positive patients and was concordant in all of them. We analyzed the response to the prednisone pretreatment and found a higher incidence of poor responders among the BCR/ABL-positive children. Regarding the event-free survival (EFS) of BCR/ABL-positive (0.53) and -negative patients (0.79) after a follow-up of 2 years, significant differences (P < 0.05) between both groups could be demonstrated.
authors.affiliation: Oncogenetic Laboratory, Children's Hospital, University of Giessen, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Schlieben
authors.forename: A
authors.initials: A
authors.lastname: Borkhardt
authors.forename: I
authors.initials: I
authors.lastname: Reinisch
authors.forename: J
authors.initials: J
authors.lastname: Ritterbach
authors.forename: J W
authors.initials: JW
authors.lastname: Janssen
authors.forename: R
authors.initials: R
authors.lastname: Ratei
authors.forename: M
authors.initials: M
authors.lastname: Schrappe
authors.forename: R
authors.initials: R
authors.lastname: Repp
authors.forename: M
authors.initials: M
authors.lastname: Zimmermann
authors.forename: H
authors.initials: H
authors.lastname: Kabisch
authors.forename: G
authors.initials: G
authors.lastname: Janka-Schaub
authors.forename: C R
authors.initials: CR
authors.lastname: Bartram
authors.forename: W D
authors.initials: WD
authors.lastname: Ludwig
authors.forename: H
authors.initials: H
authors.lastname: Riehm
authors.forename: F
authors.initials: F
authors.lastname: Lampert
authors.forename: J
authors.initials: J
authors.lastname: Harbott
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001215:Asparaginase / Q000008:administration & dosage; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D002892:Chromosomes, Human, Pair 22; D002899:Chromosomes, Human, Pair 9; D003520:Cyclophosphamide / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D003630:Daunorubicin / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D005858:Germany; D006801:Humans; D015994:Incidence; D007223:Infant; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics; D008297:Male; D015122:Mercaptopurine / Q000008:administration & dosage; D008727:Methotrexate / Q000008:administration & dosage; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics*; D011241:Prednisone / Q000008:administration & dosage; D011379:Prognosis; D011446:Prospective Studies; D014158:Transcription, Genetic; D014178:Translocation, Genetic; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D003561:Cytarabine; D014750:Vincristine; D003520:Cyclophosphamide; D015122:Mercaptopurine; D016044:Fusion Proteins, bcr-abl; D001215:Asparaginase; D011241:Prednisone; D008727:Methotrexate; D003630:Daunorubicin