title: Prognostic relevance of TLX3 (HOX11L2) expression in childhood T-cell acute lymphoblastic leukaemia treated with Berlin-Frankfurt-Münster (BFM) protocols containing early and late re-intensification elements.
abstract: TLX3 expression (TLX3+) in childhood T-cell acute lymphoblastic leukaemia (T-ALL) seems to be associated with a poor prognosis when treated with regimens that lack early and/or late re-intensification therapy elements. Because such elements are essential components of the ALL-BFM (Berlin-Frankfurt-Münster) protocols, we evaluated whether TLX3+ T-ALL patients benefit from this type of therapy. Thirty-one/131 childhood T-ALL cases (24%) enrolled into four population-based Austrian ALL-BFM therapy studies were TLX3+. The male to female ratio was 3.5:1 and median age and leucocyte count at diagnosis were 8.7 years and 58.9 x 10(9)/l, respectively. Twenty-four patients (77%) were good responders to prednisone. All were in complete remission after induction therapy. After a median observation time of 4.9 years (range 0.4-16.1 years) 28/31 TLX3+ cases remained in first complete remission after chemotherapy with one after additional stem cell transplantation. Although molecular disease was frequently present after a 4-drug induction therapy, final treatment outcome was excellent indicating that TLX3+ T-ALL cases may benefit from a BFM-type of ALL therapy with early and late re-intensification elements. Moreover, the fact that 2/3 relapses were also NUP214-ABL1+ suggests that these cases might represent the particular risk-prone TLX3+ subgroup that could benefit from a targeted tyrosine kinase inhibitor therapy.
authors.affiliation: Department of Paediatric Haematology and Oncology, St. Anna Children's Hospital, Vienna, Austria.
authors.forename: Andishe
authors.initials: A
authors.lastname: Attarbaschi
authors.forename: Markus
authors.initials: M
authors.lastname: Pisecker
authors.forename: Andrea
authors.initials: A
authors.lastname: Inthal
authors.forename: Georg
authors.initials: G
authors.lastname: Mann
authors.forename: Dasa
authors.initials: D
authors.lastname: Janousek
authors.forename: Michael
authors.initials: M
authors.lastname: Dworzak
authors.forename: Ulrike
authors.initials: U
authors.lastname: Pötschger
authors.forename: Reinhard
authors.initials: R
authors.lastname: Ullmann
authors.forename: Martin
authors.initials: M
authors.lastname: Schrappe
authors.forename: Helmut
authors.initials: H
authors.lastname: Gadner
authors.forename: Oskar A
authors.initials: OA
authors.lastname: Haas
authors.forename: Renate
authors.initials: R
authors.lastname: Panzer-Grümayer
authors.forename: Sabine
authors.initials: S
authors.lastname: Strehl
mesh_terms: D000293:Adolescent; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols; D001215:Asparaginase; D001317:Austria; D002648:Child; D002675:Child, Preschool; D003630:Daunorubicin; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D008297:Male; D015514:Oncogene Proteins, Fusion / Q000032:analysis / Q000235:genetics; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D011241:Prednisone; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014750:Vincristine
chemical_list: D000970:Antineoplastic Agents; D018398:Homeodomain Proteins; C521114:NUP214-ABL1 fusion protein, human; D015514:Oncogene Proteins, Fusion; C489494:TLX3 protein, human; D014750:Vincristine; D001215:Asparaginase; D011241:Prednisone; D003630:Daunorubicin