title: Prediction of outcome by early bone marrow response in childhood acute lymphoblastic leukemia treated in the ALL-BFM 95 trial: differential effects in precursor B-cell and T-cell leukemia.
abstract: BACKGROUND
  In the ALL-BFM 95 trial for treatment of acute lymphoblastic leukemia, response to a prednisone pre-phase (prednisone response) was used for risk stratification in combination with age and white blood cell count at diagnosis, response to induction therapy and specific genetic high-risk features.
  
  
  METHODS
  Cytomorphological marrow response was prospectively assessed on Day 15 during induction, and its prognostic value was analyzed in 1,431 patients treated on ALL-BFM 95.
  
  
  RESULTS
  The 8-year probabilities of event-free survival were 86.1%, 74.5%, and 46.4% for patients with M1, M2, and M3 Day 15 marrows, respectively. Compared to prednisone response, Day 15 marrow response was superior in outcome prediction in precursor B-cell and T-cell leukemia with, however, a differential effect depending on blast lineage. Outcome was poor in T-cell leukemia patients with prednisone poor-response independent of Day 15 marrow response, whereas among patients with prednisone good-response different risk groups could be identified by Day 15 marrow response. In contrast, prednisone response lost prognostic significance in precursor B-cell leukemia when stratified by Day 15 marrow response. Age and white blood cell count retained their independent prognostic effect.
  
  
  CONCLUSIONS
  Selective addition of Day 15 marrow response to conventional stratification criteria applied on ALL-BFM 95 (currently in use in several countries as regular chemotherapy protocol for childhood acute lymphoblastic leukemia) may significantly improve risk-adapted treatment delivery. Even though cutting-edge trial risk stratification is meanwhile dominated by minimal residual disease evaluation, an improved conventional risk assessment, as presented here, could be of great importance to countries that lack the technical and/or financial resources associated with the application of minimal residual disease analysis.
authors.affiliation: Pediatric Hematology and Oncology, University Hospital Schleswig-Holstein, Lübeck Campus, Germany.
authors.forename: Melchior
authors.initials: M
authors.lastname: Lauten
authors.forename: Anja
authors.initials: A
authors.lastname: Möricke
authors.forename: Rita
authors.initials: R
authors.lastname: Beier
authors.forename: Martin
authors.initials: M
authors.lastname: Zimmermann
authors.forename: Martin
authors.initials: M
authors.lastname: Stanulla
authors.forename: Barbara
authors.initials: B
authors.lastname: Meissner
authors.forename: Edelgard
authors.initials: E
authors.lastname: Odenwald
authors.forename: Andishe
authors.initials: A
authors.lastname: Attarbaschi
authors.forename: Charlotte
authors.initials: C
authors.lastname: Niemeyer
authors.forename: Felix
authors.initials: F
authors.lastname: Niggli
authors.forename: Hansjörg
authors.initials: H
authors.lastname: Riehm
authors.forename: Martin
authors.initials: M
authors.lastname: Schrappe
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001215:Asparaginase / Q000008:administration & dosage; D015415:Biomarkers / Q000032:analysis; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D003630:Daunorubicin / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007223:Infant; D018655:Lymphocyte Count; D008297:Male; D015122:Mercaptopurine / Q000008:administration & dosage; D018365:Neoplasm, Residual; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis* / Q000188:drug therapy / Q000401:mortality; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis* / Q000188:drug therapy / Q000401:mortality; D011239:Prednisolone / Q000008:administration & dosage; D011241:Prednisone / Q000008:administration & dosage*; D011379:Prognosis; D011446:Prospective Studies; D012074:Remission Induction; D018570:Risk Assessment; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D015415:Biomarkers; D003561:Cytarabine; D014750:Vincristine; D003520:Cyclophosphamide; D011239:Prednisolone; D015122:Mercaptopurine; D001215:Asparaginase; D011241:Prednisone; D003630:Daunorubicin