PURPOSE: This blinded prospective study was performed to optimise the risk assessment of children with a late isolated, combined or an early combined bone marrow (BM) relapse of precursor B-cell acute lymphoblastic leukaemia (ALL). The aim was to develop a reliable tool to identify patients with an intermediate risk relapse who are in need of haematopoietic stem cell transplantation (HSCT). METHODS: Included were 80 children and adolescents with first intermediate risk BM relapse of ALL recruited in trial ALL-REZ BFM P95/96. We assessed the prognostic value of minimal residual disease (MRD) after induction therapy quantified by PCR using leukaemia clone-specific T-cell receptor/immunoglobulin gene rearrangements. RESULTS: Molecular good responders (MRD < 10(-3), n=46) had a probability of event-free survival (pEFS) at 10 years of 76% standard error (SE) ± 6% and a cumulative incidence of second relapse (CIR) at 10 years of 21% SE ± 6%; pEFS of molecular poor responders (MRD ≥ 10(-3), n=34) at 10 years was 18% SE ± 7% and CIR 61% SE ± 9% (p<0.001). Cox regression analysis revealed MRD after induction to be the strongest independent prognostic parameter with a 6.6-fold increased risk (95% confidence interval 3.3-13.5, p<0.001) for molecular poor responders to suffer a subsequent adverse event compared to good responders. CONCLUSION: In patients with intermediate risk BM relapse of ALL, low MRD after induction is associated with an excellent long-term prognosis with conventional chemo-/radiotherapy whereas patients with insufficient response have an extremely poor prognosis. Therefore, in the subsequent trial ALL-REZ BFM 2002, MRD is used to allocate molecular good responders to conventional post-induction therapy and molecular poor responders to allogeneic HSCT.
PURPOSE: This blinded prospective study was performed to optimise the risk assessment of children with a late isolated, combined or an early combined bone marrow (BM) relapse of precursor B-cell acute lymphoblastic leukaemia (ALL). The aim was to develop a reliable tool to identify patients with an intermediate risk relapse who are in need of haematopoietic stem cell transplantation (HSCT). METHODS: Included were 80 children and adolescents with first intermediate risk BM relapse of ALL recruited in trial ALL-REZ BFM P95/96. We assessed the prognostic value of minimal residual disease (MRD) after induction therapy quantified by PCR using leukaemia clone-specific T-cell receptor/immunoglobulin gene rearrangements. RESULTS: Molecular good responders (MRD < 10(-3), n=46) had a probability of event-free survival (pEFS) at 10 years of 76% standard error (SE) ± 6% and a cumulative incidence of second relapse (CIR) at 10 years of 21% SE ± 6%; pEFS of molecular poor responders (MRD ≥ 10(-3), n=34) at 10 years was 18% SE ± 7% and CIR 61% SE ± 9% (p<0.001). Cox regression analysis revealed MRD after induction to be the strongest independent prognostic parameter with a 6.6-fold increased risk (95% confidence interval 3.3-13.5, p<0.001) for molecular poor responders to suffer a subsequent adverse event compared to good responders. CONCLUSION: In patients with intermediate risk BM relapse of ALL, low MRD after induction is associated with an excellent long-term prognosis with conventional chemo-/radiotherapy whereas patients with insufficient response have an extremely poor prognosis. Therefore, in the subsequent trial ALL-REZ BFM 2002, MRD is used to allocate molecular good responders to conventional post-induction therapy and molecular poor responders to allogeneic HSCT.
Authors: Leonid Karawajew; Michael Dworzak; Richard Ratei; Peter Rhein; Giuseppe Gaipa; Barbara Buldini; Giuseppe Basso; Ondrej Hrusak; Wolf-Dieter Ludwig; Günter Henze; Karl Seeger; Arend von Stackelberg; Ester Mejstrikova; Cornelia Eckert Journal: Haematologica Date: 2015-05-22 Impact factor: 9.941
Authors: Elias Jabbour; Nicholas J Short; Jeffrey L Jorgensen; Musa Yilmaz; Farhad Ravandi; Sa A Wang; Deborah A Thomas; Joseph Khoury; Richard E Champlin; Issa Khouri; Partow Kebriaei; Susan M O'Brien; Guillermo Garcia-Manero; Jorge E Cortes; Koji Sasaki; Courtney D Dinardo; Tapan M Kadia; Nitin Jain; Marina Konopleva; Rebecca Garris; Hagop M Kantarjian Journal: Cancer Date: 2016-09-07 Impact factor: 6.860
Authors: C Eckert; N Hagedorn; L Sramkova; G Mann; R Panzer-Grümayer; C Peters; J-P Bourquin; T Klingebiel; A Borkhardt; G Cario; J Alten; G Escherich; K Astrahantseff; K Seeger; G Henze; A von Stackelberg Journal: Leukemia Date: 2015-03-09 Impact factor: 11.528
Authors: William B Slayton; Kirk R Schultz; John A Kairalla; Meenakshi Devidas; Xinlei Mi; Michael A Pulsipher; Bill H Chang; Charles Mullighan; Ilaria Iacobucci; Lewis B Silverman; Michael J Borowitz; Andrew J Carroll; Nyla A Heerema; Julie M Gastier-Foster; Brent L Wood; Sherri L Mizrahy; Thomas Merchant; Valerie I Brown; Lance Sieger; Marilyn J Siegel; Elizabeth A Raetz; Naomi J Winick; Mignon L Loh; William L Carroll; Stephen P Hunger Journal: J Clin Oncol Date: 2018-05-29 Impact factor: 44.544