AIM OF THE STUDY: Non-response (NR) to treatment of childhood relapsed acute lymphoblastic leukaemia (ALL) is an end-point of protocol therapy. Subsequent management has not yet been standardised. This study analyses different approaches after NR to aid optimising future strategies. PATIENTS AND METHODS: Ninety-three children with NR to treatment according to ALL relapse-protocols of the Berlin/Frankfurt/Muenster (BFM) Study Group (03/1990-2006/1999) were retrospectively assigned to a curative (C: intensive polychemotherapies, stem cell transplantation (SCT); n=51), palliative (P: 1-2 antineoplastic agents; n=23) or supportive (S: no antineoplastic therapy; n=19) treatment approach. RESULTS: Median survival after diagnosis of NR were 121 (C), 89 (P) and 42 (S) days, respectively (p<0.001). In cohort C, a complete remission (2ndCR) was obtained in 16/51 patients, among these 13 only after SCT, and nine children achieved partial remission. Ten of the 51 patients died from treatment-related complications, 39/51 from disease progression. Today, two patients are still in continuous CR after SCT. Adverse prognostic factors were overrepresented in the non-curative cohorts. Time-point of relapse and treatment after NR were independent predictors of survival duration. Most patients without antineoplastic treatment died at home, the majority of the others in the hospital. CONCLUSIONS: Treatment after NR has been heterogeneous and customised. Therapies with curative intent are capable of inducing 2ndCR but associated with high treatment-related morbidity, -mortality and minimal survival. NR patients may, therefore, be ideal candidates for controlled phase I/II trials, thus offering them a chance to benefit from new drugs and promoting drug development for cohorts with better prognosis.
AIM OF THE STUDY: Non-response (NR) to treatment of childhood relapsed acute lymphoblastic leukaemia (ALL) is an end-point of protocol therapy. Subsequent management has not yet been standardised. This study analyses different approaches after NR to aid optimising future strategies. PATIENTS AND METHODS: Ninety-three children with NR to treatment according to ALL relapse-protocols of the Berlin/Frankfurt/Muenster (BFM) Study Group (03/1990-2006/1999) were retrospectively assigned to a curative (C: intensive polychemotherapies, stem cell transplantation (SCT); n=51), palliative (P: 1-2 antineoplastic agents; n=23) or supportive (S: no antineoplastic therapy; n=19) treatment approach. RESULTS: Median survival after diagnosis of NR were 121 (C), 89 (P) and 42 (S) days, respectively (p<0.001). In cohort C, a complete remission (2ndCR) was obtained in 16/51 patients, among these 13 only after SCT, and nine children achieved partial remission. Ten of the 51 patients died from treatment-related complications, 39/51 from disease progression. Today, two patients are still in continuous CR after SCT. Adverse prognostic factors were overrepresented in the non-curative cohorts. Time-point of relapse and treatment after NR were independent predictors of survival duration. Most patients without antineoplastic treatment died at home, the majority of the others in the hospital. CONCLUSIONS: Treatment after NR has been heterogeneous and customised. Therapies with curative intent are capable of inducing 2ndCR but associated with high treatment-related morbidity, -mortality and minimal survival. NR patients may, therefore, be ideal candidates for controlled phase I/II trials, thus offering them a chance to benefit from new drugs and promoting drug development for cohorts with better prognosis.
Authors: Sandra Preuner; Christina Peters; Ulrike Pötschger; Helga Daxberger; Gerhard Fritsch; Rene Geyeregger; André Schrauder; Arend von Stackelberg; Martin Schrappe; Peter Bader; Wolfram Ebell; Cornelia Eckert; Peter Lang; Karl-Walter Sykora; Johanna Schrum; Bernhard Kremens; Karoline Ehlert; Michael H Albert; Roland Meisel; Anita Lawitschka; Georg Mann; Renate Panzer-Grümayer; Tayfun Güngör; Wolfgang Holter; Brigitte Strahm; Bernd Gruhn; Ansgar Schulz; Wilhelm Woessmann; Thomas Lion Journal: Haematologica Date: 2016-02-11 Impact factor: 9.941
Authors: A Sureda; P Bader; S Cesaro; P Dreger; R F Duarte; C Dufour; J H F Falkenburg; D Farge-Bancel; A Gennery; N Kröger; F Lanza; J C Marsh; A Nagler; C Peters; A Velardi; M Mohty; A Madrigal Journal: Bone Marrow Transplant Date: 2015-03-23 Impact factor: 5.483
Authors: Vanessa A Fabrizio; Jaap Jan Boelens; Audrey Mauguen; Christina Baggott; Snehit Prabhu; Emily Egeler; Sharon Mavroukakis; Holly Pacenta; Christine L Phillips; Jenna Rossoff; Heather E Stefanski; Julie-An Talano; Amy Moskop; Steven P Margossian; Michael R Verneris; Gary Douglas Myers; Nicole A Karras; Patrick A Brown; Muna Qayed; Michelle Hermiston; Prakash Satwani; Christa Krupski; Amy K Keating; Rachel Wilcox; Cara A Rabik; Vasant Chinnabhandar; Michael Kunicki; A Yasemin Goksenin; Crystal L Mackall; Theodore W Laetsch; Liora M Schultz; Kevin J Curran Journal: Blood Adv Date: 2022-04-12
Authors: Kevin J Curran; Steven P Margossian; Nancy A Kernan; Lewis B Silverman; David A Williams; Neerav Shukla; Rachel Kobos; Christopher J Forlenza; Peter Steinherz; Susan Prockop; Farid Boulad; Barbara Spitzer; Maria I Cancio; Jaap Jan Boelens; Andrew L Kung; Yasmin Khakoo; Victoria Szenes; Jae H Park; Craig S Sauter; Glenn Heller; Xiuyan Wang; Brigitte Senechal; Richard J O'Reilly; Isabelle Riviere; Michel Sadelain; Renier J Brentjens Journal: Blood Date: 2019-12-26 Impact factor: 22.113