Outcome of children and adolescents with relapsed acute lymphoblastic leukaemia and non-response to salvage protocol therapy: a retrospective analysis of the ALL-REZ BFM Study Group.
OBJECTIVE
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.


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.
Department of Paediatric Oncology/Hematology, Charité Universitätsmedizin Berlin, Berlin, Germany. arend.stackelberg@charite.de
Arend
A
von Stackelberg
Enrico
E
Völzke
Jörn-Sven
JS
Kühl
Karl
K
Seeger
André
A
Schrauder
Gabriele
G
Escherich
Günter
G
Henze
Gesche
G
Tallen
D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002648:Child; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy / Q000401:mortality; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D010865:Pilot Projects; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000401:mortality / Q000628:therapy*; D011788:Quality of Life; D012008:Recurrence; D012189:Retrospective Studies; D016879:Salvage Therapy / Q000401:mortality; D033581:Stem Cell Transplantation / Q000401:mortality*; D016896:Treatment Outcome; D055815:Young Adult