Konference: 2013 18th Congress of the European Hematology Association - účast ČR

Kategorie: Maligní lymfomy a leukémie

Téma: Acute lymphoblastic leukemia - Therapeutics

Číslo abstraktu: S1123

Autoři: MD Arian Van Der Veer, PhD; MUDr. Markéta Kubričanová-Žaliová, Ph.D.; Federica Mottadelli; Paola de Lorenzo, PhD; Dr. Geertruy (Gertruuy) Te Kronnie, PhD; PhD Christine J. Harrison, FRCPath; Dr. Helene Cavé; Prof.MUDr. Jan Trka, Ph.D.; Prof. Vaskar Saha, PhD, FRCP, FRCPath; MD Martin Schrappe; Prof. MD Rob Pieters, PhD; MD Andrea Biondi; Prof. Maria Grazia Valsecchi, PhD; MD Martin Stanulla, MSc; Monique L. den Boer, PhD, MSc; Giovanni (Gianni) Cazzaniga, PhD


The BCR-ABL1-translocation (Philadelphia-chromosome) predicts for an unfavorable outcome in childhood acute lymphoblastic leukemia (ALL). BCR-ABL1-positive ALL is characterized by a high frequency (70%) of IKZF1 deletions. IKZF1 deletions are correlated to an unfavorable outcome in BCR-ABL1-negative ALL.


We studied the prognostic value of IKZF1 deletions in children with BCR-ABL1-positive ALL who were treated with and without Imatinib.


The IKZF1-status was evaluated by multiplex ligation-dependent probe amplification in 191 newly diagnosed patients; 84 cases were diagnosed before the introduction of Imatinib and 107 cases were enrolled in the European Philadelphia-chromosome positive ALL trial. 63 EsPhALL cases were stratified in the good-risk arm and were randomized for Imatinib, 44 EsPhALL cases were stratified in the poor-risk arm and all received Imatinib.


66% (126/191) of the BCR-ABL1-positive patients had an IKZF1 deletion; 36.5% of these deletions resulted in haplo-insufficiency (covering mono-allelic loss of at least exon 2), 52.4% had an exon 4-7 deletion that resulted in a dominant-negative variant. The frequency of hematopoietic stem cell transplantation (HSCT) did not differ between the IKZF1-deleted and wild-type group (both ~70%). In patients that were treated before the introduction of Imatinib, IKZF1-deleted patients had a poor 4-yr disease free survival (DFS) (30.0±6.8%) compared to wild-type patients (57.5±9.4%; p=0.01).  IKZF1-deleted patients treated according to the EsPhALL good-risk protocol had a poor 4-yr DFS (51.9±8.8%) compared to wild-type patients (78.6±13.9%; p=0.03), and this was also evident for those who received Imatinib (4-yr DFS 55.5±9.5% for IKZF1-deleted versus 75·0±21.7% for IKZF1 wild-type good-risk patients, p=0.05).

Summary / Conclusion:

This is the first study demonstrating that IKZF1 deletions are correlated to a poor outcome in a relative large cohort of childhood BCR-ABL1-positive ALL. We advocate that IKZF1-deleted patients need a more intensified or alternative therapy. In addition, since IKZF1 wild-type BCR-ABL1-positive patients treated with Imatinib have a good outcome comparable to BCR-ABL1-negative ALL, the absence of an IKZF1 deletion may be used as marker to exclude HSCT.

Abstrakta v časopise Haematologica 2013, Suppl1

Online Program

Datum přednesení příspěvku: 16. 6. 2013