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Impact of tyrosine kinase inhibitors on minimal residual disease and outcome in childhood Philadelphia chromosome‐positive acute lymphoblastic leukemia
Author(s) -
Jeha Sima,
CoustanSmith Elaine,
Pei Deqing,
Sandlund John T.,
Rubnitz Jeffrey E.,
Howard Scott C.,
Inaba Hiroto,
Bhojwani Deepa,
Metzger Monika L.,
Cheng Cheng,
Choi John K.,
Jacobsen Jeffrey,
Shurtleff Sheila A.,
Raimondi Susana,
Ribeiro Raul C.,
Pui ChingHon,
Campana Dario
Publication year - 2014
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.28598
Subject(s) - medicine , dasatinib , minimal residual disease , philadelphia chromosome , imatinib , induction chemotherapy , oncology , maintenance therapy , transplantation , chemotherapy , tyrosine kinase , imatinib mesylate , acute lymphocytic leukemia , hematopoietic stem cell transplantation , leukemia , immunology , lymphoblastic leukemia , myeloid leukemia , chromosomal translocation , biochemistry , chemistry , receptor , gene
BACKGROUND Breakpoint cluster region‐Abelson murine leukemia viral oncogene homolog 1 (BCR‐ABL1) tyrosine kinase inhibitors (TKIs) improve the outcome of patients with childhood Philadelphia chromosome (Ph)‐positive acute lymphoblastic leukemia (ALL) when they are incorporated into postremission induction chemotherapy. To date, no data are available on the impact of TKIs on minimal residual disease (MRD) at the end of induction therapy among patients who have a poor early response to 2 weeks of induction therapy that does not include TKIs. METHODS The authors analyzed the early response to TKIs during remission induction in children with Ph‐positive ALL who were treated at St. Jude Children's Research Hospital. MRD was measured on days 15 and 42 of induction. TKIs were incorporated into induction therapy on day 22 in the post‐TKI era. RESULTS TKIs produced a marked drop in MRD levels: at the end of remission induction, 9 of 11 patients who received imatinib or dasatinib and conventional induction chemotherapy achieved MRD‐negative status compared with only 2 of 16 patients who received chemotherapy alone ( P < .001). The 5‐year event‐free survival rate (± standard deviation) was 68.6% ± 19.2% for the 11 patients who received TKIs versus 31.6% ± 9.9% for the 19 patients who did not ( P = .022); notably, 2 of the former group underwent hematopoietic stem cell transplantation versus 15 of the latter group ( P = .002). MRD levels and outcomes did not differ significantly among 498 patients with standard‐risk/high‐risk, Ph‐negative ALL who were treated in the pre‐TKI or post‐TKI eras. CONCLUSIONS TKIs administered in the early phases of therapy can dramatically reduce MRD and improve the outcome of childhood Ph‐positive ALL. Cancer 2014;120:1514–1519 . © 2014 American Cancer Society .