title: Susceptibility of Ph-positive all to TKI therapy associated with Bcr-Abl rearrangement patterns: a retrospective analysis.
abstract: BACKGROUND
  Tyrosine kinase inhibitors (TKIs) have demonstrated success in the treatment of acute lymphoblastic leukemia (ALL) in patients that express BCR-ABL rearrangements (Philadelphia chromosome [Ph]). The current study aimed to assess the efficacy of TKIs and prognostic factors in the treatment of adults with Ph+-ALL.
  
  
  METHODS
  In this multicenter retrospective study, the relationship between Ph+-ALL and treatment outcomes among Chinese patients receiving TKI-containing induction/consolidation chemotherapy was examined. A total of 86 Ph+-ALL patients were included and followed for 3.85 (0.43-9.30) years. Overall survival (OS) and event-free survival (EFS) were analyzed.
  
  
  RESULTS
  A total of 86 Ph+-ALL patients (40 females and 46 males; median age: 34.0 years) were enrolled, including those with BCR/ABL transcripts 190 (n = 52), 210 (n = 25), and 230 (n = 2); BCR/ABL isoform determination was not available for 7 patients. Mortality was influenced by variable BCR/ABL transcripts and TKI administration, and BCR/ABL transcripts, hematopoietic stem cell transplantation (HSCT), and TKI administration were associated with the occurrence of events. The OS rate in the TKI administration group during steady state was significantly higher compared with those patients who did not receive TKI administration (P = 0.008), the EFS rate in the TKI administration group during steady state was significantly higher compared with those patients who did not receive TKIs (P = 0.012), and also higher than those with TKI salvage administration (P = 0.004). BCR/ABL transcripts 210 showed preferable OS and EFS compared with BCR/ABL transcripts 190 and 230 (P<0.05 for each).
  
  
  CONCLUSIONS
  The susceptibility of Ph+-ALL to TKI associated with the patterns of BCR-ABL rearrangement is demonstrated for the first time, thus adding another risk-stratifying molecular prognostic tool for the management of patients with Ph+-ALL.
authors.affiliation: Department of Hematology and BMT center, Chinese PLA General Hospital, Beijing, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Jing
authors.affiliation: Department of Hematology, General Hospital of Beijing Military Region, Beijing, China.
authors.forename: Huiren
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Hematology and BMT center, Chinese PLA General Hospital, Beijing, China; Department of Hematology, the 309th Hospital of Chinese People's Liberation Army, Beijing, China.
authors.forename: Mingjuan
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Hematology and BMT center, Chinese PLA General Hospital, Beijing, China.
authors.forename: Minhang
authors.initials: M
authors.lastname: Zhou
authors.affiliation: Department of Hematology and BMT center, Chinese PLA General Hospital, Beijing, China.
authors.forename: Yuelu
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Hematology and BMT center, Chinese PLA General Hospital, Beijing, China.
authors.forename: Chunji
authors.initials: C
authors.lastname: Gao
authors.affiliation: Department of Hematology and BMT center, Chinese PLA General Hospital, Beijing, China.
authors.forename: Quanshun
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Hematology and BMT center, Chinese PLA General Hospital, Beijing, China.
authors.forename: Honghua
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Hematology and BMT center, Chinese PLA General Hospital, Beijing, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Hematology and BMT center, Chinese PLA General Hospital, Beijing, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Bo
authors.affiliation: Department of Hematology and BMT center, Chinese PLA General Hospital, Beijing, China.
authors.forename: Wenrong
authors.initials: W
authors.lastname: Huang
authors.affiliation: Department of Hematology and BMT center, Chinese PLA General Hospital, Beijing, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Department of Hematology, the 309th Hospital of Chinese People's Liberation Army, Beijing, China.
authors.forename: Yongqing
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Hematology and BMT center, Chinese PLA General Hospital, Beijing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Yu
mesh_terms: D000328:Adult; D001483:Base Sequence; D017931:DNA Primers; D005260:Female; D015321:Gene Rearrangement; D016313:Genes, abl; D006801:Humans; D008297:Male; D010677:Philadelphia Chromosome; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000235:genetics; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D012333:RNA, Messenger / Q000235:genetics; D012189:Retrospective Studies; D016019:Survival Analysis; D055815:Young Adult
chemical_list: D017931:DNA Primers; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D011505:Protein-Tyrosine Kinases