title: [Clinical analysis of adult Philadelphia chromosome-positive acute lymphoblastic leukemia with p16 gene deletion].
abstract: Objective:To investigate the clinical implications of p16 gene deletion in adult Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+) ALL) .Methods:Retrospective analysis of clinical, immunophenotypic, cytogenetics, molecular characteristics and prognosis of 80 newly diagnosed Ph(+) ALL patients with p16 deletion.Results:Of 80 adult Ph(+) ALL, the prevalence of p16 gene deletion was 31.3%. p16 gene deletion carriers frequently accompanied with high WBC counts (WBC≥30×10(9)/L) and CD20 expression. The incidence of complex chromosome abnormality in p16 gene deletion group was higher than that in non-deletion group, with alternations in chromosome 7, 8, 19 and der (22) more frequently observed. There was no difference occurred between patients with or without p16 gene deletion in complete remission (CR) rate following induction chemotherapy combined with tyrosine kinase inhibitors (TKIs) . However, after three cycles of chemotherapy, the MMR and CMR rate in the p16 gene deletion group was lower than patients with wild-type p16 gene (P=0.034,P=0.036) . The p16 gene deletion patients showed no significant differences in MMR, CMR and relapse rate between Imatinib or Dasatinib plus chemotherapy (P>0.05) . Deletion of p16 gene was significantly associated with poor outcomes including worse overall survival (OS) (37.1%vs54.1%,P=0.037) , lower disease free-survival (DFS) (12.4%vs45.9%,P=0.026) , and increased cumulative incidence of relapse (P=0.033) . Among the 25 patients with p16 deletion, 14 underwent allo-HSCT and the median survival was 21 months, better than that of patients received chemotherapy alone (12 months) (P=0.030) .Conclusion:This study indicated that deletion of p16 was associated with poor prognosis in adult Ph(+) ALL, and the utility of second-generation TKI (Dasatinib) does not necessarily have an edge on efficacy over Imatinib, but allo-HSCT has the potential of elongating life expectancy. It is an important significance to define the status of p16 in Ph(+) ALL for predicting prognosis and guiding therapy decision-making.
authors.affiliation: Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: B L
authors.initials: BL
authors.lastname: He
authors.forename: N
authors.initials: N
authors.lastname: Xu
authors.forename: Y L
authors.initials: YL
authors.lastname: Li
authors.forename: C Y
authors.initials: CY
authors.lastname: Pan
authors.forename: R
authors.initials: R
authors.lastname: Cao
authors.forename: L B
authors.initials: LB
authors.lastname: Liao
authors.forename: C X
authors.initials: CX
authors.lastname: Yin
authors.forename: Y Q
authors.initials: YQ
authors.lastname: Lan
authors.forename: Z Y
authors.initials: ZY
authors.lastname: Lu
authors.forename: J X
authors.initials: JX
authors.lastname: Huang
authors.forename: H S
authors.initials: HS
authors.lastname: Zhou
authors.forename: Q F
authors.initials: QF
authors.lastname: Liu
authors.forename: X L
authors.initials: XL
authors.lastname: Liu
mesh_terms: D000208:Acute Disease; D000328:Adult; D018951:Antigens, CD20; D002869:Chromosome Aberrations; D000069439:Dasatinib; D018572:Disease-Free Survival; D017353:Gene Deletion; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D000068877:Imatinib Mesylate; D060828:Induction Chemotherapy; D010677:Philadelphia Chromosome; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma; D011379:Prognosis; D012008:Recurrence; D012074:Remission Induction; D012189:Retrospective Studies
chemical_list: D018951:Antigens, CD20; D000068877:Imatinib Mesylate; D000069439:Dasatinib
keywords: Hematopoietic stem cell transplantation; Leukemia, lymphoid, acute; Philadelphia chromosome; Tyrosine kinase inhibitor; p16 gene deletion