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Philadelphia chromosome‐positive acute lymphoblastic leukemia at first relapse in the era of tyrosine kinase inhibitors
Author(s) -
Abou Dalle Iman,
Kantarjian Hagop M.,
Short Nicholas J.,
Konopleva Marina,
Jain Nitin,
GarciaManero Guillermo,
Garris Rebecca,
Qiao Wei,
Cortes Jorge E.,
O'Brien Susan,
Kebriaei Partow,
Kadia Tapan,
Jabbour Elias,
Ravandi Farhad
Publication year - 2019
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.25648
Subject(s) - medicine , philadelphia chromosome , multivariate analysis , lymphoblastic leukemia , oncology , gastroenterology , leukemia , chromosomal translocation , gene , biochemistry , chemistry
Despite the advances in the management of Philadelphia chromosome‐positive (Ph+) acute lymphoblastic leukemia (ALL) with the introduction of tyrosine kinase inhibitors (TKIs), relapses remain challenging. We reviewed clinical data from adult patients with Ph + ALL who received frontline hyperCVAD chemotherapy with a TKI to determine their outcomes after first relapse. Patients with first morphological relapse after prior complete remission were evaluated for predictors of response and survival. For 57 of 233 (25%) patients, there was morphological relapse after a median of 15.9 months from first remission [range: 5.3‐94]. The choice of salvage treatments was at the discretion of the treating physician. So, 43 (75%) patients received a TKI in combination with their salvage treatment. Second remission was achieved in 41 of 49 (84%) evaluable patients. Median relapse free survival (RFS) was 10.5 months [range, 0.2‐81]. The 1‐year and 2‐year overall survival (OS) were 41% and 20% respectively. On multivariate analysis, only elevated LDH (units/L), the use of first‐generation or no TKI at the time of first relapse and the achievement of a major molecular response (MMR) had a significant effect on OS (HR: 2.82, 95% CI:1.11‐7.16, P = .029; HR = 2.39, 95% CI: 1.07,5.39, P = .034; HR = 0.39, 95% CI: 0.16‐0.94, P = .03, respectively). Whereas, only achievement of MMR was significantly prognostic for RFS with a HR of 0.48 (95% CI: 0.23‐0.98, P = .04). The OS and RFS were comparable between recipients and non‐recipients of allogeneic hematopoietic stem cell transplantation (alloHSCT) at second remission, due to a higher non‐relapse mortality (53%) seen in patients who underwent alloHSCT.