Philadelphia chromosome-positive acute lymphoblastic leukemia at first relapse in the era of tyrosine kinase inhibitors

Iman Abou Dalle, Hagop M Kantarjian, Nicholas J Short, Marina Konopleva, Nitin Jain, Guillermo Garcia-Manero, Rebecca Garris, Wei Qiao, Jorge E Cortes, Susan O'Brien, Partow Kebriaei, Tapan Kadia, Elias Jabbour, Farhad Ravandi

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1388-1395
Number of pages8
JournalAmerican Journal of Hematology
Volume94
Issue number12
DOIs
StatePublished - Dec 2019
Externally publishedYes

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    Abou Dalle, I., Kantarjian, H. M., Short, N. J., Konopleva, M., Jain, N., Garcia-Manero, G., Garris, R., Qiao, W., Cortes, J. E., O'Brien, S., Kebriaei, P., Kadia, T., Jabbour, E., & Ravandi, F. (2019). Philadelphia chromosome-positive acute lymphoblastic leukemia at first relapse in the era of tyrosine kinase inhibitors. American Journal of Hematology, 94(12), 1388-1395. https://doi.org/10.1002/ajh.25648