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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Philadelphia Chromosome
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Protein-Tyrosine Kinases
Recurrence
Survival
Salvage Therapy
Hematopoietic Stem Cell Transplantation
Multivariate Analysis
Physicians
Drug Therapy
Mortality

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Abou Dalle, I., Kantarjian, H. M., Short, N. J., Konopleva, M., Jain, N., Garcia-Manero, G., ... 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

Philadelphia chromosome-positive acute lymphoblastic leukemia at first relapse in the era of tyrosine kinase inhibitors. / Abou Dalle, Iman; Kantarjian, Hagop M; Short, Nicholas J; Konopleva, Marina; Jain, Nitin; Garcia-Manero, Guillermo; Garris, Rebecca; Qiao, Wei; Cortes, Jorge E; O'Brien, Susan; Kebriaei, Partow; Kadia, Tapan; Jabbour, Elias; Ravandi, Farhad.

In: American Journal of Hematology, Vol. 94, No. 12, 12.2019, p. 1388-1395.

Research output: Contribution to journalArticle

Abou Dalle, I, Kantarjian, HM, Short, NJ, Konopleva, M, Jain, N, Garcia-Manero, G, Garris, R, Qiao, W, Cortes, JE, 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, vol. 94, no. 12, pp. 1388-1395. https://doi.org/10.1002/ajh.25648
Abou Dalle, Iman ; Kantarjian, Hagop M ; Short, Nicholas J ; Konopleva, Marina ; Jain, Nitin ; Garcia-Manero, Guillermo ; Garris, Rebecca ; Qiao, Wei ; Cortes, Jorge E ; O'Brien, Susan ; Kebriaei, Partow ; Kadia, Tapan ; Jabbour, Elias ; Ravandi, Farhad. / Philadelphia chromosome-positive acute lymphoblastic leukemia at first relapse in the era of tyrosine kinase inhibitors. In: American Journal of Hematology. 2019 ; Vol. 94, No. 12. pp. 1388-1395.
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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.",
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AU - Short, Nicholas J

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AU - Jain, Nitin

AU - Garcia-Manero, Guillermo

AU - Garris, Rebecca

AU - Qiao, Wei

AU - Cortes, Jorge E

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AU - Kebriaei, Partow

AU - Kadia, Tapan

AU - Jabbour, Elias

AU - Ravandi, Farhad

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N2 - 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.

AB - 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.

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