Detection of MRD may predict the outcome of patients with Philadelphia chromosome-positive ALL treated with tyrosine kinase inhibitors plus chemotherapy

Farhad Ravandi, Jeffrey L. Jorgensen, Deborah A. Thomas, Susan O'Brien, Rebecca Garris, Stefan Faderl, Xuelin Huang, Sijin Wen, Jan A. Burger, Alessandra Ferrajoli, Partow Kebriaei, Richard E. Champlin, Zeev Estrov, Pramoda Challagundla, Sa A. Wang, Rajyalakshmi Luthra, Jorge E. Cortes, Hagop M. Kantarjian

Research output: Contribution to journalArticle

Abstract

From 2001 to 2011, 122 patients with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia were treated with chemotherapy 1 imatinib (n = 54) or 1 dasatinib (n = 68). One hundred fifteen (94%) achieved complete remission (CR) including 101 patients who achieved it with only 1 induction course and had at least 1 minimal residual disease (MRD) assessment; 25 patients underwent an allogeneic stem cell transplant in first CR and were excluded, leaving 76 patients as the subject of this report. MRD monitoring by multiparameter flow cytometry (MFC) and real-time quantitative polymerase chain reaction (PCR) was performed at the end of induction and at ∼3-month intervals thereafter. Median age was 54 years (range, 21-84 years). There was no difference in survival by achievement of at least a major molecular response (MMR; BCR-ABL/ABL > 0.1%) at CR (P = .22). Patients achieving MMR at 3, 6, 9, and 12 months had a better survival (P = .02, .04, .05, and .01, respectively). Negative MFC at CR did not predict for improved survival (P = .2). At 3 and 12 months, negative MRD by MFC was associated with improved survival (P = .04 and .001). MRD monitoring by PCR and MFC identifies patients who benefit from treatment intensification in first CR.

Original languageEnglish (US)
Pages (from-to)1214-1221
Number of pages8
JournalBlood
Volume122
Issue number7
DOIs
StatePublished - Aug 15 2013
Externally publishedYes

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Philadelphia Chromosome
Chemotherapy
Flow cytometry
Residual Neoplasm
Chromosomes
Protein-Tyrosine Kinases
Drug Therapy
Polymerase chain reaction
Flow Cytometry
Survival
Transplants
Monitoring
Stem cells
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Real-Time Polymerase Chain Reaction
Stem Cells
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Ravandi, F., Jorgensen, J. L., Thomas, D. A., O'Brien, S., Garris, R., Faderl, S., ... Kantarjian, H. M. (2013). Detection of MRD may predict the outcome of patients with Philadelphia chromosome-positive ALL treated with tyrosine kinase inhibitors plus chemotherapy. Blood, 122(7), 1214-1221. https://doi.org/10.1182/blood-2012-11-466482

Detection of MRD may predict the outcome of patients with Philadelphia chromosome-positive ALL treated with tyrosine kinase inhibitors plus chemotherapy. / Ravandi, Farhad; Jorgensen, Jeffrey L.; Thomas, Deborah A.; O'Brien, Susan; Garris, Rebecca; Faderl, Stefan; Huang, Xuelin; Wen, Sijin; Burger, Jan A.; Ferrajoli, Alessandra; Kebriaei, Partow; Champlin, Richard E.; Estrov, Zeev; Challagundla, Pramoda; Wang, Sa A.; Luthra, Rajyalakshmi; Cortes, Jorge E.; Kantarjian, Hagop M.

In: Blood, Vol. 122, No. 7, 15.08.2013, p. 1214-1221.

Research output: Contribution to journalArticle

Ravandi, F, Jorgensen, JL, Thomas, DA, O'Brien, S, Garris, R, Faderl, S, Huang, X, Wen, S, Burger, JA, Ferrajoli, A, Kebriaei, P, Champlin, RE, Estrov, Z, Challagundla, P, Wang, SA, Luthra, R, Cortes, JE & Kantarjian, HM 2013, 'Detection of MRD may predict the outcome of patients with Philadelphia chromosome-positive ALL treated with tyrosine kinase inhibitors plus chemotherapy', Blood, vol. 122, no. 7, pp. 1214-1221. https://doi.org/10.1182/blood-2012-11-466482
Ravandi, Farhad ; Jorgensen, Jeffrey L. ; Thomas, Deborah A. ; O'Brien, Susan ; Garris, Rebecca ; Faderl, Stefan ; Huang, Xuelin ; Wen, Sijin ; Burger, Jan A. ; Ferrajoli, Alessandra ; Kebriaei, Partow ; Champlin, Richard E. ; Estrov, Zeev ; Challagundla, Pramoda ; Wang, Sa A. ; Luthra, Rajyalakshmi ; Cortes, Jorge E. ; Kantarjian, Hagop M. / Detection of MRD may predict the outcome of patients with Philadelphia chromosome-positive ALL treated with tyrosine kinase inhibitors plus chemotherapy. In: Blood. 2013 ; Vol. 122, No. 7. pp. 1214-1221.
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abstract = "From 2001 to 2011, 122 patients with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia were treated with chemotherapy 1 imatinib (n = 54) or 1 dasatinib (n = 68). One hundred fifteen (94{\%}) achieved complete remission (CR) including 101 patients who achieved it with only 1 induction course and had at least 1 minimal residual disease (MRD) assessment; 25 patients underwent an allogeneic stem cell transplant in first CR and were excluded, leaving 76 patients as the subject of this report. MRD monitoring by multiparameter flow cytometry (MFC) and real-time quantitative polymerase chain reaction (PCR) was performed at the end of induction and at ∼3-month intervals thereafter. Median age was 54 years (range, 21-84 years). There was no difference in survival by achievement of at least a major molecular response (MMR; BCR-ABL/ABL > 0.1{\%}) at CR (P = .22). Patients achieving MMR at 3, 6, 9, and 12 months had a better survival (P = .02, .04, .05, and .01, respectively). Negative MFC at CR did not predict for improved survival (P = .2). At 3 and 12 months, negative MRD by MFC was associated with improved survival (P = .04 and .001). MRD monitoring by PCR and MFC identifies patients who benefit from treatment intensification in first CR.",
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AU - Ravandi, Farhad

AU - Jorgensen, Jeffrey L.

AU - Thomas, Deborah A.

AU - O'Brien, Susan

AU - Garris, Rebecca

AU - Faderl, Stefan

AU - Huang, Xuelin

AU - Wen, Sijin

AU - Burger, Jan A.

AU - Ferrajoli, Alessandra

AU - Kebriaei, Partow

AU - Champlin, Richard E.

AU - Estrov, Zeev

AU - Challagundla, Pramoda

AU - Wang, Sa A.

AU - Luthra, Rajyalakshmi

AU - Cortes, Jorge E.

AU - Kantarjian, Hagop M.

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N2 - From 2001 to 2011, 122 patients with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia were treated with chemotherapy 1 imatinib (n = 54) or 1 dasatinib (n = 68). One hundred fifteen (94%) achieved complete remission (CR) including 101 patients who achieved it with only 1 induction course and had at least 1 minimal residual disease (MRD) assessment; 25 patients underwent an allogeneic stem cell transplant in first CR and were excluded, leaving 76 patients as the subject of this report. MRD monitoring by multiparameter flow cytometry (MFC) and real-time quantitative polymerase chain reaction (PCR) was performed at the end of induction and at ∼3-month intervals thereafter. Median age was 54 years (range, 21-84 years). There was no difference in survival by achievement of at least a major molecular response (MMR; BCR-ABL/ABL > 0.1%) at CR (P = .22). Patients achieving MMR at 3, 6, 9, and 12 months had a better survival (P = .02, .04, .05, and .01, respectively). Negative MFC at CR did not predict for improved survival (P = .2). At 3 and 12 months, negative MRD by MFC was associated with improved survival (P = .04 and .001). MRD monitoring by PCR and MFC identifies patients who benefit from treatment intensification in first CR.

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