Minimal residual disease assessed by multi-parameter flow cytometry is highly prognostic in adult patients with acute lymphoblastic leukaemia

Farhad Ravandi, Jeffrey L. Jorgensen, Susan M. O'Brien, Elias Jabbour, Deborah A. Thomas, Gautam Borthakur, Rebecca Garris, Xuelin Huang, Guillermo Garcia-Manero, Jan A. Burger, Alessandra Ferrajoli, William Wierda, Tapan Kadia, Nitin Jain, Sa A. Wang, Sergei Konoplev, Partow Kebriaei, Richard E. Champlin, Deborah Mccue, Zeev EstrovJorge E. Cortes, Hagop M. Kantarjian

Research output: Contribution to journalArticle

Abstract

The prognostic value of minimal residual disease (MRD) assessed by multi-parameter flow cytometry (MFC) was investigated among 340 adult patients with B-cell acute lymphoblastic leukaemia (B-ALL) treated between 2004 and 2014 using regimens including the hyperCVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone, methotrexate, cytarabine) backbone. Among them, 323 (95%) achieved complete remission (CR) and were included in this study. Median age was 52 years (range, 15-84). Median white blood cell count (WBC) was 9·35 × 109/l (range, 0·4-658·1 ×1 09/l). MRD by MFC was initially assessed with a sensitivity of 0·01%, using a 15-marker, 4-colour panel and subsequently a 6-colour panel on bone marrow specimens obtained at CR achievement and at approximately 3 month intervals thereafter. MRD negative status at CR was associated with improved disease-free survival (DFS) and overall survival (OS) (P = 0·004 and P = 0·03, respectively). Similarly, achieving MRD negative status at approximately 3 and 6 months was associated with improved DFS (P = 0·004 and P < 0·0001, respectively) and OS (P = 0·004 and P < 0·0001, respectively). Multivariate analysis including age, WBC at presentation, cytogenetics (standard versus high risk) and MRD status at CR, 3 and 6 months, indicated that MRD negative status at CR was an independent predictor of DFS (P < 0·05). Achievement of an MRD negative state assessed by MFC is an important predictor of DFS and OS in adult patients with ALL.

Original languageEnglish (US)
Pages (from-to)392-400
Number of pages9
JournalBritish Journal of Haematology
Volume172
Issue number3
DOIs
StatePublished - Feb 1 2016
Externally publishedYes

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Residual Neoplasm
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Flow Cytometry
Disease-Free Survival
Leukocyte Count
Survival
Color
Cytarabine
Vincristine
Methotrexate
Cytogenetics
Doxorubicin
Cyclophosphamide
Dexamethasone
B-Lymphocytes
Multivariate Analysis
Bone Marrow

Keywords

  • Acute leukaemia
  • Flow cytometry
  • Minimal residual disease

ASJC Scopus subject areas

  • Hematology

Cite this

Ravandi, F., Jorgensen, J. L., O'Brien, S. M., Jabbour, E., Thomas, D. A., Borthakur, G., ... Kantarjian, H. M. (2016). Minimal residual disease assessed by multi-parameter flow cytometry is highly prognostic in adult patients with acute lymphoblastic leukaemia. British Journal of Haematology, 172(3), 392-400. https://doi.org/10.1111/bjh.13834

Minimal residual disease assessed by multi-parameter flow cytometry is highly prognostic in adult patients with acute lymphoblastic leukaemia. / Ravandi, Farhad; Jorgensen, Jeffrey L.; O'Brien, Susan M.; Jabbour, Elias; Thomas, Deborah A.; Borthakur, Gautam; Garris, Rebecca; Huang, Xuelin; Garcia-Manero, Guillermo; Burger, Jan A.; Ferrajoli, Alessandra; Wierda, William; Kadia, Tapan; Jain, Nitin; Wang, Sa A.; Konoplev, Sergei; Kebriaei, Partow; Champlin, Richard E.; Mccue, Deborah; Estrov, Zeev; Cortes, Jorge E.; Kantarjian, Hagop M.

In: British Journal of Haematology, Vol. 172, No. 3, 01.02.2016, p. 392-400.

Research output: Contribution to journalArticle

Ravandi, F, Jorgensen, JL, O'Brien, SM, Jabbour, E, Thomas, DA, Borthakur, G, Garris, R, Huang, X, Garcia-Manero, G, Burger, JA, Ferrajoli, A, Wierda, W, Kadia, T, Jain, N, Wang, SA, Konoplev, S, Kebriaei, P, Champlin, RE, Mccue, D, Estrov, Z, Cortes, JE & Kantarjian, HM 2016, 'Minimal residual disease assessed by multi-parameter flow cytometry is highly prognostic in adult patients with acute lymphoblastic leukaemia', British Journal of Haematology, vol. 172, no. 3, pp. 392-400. https://doi.org/10.1111/bjh.13834
Ravandi, Farhad ; Jorgensen, Jeffrey L. ; O'Brien, Susan M. ; Jabbour, Elias ; Thomas, Deborah A. ; Borthakur, Gautam ; Garris, Rebecca ; Huang, Xuelin ; Garcia-Manero, Guillermo ; Burger, Jan A. ; Ferrajoli, Alessandra ; Wierda, William ; Kadia, Tapan ; Jain, Nitin ; Wang, Sa A. ; Konoplev, Sergei ; Kebriaei, Partow ; Champlin, Richard E. ; Mccue, Deborah ; Estrov, Zeev ; Cortes, Jorge E. ; Kantarjian, Hagop M. / Minimal residual disease assessed by multi-parameter flow cytometry is highly prognostic in adult patients with acute lymphoblastic leukaemia. In: British Journal of Haematology. 2016 ; Vol. 172, No. 3. pp. 392-400.
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AU - O'Brien, Susan M.

AU - Jabbour, Elias

AU - Thomas, Deborah A.

AU - Borthakur, Gautam

AU - Garris, Rebecca

AU - Huang, Xuelin

AU - Garcia-Manero, Guillermo

AU - Burger, Jan A.

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AU - Champlin, Richard E.

AU - Mccue, Deborah

AU - Estrov, Zeev

AU - Cortes, Jorge E.

AU - Kantarjian, Hagop M.

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N2 - The prognostic value of minimal residual disease (MRD) assessed by multi-parameter flow cytometry (MFC) was investigated among 340 adult patients with B-cell acute lymphoblastic leukaemia (B-ALL) treated between 2004 and 2014 using regimens including the hyperCVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone, methotrexate, cytarabine) backbone. Among them, 323 (95%) achieved complete remission (CR) and were included in this study. Median age was 52 years (range, 15-84). Median white blood cell count (WBC) was 9·35 × 109/l (range, 0·4-658·1 ×1 09/l). MRD by MFC was initially assessed with a sensitivity of 0·01%, using a 15-marker, 4-colour panel and subsequently a 6-colour panel on bone marrow specimens obtained at CR achievement and at approximately 3 month intervals thereafter. MRD negative status at CR was associated with improved disease-free survival (DFS) and overall survival (OS) (P = 0·004 and P = 0·03, respectively). Similarly, achieving MRD negative status at approximately 3 and 6 months was associated with improved DFS (P = 0·004 and P < 0·0001, respectively) and OS (P = 0·004 and P < 0·0001, respectively). Multivariate analysis including age, WBC at presentation, cytogenetics (standard versus high risk) and MRD status at CR, 3 and 6 months, indicated that MRD negative status at CR was an independent predictor of DFS (P < 0·05). Achievement of an MRD negative state assessed by MFC is an important predictor of DFS and OS in adult patients with ALL.

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