Significance of recurrence of minimal residual disease detected by multi-parameter flow cytometry in patients with acute lymphoblastic leukemia in morphological remission

Naveen Pemmaraju, Hagop Kantarjian, Jeffrey L. Jorgensen, Elias Jabbour, Nitin Jain, Deborah Thomas, Susan O'Brien, Xuemei Wang, Xuelin Huang, Sa A. Wang, Marina Konopleva, Sergej Konoplev, Tapan Kadia, Rebecca Garris, Sherry Pierce, Guillermo Garcia-Manero, Jorge Cortes, Farhad Ravandi

Research output: Contribution to journalArticle

Abstract

We sought to determine the significance of minimal residual disease (MRD) relapse in patients with ALL after achieving MRD negative status following induction and consolidation therapy. Between January 2003 and September 2014, 647 newly diagnosed patients were treated [HyperCVAD-based (n = 531); Augmented BFM (n = 116)]. Six hundred and one (93%) achieved complete remission (CR), and 546 (91%) became MRD negative. Fifty-five patients [HyperCVAD-based (n = 49); Augmented BFM (n = 6)] developed recurrence of MRD while still in morphological CR and are the subjects of this study. MRD was assessed by 6-color (4-color prior to 2009) multi-parameter flow cytometry (MFC) at CR and multiple time points thereafter. Their median age was 44 years (range, 18–72 years), median WBC at initial presentation was 7.3 K/µL−1 (range, 0.6–303.8 K/µL−1) and median bone marrow blast percentage 88% (range, 26–98%). The median time to MRD relapse was 14 months (range 3–58 months). Forty-four (80%) patients subsequently developed morphological relapse after median of 3 months (range, <1–33 months) from detection of MRD recurrence. Treatments received after MRD positivity and prior to morphological relapse: 16 continued maintenance chemotherapy; 15 received late intensification; 9 allogeneic stem cell transplant, 9 changed chemotherapy, 6 no further therapy. Only six remain alive and in CR1 and nine are alive after morphological relapse. MRD relapse detected by MFC at any time after achieving CR is associated with a high risk for morphological relapse. SCT can result in long-term remission in some patients. Prospective studies of long-term MRD assessments, together with less toxic treatment strategies to eradicate MRD, are warranted.

Original languageEnglish (US)
Pages (from-to)279-285
Number of pages7
JournalAmerican Journal of Hematology
Volume92
Issue number3
DOIs
StatePublished - Mar 1 2017
Externally publishedYes

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Residual Neoplasm
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Flow Cytometry
Recurrence
Color
Maintenance Chemotherapy
Poisons
Therapeutics
Stem Cells
Bone Marrow
Prospective Studies
Transplants
Drug Therapy

ASJC Scopus subject areas

  • Hematology

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Significance of recurrence of minimal residual disease detected by multi-parameter flow cytometry in patients with acute lymphoblastic leukemia in morphological remission. / Pemmaraju, Naveen; Kantarjian, Hagop; Jorgensen, Jeffrey L.; Jabbour, Elias; Jain, Nitin; Thomas, Deborah; O'Brien, Susan; Wang, Xuemei; Huang, Xuelin; Wang, Sa A.; Konopleva, Marina; Konoplev, Sergej; Kadia, Tapan; Garris, Rebecca; Pierce, Sherry; Garcia-Manero, Guillermo; Cortes, Jorge; Ravandi, Farhad.

In: American Journal of Hematology, Vol. 92, No. 3, 01.03.2017, p. 279-285.

Research output: Contribution to journalArticle

Pemmaraju, N, Kantarjian, H, Jorgensen, JL, Jabbour, E, Jain, N, Thomas, D, O'Brien, S, Wang, X, Huang, X, Wang, SA, Konopleva, M, Konoplev, S, Kadia, T, Garris, R, Pierce, S, Garcia-Manero, G, Cortes, J & Ravandi, F 2017, 'Significance of recurrence of minimal residual disease detected by multi-parameter flow cytometry in patients with acute lymphoblastic leukemia in morphological remission', American Journal of Hematology, vol. 92, no. 3, pp. 279-285. https://doi.org/10.1002/ajh.24629
Pemmaraju, Naveen ; Kantarjian, Hagop ; Jorgensen, Jeffrey L. ; Jabbour, Elias ; Jain, Nitin ; Thomas, Deborah ; O'Brien, Susan ; Wang, Xuemei ; Huang, Xuelin ; Wang, Sa A. ; Konopleva, Marina ; Konoplev, Sergej ; Kadia, Tapan ; Garris, Rebecca ; Pierce, Sherry ; Garcia-Manero, Guillermo ; Cortes, Jorge ; Ravandi, Farhad. / Significance of recurrence of minimal residual disease detected by multi-parameter flow cytometry in patients with acute lymphoblastic leukemia in morphological remission. In: American Journal of Hematology. 2017 ; Vol. 92, No. 3. pp. 279-285.
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abstract = "We sought to determine the significance of minimal residual disease (MRD) relapse in patients with ALL after achieving MRD negative status following induction and consolidation therapy. Between January 2003 and September 2014, 647 newly diagnosed patients were treated [HyperCVAD-based (n = 531); Augmented BFM (n = 116)]. Six hundred and one (93{\%}) achieved complete remission (CR), and 546 (91{\%}) became MRD negative. Fifty-five patients [HyperCVAD-based (n = 49); Augmented BFM (n = 6)] developed recurrence of MRD while still in morphological CR and are the subjects of this study. MRD was assessed by 6-color (4-color prior to 2009) multi-parameter flow cytometry (MFC) at CR and multiple time points thereafter. Their median age was 44 years (range, 18–72 years), median WBC at initial presentation was 7.3 K/µL−1 (range, 0.6–303.8 K/µL−1) and median bone marrow blast percentage 88{\%} (range, 26–98{\%}). The median time to MRD relapse was 14 months (range 3–58 months). Forty-four (80{\%}) patients subsequently developed morphological relapse after median of 3 months (range, <1–33 months) from detection of MRD recurrence. Treatments received after MRD positivity and prior to morphological relapse: 16 continued maintenance chemotherapy; 15 received late intensification; 9 allogeneic stem cell transplant, 9 changed chemotherapy, 6 no further therapy. Only six remain alive and in CR1 and nine are alive after morphological relapse. MRD relapse detected by MFC at any time after achieving CR is associated with a high risk for morphological relapse. SCT can result in long-term remission in some patients. Prospective studies of long-term MRD assessments, together with less toxic treatment strategies to eradicate MRD, are warranted.",
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AU - Jabbour, Elias

AU - Jain, Nitin

AU - Thomas, Deborah

AU - O'Brien, Susan

AU - Wang, Xuemei

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AU - Wang, Sa A.

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AU - Konoplev, Sergej

AU - Kadia, Tapan

AU - Garris, Rebecca

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AU - Cortes, Jorge

AU - Ravandi, Farhad

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