The early achievement of measurable residual disease negativity in the treatment of adults with Philadelphia-negative B-cell acute lymphoblastic leukemia is a strong predictor for survival

Musa Yilmaz, Hagop Kantarjian, Xuemei Wang, Joseph D. Khoury, Farhad Ravandi, Jeffrey Jorgensen, Nicholas J. Short, Sanam Loghavi, Jorge Cortes, Guillermo Garcia-Manero, Tapan Kadia, Koji Sasaki, Marina Konopleva, Koichi Takahashi, William Wierda, Nitin Jain, Srdan Verstovsek, Zeev Estrov, Prithviraj Bose, Sherry PierceRebecca Garris, Susan O'Brien, Elias Jabbour

Research output: Contribution to journalArticle

Abstract

The minimal or measurable residual disease (MRD) status following induction/consolidation chemotherapy is an important prognostic endpoint in adult patients with newly diagnosed acute lymphoblastic leukemia (ALL). However, the optimal time-point (TP) of MRD assessment and its impact on outcome remains unclear. We analyzed 215 patients with newly diagnosed Philadelphia negative B-cell ALL who received intensive chemotherapy, and had available MRD assessment by multicolor flow cytometry at two separate TPs. The median time to first TP (1TP) and second TP (2TP) were 24 and 110 days, respectively. At 1TP, 148 patients (68%) were MRD negative and 67 (32%) were positive. Of the 148 patients with negative MRD at 1TP, 147 (99%) maintained it through 2TP. Patients who were MRD negative at both TPs, early MRD responders, had the 3-year event-free survival (EFS), and overall survival (OS) rates of 65% and 76%, respectively. Patients with improved MRD status from positive to negative, late MRD responders, had lower 3-year EFS and OS rates, 42% and 58%, respectively (P =.001). Multivariate analysis showed that KMT2A (MLL) rearrangement and MRD positivity at 1TP were the only factors correlated with worse OS. In conclusion, the earlier achievement of MRD negative remission is a stronger prognostic factor for survival.

Original languageEnglish (US)
Pages (from-to)144-150
Number of pages7
JournalAmerican Journal of Hematology
Volume95
Issue number2
DOIs
StatePublished - Feb 1 2020

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Precursor Cell Lymphoblastic Leukemia-Lymphoma
B-Lymphocytes
Survival
Therapeutics
Disease-Free Survival
Survival Rate
Consolidation Chemotherapy
Induction Chemotherapy
Flow Cytometry
Multivariate Analysis
Drug Therapy

ASJC Scopus subject areas

  • Hematology

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The early achievement of measurable residual disease negativity in the treatment of adults with Philadelphia-negative B-cell acute lymphoblastic leukemia is a strong predictor for survival. / Yilmaz, Musa; Kantarjian, Hagop; Wang, Xuemei; Khoury, Joseph D.; Ravandi, Farhad; Jorgensen, Jeffrey; Short, Nicholas J.; Loghavi, Sanam; Cortes, Jorge; Garcia-Manero, Guillermo; Kadia, Tapan; Sasaki, Koji; Konopleva, Marina; Takahashi, Koichi; Wierda, William; Jain, Nitin; Verstovsek, Srdan; Estrov, Zeev; Bose, Prithviraj; Pierce, Sherry; Garris, Rebecca; O'Brien, Susan; Jabbour, Elias.

In: American Journal of Hematology, Vol. 95, No. 2, 01.02.2020, p. 144-150.

Research output: Contribution to journalArticle

Yilmaz, M, Kantarjian, H, Wang, X, Khoury, JD, Ravandi, F, Jorgensen, J, Short, NJ, Loghavi, S, Cortes, J, Garcia-Manero, G, Kadia, T, Sasaki, K, Konopleva, M, Takahashi, K, Wierda, W, Jain, N, Verstovsek, S, Estrov, Z, Bose, P, Pierce, S, Garris, R, O'Brien, S & Jabbour, E 2020, 'The early achievement of measurable residual disease negativity in the treatment of adults with Philadelphia-negative B-cell acute lymphoblastic leukemia is a strong predictor for survival', American Journal of Hematology, vol. 95, no. 2, pp. 144-150. https://doi.org/10.1002/ajh.25671
Yilmaz, Musa ; Kantarjian, Hagop ; Wang, Xuemei ; Khoury, Joseph D. ; Ravandi, Farhad ; Jorgensen, Jeffrey ; Short, Nicholas J. ; Loghavi, Sanam ; Cortes, Jorge ; Garcia-Manero, Guillermo ; Kadia, Tapan ; Sasaki, Koji ; Konopleva, Marina ; Takahashi, Koichi ; Wierda, William ; Jain, Nitin ; Verstovsek, Srdan ; Estrov, Zeev ; Bose, Prithviraj ; Pierce, Sherry ; Garris, Rebecca ; O'Brien, Susan ; Jabbour, Elias. / The early achievement of measurable residual disease negativity in the treatment of adults with Philadelphia-negative B-cell acute lymphoblastic leukemia is a strong predictor for survival. In: American Journal of Hematology. 2020 ; Vol. 95, No. 2. pp. 144-150.
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abstract = "The minimal or measurable residual disease (MRD) status following induction/consolidation chemotherapy is an important prognostic endpoint in adult patients with newly diagnosed acute lymphoblastic leukemia (ALL). However, the optimal time-point (TP) of MRD assessment and its impact on outcome remains unclear. We analyzed 215 patients with newly diagnosed Philadelphia negative B-cell ALL who received intensive chemotherapy, and had available MRD assessment by multicolor flow cytometry at two separate TPs. The median time to first TP (1TP) and second TP (2TP) were 24 and 110 days, respectively. At 1TP, 148 patients (68{\%}) were MRD negative and 67 (32{\%}) were positive. Of the 148 patients with negative MRD at 1TP, 147 (99{\%}) maintained it through 2TP. Patients who were MRD negative at both TPs, early MRD responders, had the 3-year event-free survival (EFS), and overall survival (OS) rates of 65{\%} and 76{\%}, respectively. Patients with improved MRD status from positive to negative, late MRD responders, had lower 3-year EFS and OS rates, 42{\%} and 58{\%}, respectively (P =.001). Multivariate analysis showed that KMT2A (MLL) rearrangement and MRD positivity at 1TP were the only factors correlated with worse OS. In conclusion, the earlier achievement of MRD negative remission is a stronger prognostic factor for survival.",
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AU - Yilmaz, Musa

AU - Kantarjian, Hagop

AU - Wang, Xuemei

AU - Khoury, Joseph D.

AU - Ravandi, Farhad

AU - Jorgensen, Jeffrey

AU - Short, Nicholas J.

AU - Loghavi, Sanam

AU - Cortes, Jorge

AU - Garcia-Manero, Guillermo

AU - Kadia, Tapan

AU - Sasaki, Koji

AU - Konopleva, Marina

AU - Takahashi, Koichi

AU - Wierda, William

AU - Jain, Nitin

AU - Verstovsek, Srdan

AU - Estrov, Zeev

AU - Bose, Prithviraj

AU - Pierce, Sherry

AU - Garris, Rebecca

AU - O'Brien, Susan

AU - Jabbour, Elias

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N2 - The minimal or measurable residual disease (MRD) status following induction/consolidation chemotherapy is an important prognostic endpoint in adult patients with newly diagnosed acute lymphoblastic leukemia (ALL). However, the optimal time-point (TP) of MRD assessment and its impact on outcome remains unclear. We analyzed 215 patients with newly diagnosed Philadelphia negative B-cell ALL who received intensive chemotherapy, and had available MRD assessment by multicolor flow cytometry at two separate TPs. The median time to first TP (1TP) and second TP (2TP) were 24 and 110 days, respectively. At 1TP, 148 patients (68%) were MRD negative and 67 (32%) were positive. Of the 148 patients with negative MRD at 1TP, 147 (99%) maintained it through 2TP. Patients who were MRD negative at both TPs, early MRD responders, had the 3-year event-free survival (EFS), and overall survival (OS) rates of 65% and 76%, respectively. Patients with improved MRD status from positive to negative, late MRD responders, had lower 3-year EFS and OS rates, 42% and 58%, respectively (P =.001). Multivariate analysis showed that KMT2A (MLL) rearrangement and MRD positivity at 1TP were the only factors correlated with worse OS. In conclusion, the earlier achievement of MRD negative remission is a stronger prognostic factor for survival.

AB - The minimal or measurable residual disease (MRD) status following induction/consolidation chemotherapy is an important prognostic endpoint in adult patients with newly diagnosed acute lymphoblastic leukemia (ALL). However, the optimal time-point (TP) of MRD assessment and its impact on outcome remains unclear. We analyzed 215 patients with newly diagnosed Philadelphia negative B-cell ALL who received intensive chemotherapy, and had available MRD assessment by multicolor flow cytometry at two separate TPs. The median time to first TP (1TP) and second TP (2TP) were 24 and 110 days, respectively. At 1TP, 148 patients (68%) were MRD negative and 67 (32%) were positive. Of the 148 patients with negative MRD at 1TP, 147 (99%) maintained it through 2TP. Patients who were MRD negative at both TPs, early MRD responders, had the 3-year event-free survival (EFS), and overall survival (OS) rates of 65% and 76%, respectively. Patients with improved MRD status from positive to negative, late MRD responders, had lower 3-year EFS and OS rates, 42% and 58%, respectively (P =.001). Multivariate analysis showed that KMT2A (MLL) rearrangement and MRD positivity at 1TP were the only factors correlated with worse OS. In conclusion, the earlier achievement of MRD negative remission is a stronger prognostic factor for survival.

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