Prognostic significance of day 14 bone marrow evaluation in adults with Philadelphia chromosome–negative acute lymphoblastic leukemia

Nicholas J. Short, Hagop M. Kantarjian, Koji Sasaki, Jorge E. Cortes, Farhad Ravandi, Deborah A. Thomas, Guillermo Garcia-Manero, Issa Khouri, Partow Kebriaei, Richard E. Champlin, Sherry Pierce, Ghayas C. Issa, Marina Konopleva, Tapan M. Kadia, Carlos Bueso-Ramos, Joseph D. Khoury, Nitin Jain, Susan M. O'Brien, Elias Jabbour

Research output: Contribution to journalArticle

Abstract

BACKGROUND: The role of day 14 (D14) bone marrow (BM) assessment in detecting increased blasts in patients undergoing induction for acute lymphoblastic leukemia (ALL) is not well defined. METHODS: This study evaluated 389 adolescent and adult patients with previously untreated Philadelphia chromosome–negative ALL who received frontline induction chemotherapy and for whom a D14 BM assessment was performed. RESULTS: A D14 BM blast proportion < 10% (including blast-free aplastic BM) was observed in 319 patients (82%), 10% to 29% was observed in 31 patients (8%), and ≥30% was observed in 39 patients (10%). The composite complete remission (CR)/complete remission with inadequate platelet recovery (CRp) rates for these groups were 99.7%, 87%, and 79%, respectively. The median event-free survival (EFS) was 49, 33, and 9 months, respectively (P <.001). The median overall survival (OS) was 88, 37, and 21 months, respectively (P <.001). The D14 BM blast group was the only factor predictive for the achievement of CR/CRp (P <.001). According to a multivariate analysis, the D14 BM blast group was independently prognostic for both EFS (hazard ratio [HR], 1.44; 95% confidence interval [CI], 1.12-1.85; P =.004) and OS (HR, 1.45; 95% CI, 1.14-1.85; P =.003). However, when minimal residual disease (MRD) assessment at the time of CR was added to the model, the D14 BM blast group was no longer prognostic for EFS or OS. CONCLUSIONS: An assessment of residual D14 BM blasts in patients with ALL is highly predictive of the achievement of CR with induction chemotherapy and of EFS and OS. However, the D14 BM blast assessment is less prognostic of long-term outcomes when an MRD assessment is also available. Cancer 2016;122:3812–3820.

Original languageEnglish (US)
Pages (from-to)3812-3820
Number of pages9
JournalCancer
Volume122
Issue number24
DOIs
StatePublished - Dec 15 2016
Externally publishedYes

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Precursor Cell Lymphoblastic Leukemia-Lymphoma
Bone Marrow
Disease-Free Survival
Induction Chemotherapy
Survival
Residual Neoplasm
Confidence Intervals
Remission Induction
Blood Platelets
Multivariate Analysis

Keywords

  • acute lymphoblastic leukemia
  • blasts
  • day 14
  • minimal residual disease
  • prognosis

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Prognostic significance of day 14 bone marrow evaluation in adults with Philadelphia chromosome–negative acute lymphoblastic leukemia. / Short, Nicholas J.; Kantarjian, Hagop M.; Sasaki, Koji; Cortes, Jorge E.; Ravandi, Farhad; Thomas, Deborah A.; Garcia-Manero, Guillermo; Khouri, Issa; Kebriaei, Partow; Champlin, Richard E.; Pierce, Sherry; Issa, Ghayas C.; Konopleva, Marina; Kadia, Tapan M.; Bueso-Ramos, Carlos; Khoury, Joseph D.; Jain, Nitin; O'Brien, Susan M.; Jabbour, Elias.

In: Cancer, Vol. 122, No. 24, 15.12.2016, p. 3812-3820.

Research output: Contribution to journalArticle

Short, NJ, Kantarjian, HM, Sasaki, K, Cortes, JE, Ravandi, F, Thomas, DA, Garcia-Manero, G, Khouri, I, Kebriaei, P, Champlin, RE, Pierce, S, Issa, GC, Konopleva, M, Kadia, TM, Bueso-Ramos, C, Khoury, JD, Jain, N, O'Brien, SM & Jabbour, E 2016, 'Prognostic significance of day 14 bone marrow evaluation in adults with Philadelphia chromosome–negative acute lymphoblastic leukemia', Cancer, vol. 122, no. 24, pp. 3812-3820. https://doi.org/10.1002/cncr.30262
Short, Nicholas J. ; Kantarjian, Hagop M. ; Sasaki, Koji ; Cortes, Jorge E. ; Ravandi, Farhad ; Thomas, Deborah A. ; Garcia-Manero, Guillermo ; Khouri, Issa ; Kebriaei, Partow ; Champlin, Richard E. ; Pierce, Sherry ; Issa, Ghayas C. ; Konopleva, Marina ; Kadia, Tapan M. ; Bueso-Ramos, Carlos ; Khoury, Joseph D. ; Jain, Nitin ; O'Brien, Susan M. ; Jabbour, Elias. / Prognostic significance of day 14 bone marrow evaluation in adults with Philadelphia chromosome–negative acute lymphoblastic leukemia. In: Cancer. 2016 ; Vol. 122, No. 24. pp. 3812-3820.
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title = "Prognostic significance of day 14 bone marrow evaluation in adults with Philadelphia chromosome–negative acute lymphoblastic leukemia",
abstract = "BACKGROUND: The role of day 14 (D14) bone marrow (BM) assessment in detecting increased blasts in patients undergoing induction for acute lymphoblastic leukemia (ALL) is not well defined. METHODS: This study evaluated 389 adolescent and adult patients with previously untreated Philadelphia chromosome–negative ALL who received frontline induction chemotherapy and for whom a D14 BM assessment was performed. RESULTS: A D14 BM blast proportion < 10{\%} (including blast-free aplastic BM) was observed in 319 patients (82{\%}), 10{\%} to 29{\%} was observed in 31 patients (8{\%}), and ≥30{\%} was observed in 39 patients (10{\%}). The composite complete remission (CR)/complete remission with inadequate platelet recovery (CRp) rates for these groups were 99.7{\%}, 87{\%}, and 79{\%}, respectively. The median event-free survival (EFS) was 49, 33, and 9 months, respectively (P <.001). The median overall survival (OS) was 88, 37, and 21 months, respectively (P <.001). The D14 BM blast group was the only factor predictive for the achievement of CR/CRp (P <.001). According to a multivariate analysis, the D14 BM blast group was independently prognostic for both EFS (hazard ratio [HR], 1.44; 95{\%} confidence interval [CI], 1.12-1.85; P =.004) and OS (HR, 1.45; 95{\%} CI, 1.14-1.85; P =.003). However, when minimal residual disease (MRD) assessment at the time of CR was added to the model, the D14 BM blast group was no longer prognostic for EFS or OS. CONCLUSIONS: An assessment of residual D14 BM blasts in patients with ALL is highly predictive of the achievement of CR with induction chemotherapy and of EFS and OS. However, the D14 BM blast assessment is less prognostic of long-term outcomes when an MRD assessment is also available. Cancer 2016;122:3812–3820.",
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author = "Short, {Nicholas J.} and Kantarjian, {Hagop M.} and Koji Sasaki and Cortes, {Jorge E.} and Farhad Ravandi and Thomas, {Deborah A.} and Guillermo Garcia-Manero and Issa Khouri and Partow Kebriaei and Champlin, {Richard E.} and Sherry Pierce and Issa, {Ghayas C.} and Marina Konopleva and Kadia, {Tapan M.} and Carlos Bueso-Ramos and Khoury, {Joseph D.} and Nitin Jain and O'Brien, {Susan M.} and Elias Jabbour",
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T1 - Prognostic significance of day 14 bone marrow evaluation in adults with Philadelphia chromosome–negative acute lymphoblastic leukemia

AU - Short, Nicholas J.

AU - Kantarjian, Hagop M.

AU - Sasaki, Koji

AU - Cortes, Jorge E.

AU - Ravandi, Farhad

AU - Thomas, Deborah A.

AU - Garcia-Manero, Guillermo

AU - Khouri, Issa

AU - Kebriaei, Partow

AU - Champlin, Richard E.

AU - Pierce, Sherry

AU - Issa, Ghayas C.

AU - Konopleva, Marina

AU - Kadia, Tapan M.

AU - Bueso-Ramos, Carlos

AU - Khoury, Joseph D.

AU - Jain, Nitin

AU - O'Brien, Susan M.

AU - Jabbour, Elias

PY - 2016/12/15

Y1 - 2016/12/15

N2 - BACKGROUND: The role of day 14 (D14) bone marrow (BM) assessment in detecting increased blasts in patients undergoing induction for acute lymphoblastic leukemia (ALL) is not well defined. METHODS: This study evaluated 389 adolescent and adult patients with previously untreated Philadelphia chromosome–negative ALL who received frontline induction chemotherapy and for whom a D14 BM assessment was performed. RESULTS: A D14 BM blast proportion < 10% (including blast-free aplastic BM) was observed in 319 patients (82%), 10% to 29% was observed in 31 patients (8%), and ≥30% was observed in 39 patients (10%). The composite complete remission (CR)/complete remission with inadequate platelet recovery (CRp) rates for these groups were 99.7%, 87%, and 79%, respectively. The median event-free survival (EFS) was 49, 33, and 9 months, respectively (P <.001). The median overall survival (OS) was 88, 37, and 21 months, respectively (P <.001). The D14 BM blast group was the only factor predictive for the achievement of CR/CRp (P <.001). According to a multivariate analysis, the D14 BM blast group was independently prognostic for both EFS (hazard ratio [HR], 1.44; 95% confidence interval [CI], 1.12-1.85; P =.004) and OS (HR, 1.45; 95% CI, 1.14-1.85; P =.003). However, when minimal residual disease (MRD) assessment at the time of CR was added to the model, the D14 BM blast group was no longer prognostic for EFS or OS. CONCLUSIONS: An assessment of residual D14 BM blasts in patients with ALL is highly predictive of the achievement of CR with induction chemotherapy and of EFS and OS. However, the D14 BM blast assessment is less prognostic of long-term outcomes when an MRD assessment is also available. Cancer 2016;122:3812–3820.

AB - BACKGROUND: The role of day 14 (D14) bone marrow (BM) assessment in detecting increased blasts in patients undergoing induction for acute lymphoblastic leukemia (ALL) is not well defined. METHODS: This study evaluated 389 adolescent and adult patients with previously untreated Philadelphia chromosome–negative ALL who received frontline induction chemotherapy and for whom a D14 BM assessment was performed. RESULTS: A D14 BM blast proportion < 10% (including blast-free aplastic BM) was observed in 319 patients (82%), 10% to 29% was observed in 31 patients (8%), and ≥30% was observed in 39 patients (10%). The composite complete remission (CR)/complete remission with inadequate platelet recovery (CRp) rates for these groups were 99.7%, 87%, and 79%, respectively. The median event-free survival (EFS) was 49, 33, and 9 months, respectively (P <.001). The median overall survival (OS) was 88, 37, and 21 months, respectively (P <.001). The D14 BM blast group was the only factor predictive for the achievement of CR/CRp (P <.001). According to a multivariate analysis, the D14 BM blast group was independently prognostic for both EFS (hazard ratio [HR], 1.44; 95% confidence interval [CI], 1.12-1.85; P =.004) and OS (HR, 1.45; 95% CI, 1.14-1.85; P =.003). However, when minimal residual disease (MRD) assessment at the time of CR was added to the model, the D14 BM blast group was no longer prognostic for EFS or OS. CONCLUSIONS: An assessment of residual D14 BM blasts in patients with ALL is highly predictive of the achievement of CR with induction chemotherapy and of EFS and OS. However, the D14 BM blast assessment is less prognostic of long-term outcomes when an MRD assessment is also available. Cancer 2016;122:3812–3820.

KW - acute lymphoblastic leukemia

KW - blasts

KW - day 14

KW - minimal residual disease

KW - prognosis

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