Prognostic impact of pretreatment cytogenetics in adult Philadelphia chromosome–negative acute lymphoblastic leukemia in the era of minimal residual disease

Ghayas C. Issa, Hagop M. Kantarjian, C. Cameron Yin, Wei Qiao, Farhad Ravandi, Deborah Thomas, Nicholas J. Short, Koji Sasaki, Guillermo Garcia-Manero, Tapan M. Kadia, Jorge E. Cortes, Naval Daver, Gautam Borthakur, Nitin Jain, Marina Konopleva, Issa Khouri, Partow Kebriaei, Richard E. Champlin, Sherry Pierce, Susan M. O’BrienElias Jabbour

Research output: Contribution to journalArticle

Abstract

BACKGROUND: The introduction of novel prognostic factors such as minimal residual disease (MRD) and genomic profiling has led to the reevaluation of the role of cytogenetics and other conventional factors in risk stratification for acute lymphoblastic leukemia (ALL). METHODS: This study assessed the impact of baseline cytogenetics on the outcomes of 428 adult patients with Philadelphia chromosome–negative ALL who were receiving frontline chemotherapy. Three hundred thirty patients (77%) were treated with hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone–based regimens, and 98 (23%) were treated with the augmented Berlin-Frankfurt-Munster regimen. RESULTS: The median age was 40 years (range, 13-86 years). One hundred eighty-six patients (43%) had diploid cytogenetics, 32 (7%) had complex cytogenetics (defined as ≥ 5 chromosomal abnormalities), 27 (6%) had low hypodiploidy/near-triploidy (Ho-Tr), 24 (6%) had high hyperdiploidy, and 24 (6%) had a mixed-lineage leukemia (MLL) rearrangement. Patients with an MLL rearrangement, Ho-Tr, or a complex karyotype had significantly worse relapse-free survival (RFS) and overall survival (OS) than the diploid group. According to a multivariate analysis including all the baseline characteristics and MRD status, Ho-Tr and a complex karyotype were independent predictive factors for worse RFS and OS. Furthermore, survival among all cytogenetic groups was similar, regardless of the treatment received. CONCLUSIONS: A complex karyotype and Ho-Tr are adverse prognostic factors for adults with ALL independently of the MRD status. These findings suggest that pretreatment cytogenetics remain a valuable prognostic tool in this population. Cancer 2017;123:459–467.

Original languageEnglish (US)
Pages (from-to)459-467
Number of pages9
JournalCancer
Volume123
Issue number3
DOIs
StatePublished - Feb 1 2017
Externally publishedYes

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Residual Neoplasm
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Cytogenetics
Triploidy
Karyotype
Survival
Diploidy
Leukemia
Recurrence
Polyploidy
Vincristine
Berlin
Chromosome Aberrations
Doxorubicin
Cyclophosphamide
Multivariate Analysis
Drug Therapy
Population
Neoplasms

Keywords

  • acute lymphoblastic leukemia (ALL)
  • complex
  • cytogenetics
  • hypodiploidy
  • minimal residual disease
  • prognosis

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Prognostic impact of pretreatment cytogenetics in adult Philadelphia chromosome–negative acute lymphoblastic leukemia in the era of minimal residual disease. / Issa, Ghayas C.; Kantarjian, Hagop M.; Yin, C. Cameron; Qiao, Wei; Ravandi, Farhad; Thomas, Deborah; Short, Nicholas J.; Sasaki, Koji; Garcia-Manero, Guillermo; Kadia, Tapan M.; Cortes, Jorge E.; Daver, Naval; Borthakur, Gautam; Jain, Nitin; Konopleva, Marina; Khouri, Issa; Kebriaei, Partow; Champlin, Richard E.; Pierce, Sherry; O’Brien, Susan M.; Jabbour, Elias.

In: Cancer, Vol. 123, No. 3, 01.02.2017, p. 459-467.

Research output: Contribution to journalArticle

Issa, GC, Kantarjian, HM, Yin, CC, Qiao, W, Ravandi, F, Thomas, D, Short, NJ, Sasaki, K, Garcia-Manero, G, Kadia, TM, Cortes, JE, Daver, N, Borthakur, G, Jain, N, Konopleva, M, Khouri, I, Kebriaei, P, Champlin, RE, Pierce, S, O’Brien, SM & Jabbour, E 2017, 'Prognostic impact of pretreatment cytogenetics in adult Philadelphia chromosome–negative acute lymphoblastic leukemia in the era of minimal residual disease', Cancer, vol. 123, no. 3, pp. 459-467. https://doi.org/10.1002/cncr.30376
Issa, Ghayas C. ; Kantarjian, Hagop M. ; Yin, C. Cameron ; Qiao, Wei ; Ravandi, Farhad ; Thomas, Deborah ; Short, Nicholas J. ; Sasaki, Koji ; Garcia-Manero, Guillermo ; Kadia, Tapan M. ; Cortes, Jorge E. ; Daver, Naval ; Borthakur, Gautam ; Jain, Nitin ; Konopleva, Marina ; Khouri, Issa ; Kebriaei, Partow ; Champlin, Richard E. ; Pierce, Sherry ; O’Brien, Susan M. ; Jabbour, Elias. / Prognostic impact of pretreatment cytogenetics in adult Philadelphia chromosome–negative acute lymphoblastic leukemia in the era of minimal residual disease. In: Cancer. 2017 ; Vol. 123, No. 3. pp. 459-467.
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abstract = "BACKGROUND: The introduction of novel prognostic factors such as minimal residual disease (MRD) and genomic profiling has led to the reevaluation of the role of cytogenetics and other conventional factors in risk stratification for acute lymphoblastic leukemia (ALL). METHODS: This study assessed the impact of baseline cytogenetics on the outcomes of 428 adult patients with Philadelphia chromosome–negative ALL who were receiving frontline chemotherapy. Three hundred thirty patients (77{\%}) were treated with hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone–based regimens, and 98 (23{\%}) were treated with the augmented Berlin-Frankfurt-Munster regimen. RESULTS: The median age was 40 years (range, 13-86 years). One hundred eighty-six patients (43{\%}) had diploid cytogenetics, 32 (7{\%}) had complex cytogenetics (defined as ≥ 5 chromosomal abnormalities), 27 (6{\%}) had low hypodiploidy/near-triploidy (Ho-Tr), 24 (6{\%}) had high hyperdiploidy, and 24 (6{\%}) had a mixed-lineage leukemia (MLL) rearrangement. Patients with an MLL rearrangement, Ho-Tr, or a complex karyotype had significantly worse relapse-free survival (RFS) and overall survival (OS) than the diploid group. According to a multivariate analysis including all the baseline characteristics and MRD status, Ho-Tr and a complex karyotype were independent predictive factors for worse RFS and OS. Furthermore, survival among all cytogenetic groups was similar, regardless of the treatment received. CONCLUSIONS: A complex karyotype and Ho-Tr are adverse prognostic factors for adults with ALL independently of the MRD status. These findings suggest that pretreatment cytogenetics remain a valuable prognostic tool in this population. Cancer 2017;123:459–467.",
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T1 - Prognostic impact of pretreatment cytogenetics in adult Philadelphia chromosome–negative acute lymphoblastic leukemia in the era of minimal residual disease

AU - Issa, Ghayas C.

AU - Kantarjian, Hagop M.

AU - Yin, C. Cameron

AU - Qiao, Wei

AU - Ravandi, Farhad

AU - Thomas, Deborah

AU - Short, Nicholas J.

AU - Sasaki, Koji

AU - Garcia-Manero, Guillermo

AU - Kadia, Tapan M.

AU - Cortes, Jorge E.

AU - Daver, Naval

AU - Borthakur, Gautam

AU - Jain, Nitin

AU - Konopleva, Marina

AU - Khouri, Issa

AU - Kebriaei, Partow

AU - Champlin, Richard E.

AU - Pierce, Sherry

AU - O’Brien, Susan M.

AU - Jabbour, Elias

PY - 2017/2/1

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N2 - BACKGROUND: The introduction of novel prognostic factors such as minimal residual disease (MRD) and genomic profiling has led to the reevaluation of the role of cytogenetics and other conventional factors in risk stratification for acute lymphoblastic leukemia (ALL). METHODS: This study assessed the impact of baseline cytogenetics on the outcomes of 428 adult patients with Philadelphia chromosome–negative ALL who were receiving frontline chemotherapy. Three hundred thirty patients (77%) were treated with hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone–based regimens, and 98 (23%) were treated with the augmented Berlin-Frankfurt-Munster regimen. RESULTS: The median age was 40 years (range, 13-86 years). One hundred eighty-six patients (43%) had diploid cytogenetics, 32 (7%) had complex cytogenetics (defined as ≥ 5 chromosomal abnormalities), 27 (6%) had low hypodiploidy/near-triploidy (Ho-Tr), 24 (6%) had high hyperdiploidy, and 24 (6%) had a mixed-lineage leukemia (MLL) rearrangement. Patients with an MLL rearrangement, Ho-Tr, or a complex karyotype had significantly worse relapse-free survival (RFS) and overall survival (OS) than the diploid group. According to a multivariate analysis including all the baseline characteristics and MRD status, Ho-Tr and a complex karyotype were independent predictive factors for worse RFS and OS. Furthermore, survival among all cytogenetic groups was similar, regardless of the treatment received. CONCLUSIONS: A complex karyotype and Ho-Tr are adverse prognostic factors for adults with ALL independently of the MRD status. These findings suggest that pretreatment cytogenetics remain a valuable prognostic tool in this population. Cancer 2017;123:459–467.

AB - BACKGROUND: The introduction of novel prognostic factors such as minimal residual disease (MRD) and genomic profiling has led to the reevaluation of the role of cytogenetics and other conventional factors in risk stratification for acute lymphoblastic leukemia (ALL). METHODS: This study assessed the impact of baseline cytogenetics on the outcomes of 428 adult patients with Philadelphia chromosome–negative ALL who were receiving frontline chemotherapy. Three hundred thirty patients (77%) were treated with hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone–based regimens, and 98 (23%) were treated with the augmented Berlin-Frankfurt-Munster regimen. RESULTS: The median age was 40 years (range, 13-86 years). One hundred eighty-six patients (43%) had diploid cytogenetics, 32 (7%) had complex cytogenetics (defined as ≥ 5 chromosomal abnormalities), 27 (6%) had low hypodiploidy/near-triploidy (Ho-Tr), 24 (6%) had high hyperdiploidy, and 24 (6%) had a mixed-lineage leukemia (MLL) rearrangement. Patients with an MLL rearrangement, Ho-Tr, or a complex karyotype had significantly worse relapse-free survival (RFS) and overall survival (OS) than the diploid group. According to a multivariate analysis including all the baseline characteristics and MRD status, Ho-Tr and a complex karyotype were independent predictive factors for worse RFS and OS. Furthermore, survival among all cytogenetic groups was similar, regardless of the treatment received. CONCLUSIONS: A complex karyotype and Ho-Tr are adverse prognostic factors for adults with ALL independently of the MRD status. These findings suggest that pretreatment cytogenetics remain a valuable prognostic tool in this population. Cancer 2017;123:459–467.

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