Impact of complete molecular response on survival in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia

Nicholas J. Short, Elias Jabbour, Koji Sasaki, Keyur Patel, Susan M. O'Brien, Jorge E. Cortes, Rebecca Garris, Ghayas C. Issa, Guillermo Garcia-Manero, Rajyalakshmi Luthra, Deborah Thomas, Hagop Kantarjian, Farhad Ravandi

Research output: Contribution to journalArticle

Abstract

The impact of achieving complete molecular response (CMR) in Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) remains undefined. We evaluated the impact of CMR on outcomes among 85 patients with Ph+ ALL who received first-line hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with methotrexate and high-dose cytarabine plus a tyrosine kinase inhibitor, had minimal residual disease (MRD) assessments for BCR-ABL1 by quantitative polymerase chain reaction at complete remission (CR) and at 3-month time points, and did not undergo allogeneic stem cell transplantation (SCT). MRD status at 3 months had better discrimination for overall survival (OS; P = .005) and relapse-free survival (RFS; P = .002) than did MRD status at CR (P = .11 and P = .04, respectively). At 3 months, achievement of CMR vs response less than CMR was associated with longer median OS (127 vs 38 months, respectively; P = .009) and RFS (126 vs 18 months, respectively; P = .007). By multivariate analysis, only CMR at 3 months was prognostic for OS (hazard ratio, 0.42; 95% confidence interval, 0.21-0.82; P = .01). Patients with Ph+ ALL who achieve CMR at 3 months have superior survival compared with those with lesser molecular responses and have excellent long-term outcomes even without SCT.

Original languageEnglish (US)
Pages (from-to)504-507
Number of pages4
JournalBlood
Volume128
Issue number4
DOIs
StatePublished - Jul 28 2016
Externally publishedYes

Fingerprint

Philadelphia Chromosome
Residual Neoplasm
Chromosomes
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Stem Cell Transplantation
Stem cells
Survival
Polymerase chain reaction
Cytarabine
Vincristine
Methotrexate
Protein-Tyrosine Kinases
Doxorubicin
Cyclophosphamide
Dexamethasone
Hazards
Multivariate Analysis
Confidence Intervals
Recurrence
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Impact of complete molecular response on survival in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. / Short, Nicholas J.; Jabbour, Elias; Sasaki, Koji; Patel, Keyur; O'Brien, Susan M.; Cortes, Jorge E.; Garris, Rebecca; Issa, Ghayas C.; Garcia-Manero, Guillermo; Luthra, Rajyalakshmi; Thomas, Deborah; Kantarjian, Hagop; Ravandi, Farhad.

In: Blood, Vol. 128, No. 4, 28.07.2016, p. 504-507.

Research output: Contribution to journalArticle

Short, NJ, Jabbour, E, Sasaki, K, Patel, K, O'Brien, SM, Cortes, JE, Garris, R, Issa, GC, Garcia-Manero, G, Luthra, R, Thomas, D, Kantarjian, H & Ravandi, F 2016, 'Impact of complete molecular response on survival in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia', Blood, vol. 128, no. 4, pp. 504-507. https://doi.org/10.1182/blood-2016-03-707562
Short, Nicholas J. ; Jabbour, Elias ; Sasaki, Koji ; Patel, Keyur ; O'Brien, Susan M. ; Cortes, Jorge E. ; Garris, Rebecca ; Issa, Ghayas C. ; Garcia-Manero, Guillermo ; Luthra, Rajyalakshmi ; Thomas, Deborah ; Kantarjian, Hagop ; Ravandi, Farhad. / Impact of complete molecular response on survival in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. In: Blood. 2016 ; Vol. 128, No. 4. pp. 504-507.
@article{5bd20459977141bd8bda19bfdd0b3616,
title = "Impact of complete molecular response on survival in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia",
abstract = "The impact of achieving complete molecular response (CMR) in Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) remains undefined. We evaluated the impact of CMR on outcomes among 85 patients with Ph+ ALL who received first-line hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with methotrexate and high-dose cytarabine plus a tyrosine kinase inhibitor, had minimal residual disease (MRD) assessments for BCR-ABL1 by quantitative polymerase chain reaction at complete remission (CR) and at 3-month time points, and did not undergo allogeneic stem cell transplantation (SCT). MRD status at 3 months had better discrimination for overall survival (OS; P = .005) and relapse-free survival (RFS; P = .002) than did MRD status at CR (P = .11 and P = .04, respectively). At 3 months, achievement of CMR vs response less than CMR was associated with longer median OS (127 vs 38 months, respectively; P = .009) and RFS (126 vs 18 months, respectively; P = .007). By multivariate analysis, only CMR at 3 months was prognostic for OS (hazard ratio, 0.42; 95{\%} confidence interval, 0.21-0.82; P = .01). Patients with Ph+ ALL who achieve CMR at 3 months have superior survival compared with those with lesser molecular responses and have excellent long-term outcomes even without SCT.",
author = "Short, {Nicholas J.} and Elias Jabbour and Koji Sasaki and Keyur Patel and O'Brien, {Susan M.} and Cortes, {Jorge E.} and Rebecca Garris and Issa, {Ghayas C.} and Guillermo Garcia-Manero and Rajyalakshmi Luthra and Deborah Thomas and Hagop Kantarjian and Farhad Ravandi",
year = "2016",
month = "7",
day = "28",
doi = "10.1182/blood-2016-03-707562",
language = "English (US)",
volume = "128",
pages = "504--507",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "4",

}

TY - JOUR

T1 - Impact of complete molecular response on survival in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia

AU - Short, Nicholas J.

AU - Jabbour, Elias

AU - Sasaki, Koji

AU - Patel, Keyur

AU - O'Brien, Susan M.

AU - Cortes, Jorge E.

AU - Garris, Rebecca

AU - Issa, Ghayas C.

AU - Garcia-Manero, Guillermo

AU - Luthra, Rajyalakshmi

AU - Thomas, Deborah

AU - Kantarjian, Hagop

AU - Ravandi, Farhad

PY - 2016/7/28

Y1 - 2016/7/28

N2 - The impact of achieving complete molecular response (CMR) in Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) remains undefined. We evaluated the impact of CMR on outcomes among 85 patients with Ph+ ALL who received first-line hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with methotrexate and high-dose cytarabine plus a tyrosine kinase inhibitor, had minimal residual disease (MRD) assessments for BCR-ABL1 by quantitative polymerase chain reaction at complete remission (CR) and at 3-month time points, and did not undergo allogeneic stem cell transplantation (SCT). MRD status at 3 months had better discrimination for overall survival (OS; P = .005) and relapse-free survival (RFS; P = .002) than did MRD status at CR (P = .11 and P = .04, respectively). At 3 months, achievement of CMR vs response less than CMR was associated with longer median OS (127 vs 38 months, respectively; P = .009) and RFS (126 vs 18 months, respectively; P = .007). By multivariate analysis, only CMR at 3 months was prognostic for OS (hazard ratio, 0.42; 95% confidence interval, 0.21-0.82; P = .01). Patients with Ph+ ALL who achieve CMR at 3 months have superior survival compared with those with lesser molecular responses and have excellent long-term outcomes even without SCT.

AB - The impact of achieving complete molecular response (CMR) in Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) remains undefined. We evaluated the impact of CMR on outcomes among 85 patients with Ph+ ALL who received first-line hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with methotrexate and high-dose cytarabine plus a tyrosine kinase inhibitor, had minimal residual disease (MRD) assessments for BCR-ABL1 by quantitative polymerase chain reaction at complete remission (CR) and at 3-month time points, and did not undergo allogeneic stem cell transplantation (SCT). MRD status at 3 months had better discrimination for overall survival (OS; P = .005) and relapse-free survival (RFS; P = .002) than did MRD status at CR (P = .11 and P = .04, respectively). At 3 months, achievement of CMR vs response less than CMR was associated with longer median OS (127 vs 38 months, respectively; P = .009) and RFS (126 vs 18 months, respectively; P = .007). By multivariate analysis, only CMR at 3 months was prognostic for OS (hazard ratio, 0.42; 95% confidence interval, 0.21-0.82; P = .01). Patients with Ph+ ALL who achieve CMR at 3 months have superior survival compared with those with lesser molecular responses and have excellent long-term outcomes even without SCT.

UR - http://www.scopus.com/inward/record.url?scp=84979888012&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84979888012&partnerID=8YFLogxK

U2 - 10.1182/blood-2016-03-707562

DO - 10.1182/blood-2016-03-707562

M3 - Article

C2 - 27235138

AN - SCOPUS:84979888012

VL - 128

SP - 504

EP - 507

JO - Blood

JF - Blood

SN - 0006-4971

IS - 4

ER -