UKALLXII/ECOG2993: Addition of imatinib to a standard treatment regimen enhances long-term outcomes in Philadelphia positive acute lymphoblastic leukemia

Adele K. Fielding, Jacob M. Rowe, Georgina Buck, Letizia Foroni, Gareth Gerrard, Mark R Litzow, Hillard Lazarus, Selina M. Luger, David I. Marks, Andrew K. McMillan, Anthony V. Moorman, Bella Patel, Elisabeth Paietta, Martin S. Tallman, Anthony H. Goldstone

Research output: Contribution to journalArticle

157 Citations (Scopus)

Abstract

The Philadelphia chromosome positive arm of the UKALLXII/ECOG2993 study for adult acute lymphoblastic leukemia (ALL) enrolled 266 patients between 1993 and 2003 (preimatinib cohort). In 2003 imatinib was introduced as a single-agent course following induction (N 5 86, late imatinib). In 2005 imatinib was added to the second phase of induction (N 5 89, early imatinib). The complete remission (CR) rate was 92% in the imatinib cohort vs 82% in the preimatinib cohort (P 5 .004). At 4 years, the overall survival (OS) of all patients in the imatinib cohort was 38% vs 22% in the preimatinib cohort (P 5 .003). The magnitude of the difference between the preimatinib and imatinib cohorts in event-free survival (EFS), OS, and relapse-free survival (RFS) seen in univariate analysis was even greater in the multivariate analysis. In the preimatinib cohort, 31% of those starting treatment achieved hematopoietic stem cell transplant (alloHSCT) compared with 46% in the imatinib cohort. A Cox multivariate analysis taking alloHSCT into account showed a modest additional benefit to imatinib (hazard ratio for EFS 5 0.64, 95% confidence interval 0.44-0.93, P 5 .02), but no significant benefit for OS and RFS. Adding imatinib to standard therapy improves CR rate and long-term OS for adults with ALL. A proportion of the OS benefit derives from the fact that imatinib facilitates alloHSCT. This trial was registered at clinicaltrials.gov as NCT00002514.

Original languageEnglish (US)
Pages (from-to)843-850
Number of pages8
JournalBlood
Volume123
Issue number6
DOIs
StatePublished - Feb 6 2014

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Precursor Cell Lymphoblastic Leukemia-Lymphoma
Survival
Therapeutics
Disease-Free Survival
Imatinib Mesylate
Multivariate Analysis
Recurrence
Philadelphia Chromosome
Transplants
Chromosomes
Hematopoietic Stem Cells
Stem cells
Hazards
Arm
Confidence Intervals

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

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UKALLXII/ECOG2993 : Addition of imatinib to a standard treatment regimen enhances long-term outcomes in Philadelphia positive acute lymphoblastic leukemia. / Fielding, Adele K.; Rowe, Jacob M.; Buck, Georgina; Foroni, Letizia; Gerrard, Gareth; Litzow, Mark R; Lazarus, Hillard; Luger, Selina M.; Marks, David I.; McMillan, Andrew K.; Moorman, Anthony V.; Patel, Bella; Paietta, Elisabeth; Tallman, Martin S.; Goldstone, Anthony H.

In: Blood, Vol. 123, No. 6, 06.02.2014, p. 843-850.

Research output: Contribution to journalArticle

Fielding, AK, Rowe, JM, Buck, G, Foroni, L, Gerrard, G, Litzow, MR, Lazarus, H, Luger, SM, Marks, DI, McMillan, AK, Moorman, AV, Patel, B, Paietta, E, Tallman, MS & Goldstone, AH 2014, 'UKALLXII/ECOG2993: Addition of imatinib to a standard treatment regimen enhances long-term outcomes in Philadelphia positive acute lymphoblastic leukemia', Blood, vol. 123, no. 6, pp. 843-850. https://doi.org/10.1182/blood-2013-09-529008
Fielding, Adele K. ; Rowe, Jacob M. ; Buck, Georgina ; Foroni, Letizia ; Gerrard, Gareth ; Litzow, Mark R ; Lazarus, Hillard ; Luger, Selina M. ; Marks, David I. ; McMillan, Andrew K. ; Moorman, Anthony V. ; Patel, Bella ; Paietta, Elisabeth ; Tallman, Martin S. ; Goldstone, Anthony H. / UKALLXII/ECOG2993 : Addition of imatinib to a standard treatment regimen enhances long-term outcomes in Philadelphia positive acute lymphoblastic leukemia. In: Blood. 2014 ; Vol. 123, No. 6. pp. 843-850.
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title = "UKALLXII/ECOG2993: Addition of imatinib to a standard treatment regimen enhances long-term outcomes in Philadelphia positive acute lymphoblastic leukemia",
abstract = "The Philadelphia chromosome positive arm of the UKALLXII/ECOG2993 study for adult acute lymphoblastic leukemia (ALL) enrolled 266 patients between 1993 and 2003 (preimatinib cohort). In 2003 imatinib was introduced as a single-agent course following induction (N 5 86, late imatinib). In 2005 imatinib was added to the second phase of induction (N 5 89, early imatinib). The complete remission (CR) rate was 92{\%} in the imatinib cohort vs 82{\%} in the preimatinib cohort (P 5 .004). At 4 years, the overall survival (OS) of all patients in the imatinib cohort was 38{\%} vs 22{\%} in the preimatinib cohort (P 5 .003). The magnitude of the difference between the preimatinib and imatinib cohorts in event-free survival (EFS), OS, and relapse-free survival (RFS) seen in univariate analysis was even greater in the multivariate analysis. In the preimatinib cohort, 31{\%} of those starting treatment achieved hematopoietic stem cell transplant (alloHSCT) compared with 46{\%} in the imatinib cohort. A Cox multivariate analysis taking alloHSCT into account showed a modest additional benefit to imatinib (hazard ratio for EFS 5 0.64, 95{\%} confidence interval 0.44-0.93, P 5 .02), but no significant benefit for OS and RFS. Adding imatinib to standard therapy improves CR rate and long-term OS for adults with ALL. A proportion of the OS benefit derives from the fact that imatinib facilitates alloHSCT. This trial was registered at clinicaltrials.gov as NCT00002514.",
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T2 - Addition of imatinib to a standard treatment regimen enhances long-term outcomes in Philadelphia positive acute lymphoblastic leukemia

AU - Fielding, Adele K.

AU - Rowe, Jacob M.

AU - Buck, Georgina

AU - Foroni, Letizia

AU - Gerrard, Gareth

AU - Litzow, Mark R

AU - Lazarus, Hillard

AU - Luger, Selina M.

AU - Marks, David I.

AU - McMillan, Andrew K.

AU - Moorman, Anthony V.

AU - Patel, Bella

AU - Paietta, Elisabeth

AU - Tallman, Martin S.

AU - Goldstone, Anthony H.

PY - 2014/2/6

Y1 - 2014/2/6

N2 - The Philadelphia chromosome positive arm of the UKALLXII/ECOG2993 study for adult acute lymphoblastic leukemia (ALL) enrolled 266 patients between 1993 and 2003 (preimatinib cohort). In 2003 imatinib was introduced as a single-agent course following induction (N 5 86, late imatinib). In 2005 imatinib was added to the second phase of induction (N 5 89, early imatinib). The complete remission (CR) rate was 92% in the imatinib cohort vs 82% in the preimatinib cohort (P 5 .004). At 4 years, the overall survival (OS) of all patients in the imatinib cohort was 38% vs 22% in the preimatinib cohort (P 5 .003). The magnitude of the difference between the preimatinib and imatinib cohorts in event-free survival (EFS), OS, and relapse-free survival (RFS) seen in univariate analysis was even greater in the multivariate analysis. In the preimatinib cohort, 31% of those starting treatment achieved hematopoietic stem cell transplant (alloHSCT) compared with 46% in the imatinib cohort. A Cox multivariate analysis taking alloHSCT into account showed a modest additional benefit to imatinib (hazard ratio for EFS 5 0.64, 95% confidence interval 0.44-0.93, P 5 .02), but no significant benefit for OS and RFS. Adding imatinib to standard therapy improves CR rate and long-term OS for adults with ALL. A proportion of the OS benefit derives from the fact that imatinib facilitates alloHSCT. This trial was registered at clinicaltrials.gov as NCT00002514.

AB - The Philadelphia chromosome positive arm of the UKALLXII/ECOG2993 study for adult acute lymphoblastic leukemia (ALL) enrolled 266 patients between 1993 and 2003 (preimatinib cohort). In 2003 imatinib was introduced as a single-agent course following induction (N 5 86, late imatinib). In 2005 imatinib was added to the second phase of induction (N 5 89, early imatinib). The complete remission (CR) rate was 92% in the imatinib cohort vs 82% in the preimatinib cohort (P 5 .004). At 4 years, the overall survival (OS) of all patients in the imatinib cohort was 38% vs 22% in the preimatinib cohort (P 5 .003). The magnitude of the difference between the preimatinib and imatinib cohorts in event-free survival (EFS), OS, and relapse-free survival (RFS) seen in univariate analysis was even greater in the multivariate analysis. In the preimatinib cohort, 31% of those starting treatment achieved hematopoietic stem cell transplant (alloHSCT) compared with 46% in the imatinib cohort. A Cox multivariate analysis taking alloHSCT into account showed a modest additional benefit to imatinib (hazard ratio for EFS 5 0.64, 95% confidence interval 0.44-0.93, P 5 .02), but no significant benefit for OS and RFS. Adding imatinib to standard therapy improves CR rate and long-term OS for adults with ALL. A proportion of the OS benefit derives from the fact that imatinib facilitates alloHSCT. This trial was registered at clinicaltrials.gov as NCT00002514.

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