Improved early event-free survival with imatinib in Philadelphia chromosome - Positive acute lymphoblastic leukemia

A Children's Oncology Group Study

Kirk R. Schultz, W. Paul Bowman, Alexander Aledo, William B. Slayton, Harland Sather, Meenakshi Devidas, Chenguang Wang, Stella M. Davies, Paul S. Gaynon, Michael Trigg, Robert Rutledge, Laura Burden, Dean Jorstad, Andrew Carroll, Nyla A. Heerema, Naomi Winick, Michael J. Borowitz, Stephen P. Hunger, William L. Carroll, Bruce Camitta

Research output: Contribution to journalArticle

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Abstract

Purpose: Imatinib mesylate is a targeted agent that may be used against Philadelphia chromosome - positive (Ph+) acute lymphoblastic leukemia (ALL), one of the highest risk pediatric ALL groups. Patients and Methods: We evaluated whether imatinib (340 mg/m2/d) with an intensive chemotherapy regimen improved outcome in children ages 1 to 21 years with Ph+ ALL (N = 92) and compared toxicities to Ph- ALL patients (N = 65) given the same chemotherapy without imatinib. Exposure to imatinib was increased progressively in five patient cohorts that received imatinib from 42 (cohort 1; n = 7) to 280 continuous days (cohort 5; n = 50) before maintenance therapy. Patients with human leukocyte antigen (HLA) -identical sibling donors underwent blood and marrow transplantation (BMT) with imatinib given for 6 months following BMT. Results: Continuous imatinib exposure improved outcome in cohort 5 patients with a 3-year event-free survival (EFS) of 80% ± 11% (95% CI, 64% to 90%), more than twice historical controls (35% ± 4%; P < .0001). Three-year EFS was similar for patients in cohort 5 treated with chemotherapy plus imatinib (88% ± 11%; 95% CI, 66% to 96%) or sibling donor BMT (57% ± 22%; 95% CI, 30.4% to 76.1%). There were no significant toxicities associated with adding imatinib to intensive chemotherapy. The higher imatinib dosing in cohort 5 appears to improve survival by having an impact on the outcome of children with a higher burden of minimal residual disease after induction. Conclusion: Imatinib plus intensive chemotherapy improved 3-year EFS in children and adolescents with Ph+ ALL, with no appreciable increase in toxicity. BMT plus imatinib offered no advantage over BMT alone. Additional follow-up is required to determine the impact of this treatment on long-term EFS and determine whether chemotherapy plus imatinib can replace BMT.

Original languageEnglish (US)
Pages (from-to)5175-5181
Number of pages7
JournalJournal of Clinical Oncology
Volume27
Issue number31
DOIs
StatePublished - Nov 1 2009

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Philadelphia Chromosome
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Disease-Free Survival
Transplantation
Bone Marrow
Drug Therapy
Blood Donors
Imatinib Mesylate
Siblings
Residual Neoplasm
HLA Antigens

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

Improved early event-free survival with imatinib in Philadelphia chromosome - Positive acute lymphoblastic leukemia : A Children's Oncology Group Study. / Schultz, Kirk R.; Bowman, W. Paul; Aledo, Alexander; Slayton, William B.; Sather, Harland; Devidas, Meenakshi; Wang, Chenguang; Davies, Stella M.; Gaynon, Paul S.; Trigg, Michael; Rutledge, Robert; Burden, Laura; Jorstad, Dean; Carroll, Andrew; Heerema, Nyla A.; Winick, Naomi; Borowitz, Michael J.; Hunger, Stephen P.; Carroll, William L.; Camitta, Bruce.

In: Journal of Clinical Oncology, Vol. 27, No. 31, 01.11.2009, p. 5175-5181.

Research output: Contribution to journalArticle

Schultz, KR, Bowman, WP, Aledo, A, Slayton, WB, Sather, H, Devidas, M, Wang, C, Davies, SM, Gaynon, PS, Trigg, M, Rutledge, R, Burden, L, Jorstad, D, Carroll, A, Heerema, NA, Winick, N, Borowitz, MJ, Hunger, SP, Carroll, WL & Camitta, B 2009, 'Improved early event-free survival with imatinib in Philadelphia chromosome - Positive acute lymphoblastic leukemia: A Children's Oncology Group Study', Journal of Clinical Oncology, vol. 27, no. 31, pp. 5175-5181. https://doi.org/10.1200/JCO.2008.21.2514
Schultz, Kirk R. ; Bowman, W. Paul ; Aledo, Alexander ; Slayton, William B. ; Sather, Harland ; Devidas, Meenakshi ; Wang, Chenguang ; Davies, Stella M. ; Gaynon, Paul S. ; Trigg, Michael ; Rutledge, Robert ; Burden, Laura ; Jorstad, Dean ; Carroll, Andrew ; Heerema, Nyla A. ; Winick, Naomi ; Borowitz, Michael J. ; Hunger, Stephen P. ; Carroll, William L. ; Camitta, Bruce. / Improved early event-free survival with imatinib in Philadelphia chromosome - Positive acute lymphoblastic leukemia : A Children's Oncology Group Study. In: Journal of Clinical Oncology. 2009 ; Vol. 27, No. 31. pp. 5175-5181.
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abstract = "Purpose: Imatinib mesylate is a targeted agent that may be used against Philadelphia chromosome - positive (Ph+) acute lymphoblastic leukemia (ALL), one of the highest risk pediatric ALL groups. Patients and Methods: We evaluated whether imatinib (340 mg/m2/d) with an intensive chemotherapy regimen improved outcome in children ages 1 to 21 years with Ph+ ALL (N = 92) and compared toxicities to Ph- ALL patients (N = 65) given the same chemotherapy without imatinib. Exposure to imatinib was increased progressively in five patient cohorts that received imatinib from 42 (cohort 1; n = 7) to 280 continuous days (cohort 5; n = 50) before maintenance therapy. Patients with human leukocyte antigen (HLA) -identical sibling donors underwent blood and marrow transplantation (BMT) with imatinib given for 6 months following BMT. Results: Continuous imatinib exposure improved outcome in cohort 5 patients with a 3-year event-free survival (EFS) of 80{\%} ± 11{\%} (95{\%} CI, 64{\%} to 90{\%}), more than twice historical controls (35{\%} ± 4{\%}; P < .0001). Three-year EFS was similar for patients in cohort 5 treated with chemotherapy plus imatinib (88{\%} ± 11{\%}; 95{\%} CI, 66{\%} to 96{\%}) or sibling donor BMT (57{\%} ± 22{\%}; 95{\%} CI, 30.4{\%} to 76.1{\%}). There were no significant toxicities associated with adding imatinib to intensive chemotherapy. The higher imatinib dosing in cohort 5 appears to improve survival by having an impact on the outcome of children with a higher burden of minimal residual disease after induction. Conclusion: Imatinib plus intensive chemotherapy improved 3-year EFS in children and adolescents with Ph+ ALL, with no appreciable increase in toxicity. BMT plus imatinib offered no advantage over BMT alone. Additional follow-up is required to determine the impact of this treatment on long-term EFS and determine whether chemotherapy plus imatinib can replace BMT.",
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T2 - A Children's Oncology Group Study

AU - Schultz, Kirk R.

AU - Bowman, W. Paul

AU - Aledo, Alexander

AU - Slayton, William B.

AU - Sather, Harland

AU - Devidas, Meenakshi

AU - Wang, Chenguang

AU - Davies, Stella M.

AU - Gaynon, Paul S.

AU - Trigg, Michael

AU - Rutledge, Robert

AU - Burden, Laura

AU - Jorstad, Dean

AU - Carroll, Andrew

AU - Heerema, Nyla A.

AU - Winick, Naomi

AU - Borowitz, Michael J.

AU - Hunger, Stephen P.

AU - Carroll, William L.

AU - Camitta, Bruce

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N2 - Purpose: Imatinib mesylate is a targeted agent that may be used against Philadelphia chromosome - positive (Ph+) acute lymphoblastic leukemia (ALL), one of the highest risk pediatric ALL groups. Patients and Methods: We evaluated whether imatinib (340 mg/m2/d) with an intensive chemotherapy regimen improved outcome in children ages 1 to 21 years with Ph+ ALL (N = 92) and compared toxicities to Ph- ALL patients (N = 65) given the same chemotherapy without imatinib. Exposure to imatinib was increased progressively in five patient cohorts that received imatinib from 42 (cohort 1; n = 7) to 280 continuous days (cohort 5; n = 50) before maintenance therapy. Patients with human leukocyte antigen (HLA) -identical sibling donors underwent blood and marrow transplantation (BMT) with imatinib given for 6 months following BMT. Results: Continuous imatinib exposure improved outcome in cohort 5 patients with a 3-year event-free survival (EFS) of 80% ± 11% (95% CI, 64% to 90%), more than twice historical controls (35% ± 4%; P < .0001). Three-year EFS was similar for patients in cohort 5 treated with chemotherapy plus imatinib (88% ± 11%; 95% CI, 66% to 96%) or sibling donor BMT (57% ± 22%; 95% CI, 30.4% to 76.1%). There were no significant toxicities associated with adding imatinib to intensive chemotherapy. The higher imatinib dosing in cohort 5 appears to improve survival by having an impact on the outcome of children with a higher burden of minimal residual disease after induction. Conclusion: Imatinib plus intensive chemotherapy improved 3-year EFS in children and adolescents with Ph+ ALL, with no appreciable increase in toxicity. BMT plus imatinib offered no advantage over BMT alone. Additional follow-up is required to determine the impact of this treatment on long-term EFS and determine whether chemotherapy plus imatinib can replace BMT.

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