B-cell acute lymphoblastic leukemia, pediatric, Ph-positive

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David Noyd, MD, MPH
University of Washington
Seattle, WA, USA

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This page contains studies that were specific to pediatric populations. For the more general pediatric B-ALL page, follow this link. For the more general Ph+ B-ALL page, follow this link.

4 regimens on this page
5 variants on this page


Guidelines

Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.

NCCN

Upfront induction therapy

Daunorubicin, Pegaspargase, Vincristine, Prednisone, Dasatinib

Regimen variant #1, 60 mg/m2

Study Dates of enrollment Evidence
Hunger et al. 2023 (COG AALL1122) 2012-03-13 to 2014-05-27 Phase 2 (RT)

Note: Minimal details were available in the abstract.

Chemotherapy

Glucocorticoid therapy

Targeted therapy

28-day course

Subsequent treatment

  • See paper for details


Regimen variant #2, 80 mg/m2

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Shen et al. 2020 (CCCG-ALL-2015-Ph) 2015-2018 Phase 3 (E-switch-ic) Daunorubicin, Pegaspargase, Vincristine, Prednisone, Imatinib Superior EFS (primary endpoint)

Chemotherapy

Glucocorticoid therapy

Targeted therapy

28-day course

Subsequent treatment

  • See paper for details

References

  1. CCCG-ALL-2015-Ph: Shen S, Chen X, Cai J, Yu J, Gao J, Hu S, Zhai X, Liang C, Ju X, Jiang H, Jin R, Wu X, Wang N, Tian X, Pan K, Jiang H, Sun L, Fang Y, Li CK, Hu Q, Yang M, Zhu Y, Zhang H, Li C, Pei D, Jeha S, Yang JJ, Cheng C, Tang J, Zhu X, Pui CH. Effect of Dasatinib vs Imatinib in the Treatment of Pediatric Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: A Randomized Clinical Trial. JAMA Oncol. 2020 Mar 1;6(3):358-366. Epub 2020 Jan 16. link to original article link to PMC article PubMed ChiCTR-IPR-14005706
  2. COG AALL1122: Hunger SP, Tran TH, Saha V, Devidas M, Valsecchi MG, Gastier-Foster JM, Cazzaniga G, Reshmi SC, Borowitz MJ, Moorman AV, Heerema NA, Carroll AJ, Martin-Regueira P, Loh ML, Raetz EA, Schultz KR, Slayton WB, Cario G, Schrappe M, Silverman LB, Biondi A. Dasatinib with intensive chemotherapy in de novo paediatric Philadelphia chromosome-positive acute lymphoblastic leukaemia (CA180-372/COG AALL1122): a single-arm, multicentre, phase 2 trial. Lancet Haematol. 2023 Jul;10(7):e510-e520. link to original article contains partial dosing details in abstract PubMed NCT01460160

Daunorubicin, Pegaspargase, Vincristine, Prednisone, Imatinib

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Shen et al. 2020 (CCCG-ALL-2015-Ph) 2015-2018 Phase 3 (C) Daunorubicin, Pegaspargase, Vincristine, Prednisone, Dasatinib Inferior EFS

Chemotherapy

Glucocorticoid therapy

Targeted therapy

28-day course

Subsequent treatment

  • See paper for details

References

  1. CCCG-ALL-2015-Ph: Shen S, Chen X, Cai J, Yu J, Gao J, Hu S, Zhai X, Liang C, Ju X, Jiang H, Jin R, Wu X, Wang N, Tian X, Pan K, Jiang H, Sun L, Fang Y, Li CK, Hu Q, Yang M, Zhu Y, Zhang H, Li C, Pei D, Jeha S, Yang JJ, Cheng C, Tang J, Zhu X, Pui CH. Effect of Dasatinib vs Imatinib in the Treatment of Pediatric Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: A Randomized Clinical Trial. JAMA Oncol. 2020 Mar 1;6(3):358-366. Epub 2020 Jan 16. link to original article link to PMC article PubMed ChiCTR-IPR-14005706

Consolidation after upfront therapy (including post-remission therapy)

Note that many of these regimens are complex and as such will be referred to by their study name, not by the individual drug names. This is also a phase of treatment often referred to as post-remission or postinduction therapy.

Etoposide, Ifosfamide, Imatinib

Regimen

Study Dates of enrollment Evidence
Schultz et al. 2009 (COG AALL0031) 2002-2006 Phase 2 (RT)

Note: the schedule is not specified for etoposide and ifosfamide, and the filgrastim dose is erroneous within the manuscript.

Preceding treatment

  • Induction (see paper for details)

Chemotherapy

Targeted therapy

Supportive therapy

21-day course

Subsequent treatment

  • Consolidation block 2 (see paper for details)

References

  1. COG AALL0031: 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. Improved early event-free survival with imatinib in Philadelphia chromosome-positive acute lymphoblastic leukemia: a Children's Oncology Group study. J Clin Oncol. 2009 Nov 1;27(31):5175-81. Epub 2009 Oct 5. link to original article link to PMC article PubMed NCT00022737
    1. Update: Schultz KR, Carroll A, Heerema NA, Bowman WP, Aledo A, Slayton WB, Sather H, Devidas M, Zheng HW, Davies SM, Gaynon PS, Trigg M, Rutledge R, Jorstad D, Winick N, Borowitz MJ, Hunger SP, Carroll WL, Camitta B; Children’s Oncology Group. Long-term follow-up of imatinib in pediatric Philadelphia chromosome-positive acute lymphoblastic leukemia: Children's Oncology Group study AALL0031. Leukemia. 2014 Jul;28(7):1467-71. Epub 2014 Jan 20. link to original article link to PMC article PubMed

Imatinib-based consolidation

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Biondi et al. 2012 (EsPhALL) 2004-2009 Phase 3 (E-esc) No imatinib in consolidation Did not meet primary endpoint of DFS481

1This regimen did not meet the primary efficacy endpoint in the ITT population, but there was a possible signal in the as-treated population.
See paper for details beyond "IB". To be completed (?)

Preceding treatment

  • Berlin–Frankfurt–Munster high-risk backbone

References

  1. EsPhALL: Biondi A, Schrappe M, De Lorenzo P, Castor A, Lucchini G, Gandemer V, Pieters R, Stary J, Escherich G, Campbell M, Li CK, Vora A, Aricò M, Röttgers S, Saha V, Valsecchi MG. Imatinib after induction for treatment of children and adolescents with Philadelphia-chromosome-positive acute lymphoblastic leukaemia (EsPhALL): a randomised, open-label, intergroup study. Lancet Oncol. 2012 Sep;13(9):936-45. Epub 2012 Aug 14. link to original article link to PMC article PubMed NCT00287105