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

Section editor
	David Noyd, MD, MPH University of Washington Seattle, WA, USA LinkedIn

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 4 variants on this page

Guidelines

NCCN

• NCCN does not have guidelines at this granular level; please see NCCN Guidelines - Pediatric Acute Lymphoblastic Leukemia.

Upfront induction therapy

Daunorubicin, Pegaspargase, Vincristine, Prednisone, Dasatinib

Regimen

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

• Daunorubicin (Cerubidine)
• Pegaspargase (Oncaspar)
• Vincristine (Oncovin)

Glucocorticoid therapy

• Prednisone (Sterapred)

Targeted therapy

• Dasatinib (Sprycel) 80 mg/m²/day PO

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: 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

• Daunorubicin (Cerubidine)
• Pegaspargase (Oncaspar)
• Vincristine (Oncovin)

Glucocorticoid therapy

• Prednisone (Sterapred)

Targeted therapy

• Imatinib (Gleevec) 300 mg/m²/day PO

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

• Etoposide (Vepesid) 100 mg/m² IV (schedule not specified)
• Ifosfamide (Ifex) 3400 mg/m² IV (schedule not specified)

Targeted therapy

• Imatinib (Gleevec) 340 mg/m² PO once per day

Supportive therapy

• Filgrastim (Neupogen) 5 mcg/kg SC once per day on days 6 to 15

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

Chemotherapy

• Cyclophosphamide (Cytoxan)
• Mercaptopurine (6-MP)
• Cytarabine (Ara-C)

Targeted therapy

• Imatinib (Gleevec)

CNS therapy, prophylaxis

• Methotrexate (MTX)

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