Pediatric-inspired treatment regimens for adolescents and young adults with philadelphia chromosome–negative acute lymphoblastic leukemia: A review

Stuart E. Siegel, Wendy Stock, Rebecca H. Johnson, Anjali Advani, Lori Muffly, Dan Douer, Damon Reed, Mark Lewis, David R. Freyer, Bijal Shah, Selina Luger, Brandon Hayes-Lattin, Jerry Jaboin, Peter F. Coccia, Daniel J. DeAngelo, Nita Seibel, Archie Bleyer

Research output: Contribution to journalReview article

21 Citations (Scopus)

Abstract

IMPORTANCE The incidence of acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) in adolescent and young adult (AYA) patients (age range, 15-39 years) in the United States is increasing at a greater rate than in younger or older persons. Their optimal treatment has been increasingly debated as pediatric regimens have become more widely used in the age group. This review compares the basic features of pediatric and adult chemotherapy regimens for ALL and LBL, recognizes and describes the challenges of the pediatric regimen, and suggests strategies to facilitate its adoption for AYAs with ALL and LBL. OBSERVATIONS All but 2 of 25 published comparisons of outcomes with pediatric and adult regimens for ALL and LBL in AYAs and 1 meta-analysis favor the pediatric regimen. After more than a half-century of clinical trials of the pediatric regimens, including at least 160 phase 3 trials in the United States, the pediatric regimens have become far more complex than most adult regimens. Asparaginase, a critical component of the pediatric regimens, is more difficult to administer to AYAs (and older patients) but nonetheless has a favorable benefit to toxicity ratio for AYAs. A dramatic reduction in outcome of ALL and LBL during the AYA years (the “survival cliff”) is coincident with similar reductions in proportions of AYAs referred to academic centers and enrolled on clinical trials (the “accrual cliff” and “referral cliff”). CONCLUSIONS AND RELEVANCE The accumulating data increasingly support treating AYAs with ALL and LBL with a pediatric-inspired regimen or an approved institutional or national clinical trial tailored for this patient group. A need to develop clinical trials specifically for AYAs and to encourage their participation is paramount, with a goal to improve both the quantity and quality of survival.

Original languageEnglish (US)
Pages (from-to)725-734
Number of pages10
JournalJAMA oncology
Volume4
Issue number5
StatePublished - May 1 2018

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Precursor Cell Lymphoblastic Leukemia-Lymphoma
Young Adult
Pediatrics
Therapeutics
Clinical Trials
Asparaginase
Survival
Meta-Analysis
Referral and Consultation
Age Groups
Drug Therapy

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Siegel, S. E., Stock, W., Johnson, R. H., Advani, A., Muffly, L., Douer, D., ... Bleyer, A. (2018). Pediatric-inspired treatment regimens for adolescents and young adults with philadelphia chromosome–negative acute lymphoblastic leukemia: A review. JAMA oncology, 4(5), 725-734.

Pediatric-inspired treatment regimens for adolescents and young adults with philadelphia chromosome–negative acute lymphoblastic leukemia : A review. / Siegel, Stuart E.; Stock, Wendy; Johnson, Rebecca H.; Advani, Anjali; Muffly, Lori; Douer, Dan; Reed, Damon; Lewis, Mark; Freyer, David R.; Shah, Bijal; Luger, Selina; Hayes-Lattin, Brandon; Jaboin, Jerry; Coccia, Peter F.; DeAngelo, Daniel J.; Seibel, Nita; Bleyer, Archie.

In: JAMA oncology, Vol. 4, No. 5, 01.05.2018, p. 725-734.

Research output: Contribution to journalReview article

Siegel, SE, Stock, W, Johnson, RH, Advani, A, Muffly, L, Douer, D, Reed, D, Lewis, M, Freyer, DR, Shah, B, Luger, S, Hayes-Lattin, B, Jaboin, J, Coccia, PF, DeAngelo, DJ, Seibel, N & Bleyer, A 2018, 'Pediatric-inspired treatment regimens for adolescents and young adults with philadelphia chromosome–negative acute lymphoblastic leukemia: A review', JAMA oncology, vol. 4, no. 5, pp. 725-734.
Siegel, Stuart E. ; Stock, Wendy ; Johnson, Rebecca H. ; Advani, Anjali ; Muffly, Lori ; Douer, Dan ; Reed, Damon ; Lewis, Mark ; Freyer, David R. ; Shah, Bijal ; Luger, Selina ; Hayes-Lattin, Brandon ; Jaboin, Jerry ; Coccia, Peter F. ; DeAngelo, Daniel J. ; Seibel, Nita ; Bleyer, Archie. / Pediatric-inspired treatment regimens for adolescents and young adults with philadelphia chromosome–negative acute lymphoblastic leukemia : A review. In: JAMA oncology. 2018 ; Vol. 4, No. 5. pp. 725-734.
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abstract = "IMPORTANCE The incidence of acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) in adolescent and young adult (AYA) patients (age range, 15-39 years) in the United States is increasing at a greater rate than in younger or older persons. Their optimal treatment has been increasingly debated as pediatric regimens have become more widely used in the age group. This review compares the basic features of pediatric and adult chemotherapy regimens for ALL and LBL, recognizes and describes the challenges of the pediatric regimen, and suggests strategies to facilitate its adoption for AYAs with ALL and LBL. OBSERVATIONS All but 2 of 25 published comparisons of outcomes with pediatric and adult regimens for ALL and LBL in AYAs and 1 meta-analysis favor the pediatric regimen. After more than a half-century of clinical trials of the pediatric regimens, including at least 160 phase 3 trials in the United States, the pediatric regimens have become far more complex than most adult regimens. Asparaginase, a critical component of the pediatric regimens, is more difficult to administer to AYAs (and older patients) but nonetheless has a favorable benefit to toxicity ratio for AYAs. A dramatic reduction in outcome of ALL and LBL during the AYA years (the “survival cliff”) is coincident with similar reductions in proportions of AYAs referred to academic centers and enrolled on clinical trials (the “accrual cliff” and “referral cliff”). CONCLUSIONS AND RELEVANCE The accumulating data increasingly support treating AYAs with ALL and LBL with a pediatric-inspired regimen or an approved institutional or national clinical trial tailored for this patient group. A need to develop clinical trials specifically for AYAs and to encourage their participation is paramount, with a goal to improve both the quantity and quality of survival.",
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AU - Siegel, Stuart E.

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AU - Muffly, Lori

AU - Douer, Dan

AU - Reed, Damon

AU - Lewis, Mark

AU - Freyer, David R.

AU - Shah, Bijal

AU - Luger, Selina

AU - Hayes-Lattin, Brandon

AU - Jaboin, Jerry

AU - Coccia, Peter F.

AU - DeAngelo, Daniel J.

AU - Seibel, Nita

AU - Bleyer, Archie

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N2 - IMPORTANCE The incidence of acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) in adolescent and young adult (AYA) patients (age range, 15-39 years) in the United States is increasing at a greater rate than in younger or older persons. Their optimal treatment has been increasingly debated as pediatric regimens have become more widely used in the age group. This review compares the basic features of pediatric and adult chemotherapy regimens for ALL and LBL, recognizes and describes the challenges of the pediatric regimen, and suggests strategies to facilitate its adoption for AYAs with ALL and LBL. OBSERVATIONS All but 2 of 25 published comparisons of outcomes with pediatric and adult regimens for ALL and LBL in AYAs and 1 meta-analysis favor the pediatric regimen. After more than a half-century of clinical trials of the pediatric regimens, including at least 160 phase 3 trials in the United States, the pediatric regimens have become far more complex than most adult regimens. Asparaginase, a critical component of the pediatric regimens, is more difficult to administer to AYAs (and older patients) but nonetheless has a favorable benefit to toxicity ratio for AYAs. A dramatic reduction in outcome of ALL and LBL during the AYA years (the “survival cliff”) is coincident with similar reductions in proportions of AYAs referred to academic centers and enrolled on clinical trials (the “accrual cliff” and “referral cliff”). CONCLUSIONS AND RELEVANCE The accumulating data increasingly support treating AYAs with ALL and LBL with a pediatric-inspired regimen or an approved institutional or national clinical trial tailored for this patient group. A need to develop clinical trials specifically for AYAs and to encourage their participation is paramount, with a goal to improve both the quantity and quality of survival.

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