Outcomes in Children, Adolescents, and Young Adults With Down Syndrome and ALL: A Report From the Children's Oncology Group

Karen R. Rabin; Meenakshi Devidas; Zhiguo Chen; Lingyun Ji; John Kairalla; Johann K. Hitzler; Jun J. Yang; Andrew J. Carroll; Nyla A. Heerema; Michael J. Borowitz; Brent L. Wood; Kathryn G. Roberts; Charles G. Mullighan; Richard C. Harvey; I. Ming Chen; Cheryl L. Willman; Shalini C. Reshmi; Julie M. Gastier-Foster; Deepa Bhojwani; Susan R. Rheingold; Kelly W. Maloney; Leonard A. Mattano; Eric C. Larsen; Reuven J. Schore; Michael J. Burke; Wanda L. Salzer; Naomi J. Winick; William L. Carroll; Elizabeth A. Raetz; Mignon L. Loh; Stephen P. Hunger; Anne L. Angiolillo

doi:10.1200/JCO.23.00389

Outcomes in Children, Adolescents, and Young Adults With Down Syndrome and ALL: A Report From the Children's Oncology Group

Karen R. Rabin, Meenakshi Devidas, Zhiguo Chen, Lingyun Ji, John Kairalla, Johann K. Hitzler, Jun J. Yang, Andrew J. Carroll, Nyla A. Heerema, Michael J. Borowitz, Brent L. Wood, Kathryn G. Roberts, Charles G. Mullighan, Richard C. Harvey, I. Ming Chen, Cheryl L. Willman, Shalini C. Reshmi, Julie M. Gastier-Foster, Deepa Bhojwani, Susan R. RheingoldKelly W. Maloney, Leonard A. Mattano, Eric C. Larsen, Reuven J. Schore, Michael J. Burke, Wanda L. Salzer, Naomi J. Winick, William L. Carroll, Elizabeth A. Raetz, Mignon L. Loh, Stephen P. Hunger, Anne L. Angiolillo

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Abstract

PURPOSE Patients with Down syndrome (DS) and B-ALL experience increased rates of relapse, toxicity, and death. We report results for patients with DS B-ALL enrolled on Children's Oncology Group trials between 2003 and 2019. METHODS We analyzed data for DS (n = 743) and non-DS (n = 20,067) patients age 1-30 years on four B-ALL standard-risk (SR) and high-risk trials. RESULTS Patients with DS exhibitedmore frequentminimal residual disease (MRD). 0.01% at end induction (30.8% v 21.5%; P <. 001). This difference persisted at end consolidation only in National Cancer Institute (NCI) high-risk patients (34.0% v 11.7%; P <. 0001). Five-year event-free survival (EFS) and overall survival (OS) were significantly poorer for DS versus non-DS patients overall (EFS, 79.2% ± 1.6% v 87.5% ± 0.3%; P <. 0001; OS, 86.8% ± 1.4% v 93.6% ± 0.2%; P <. 0001), andwithinNCI SR and high-risk subgroups. Multivariable Cox regression analysis of the DS cohort for risk factors associated with inferior EFS identified age >10 years, white blood count >50 3103/mL, and end-induction MRD ≥0.01%, but not cytogenetics or CRLF2 overexpression. Patients with DS demonstrated higher 5-year cumulative incidence of relapse (11.5% ± 1.2% v 9.1% ± 0.2%; P =. 0008), death in remission (4.9% ± 0.8% v 1.7% ± 0.1%; P <. 0001), and induction death (3.4% v 0.8%; P <. 0001). Mucositis, infections, and hyperglycemia were significantlymore frequent in all patients with DS, while seizures were more frequent in patients with DS on high-risk trials (4.1% v 1.8%; P =. 005). CONCLUSION Patients with DS-ALL exhibit an increased rate of relapse and particularly of treatment-related mortality. Novel, less-toxic therapeutic strategies are needed to improve outcomes.

Original language	English
Pages (from-to)	218-227
Number of pages	10
Journal	Journal of Clinical Oncology
Volume	42
Issue number	2
DOIs	https://doi.org/10.1200/JCO.23.00389
State	Published - 10 Jan 2024
Externally published	Yes

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Rabin, K. R., Devidas, M., Chen, Z., Ji, L., Kairalla, J., Hitzler, J. K., Yang, J. J., Carroll, A. J., Heerema, N. A., Borowitz, M. J., Wood, B. L., Roberts, K. G., Mullighan, C. G., Harvey, R. C., Chen, I. M., Willman, C. L., Reshmi, S. C., Gastier-Foster, J. M., Bhojwani, D., ... Angiolillo, A. L. (2024). Outcomes in Children, Adolescents, and Young Adults With Down Syndrome and ALL: A Report From the Children's Oncology Group. Journal of Clinical Oncology, 42(2), 218-227. https://doi.org/10.1200/JCO.23.00389

@article{fd4015920a7f4b18bd2fbcb448ae395a,

title = "Outcomes in Children, Adolescents, and Young Adults With Down Syndrome and ALL: A Report From the Children's Oncology Group",

abstract = "PURPOSE Patients with Down syndrome (DS) and B-ALL experience increased rates of relapse, toxicity, and death. We report results for patients with DS B-ALL enrolled on Children's Oncology Group trials between 2003 and 2019. METHODS We analyzed data for DS (n = 743) and non-DS (n = 20,067) patients age 1-30 years on four B-ALL standard-risk (SR) and high-risk trials. RESULTS Patients with DS exhibitedmore frequentminimal residual disease (MRD). 0.01% at end induction (30.8% v 21.5%; P <. 001). This difference persisted at end consolidation only in National Cancer Institute (NCI) high-risk patients (34.0% v 11.7%; P <. 0001). Five-year event-free survival (EFS) and overall survival (OS) were significantly poorer for DS versus non-DS patients overall (EFS, 79.2% ± 1.6% v 87.5% ± 0.3%; P <. 0001; OS, 86.8% ± 1.4% v 93.6% ± 0.2%; P <. 0001), andwithinNCI SR and high-risk subgroups. Multivariable Cox regression analysis of the DS cohort for risk factors associated with inferior EFS identified age >10 years, white blood count >50 3103/mL, and end-induction MRD ≥0.01%, but not cytogenetics or CRLF2 overexpression. Patients with DS demonstrated higher 5-year cumulative incidence of relapse (11.5% ± 1.2% v 9.1% ± 0.2%; P =. 0008), death in remission (4.9% ± 0.8% v 1.7% ± 0.1%; P <. 0001), and induction death (3.4% v 0.8%; P <. 0001). Mucositis, infections, and hyperglycemia were significantlymore frequent in all patients with DS, while seizures were more frequent in patients with DS on high-risk trials (4.1% v 1.8%; P =. 005). CONCLUSION Patients with DS-ALL exhibit an increased rate of relapse and particularly of treatment-related mortality. Novel, less-toxic therapeutic strategies are needed to improve outcomes.",

author = "Rabin, {Karen R.} and Meenakshi Devidas and Zhiguo Chen and Lingyun Ji and John Kairalla and Hitzler, {Johann K.} and Yang, {Jun J.} and Carroll, {Andrew J.} and Heerema, {Nyla A.} and Borowitz, {Michael J.} and Wood, {Brent L.} and Roberts, {Kathryn G.} and Mullighan, {Charles G.} and Harvey, {Richard C.} and Chen, {I. Ming} and Willman, {Cheryl L.} and Reshmi, {Shalini C.} and Gastier-Foster, {Julie M.} and Deepa Bhojwani and Rheingold, {Susan R.} and Maloney, {Kelly W.} and Mattano, {Leonard A.} and Larsen, {Eric C.} and Schore, {Reuven J.} and Burke, {Michael J.} and Salzer, {Wanda L.} and Winick, {Naomi J.} and Carroll, {William L.} and Raetz, {Elizabeth A.} and Loh, {Mignon L.} and Hunger, {Stephen P.} and Angiolillo, {Anne L.}",

note = "Publisher Copyright: {\textcopyright} 2023 by American Society of Clinical Oncology.",

year = "2024",

month = jan,

day = "10",

doi = "10.1200/JCO.23.00389",

language = "English",

volume = "42",

pages = "218--227",

journal = "Journal of Clinical Oncology",

issn = "0732-183X",

publisher = "American Society of Clinical Oncology",

number = "2",

}

Rabin, KR, Devidas, M, Chen, Z, Ji, L, Kairalla, J, Hitzler, JK, Yang, JJ, Carroll, AJ, Heerema, NA, Borowitz, MJ, Wood, BL, Roberts, KG, Mullighan, CG, Harvey, RC, Chen, IM, Willman, CL, Reshmi, SC, Gastier-Foster, JM, Bhojwani, D, Rheingold, SR, Maloney, KW, Mattano, LA, Larsen, EC, Schore, RJ, Burke, MJ, Salzer, WL, Winick, NJ, Carroll, WL, Raetz, EA, Loh, ML, Hunger, SP & Angiolillo, AL 2024, 'Outcomes in Children, Adolescents, and Young Adults With Down Syndrome and ALL: A Report From the Children's Oncology Group', Journal of Clinical Oncology, vol. 42, no. 2, pp. 218-227. https://doi.org/10.1200/JCO.23.00389

TY - JOUR

T1 - Outcomes in Children, Adolescents, and Young Adults With Down Syndrome and ALL

T2 - A Report From the Children's Oncology Group

AU - Rabin, Karen R.

AU - Devidas, Meenakshi

AU - Chen, Zhiguo

AU - Ji, Lingyun

AU - Kairalla, John

AU - Hitzler, Johann K.

AU - Yang, Jun J.

AU - Carroll, Andrew J.

AU - Heerema, Nyla A.

AU - Borowitz, Michael J.

AU - Wood, Brent L.

AU - Roberts, Kathryn G.

AU - Mullighan, Charles G.

AU - Harvey, Richard C.

AU - Chen, I. Ming

AU - Willman, Cheryl L.

AU - Reshmi, Shalini C.

AU - Gastier-Foster, Julie M.

AU - Bhojwani, Deepa

AU - Rheingold, Susan R.

AU - Maloney, Kelly W.

AU - Mattano, Leonard A.

AU - Larsen, Eric C.

AU - Schore, Reuven J.

AU - Burke, Michael J.

AU - Salzer, Wanda L.

AU - Winick, Naomi J.

AU - Carroll, William L.

AU - Raetz, Elizabeth A.

AU - Loh, Mignon L.

AU - Hunger, Stephen P.

AU - Angiolillo, Anne L.

PY - 2024/1/10

Y1 - 2024/1/10

N2 - PURPOSE Patients with Down syndrome (DS) and B-ALL experience increased rates of relapse, toxicity, and death. We report results for patients with DS B-ALL enrolled on Children's Oncology Group trials between 2003 and 2019. METHODS We analyzed data for DS (n = 743) and non-DS (n = 20,067) patients age 1-30 years on four B-ALL standard-risk (SR) and high-risk trials. RESULTS Patients with DS exhibitedmore frequentminimal residual disease (MRD). 0.01% at end induction (30.8% v 21.5%; P <. 001). This difference persisted at end consolidation only in National Cancer Institute (NCI) high-risk patients (34.0% v 11.7%; P <. 0001). Five-year event-free survival (EFS) and overall survival (OS) were significantly poorer for DS versus non-DS patients overall (EFS, 79.2% ± 1.6% v 87.5% ± 0.3%; P <. 0001; OS, 86.8% ± 1.4% v 93.6% ± 0.2%; P <. 0001), andwithinNCI SR and high-risk subgroups. Multivariable Cox regression analysis of the DS cohort for risk factors associated with inferior EFS identified age >10 years, white blood count >50 3103/mL, and end-induction MRD ≥0.01%, but not cytogenetics or CRLF2 overexpression. Patients with DS demonstrated higher 5-year cumulative incidence of relapse (11.5% ± 1.2% v 9.1% ± 0.2%; P =. 0008), death in remission (4.9% ± 0.8% v 1.7% ± 0.1%; P <. 0001), and induction death (3.4% v 0.8%; P <. 0001). Mucositis, infections, and hyperglycemia were significantlymore frequent in all patients with DS, while seizures were more frequent in patients with DS on high-risk trials (4.1% v 1.8%; P =. 005). CONCLUSION Patients with DS-ALL exhibit an increased rate of relapse and particularly of treatment-related mortality. Novel, less-toxic therapeutic strategies are needed to improve outcomes.

AB - PURPOSE Patients with Down syndrome (DS) and B-ALL experience increased rates of relapse, toxicity, and death. We report results for patients with DS B-ALL enrolled on Children's Oncology Group trials between 2003 and 2019. METHODS We analyzed data for DS (n = 743) and non-DS (n = 20,067) patients age 1-30 years on four B-ALL standard-risk (SR) and high-risk trials. RESULTS Patients with DS exhibitedmore frequentminimal residual disease (MRD). 0.01% at end induction (30.8% v 21.5%; P <. 001). This difference persisted at end consolidation only in National Cancer Institute (NCI) high-risk patients (34.0% v 11.7%; P <. 0001). Five-year event-free survival (EFS) and overall survival (OS) were significantly poorer for DS versus non-DS patients overall (EFS, 79.2% ± 1.6% v 87.5% ± 0.3%; P <. 0001; OS, 86.8% ± 1.4% v 93.6% ± 0.2%; P <. 0001), andwithinNCI SR and high-risk subgroups. Multivariable Cox regression analysis of the DS cohort for risk factors associated with inferior EFS identified age >10 years, white blood count >50 3103/mL, and end-induction MRD ≥0.01%, but not cytogenetics or CRLF2 overexpression. Patients with DS demonstrated higher 5-year cumulative incidence of relapse (11.5% ± 1.2% v 9.1% ± 0.2%; P =. 0008), death in remission (4.9% ± 0.8% v 1.7% ± 0.1%; P <. 0001), and induction death (3.4% v 0.8%; P <. 0001). Mucositis, infections, and hyperglycemia were significantlymore frequent in all patients with DS, while seizures were more frequent in patients with DS on high-risk trials (4.1% v 1.8%; P =. 005). CONCLUSION Patients with DS-ALL exhibit an increased rate of relapse and particularly of treatment-related mortality. Novel, less-toxic therapeutic strategies are needed to improve outcomes.

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U2 - 10.1200/JCO.23.00389

DO - 10.1200/JCO.23.00389

M3 - Article

C2 - 37890117

AN - SCOPUS:85181760556

SN - 0732-183X

VL - 42

SP - 218

EP - 227

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

IS - 2

ER -

Outcomes in Children, Adolescents, and Young Adults With Down Syndrome and ALL: A Report From the Children's Oncology Group

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