Determinants of survival after first relapse of acute lymphoblastic leukemia: a Children’s Oncology Group study

Susan R. Rheingold; Deepa Bhojwani; Lingyun Ji; Xinxin Xu; Meenakshi Devidas; John A. Kairalla; Mary Shago; Nyla A. Heerema; Andrew J. Carroll; Heather Breidenbach; Michael Borowitz; Brent L. Wood; Anne L. Angiolillo; Barbara L. Asselin; W. Paul Bowman; Patrick Brown; Zo Ann E. Dreyer; Kimberly P. Dunsmore; Joanne M. Hilden; Eric Larsen; Kelly Maloney; Yousif Matloub; Leonard A. Mattano; Stuart S. Winter; Lia Gore; Naomi J. Winick; William L. Carroll; Stephen P. Hunger; Elizabeth A. Raetz; Mignon L. Loh

doi:10.1038/s41375-024-02395-4

Determinants of survival after first relapse of acute lymphoblastic leukemia: a Children’s Oncology Group study

Susan R. Rheingold, Deepa Bhojwani, Lingyun Ji, Xinxin Xu, Meenakshi Devidas, John A. Kairalla, Mary Shago, Nyla A. Heerema, Andrew J. Carroll, Heather Breidenbach, Michael Borowitz, Brent L. Wood, Anne L. Angiolillo, Barbara L. Asselin, W. Paul Bowman, Patrick Brown, Zo Ann E. Dreyer, Kimberly P. Dunsmore, Joanne M. Hilden, Eric LarsenKelly Maloney, Yousif Matloub, Leonard A. Mattano, Stuart S. Winter, Lia Gore, Naomi J. Winick, William L. Carroll, Stephen P. Hunger, Elizabeth A. Raetz, Mignon L. Loh

Research output: Contribution to journal › Article › peer-review

Abstract

Limited prognostic factors have been associated with overall survival (OS) post-relapse in childhood Acute Lymphoblastic Leukemia (ALL). Patients enrolled on 12 Children’s Oncology Group frontline ALL trials (1996–2014) were analyzed to assess for additional prognostic factors associated with OS post-relapse. Among 16,115 patients, 2053 (12.7%) relapsed. Relapse rates were similar for B-ALL (12.5%) and T-ALL (11.2%) while higher for infants (34.2%). Approximately 50% of B-ALL relapses occurred late (≥36 months) and 72.5% involved the marrow. Conversely, 64.8% of T-ALL relapses occurred early (<18 months) and 47.1% involved the central nervous system. The 5-year OS post-relapse for the entire cohort was 48.9 ± 1.2%; B-ALL:52.5 ± 1.3%, T-ALL:35.5 ± 3.3%, and infant ALL:21.5 ± 3.9%. OS varied by early, intermediate and late time-to-relapse; 25.8 ± 2.4%, 49.5 ± 2.2%, and 66.4 ± 1.8% respectively for B-ALL and 29.8 ± 3.9%, 33.3 ± 7.6%, 58 ± 9.8% for T-ALL. Patients with ETV6::RUNX1 or Trisomy 4 + 10 had median time-to-relapse of 43 months and higher OS post-relapse 74.4 ± 3.1% and 70.2 ± 3.6%, respectively. Patients with hypodiploidy, KMT2A-rearrangement, and TCF3::PBX1 had short median time-to-relapse (12.5-18 months) and poor OS post-relapse (14.2 ± 6.1%, 31.9 ± 7.7%, 36.8 ± 6.6%). Site-of-relapse varied by cytogenetic subtype. This large dataset provided the opportunity to identify risk factors for OS post-relapse to inform trial design and highlight populations with dismal outcomes post-relapse.

Original language	English (US)
Pages (from-to)	2382-2394
Number of pages	13
Journal	Leukemia
Volume	38
Issue number	11
DOIs	https://doi.org/10.1038/s41375-024-02395-4
State	Published - Nov 2024
Externally published	Yes

ASJC Scopus subject areas

Hematology
Oncology
Cancer Research

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10.1038/s41375-024-02395-4

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Rheingold, S. R., Bhojwani, D., Ji, L., Xu, X., Devidas, M., Kairalla, J. A., Shago, M., Heerema, N. A., Carroll, A. J., Breidenbach, H., Borowitz, M., Wood, B. L., Angiolillo, A. L., Asselin, B. L., Bowman, W. P., Brown, P., Dreyer, Z. A. E., Dunsmore, K. P., Hilden, J. M., ... Loh, M. L. (2024). Determinants of survival after first relapse of acute lymphoblastic leukemia: a Children’s Oncology Group study. Leukemia, 38(11), 2382-2394. https://doi.org/10.1038/s41375-024-02395-4

Rheingold, SR, Bhojwani, D, Ji, L, Xu, X, Devidas, M, Kairalla, JA, Shago, M, Heerema, NA, Carroll, AJ, Breidenbach, H, Borowitz, M, Wood, BL, Angiolillo, AL, Asselin, BL, Bowman, WP, Brown, P, Dreyer, ZAE, Dunsmore, KP, Hilden, JM, Larsen, E, Maloney, K, Matloub, Y, Mattano, LA, Winter, SS, Gore, L, Winick, NJ, Carroll, WL, Hunger, SP, Raetz, EA & Loh, ML 2024, 'Determinants of survival after first relapse of acute lymphoblastic leukemia: a Children’s Oncology Group study', Leukemia, vol. 38, no. 11, pp. 2382-2394. https://doi.org/10.1038/s41375-024-02395-4

@article{e8535b09ad6443ffbb9ce18e547cfef4,

title = "Determinants of survival after first relapse of acute lymphoblastic leukemia: a Children{\textquoteright}s Oncology Group study",

abstract = "Limited prognostic factors have been associated with overall survival (OS) post-relapse in childhood Acute Lymphoblastic Leukemia (ALL). Patients enrolled on 12 Children{\textquoteright}s Oncology Group frontline ALL trials (1996–2014) were analyzed to assess for additional prognostic factors associated with OS post-relapse. Among 16,115 patients, 2053 (12.7%) relapsed. Relapse rates were similar for B-ALL (12.5%) and T-ALL (11.2%) while higher for infants (34.2%). Approximately 50% of B-ALL relapses occurred late (≥36 months) and 72.5% involved the marrow. Conversely, 64.8% of T-ALL relapses occurred early (<18 months) and 47.1% involved the central nervous system. The 5-year OS post-relapse for the entire cohort was 48.9 ± 1.2%; B-ALL:52.5 ± 1.3%, T-ALL:35.5 ± 3.3%, and infant ALL:21.5 ± 3.9%. OS varied by early, intermediate and late time-to-relapse; 25.8 ± 2.4%, 49.5 ± 2.2%, and 66.4 ± 1.8% respectively for B-ALL and 29.8 ± 3.9%, 33.3 ± 7.6%, 58 ± 9.8% for T-ALL. Patients with ETV6::RUNX1 or Trisomy 4 + 10 had median time-to-relapse of 43 months and higher OS post-relapse 74.4 ± 3.1% and 70.2 ± 3.6%, respectively. Patients with hypodiploidy, KMT2A-rearrangement, and TCF3::PBX1 had short median time-to-relapse (12.5-18 months) and poor OS post-relapse (14.2 ± 6.1%, 31.9 ± 7.7%, 36.8 ± 6.6%). Site-of-relapse varied by cytogenetic subtype. This large dataset provided the opportunity to identify risk factors for OS post-relapse to inform trial design and highlight populations with dismal outcomes post-relapse.",

author = "Rheingold, {Susan R.} and Deepa Bhojwani and Lingyun Ji and Xinxin Xu and Meenakshi Devidas and Kairalla, {John A.} and Mary Shago and Heerema, {Nyla A.} and Carroll, {Andrew J.} and Heather Breidenbach and Michael Borowitz and Wood, {Brent L.} and Angiolillo, {Anne L.} and Asselin, {Barbara L.} and Bowman, {W. Paul} and Patrick Brown and Dreyer, {Zo Ann E.} and Dunsmore, {Kimberly P.} and Hilden, {Joanne M.} and Eric Larsen and Kelly Maloney and Yousif Matloub and Mattano, {Leonard A.} and Winter, {Stuart S.} and Lia Gore and Winick, {Naomi J.} and Carroll, {William L.} and Hunger, {Stephen P.} and Raetz, {Elizabeth A.} and Loh, {Mignon L.}",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2024.",

year = "2024",

month = nov,

doi = "10.1038/s41375-024-02395-4",

language = "English (US)",

volume = "38",

pages = "2382--2394",

journal = "Leukemia",

issn = "0887-6924",

publisher = "Springer Nature",

number = "11",

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TY - JOUR

T1 - Determinants of survival after first relapse of acute lymphoblastic leukemia

T2 - a Children’s Oncology Group study

AU - Rheingold, Susan R.

AU - Bhojwani, Deepa

AU - Ji, Lingyun

AU - Xu, Xinxin

AU - Devidas, Meenakshi

AU - Kairalla, John A.

AU - Shago, Mary

AU - Heerema, Nyla A.

AU - Carroll, Andrew J.

AU - Breidenbach, Heather

AU - Borowitz, Michael

AU - Wood, Brent L.

AU - Angiolillo, Anne L.

AU - Asselin, Barbara L.

AU - Bowman, W. Paul

AU - Brown, Patrick

AU - Dreyer, Zo Ann E.

AU - Dunsmore, Kimberly P.

AU - Hilden, Joanne M.

AU - Larsen, Eric

AU - Maloney, Kelly

AU - Matloub, Yousif

AU - Mattano, Leonard A.

AU - Winter, Stuart S.

AU - Gore, Lia

AU - Winick, Naomi J.

AU - Carroll, William L.

AU - Hunger, Stephen P.

AU - Raetz, Elizabeth A.

AU - Loh, Mignon L.

PY - 2024/11

Y1 - 2024/11

N2 - Limited prognostic factors have been associated with overall survival (OS) post-relapse in childhood Acute Lymphoblastic Leukemia (ALL). Patients enrolled on 12 Children’s Oncology Group frontline ALL trials (1996–2014) were analyzed to assess for additional prognostic factors associated with OS post-relapse. Among 16,115 patients, 2053 (12.7%) relapsed. Relapse rates were similar for B-ALL (12.5%) and T-ALL (11.2%) while higher for infants (34.2%). Approximately 50% of B-ALL relapses occurred late (≥36 months) and 72.5% involved the marrow. Conversely, 64.8% of T-ALL relapses occurred early (<18 months) and 47.1% involved the central nervous system. The 5-year OS post-relapse for the entire cohort was 48.9 ± 1.2%; B-ALL:52.5 ± 1.3%, T-ALL:35.5 ± 3.3%, and infant ALL:21.5 ± 3.9%. OS varied by early, intermediate and late time-to-relapse; 25.8 ± 2.4%, 49.5 ± 2.2%, and 66.4 ± 1.8% respectively for B-ALL and 29.8 ± 3.9%, 33.3 ± 7.6%, 58 ± 9.8% for T-ALL. Patients with ETV6::RUNX1 or Trisomy 4 + 10 had median time-to-relapse of 43 months and higher OS post-relapse 74.4 ± 3.1% and 70.2 ± 3.6%, respectively. Patients with hypodiploidy, KMT2A-rearrangement, and TCF3::PBX1 had short median time-to-relapse (12.5-18 months) and poor OS post-relapse (14.2 ± 6.1%, 31.9 ± 7.7%, 36.8 ± 6.6%). Site-of-relapse varied by cytogenetic subtype. This large dataset provided the opportunity to identify risk factors for OS post-relapse to inform trial design and highlight populations with dismal outcomes post-relapse.

AB - Limited prognostic factors have been associated with overall survival (OS) post-relapse in childhood Acute Lymphoblastic Leukemia (ALL). Patients enrolled on 12 Children’s Oncology Group frontline ALL trials (1996–2014) were analyzed to assess for additional prognostic factors associated with OS post-relapse. Among 16,115 patients, 2053 (12.7%) relapsed. Relapse rates were similar for B-ALL (12.5%) and T-ALL (11.2%) while higher for infants (34.2%). Approximately 50% of B-ALL relapses occurred late (≥36 months) and 72.5% involved the marrow. Conversely, 64.8% of T-ALL relapses occurred early (<18 months) and 47.1% involved the central nervous system. The 5-year OS post-relapse for the entire cohort was 48.9 ± 1.2%; B-ALL:52.5 ± 1.3%, T-ALL:35.5 ± 3.3%, and infant ALL:21.5 ± 3.9%. OS varied by early, intermediate and late time-to-relapse; 25.8 ± 2.4%, 49.5 ± 2.2%, and 66.4 ± 1.8% respectively for B-ALL and 29.8 ± 3.9%, 33.3 ± 7.6%, 58 ± 9.8% for T-ALL. Patients with ETV6::RUNX1 or Trisomy 4 + 10 had median time-to-relapse of 43 months and higher OS post-relapse 74.4 ± 3.1% and 70.2 ± 3.6%, respectively. Patients with hypodiploidy, KMT2A-rearrangement, and TCF3::PBX1 had short median time-to-relapse (12.5-18 months) and poor OS post-relapse (14.2 ± 6.1%, 31.9 ± 7.7%, 36.8 ± 6.6%). Site-of-relapse varied by cytogenetic subtype. This large dataset provided the opportunity to identify risk factors for OS post-relapse to inform trial design and highlight populations with dismal outcomes post-relapse.

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Determinants of survival after first relapse of acute lymphoblastic leukemia: a Children’s Oncology Group study

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