Successful outcomes of newly diagnosed t lymphoblastic lymphoma: Results from children's oncology group AALL0434

Robert J. Hayashi; Stuart S. Winter; Kimberly P. Dunsmore; Meenakshi Devidas; Zhiguo Chen; Brent L. Wood; Michelle L. Hermiston; David T. Teachey; Sherrie L. Perkins; Rodney R. Miles; Elizabeth A. Raetz; Mignon L. Loh; Naomi J. Winick; William L. Carroll; Stephen P. Hunger; Megan S. Lim; Thomas G. Gross; Catherine M. Bollard

doi:10.1200/JCO.20.00531

Successful outcomes of newly diagnosed t lymphoblastic lymphoma: Results from children's oncology group AALL0434

Robert J. Hayashi, Stuart S. Winter, Kimberly P. Dunsmore, Meenakshi Devidas, Zhiguo Chen, Brent L. Wood, Michelle L. Hermiston, David T. Teachey, Sherrie L. Perkins, Rodney R. Miles, Elizabeth A. Raetz, Mignon L. Loh, Naomi J. Winick, William L. Carroll, Stephen P. Hunger, Megan S. Lim, Thomas G. Gross, Catherine M. Bollard

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

38 Scopus citations

Abstract

PURPOSE The Children's Oncology Group (COG) protocol AALL0434 evaluated the safety and efficacy of multiagent chemotherapy with Capizzi-based methotrexate/pegaspargase (C-MTX) in patients with newly diagnosed pediatric T-cell lymphoblastic lymphoma (T-LL) and gained preliminary data using nelarabine in high-risk patients. PATIENTS AND METHODS The trial enrolled 299 patients, age 1-31 years. High-risk (HR) patients had ≤ 1% minimal detectable disease (MDD) in the bone marrow at diagnosis or received prior steroid treatment. Induction failure was defined as failure to achieve a partial response (PR) by the end of the 4-week induction. All patients received the augmented Berlin-Frankfurt-Muenster (ABFM) C-MTX regimen. HR patients were randomly assigned to receive or not receive 6 5-day courses of nelarabine incorporated into ABFM. Patients with induction failure were nonrandomly assigned to ABFM C-MTX plus nelarabine. No patients received prophylactic cranial radiation; however, patients with CNS3 disease (CSF WBC ≤ 5/μL with blasts or cranial nerve palsies, brain/eye involvement, or hypothalamic syndrome) were ineligible. RESULTS At end-induction, 98.8% of evaluable participants had at least a PR. The 4-year event-free survival (EFS) and overall survival (OS) were 84.7% ± 2.3% and 89.0% ± 2.0%. The 4-year disease-free survival (DFS) from end-induction was 85.9% ± 2.6%. There was no difference in DFS observed between the HR and standard-risk groups (P = .29) or by treatment regimen (P = .55). Disease stage, tumor response, and MDD at diagnosis did not demonstrate thresholds that resulted in differences in EFS. Nelarabine did not show an advantage for HR patients. CNS relapse occurred in only 4 patients. CONCLUSION COG AALL0434 produced excellent outcomes in one of the largest trials ever conducted for patients with newly diagnosed T-LL. The COG ABFM regimen with C-MTX provided excellent EFS and OS without cranial radiation.

Original language	English (US)
Pages (from-to)	3062-3070
Number of pages	9
Journal	Journal of Clinical Oncology
Volume	38
Issue number	26
DOIs	https://doi.org/10.1200/JCO.20.00531
State	Published - Sep 10 2020

ASJC Scopus subject areas

Oncology
Cancer Research

Access to Document

10.1200/JCO.20.00531

Cite this

Hayashi, R. J., Winter, S. S., Dunsmore, K. P., Devidas, M., Chen, Z., Wood, B. L., Hermiston, M. L., Teachey, D. T., Perkins, S. L., Miles, R. R., Raetz, E. A., Loh, M. L., Winick, N. J., Carroll, W. L., Hunger, S. P., Lim, M. S., Gross, T. G., & Bollard, C. M. (2020). Successful outcomes of newly diagnosed t lymphoblastic lymphoma: Results from children's oncology group AALL0434. Journal of Clinical Oncology, 38(26), 3062-3070. https://doi.org/10.1200/JCO.20.00531

Hayashi, RJ, Winter, SS, Dunsmore, KP, Devidas, M, Chen, Z, Wood, BL, Hermiston, ML, Teachey, DT, Perkins, SL, Miles, RR, Raetz, EA, Loh, ML, Winick, NJ, Carroll, WL, Hunger, SP, Lim, MS, Gross, TG & Bollard, CM 2020, 'Successful outcomes of newly diagnosed t lymphoblastic lymphoma: Results from children's oncology group AALL0434', Journal of Clinical Oncology, vol. 38, no. 26, pp. 3062-3070. https://doi.org/10.1200/JCO.20.00531

@article{f5902a5d5a9c4ac8a1f37c81e3b077b0,

title = "Successful outcomes of newly diagnosed t lymphoblastic lymphoma: Results from children's oncology group AALL0434",

abstract = "PURPOSE The Children's Oncology Group (COG) protocol AALL0434 evaluated the safety and efficacy of multiagent chemotherapy with Capizzi-based methotrexate/pegaspargase (C-MTX) in patients with newly diagnosed pediatric T-cell lymphoblastic lymphoma (T-LL) and gained preliminary data using nelarabine in high-risk patients. PATIENTS AND METHODS The trial enrolled 299 patients, age 1-31 years. High-risk (HR) patients had ≤ 1% minimal detectable disease (MDD) in the bone marrow at diagnosis or received prior steroid treatment. Induction failure was defined as failure to achieve a partial response (PR) by the end of the 4-week induction. All patients received the augmented Berlin-Frankfurt-Muenster (ABFM) C-MTX regimen. HR patients were randomly assigned to receive or not receive 6 5-day courses of nelarabine incorporated into ABFM. Patients with induction failure were nonrandomly assigned to ABFM C-MTX plus nelarabine. No patients received prophylactic cranial radiation; however, patients with CNS3 disease (CSF WBC ≤ 5/μL with blasts or cranial nerve palsies, brain/eye involvement, or hypothalamic syndrome) were ineligible. RESULTS At end-induction, 98.8% of evaluable participants had at least a PR. The 4-year event-free survival (EFS) and overall survival (OS) were 84.7% ± 2.3% and 89.0% ± 2.0%. The 4-year disease-free survival (DFS) from end-induction was 85.9% ± 2.6%. There was no difference in DFS observed between the HR and standard-risk groups (P = .29) or by treatment regimen (P = .55). Disease stage, tumor response, and MDD at diagnosis did not demonstrate thresholds that resulted in differences in EFS. Nelarabine did not show an advantage for HR patients. CNS relapse occurred in only 4 patients. CONCLUSION COG AALL0434 produced excellent outcomes in one of the largest trials ever conducted for patients with newly diagnosed T-LL. The COG ABFM regimen with C-MTX provided excellent EFS and OS without cranial radiation.",

author = "Hayashi, {Robert J.} and Winter, {Stuart S.} and Dunsmore, {Kimberly P.} and Meenakshi Devidas and Zhiguo Chen and Wood, {Brent L.} and Hermiston, {Michelle L.} and Teachey, {David T.} and Perkins, {Sherrie L.} and Miles, {Rodney R.} and Raetz, {Elizabeth A.} and Loh, {Mignon L.} and Winick, {Naomi J.} and Carroll, {William L.} and Hunger, {Stephen P.} and Lim, {Megan S.} and Gross, {Thomas G.} and Bollard, {Catherine M.}",

year = "2020",

month = sep,

day = "10",

doi = "10.1200/JCO.20.00531",

language = "English (US)",

volume = "38",

pages = "3062--3070",

journal = "Journal of Clinical Oncology",

issn = "0732-183X",

publisher = "American Society of Clinical Oncology",

number = "26",

}

TY - JOUR

T1 - Successful outcomes of newly diagnosed t lymphoblastic lymphoma

T2 - Results from children's oncology group AALL0434

AU - Hayashi, Robert J.

AU - Winter, Stuart S.

AU - Dunsmore, Kimberly P.

AU - Devidas, Meenakshi

AU - Chen, Zhiguo

AU - Wood, Brent L.

AU - Hermiston, Michelle L.

AU - Teachey, David T.

AU - Perkins, Sherrie L.

AU - Miles, Rodney R.

AU - Raetz, Elizabeth A.

AU - Loh, Mignon L.

AU - Winick, Naomi J.

AU - Carroll, William L.

AU - Hunger, Stephen P.

AU - Lim, Megan S.

AU - Gross, Thomas G.

AU - Bollard, Catherine M.

PY - 2020/9/10

Y1 - 2020/9/10

N2 - PURPOSE The Children's Oncology Group (COG) protocol AALL0434 evaluated the safety and efficacy of multiagent chemotherapy with Capizzi-based methotrexate/pegaspargase (C-MTX) in patients with newly diagnosed pediatric T-cell lymphoblastic lymphoma (T-LL) and gained preliminary data using nelarabine in high-risk patients. PATIENTS AND METHODS The trial enrolled 299 patients, age 1-31 years. High-risk (HR) patients had ≤ 1% minimal detectable disease (MDD) in the bone marrow at diagnosis or received prior steroid treatment. Induction failure was defined as failure to achieve a partial response (PR) by the end of the 4-week induction. All patients received the augmented Berlin-Frankfurt-Muenster (ABFM) C-MTX regimen. HR patients were randomly assigned to receive or not receive 6 5-day courses of nelarabine incorporated into ABFM. Patients with induction failure were nonrandomly assigned to ABFM C-MTX plus nelarabine. No patients received prophylactic cranial radiation; however, patients with CNS3 disease (CSF WBC ≤ 5/μL with blasts or cranial nerve palsies, brain/eye involvement, or hypothalamic syndrome) were ineligible. RESULTS At end-induction, 98.8% of evaluable participants had at least a PR. The 4-year event-free survival (EFS) and overall survival (OS) were 84.7% ± 2.3% and 89.0% ± 2.0%. The 4-year disease-free survival (DFS) from end-induction was 85.9% ± 2.6%. There was no difference in DFS observed between the HR and standard-risk groups (P = .29) or by treatment regimen (P = .55). Disease stage, tumor response, and MDD at diagnosis did not demonstrate thresholds that resulted in differences in EFS. Nelarabine did not show an advantage for HR patients. CNS relapse occurred in only 4 patients. CONCLUSION COG AALL0434 produced excellent outcomes in one of the largest trials ever conducted for patients with newly diagnosed T-LL. The COG ABFM regimen with C-MTX provided excellent EFS and OS without cranial radiation.

AB - PURPOSE The Children's Oncology Group (COG) protocol AALL0434 evaluated the safety and efficacy of multiagent chemotherapy with Capizzi-based methotrexate/pegaspargase (C-MTX) in patients with newly diagnosed pediatric T-cell lymphoblastic lymphoma (T-LL) and gained preliminary data using nelarabine in high-risk patients. PATIENTS AND METHODS The trial enrolled 299 patients, age 1-31 years. High-risk (HR) patients had ≤ 1% minimal detectable disease (MDD) in the bone marrow at diagnosis or received prior steroid treatment. Induction failure was defined as failure to achieve a partial response (PR) by the end of the 4-week induction. All patients received the augmented Berlin-Frankfurt-Muenster (ABFM) C-MTX regimen. HR patients were randomly assigned to receive or not receive 6 5-day courses of nelarabine incorporated into ABFM. Patients with induction failure were nonrandomly assigned to ABFM C-MTX plus nelarabine. No patients received prophylactic cranial radiation; however, patients with CNS3 disease (CSF WBC ≤ 5/μL with blasts or cranial nerve palsies, brain/eye involvement, or hypothalamic syndrome) were ineligible. RESULTS At end-induction, 98.8% of evaluable participants had at least a PR. The 4-year event-free survival (EFS) and overall survival (OS) were 84.7% ± 2.3% and 89.0% ± 2.0%. The 4-year disease-free survival (DFS) from end-induction was 85.9% ± 2.6%. There was no difference in DFS observed between the HR and standard-risk groups (P = .29) or by treatment regimen (P = .55). Disease stage, tumor response, and MDD at diagnosis did not demonstrate thresholds that resulted in differences in EFS. Nelarabine did not show an advantage for HR patients. CNS relapse occurred in only 4 patients. CONCLUSION COG AALL0434 produced excellent outcomes in one of the largest trials ever conducted for patients with newly diagnosed T-LL. The COG ABFM regimen with C-MTX provided excellent EFS and OS without cranial radiation.

UR - http://www.scopus.com/inward/record.url?scp=85090509404&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85090509404&partnerID=8YFLogxK

U2 - 10.1200/JCO.20.00531

DO - 10.1200/JCO.20.00531

M3 - Article

C2 - 32552472

AN - SCOPUS:85090509404

SN - 0732-183X

VL - 38

SP - 3062

EP - 3070

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

IS - 26

ER -

Successful outcomes of newly diagnosed t lymphoblastic lymphoma: Results from children's oncology group AALL0434

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this