Hematopoietic stem-cell transplantation does not improve the poor outcome of children with hypodiploid acute lymphoblastic leukemia

A report from children's oncology group

Jennifer L. McNeer, Meenakshi Devidas, Yunfeng Dai, Andrew J. Carroll, Nyla A. Heerema, Julie M. Gastier-Foster, Samir B. Kahwash, Michael J Borowitz, Brent L. Wood, Eric Larsen, Kelly W. Maloney, Leonard Mattano, Naomi J. Winick, Kirk R. Schultz, Stephen P. Hunger, William L. Carroll, Mignon L. Loh, Elizabeth A. Raetz

Research output: Contribution to journalArticle

Abstract

PURPOSE Children and young adults with hypodiploid B-lymphoblastic leukemia (B-ALL) fare poorly and hematopoietic stem-cell transplantation (HSCT) is often pursued in first complete remission (CR1). We retrospectively reviewed the outcomes of children and young adults with hypodiploid B-ALL who were enrolled in recent Children's Oncology Group (COG) trials to evaluate the impact of HSCT on outcome. PATIENTS AND METHODS Cytogenetic analyses and DNA index were performed at COG-approved laboratories, and hypodiploidy was defined as modal chromosome number less than 44 and/or DNA index less than 0.81. Minimal residual disease (MRD) was determined centrally using flow cytometry at two reference laboratories. Patients with hypodiploid ALL came off protocol therapy postinduction and we retrospectively collected details on their subsequent therapy and outcomes. Event-free survival (EFS) and overall survival (OS) were estimated for the cohort. RESULTS Between 2003 and 2011, 8,522 patients with National Cancer Institute standard-risk and high-risk B-ALL were enrolled in COG AALL03B1 (ClinicalTrials.gov identifier: NCT00482352). Hypodiploidy occurred in 1.5% of patients (n = 131), 98.3% of whom achieved CR after induction therapy. Five-year EFS and OS were 52.2% 6 4.9% and 58.9% 6 4.8%, respectively. Outcomes for patients undergoing CR1 HSCT were not significantly improved: 5-year EFS and OS were 57.4% 6 7.0% and 66.2% 6 6.6% compared with 47.8% 6 7.5% and 53.8% 6 7.6%, respectively (P = .49 and .34, respectively) for those who did not undergo transplantation. Patients with MRD of 0.01% or greater at the end of induction had 5-year EFS and OS of 26.7% 6 9.3% and 29.3% 6 10.1%, respectively, and HSCT had no significant impact on outcomes. CONCLUSION Children and young adults with hypodiploid B-ALL continue to fare poorly and do not seem to benefit from CR1 HSCT. This is especially true for patients with MRD of 0.01% or greater at the end of induction. New treatment strategies are urgently needed for these patients.

Original languageEnglish (US)
Pages (from-to)780-789
Number of pages10
JournalJournal of Clinical Oncology
Volume37
Issue number10
DOIs
StatePublished - Jan 1 2019

Fingerprint

Hematopoietic Stem Cell Transplantation
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Disease-Free Survival
Residual Neoplasm
Young Adult
Survival
National Cancer Institute (U.S.)
Cytogenetic Analysis
DNA
Therapeutics
Flow Cytometry
Chromosomes
Transplantation

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Hematopoietic stem-cell transplantation does not improve the poor outcome of children with hypodiploid acute lymphoblastic leukemia : A report from children's oncology group. / McNeer, Jennifer L.; Devidas, Meenakshi; Dai, Yunfeng; Carroll, Andrew J.; Heerema, Nyla A.; Gastier-Foster, Julie M.; Kahwash, Samir B.; Borowitz, Michael J; Wood, Brent L.; Larsen, Eric; Maloney, Kelly W.; Mattano, Leonard; Winick, Naomi J.; Schultz, Kirk R.; Hunger, Stephen P.; Carroll, William L.; Loh, Mignon L.; Raetz, Elizabeth A.

In: Journal of Clinical Oncology, Vol. 37, No. 10, 01.01.2019, p. 780-789.

Research output: Contribution to journalArticle

McNeer, JL, Devidas, M, Dai, Y, Carroll, AJ, Heerema, NA, Gastier-Foster, JM, Kahwash, SB, Borowitz, MJ, Wood, BL, Larsen, E, Maloney, KW, Mattano, L, Winick, NJ, Schultz, KR, Hunger, SP, Carroll, WL, Loh, ML & Raetz, EA 2019, 'Hematopoietic stem-cell transplantation does not improve the poor outcome of children with hypodiploid acute lymphoblastic leukemia: A report from children's oncology group', Journal of Clinical Oncology, vol. 37, no. 10, pp. 780-789. https://doi.org/10.1200/JCO.18.00884
McNeer, Jennifer L. ; Devidas, Meenakshi ; Dai, Yunfeng ; Carroll, Andrew J. ; Heerema, Nyla A. ; Gastier-Foster, Julie M. ; Kahwash, Samir B. ; Borowitz, Michael J ; Wood, Brent L. ; Larsen, Eric ; Maloney, Kelly W. ; Mattano, Leonard ; Winick, Naomi J. ; Schultz, Kirk R. ; Hunger, Stephen P. ; Carroll, William L. ; Loh, Mignon L. ; Raetz, Elizabeth A. / Hematopoietic stem-cell transplantation does not improve the poor outcome of children with hypodiploid acute lymphoblastic leukemia : A report from children's oncology group. In: Journal of Clinical Oncology. 2019 ; Vol. 37, No. 10. pp. 780-789.
@article{a030a997220c458b82c8da540ac34209,
title = "Hematopoietic stem-cell transplantation does not improve the poor outcome of children with hypodiploid acute lymphoblastic leukemia: A report from children's oncology group",
abstract = "PURPOSE Children and young adults with hypodiploid B-lymphoblastic leukemia (B-ALL) fare poorly and hematopoietic stem-cell transplantation (HSCT) is often pursued in first complete remission (CR1). We retrospectively reviewed the outcomes of children and young adults with hypodiploid B-ALL who were enrolled in recent Children's Oncology Group (COG) trials to evaluate the impact of HSCT on outcome. PATIENTS AND METHODS Cytogenetic analyses and DNA index were performed at COG-approved laboratories, and hypodiploidy was defined as modal chromosome number less than 44 and/or DNA index less than 0.81. Minimal residual disease (MRD) was determined centrally using flow cytometry at two reference laboratories. Patients with hypodiploid ALL came off protocol therapy postinduction and we retrospectively collected details on their subsequent therapy and outcomes. Event-free survival (EFS) and overall survival (OS) were estimated for the cohort. RESULTS Between 2003 and 2011, 8,522 patients with National Cancer Institute standard-risk and high-risk B-ALL were enrolled in COG AALL03B1 (ClinicalTrials.gov identifier: NCT00482352). Hypodiploidy occurred in 1.5{\%} of patients (n = 131), 98.3{\%} of whom achieved CR after induction therapy. Five-year EFS and OS were 52.2{\%} 6 4.9{\%} and 58.9{\%} 6 4.8{\%}, respectively. Outcomes for patients undergoing CR1 HSCT were not significantly improved: 5-year EFS and OS were 57.4{\%} 6 7.0{\%} and 66.2{\%} 6 6.6{\%} compared with 47.8{\%} 6 7.5{\%} and 53.8{\%} 6 7.6{\%}, respectively (P = .49 and .34, respectively) for those who did not undergo transplantation. Patients with MRD of 0.01{\%} or greater at the end of induction had 5-year EFS and OS of 26.7{\%} 6 9.3{\%} and 29.3{\%} 6 10.1{\%}, respectively, and HSCT had no significant impact on outcomes. CONCLUSION Children and young adults with hypodiploid B-ALL continue to fare poorly and do not seem to benefit from CR1 HSCT. This is especially true for patients with MRD of 0.01{\%} or greater at the end of induction. New treatment strategies are urgently needed for these patients.",
author = "McNeer, {Jennifer L.} and Meenakshi Devidas and Yunfeng Dai and Carroll, {Andrew J.} and Heerema, {Nyla A.} and Gastier-Foster, {Julie M.} and Kahwash, {Samir B.} and Borowitz, {Michael J} and Wood, {Brent L.} and Eric Larsen and Maloney, {Kelly W.} and Leonard Mattano and Winick, {Naomi J.} and Schultz, {Kirk R.} and Hunger, {Stephen P.} and Carroll, {William L.} and Loh, {Mignon L.} and Raetz, {Elizabeth A.}",
year = "2019",
month = "1",
day = "1",
doi = "10.1200/JCO.18.00884",
language = "English (US)",
volume = "37",
pages = "780--789",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "10",

}

TY - JOUR

T1 - Hematopoietic stem-cell transplantation does not improve the poor outcome of children with hypodiploid acute lymphoblastic leukemia

T2 - A report from children's oncology group

AU - McNeer, Jennifer L.

AU - Devidas, Meenakshi

AU - Dai, Yunfeng

AU - Carroll, Andrew J.

AU - Heerema, Nyla A.

AU - Gastier-Foster, Julie M.

AU - Kahwash, Samir B.

AU - Borowitz, Michael J

AU - Wood, Brent L.

AU - Larsen, Eric

AU - Maloney, Kelly W.

AU - Mattano, Leonard

AU - Winick, Naomi J.

AU - Schultz, Kirk R.

AU - Hunger, Stephen P.

AU - Carroll, William L.

AU - Loh, Mignon L.

AU - Raetz, Elizabeth A.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - PURPOSE Children and young adults with hypodiploid B-lymphoblastic leukemia (B-ALL) fare poorly and hematopoietic stem-cell transplantation (HSCT) is often pursued in first complete remission (CR1). We retrospectively reviewed the outcomes of children and young adults with hypodiploid B-ALL who were enrolled in recent Children's Oncology Group (COG) trials to evaluate the impact of HSCT on outcome. PATIENTS AND METHODS Cytogenetic analyses and DNA index were performed at COG-approved laboratories, and hypodiploidy was defined as modal chromosome number less than 44 and/or DNA index less than 0.81. Minimal residual disease (MRD) was determined centrally using flow cytometry at two reference laboratories. Patients with hypodiploid ALL came off protocol therapy postinduction and we retrospectively collected details on their subsequent therapy and outcomes. Event-free survival (EFS) and overall survival (OS) were estimated for the cohort. RESULTS Between 2003 and 2011, 8,522 patients with National Cancer Institute standard-risk and high-risk B-ALL were enrolled in COG AALL03B1 (ClinicalTrials.gov identifier: NCT00482352). Hypodiploidy occurred in 1.5% of patients (n = 131), 98.3% of whom achieved CR after induction therapy. Five-year EFS and OS were 52.2% 6 4.9% and 58.9% 6 4.8%, respectively. Outcomes for patients undergoing CR1 HSCT were not significantly improved: 5-year EFS and OS were 57.4% 6 7.0% and 66.2% 6 6.6% compared with 47.8% 6 7.5% and 53.8% 6 7.6%, respectively (P = .49 and .34, respectively) for those who did not undergo transplantation. Patients with MRD of 0.01% or greater at the end of induction had 5-year EFS and OS of 26.7% 6 9.3% and 29.3% 6 10.1%, respectively, and HSCT had no significant impact on outcomes. CONCLUSION Children and young adults with hypodiploid B-ALL continue to fare poorly and do not seem to benefit from CR1 HSCT. This is especially true for patients with MRD of 0.01% or greater at the end of induction. New treatment strategies are urgently needed for these patients.

AB - PURPOSE Children and young adults with hypodiploid B-lymphoblastic leukemia (B-ALL) fare poorly and hematopoietic stem-cell transplantation (HSCT) is often pursued in first complete remission (CR1). We retrospectively reviewed the outcomes of children and young adults with hypodiploid B-ALL who were enrolled in recent Children's Oncology Group (COG) trials to evaluate the impact of HSCT on outcome. PATIENTS AND METHODS Cytogenetic analyses and DNA index were performed at COG-approved laboratories, and hypodiploidy was defined as modal chromosome number less than 44 and/or DNA index less than 0.81. Minimal residual disease (MRD) was determined centrally using flow cytometry at two reference laboratories. Patients with hypodiploid ALL came off protocol therapy postinduction and we retrospectively collected details on their subsequent therapy and outcomes. Event-free survival (EFS) and overall survival (OS) were estimated for the cohort. RESULTS Between 2003 and 2011, 8,522 patients with National Cancer Institute standard-risk and high-risk B-ALL were enrolled in COG AALL03B1 (ClinicalTrials.gov identifier: NCT00482352). Hypodiploidy occurred in 1.5% of patients (n = 131), 98.3% of whom achieved CR after induction therapy. Five-year EFS and OS were 52.2% 6 4.9% and 58.9% 6 4.8%, respectively. Outcomes for patients undergoing CR1 HSCT were not significantly improved: 5-year EFS and OS were 57.4% 6 7.0% and 66.2% 6 6.6% compared with 47.8% 6 7.5% and 53.8% 6 7.6%, respectively (P = .49 and .34, respectively) for those who did not undergo transplantation. Patients with MRD of 0.01% or greater at the end of induction had 5-year EFS and OS of 26.7% 6 9.3% and 29.3% 6 10.1%, respectively, and HSCT had no significant impact on outcomes. CONCLUSION Children and young adults with hypodiploid B-ALL continue to fare poorly and do not seem to benefit from CR1 HSCT. This is especially true for patients with MRD of 0.01% or greater at the end of induction. New treatment strategies are urgently needed for these patients.

UR - http://www.scopus.com/inward/record.url?scp=85062623360&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85062623360&partnerID=8YFLogxK

U2 - 10.1200/JCO.18.00884

DO - 10.1200/JCO.18.00884

M3 - Article

VL - 37

SP - 780

EP - 789

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 10

ER -