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J Clin Oncol. 2019 Apr 1;37(10):780-789. doi: 10.1200/JCO.18.00884. Epub 2019 Feb 11.

Hematopoietic Stem-Cell Transplantation Does Not Improve the Poor Outcome of Children With Hypodiploid Acute Lymphoblastic Leukemia: A Report From Children's Oncology Group.

Author information

1
1 University of Chicago, Chicago, IL.
2
2 University of Florida, Gainesville, FL.
3
3 University of Alabama at Birmingham, Birmingham, AL.
4
4 The Ohio State University, Columbus, OH.
5
5 Nationwide Children's Hospital and The Ohio State University, Columbus, OH.
6
6 Johns Hopkins Medical Institutions, Baltimore, MD.
7
7 University of Washington, Seattle, WA.
8
8 Maine Children's Cancer Program, Scarborough, ME.
9
9 Children's Hospital Colorado, Aurora, CO.
10
10 HARP Pharma Consulting, Mystic, CT.
11
11 University of Texas Southwestern Medical Center, Dallas, TX.
12
12 BC Children's Hospital and Research Institute, Vancouver, British Columbia, Canada.
13
13 Children's Hospital of Philadelphia, Philadelphia, PA.
14
14 New York University Langone Medical Center, New York, NY.
15
15 University of California, San Francisco, San Francisco, CA.

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% ± 4.9% and 58.9% ± 4.8%, respectively. Outcomes for patients undergoing CR1 HSCT were not significantly improved: 5-year EFS and OS were 57.4% ± 7.0% and 66.2% ± 6.6% compared with 47.8% ± 7.5% and 53.8% ± 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% ± 9.3% and 29.3% ± 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.

PMID:
30742559
PMCID:
PMC6440386
[Available on 2020-04-01]
DOI:
10.1200/JCO.18.00884

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