Prognostic impact of minimal residual disease at the end of consolidation in NCI standard-risk B-lymphoblastic leukemia: A report from the Children's Oncology Group
Corresponding Author
Rachel E. Rau
Division of Pediatric Hematology/Oncology, Texas Children's Cancer Center, Baylor College of Medicine, Houston, Texas, USA
Correspondence
Rachel E. Rau, Baylor College of Medicine/Texas Children's Hospital, 1102 Bates Ave, Suite 1025, Houston, TX 77030, USA.
Email:[email protected]
Search for more papers by this authorYunfeng Dai
Department of Biostatistics, Colleges of Medicine, Public Health and Health Professions, University of Florida, Gainesville, Florida, USA
Search for more papers by this authorMeenakshi Devidas
Department of Global Pediatric Medicine, St Jude Children's Research Hospital, Memphis, Tennessee, USA
Search for more papers by this authorKaren R. Rabin
Division of Pediatric Hematology/Oncology, Texas Children's Cancer Center, Baylor College of Medicine, Houston, Texas, USA
Search for more papers by this authorPatrick Zweidler-McKay
Immunogen, Inc., Waltham, Massachusetts, USA
Search for more papers by this authorAnne Angiolillo
Division of Pediatric Oncology, Children's National Medical Center, Washington, DC and the George Washington University School of Medicine and Health Sciences, Washington, District of Columbia, USA
Search for more papers by this authorReuven J. Schore
Division of Pediatric Oncology, Children's National Medical Center, Washington, DC and the George Washington University School of Medicine and Health Sciences, Washington, District of Columbia, USA
Search for more papers by this authorMichael J. Burke
Division of Pediatric Hematology-Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
Search for more papers by this authorWanda L. Salzer
U.S. Army Medical Research and Materiel Command, Fort Detrick, Frederick, Maryland, USA
Search for more papers by this authorNyla A. Heerema
Department of Pathology, The Ohio State University Wexner School of Medicine, Columbus, Ohio, USA
Search for more papers by this authorAndrew J. Carroll
Department of Genetics, University of Alabama at Birmingham, Birmingham, Alabama, USA
Search for more papers by this authorNaomi J. Winick
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas, USA
Search for more papers by this authorStephen P. Hunger
Department of Pediatrics and the Center for Childhood Cancer Research, Children's Hospital of Philadelphia and the Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
Search for more papers by this authorElizabeth A. Raetz
Department of Pediatrics, New York University Langone Medical Center, New York, New York, USA
Search for more papers by this authorMignon L. Loh
Department of Pediatrics, Benioff Children's Hospital and the Helen Diller Family Comprehensive Cancer Center, University of California School of Medicine, San Francisco, California, USA
Search for more papers by this authorBrent L. Wood
Department of Pathology and Laboratory Medicine, Children's Hospital of Los Angeles, University of Southern California, Los Angeles, California, USA
Search for more papers by this authorMichael J. Borowitz
Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
Search for more papers by this authorCorresponding Author
Rachel E. Rau
Division of Pediatric Hematology/Oncology, Texas Children's Cancer Center, Baylor College of Medicine, Houston, Texas, USA
Correspondence
Rachel E. Rau, Baylor College of Medicine/Texas Children's Hospital, 1102 Bates Ave, Suite 1025, Houston, TX 77030, USA.
Email:[email protected]
Search for more papers by this authorYunfeng Dai
Department of Biostatistics, Colleges of Medicine, Public Health and Health Professions, University of Florida, Gainesville, Florida, USA
Search for more papers by this authorMeenakshi Devidas
Department of Global Pediatric Medicine, St Jude Children's Research Hospital, Memphis, Tennessee, USA
Search for more papers by this authorKaren R. Rabin
Division of Pediatric Hematology/Oncology, Texas Children's Cancer Center, Baylor College of Medicine, Houston, Texas, USA
Search for more papers by this authorPatrick Zweidler-McKay
Immunogen, Inc., Waltham, Massachusetts, USA
Search for more papers by this authorAnne Angiolillo
Division of Pediatric Oncology, Children's National Medical Center, Washington, DC and the George Washington University School of Medicine and Health Sciences, Washington, District of Columbia, USA
Search for more papers by this authorReuven J. Schore
Division of Pediatric Oncology, Children's National Medical Center, Washington, DC and the George Washington University School of Medicine and Health Sciences, Washington, District of Columbia, USA
Search for more papers by this authorMichael J. Burke
Division of Pediatric Hematology-Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
Search for more papers by this authorWanda L. Salzer
U.S. Army Medical Research and Materiel Command, Fort Detrick, Frederick, Maryland, USA
Search for more papers by this authorNyla A. Heerema
Department of Pathology, The Ohio State University Wexner School of Medicine, Columbus, Ohio, USA
Search for more papers by this authorAndrew J. Carroll
Department of Genetics, University of Alabama at Birmingham, Birmingham, Alabama, USA
Search for more papers by this authorNaomi J. Winick
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas, USA
Search for more papers by this authorStephen P. Hunger
Department of Pediatrics and the Center for Childhood Cancer Research, Children's Hospital of Philadelphia and the Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
Search for more papers by this authorElizabeth A. Raetz
Department of Pediatrics, New York University Langone Medical Center, New York, New York, USA
Search for more papers by this authorMignon L. Loh
Department of Pediatrics, Benioff Children's Hospital and the Helen Diller Family Comprehensive Cancer Center, University of California School of Medicine, San Francisco, California, USA
Search for more papers by this authorBrent L. Wood
Department of Pathology and Laboratory Medicine, Children's Hospital of Los Angeles, University of Southern California, Los Angeles, California, USA
Search for more papers by this authorMichael J. Borowitz
Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
Search for more papers by this authorAbstract
The 5-year disease-free survival (DFS) of National Cancer Institute (NCI) high-risk (HR) B-lymphoblastic leukemia (B-ALL) patients with end of induction (EOI) minimal residual disease (MRD) ≥0.1% and end of consolidation (EOC) MRD ≥0.01% is 39 ± 7%, warranting consideration of hematopoietic stem cell transplant (HSCT). However, the impact of EOC MRD in NCI standard-risk (SR) B-ALL patients using COG regimens is unknown. We found that SR patients with MRD ≥0.01% at both EOI and EOC have a 4-year DFS/overall survival (OS) of 72.9 ± 19.0%/91.7 ± 10.8% versus 90.7 ± 2.9%/95.5 ± 2.0% (p = .0019/.25) for those with EOI MRD ≥0.01% and EOC MRD <0.01%. These data suggest that routine use of HSCT may not be warranted in EOC MRD ≥0.01% SR patients.
CONFLICT OF INTEREST
Rachel E. Rau is a consultant for Jazz and Servier. Patrick Zweidler-McKay is a paid employee of Immunogen. Michael J. Burke is a consultant and speaker for Jazz and Amgen and speaker for Servier. Stephen P. Hunger has received consulting fees from Novartis, honoraria from Amgen, and owns common stock in Amgen. Elizabeth A. Raetz serves on a DSMB for Celgene and receives research funding (institutional) from Pfizer. Mignon L. Loh is a consultant to MediSix Therapeutics. Brent L. Wood has received honoraria from Amgen, Seattle Genetics, AbbVie, and Janssen Pharmaceuticals, receives research funding (institutional) from Amgen, Seattle Genetics, Pfizer, Juno Therapeutics, BiolineRx, Biosight, and Stemline Therapeutics. Michael J. Borowitz is on the scientific advisory board for Amgen. The remaining authors have no conflict of interest to report.
Supporting Information
| Filename | Description |
|---|---|
| pbc28929-sup-0001-SuppMat.docx104.3 KB | Figure S1 Incidence of isolated central nervous system (CNS) relapse and combined bone marrow and CNS relapse Figure S2 Disease-free survival (DFS) and overall survival (OS) for NCI SR B-ALL patients with EOI MRD >0.1% by MRD at EOC Table S1 Comparison of patient characteristics for EOI MRD-positive patients with EOC MRD versus without EOC MRD Table S2 Characteristics of EOI MRD-positive patients, by EOC MRD status Table S3 Logistic regression analysis of EOC MRD status by increasing EOI MRD levels Table S4 Cytogenetic features of NCI SR EOC MRD-positive patients Table S5 Percentage EOC MRD-positive in EOI MRD-positive NCI SR patients, by treatment arms (p-value = .79) Table S6 Characteristics and follow-up information for NCI SR EOC MRD-positive patients |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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