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Biol Blood Marrow Transplant. 2018 Oct;24(10):2040-2046. doi: 10.1016/j.bbmt.2018.06.010. Epub 2018 Jun 19.

Outcomes of Measurable Residual Disease in Pediatric Acute Myeloid Leukemia before and after Hematopoietic Stem Cell Transplant: Validation of Difference from Normal Flow Cytometry with Chimerism Studies and Wilms Tumor 1 Gene Expression.

Author information

1
Division of Blood and Marrow Transplantation Center for Cancer and Blood Disorders, Children's National Health System, George Washington University School of Medicine and Health Sciences, Washington, DC, USA. Electronic address: dajacobs@cnmc.org.
2
Laboratory, Hematologics, Inc., Seattle, WA, USA.
3
Center for International Blood and Marrow Transplant Research; Division of Biostatistics, Medical College of Wisconsin, Milwaukee, WI, USA.
4
Center for International Blood and Marrow Transplant Research, National Marrow Donor Program/Be The Match, Minneapolis, MN, USA.
5
Department of Pediatrics, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA.
6
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
7
University of Colorado - Children's Hospital, Aurora, CO, USA.
8
Blood and Marrow Transplant Program, University of Michigan Health System, Ann Arbor, MI, USA.
9
Département de pédiatrie, CHU Sainte Justine, Université de Montréal, Montreal, Quebec, Canada.
10
Department of Pediatric Oncology, Boston Children's Hospital, Dana-Farber Cancer Institute, Boston, MA, USA.
11
Pediatric Blood and Marrow Transplant, Duke University Medical School, Durham, NC, USA.
12
Pediatric Hematology-Oncology, Johns Hopkins All Children's Hospital, St. Petersburg, FL, USA.
13
Department of Pediatrics, University of California San Francisco Benioff Children's Hospital, San Francisco, CA, USA.
14
Pediatric Blood & Marrow Transplant Program, Department of Pediatrics, Doernbecher Children's Hospital, Oregon Health & Science University, Portland, OR, USA.
15
Pediatric Hematology/Oncology, Primary Children's Hospital, University of Utah, Salt Lake City, UT, USA.
16
Pediatric Bone Marrow Transplantation, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA.
17
Department of Pediatrics, British Columbia Children's Hospital, Vancouver, British Columbia, Canada.
18
Pediatric Hematology-Oncology, St. Louis Children's Hospital, Washington University in St. Louis, St. Louis, MO, USA.
19
General Pediatrics, Children's Hospital of Michigan, Detroit Medical Center, Detroit, MI, USA.
20
Division of Pediatric Hematology/Oncology, Medical University of South Carolina, Charleston, SC, USA.
21
Hematology / Oncology, Phoenix Children's Hospital, Phoenix, AZ, USA.
22
Departments of Oncology, Paediatrics, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada.
23
Pediatric Hematology-Oncology, Loma Linda University Medical Center, Loma Linda, CA, USA.
24
Division of Hematology-Oncology, Department of Pediatrics, University of North Carolina Chapel Hill, NC, USA.
25
Department of Pediatrics, Hackensack University Medical Center, Hackensack, NJ, USA.
26
Division of Hematology/Oncology - Bone Marrow, Pediatric Hematology & Medical Oncology, Aflac Cancer and Blood Disorders Center, Emory University School of Medicine, Atlanta, GA, USA.
27
Stem Cell Transplantation, Morgan Stanley Children's Hospital of New York-Presbyterian - Columbia University Medical Center, New York, NY, USA.
28
Pediatrics, Roswell Park Cancer Institute, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, USA.
29
Division of Hematology and Oncology, Children's of Alabama, University of Alabama at Birmingham, Birmingham, AL, USA.
30
Pediatric Hematology - Medical Oncology, Texas Transplant Institute, Methodist Children's Hospital, San Antonio, TX, USA.
31
Pediatric Hematology/Oncology, Penn State Health Children's Hospital, Hershey, PA, USA.
32
Department of Pediatric Hematology Oncology, Children's Hospital of Wisconsin, Milwaukee, WI, USA.
33
Department of Pediatrics, Division of Hematology/Oncology, Riley Children's Hospital at Indiana University Health, Indianapolis, IN, USA.
34
Pediatric Medical Oncology, Norton Children's Hospital, University of Louisville Hospital, Louisville, KY, USA.
35
Pediatric Hematology and Oncology, Virginia Commonwealth University, Massey Cancer Center, Richmond, VA, USA.
36
Department of Pediatrics, University Hospitals Rainbow Babies and Children's Hospital, Cleveland, OH, USA.
37
Pediatric Hematology/Oncology, Westchester Medical Center, Westchester, NY, USA.
38
Hematology Pediatrics, Montreal Children's Hospital, McGill University Health Centre, Montreal, Quebec, Canada.
39
Pediatric Oncology Branch, National Institutes of Health, Bethesda, MD, USA.
40
Pediatric Oncology, Children's Hospital at Montefiore, Bronx, NY, USA.
41
Division of Hematology, Oncology, and Blood and Marrow Transplantation, Children's Hospital Los Angeles, USC Keck School of Medicine, Los Angeles, CA, USA.

Abstract

We enrolled 150 patients in a prospective multicenter study of children with acute myeloid leukemia undergoing hematopoietic stem cell transplantation (HSCT) to compare the detection of measurable residual disease (MRD) by a "difference from normal" flow cytometry (ΔN) approach with assessment of Wilms tumor 1 (WT1) gene expression without access to the diagnostic specimen. Prospective analysis of the specimens using this approach showed that 23% of patients screened for HSCT had detectable residual disease by ΔN (.04% to 53%). Of those patients who proceeded to transplant as being in morphologic remission, 10 had detectable disease (.04% to 14%) by ΔN. The disease-free survival of this group was 10% (0 to 35%) compared with 55% (46% to 64%, P < .001) for those without disease. The ΔN assay was validated using the post-HSCT specimen by sorting abnormal or suspicious cells to confirm recipient or donor origin by chimerism studies. All 15 patients who had confirmation of tumor detection relapsed, whereas the 2 patients with suspicious phenotype cells lacking this confirmation did not. The phenotype of the relapse specimen was then used retrospectively to assess the pre-HSCT specimen, allowing identification of additional samples with low levels of MRD involvement that were previously undetected. Quantitative assessment of WT1 gene expression was not predictive of relapse or other outcomes in either pre- or post-transplant specimens. MRD detected by ΔN was highly specific, but did not identify most relapsing patients. The application of the assay was limited by poor quality among one-third of the specimens and lack of a diagnostic phenotype for comparison.

KEYWORDS:

Cytogenetics and molecular genetics; Laboratory hematology; Measurable residual disease; Stem cell transplantation

PMID:
29933069
PMCID:
PMC6239928
DOI:
10.1016/j.bbmt.2018.06.010
[Indexed for MEDLINE]
Free PMC Article

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