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.

Autor: Jacobsohn DA; 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., Loken MR; Laboratory, Hematologics, Inc., Seattle, WA, USA., Fei M; Center for International Blood and Marrow Transplant Research; Division of Biostatistics, Medical College of Wisconsin, Milwaukee, WI, USA., Adams A; Center for International Blood and Marrow Transplant Research, National Marrow Donor Program/Be The Match, Minneapolis, MN, USA., Brodersen LE; Laboratory, Hematologics, Inc., Seattle, WA, USA., Logan BR; Center for International Blood and Marrow Transplant Research; Division of Biostatistics, Medical College of Wisconsin, Milwaukee, WI, USA., Ahn KW; Center for International Blood and Marrow Transplant Research; Division of Biostatistics, Medical College of Wisconsin, Milwaukee, WI, USA., Shaw BE; Center for International Blood and Marrow Transplant Research; Division of Biostatistics, Medical College of Wisconsin, Milwaukee, WI, USA., Kletzel M; Department of Pediatrics, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA., Olszewski M; Department of Pediatrics, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA., Khan S; Department of Pediatrics, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA., Meshinchi S; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA., Keating A; University of Colorado - Children's Hospital, Aurora, CO, USA., Harris A; Blood and Marrow Transplant Program, University of Michigan Health System, Ann Arbor, MI, USA., Teira P; Département de pédiatrie, CHU Sainte Justine, Université de Montréal, Montreal, Quebec, Canada., Duerst RE; Department of Pediatrics, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA., Margossian SP; Department of Pediatric Oncology, Boston Children's Hospital, Dana-Farber Cancer Institute, Boston, MA, USA., Martin PL; Pediatric Blood and Marrow Transplant, Duke University Medical School, Durham, NC, USA., Petrovic A; Pediatric Hematology-Oncology, Johns Hopkins All Children's Hospital, St. Petersburg, FL, USA., Dvorak CC; Department of Pediatrics, University of California San Francisco Benioff Children's Hospital, San Francisco, CA, USA., Nemecek ER; Pediatric Blood & Marrow Transplant Program, Department of Pediatrics, Doernbecher Children's Hospital, Oregon Health & Science University, Portland, OR, USA., Boyer MW; Pediatric Hematology/Oncology, Primary Children's Hospital, University of Utah, Salt Lake City, UT, USA., Chen AR; Pediatric Bone Marrow Transplantation, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA., Davis JH; Department of Pediatrics, British Columbia Children's Hospital, Vancouver, British Columbia, Canada., Shenoy S; Pediatric Hematology-Oncology, St. Louis Children's Hospital, Washington University in St. Louis, St. Louis, MO, USA., Savasan S; General Pediatrics, Children's Hospital of Michigan, Detroit Medical Center, Detroit, MI, USA., Hudspeth MP; Division of Pediatric Hematology/Oncology, Medical University of South Carolina, Charleston, SC, USA., Adams RH; Hematology / Oncology, Phoenix Children's Hospital, Phoenix, AZ, USA., Lewis VA; Departments of Oncology, Paediatrics, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada., Kheradpour A; Pediatric Hematology-Oncology, Loma Linda University Medical Center, Loma Linda, CA, USA., Kasow KA; Division of Hematology-Oncology, Department of Pediatrics, University of North Carolina Chapel Hill, NC, USA., Gillio AP; Department of Pediatrics, Hackensack University Medical Center, Hackensack, NJ, USA., Haight AE; Division of Hematology/Oncology - Bone Marrow, Pediatric Hematology & Medical Oncology, Aflac Cancer and Blood Disorders Center, Emory University School of Medicine, Atlanta, GA, USA., Bhatia M; Stem Cell Transplantation, Morgan Stanley Children's Hospital of New York-Presbyterian - Columbia University Medical Center, New York, NY, USA., Bambach BJ; Pediatrics, Roswell Park Cancer Institute, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, USA., Haines HL; Division of Hematology and Oncology, Children's of Alabama, University of Alabama at Birmingham, Birmingham, AL, USA., Quigg TC; Pediatric Hematology - Medical Oncology, Texas Transplant Institute, Methodist Children's Hospital, San Antonio, TX, USA., Greiner RJ; Pediatric Hematology/Oncology, Penn State Health Children's Hospital, Hershey, PA, USA., Talano JM; Department of Pediatric Hematology Oncology, Children's Hospital of Wisconsin, Milwaukee, WI, USA., Delgado DC; Department of Pediatrics, Division of Hematology/Oncology, Riley Children's Hospital at Indiana University Health, Indianapolis, IN, USA., Cheerva A; Pediatric Medical Oncology, Norton Children's Hospital, University of Louisville Hospital, Louisville, KY, USA., Gowda M; Pediatric Hematology and Oncology, Virginia Commonwealth University, Massey Cancer Center, Richmond, VA, USA., Ahuja S; Department of Pediatrics, University Hospitals Rainbow Babies and Children's Hospital, Cleveland, OH, USA., Ozkaynak M; Pediatric Hematology/Oncology, Westchester Medical Center, Westchester, NY, USA., Mitchell D; Hematology Pediatrics, Montreal Children's Hospital, McGill University Health Centre, Montreal, Quebec, Canada., Schultz KR; Department of Pediatrics, British Columbia Children's Hospital, Vancouver, British Columbia, Canada., Fry TJ; Pediatric Oncology Branch, National Institutes of Health, Bethesda, MD, USA., Loeb DM; Pediatric Oncology, Children's Hospital at Montefiore, Bronx, NY, USA., Pulsipher MA; Division of Hematology, Oncology, and Blood and Marrow Transplantation, Children's Hospital Los Angeles, USC Keck School of Medicine, Los Angeles, CA, USA.
Jazyk: angličtina
Zdroj: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation [Biol Blood Marrow Transplant] 2018 Oct; Vol. 24 (10), pp. 2040-2046. Date of Electronic Publication: 2018 Jun 19.
DOI: 10.1016/j.bbmt.2018.06.010
Abstrakt: 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.
(Copyright © 2018. Published by Elsevier Inc.)
Databáze: MEDLINE
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