Haneen Shalabi1, Constance M Yuan2, Amita Kulshreshtha1, Alina Dulau-Florea3, Dalia Salem2,4, Gaurav K Gupta3, Mark Roth2, Armando C Filie2, Bonnie Yates1, Cindy Delbrook1, Joanne Derdak1, Crystal L Mackall1,5, Daniel W Lee1,6, Terry J Fry1,7, Alan S Wayne1,8, Maryalice Stetler-Stevenson2, Nirali N Shah1. 1. Pediatric Oncology Branch, Center for Cancer Research (CCR), National Cancer Institute (NCI), NIH, Bethesda, Maryland. 2. Laboratory of Pathology, CCR, NCI, NIH, Bethesda, Maryland. 3. Department of Laboratory Medicine, Clinical Center, Hematology Section, NIH, Bethesda, Maryland. 4. Mansoura University Faculty of Medicine, Clinical Pathology, Mansoura, Egypt. 5. Cancer Immunology and Immunotherapy Program, Stanford University, Stanford, California. 6. Division of Pediatric Hematology/Oncology, Department of Pediatrics, University of Virginia, Charlottesville, Virginia. 7. Division of Human Immunology and Immunotherapy Initiative, Pediatric Hematology/Oncology, Children's Hospital of Colorado, Aurora, Colorado. 8. Children's Center for Cancer and Blood Diseases, Division of Hematology, Oncology and Blood and Marrow Transplantation, Children's Hospital Los Angeles, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California.
Abstract
BACKGROUND: Accurate disease detection is integral to risk stratification in B-cell acute lymphoblastic leukemia (ALL). The gold standard used to evaluate response in the United States includes morphologic evaluation and minimal residual disease (MRD) testing of aspirated bone marrow (BM) by flow cytometry (FC). This MRD assessment is usually made on a single aspirate sample that is subject to variability in collection techniques and sampling error. Additionally, central nervous system (CNS) assessments for ALL include evaluations of cytopathology and cell counts, which can miss subclinical involvement. PROCEDURE: We retrospectively compared BM biopsy, aspirate, and FC samples obtained from children and young adults with relapsed/refractory ALL to identify the frequency and degree of disease discrepancies in this population. We also compared CNS FC and cytopathology techniques. RESULTS: Sixty of 410 (14.6%) BM samples had discrepant results, 41 (10%) of which were clinically relevant as they resulted in a change in the assignment of marrow status. Discrepant BM results were found in 28 of 89 (31.5%) patients evaluated. Additionally, cerebrospinal fluid (CSF) FC identified disease in 9.7% of cases where cytopathology was negative. CONCLUSIONS: These results support further investigation of the role of concurrent BM biopsy, with aspirate and FC evaluations, and the addition of FC to CSF evaluations, to fully assess disease status and response, particularly in patients with relapsed/refractory ALL. Prospective studies incorporating more comprehensive analysis to evaluate the impact on clinical outcomes are warranted. Published 2020. This article is a U.S. Government work and is in the public domain in the USA.
BACKGROUND: Accurate disease detection is integral to risk stratification in B-cell acute lymphoblastic leukemia (ALL). The gold standard used to evaluate response in the United States includes morphologic evaluation and minimal residual disease (MRD) testing of aspirated bone marrow (BM) by flow cytometry (FC). This MRD assessment is usually made on a single aspirate sample that is subject to variability in collection techniques and sampling error. Additionally, central nervous system (CNS) assessments for ALL include evaluations of cytopathology and cell counts, which can miss subclinical involvement. PROCEDURE: We retrospectively compared BM biopsy, aspirate, and FC samples obtained from children and young adults with relapsed/refractory ALL to identify the frequency and degree of disease discrepancies in this population. We also compared CNS FC and cytopathology techniques. RESULTS: Sixty of 410 (14.6%) BM samples had discrepant results, 41 (10%) of which were clinically relevant as they resulted in a change in the assignment of marrow status. Discrepant BM results were found in 28 of 89 (31.5%) patients evaluated. Additionally, cerebrospinal fluid (CSF) FC identified disease in 9.7% of cases where cytopathology was negative. CONCLUSIONS: These results support further investigation of the role of concurrent BM biopsy, with aspirate and FC evaluations, and the addition of FC to CSF evaluations, to fully assess disease status and response, particularly in patients with relapsed/refractory ALL. Prospective studies incorporating more comprehensive analysis to evaluate the impact on clinical outcomes are warranted. Published 2020. This article is a U.S. Government work and is in the public domain in the USA.
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