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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. Biol Blood Marrow Transplant 2018 10;24(10):2040-2046

Date

06/23/2018

Pubmed ID

29933069

Pubmed Central ID

PMC6239928

DOI

10.1016/j.bbmt.2018.06.010

Scopus ID

2-s2.0-85050818070   20 Citations

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 (I?N) 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 I?N (.04% to 53%). Of those patients who proceeded to transplant as being in morphologic remission, 10 had detectable disease (.04% to 14%) by I?N. 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 I?N 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 I?N 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.

Author List

Jacobsohn DA, Loken MR, Fei M, Adams A, Brodersen LE, Logan BR, Ahn KW, Shaw BE, Kletzel M, Olszewski M, Khan S, Meshinchi S, Keating A, Harris A, Teira P, Duerst RE, Margossian SP, Martin PL, Petrovic A, Dvorak CC, Nemecek ER, Boyer MW, Chen AR, Davis JH, Shenoy S, Savasan S, Hudspeth MP, Adams RH, Lewis VA, Kheradpour A, Kasow KA, Gillio AP, Haight AE, Bhatia M, Bambach BJ, Haines HL, Quigg TC, Greiner RJ, Talano JM, Delgado DC, Cheerva A, Gowda M, Ahuja S, Ozkaynak M, Mitchell D, Schultz KR, Fry TJ, Loeb DM, Pulsipher MA

Authors

Kwang Woo Ahn PhD Professor in the Institute for Health and Equity department at Medical College of Wisconsin
Brent R. Logan PhD Director, Professor in the Institute for Health and Equity department at Medical College of Wisconsin
Bronwen E. Shaw MBChB, PhD Center Director, Professor in the Medicine department at Medical College of Wisconsin
Julie-An M. Talano MD Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adolescent
Adult
Allografts
Child
Child, Preschool
Disease-Free Survival
Female
Flow Cytometry
Hematopoietic Stem Cell Transplantation
Humans
Infant
Infant, Newborn
Leukemia, Myeloid, Acute
Male
Neoplasm, Residual
Transplantation Conditioning
Transplantation, Homologous
Unrelated Donors
WT1 Proteins