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

David A. Jacobsohn, Michael R. Loken, Mingwei Fei, Alexia Adams, Lisa Eidenschink Brodersen, Brent R. Logan, Kwang Woo Ahn, Bronwen E. Shaw, Morris Kletzel, Marie Olszewski, Sana Khan, Soheil Meshinchi, Amy Keating, Andrew Harris, Pierre Teira, Reggie E. Duerst, Steven P. Margossian, Paul L. Martin, Aleksandra Petrovic, Christopher C. DvorakEneida R. Nemecek, Michael W. Boyer, Allen R. Chen, Jeffrey H. Davis, Shalini Shenoy, Sureyya Savasan, Michelle P. Hudspeth, Roberta H. Adams, Victor A. Lewis, Albert Kheradpour, Kimberly A. Kasow, Alfred P. Gillio, Ann E. Haight, Monica Bhatia, Barbara J. Bambach, Hilary L. Haines, Troy C. Quigg, Robert J. Greiner, Julie An M. Talano, David C. Delgado, Alexandra Cheerva, Madhu Gowda, Sanjay Ahuja, Mehmet Ozkaynak, David Mitchell, Kirk R. Schultz, Terry J. Fry, David M. Loeb, Michael A. Pulsipher

Research output: Contribution to journalArticle

9 Scopus 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 (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.

Original languageEnglish (US)
Pages (from-to)2040-2046
Number of pages7
JournalBiology of Blood and Marrow Transplantation
Volume24
Issue number10
DOIs
StatePublished - Oct 2018

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Keywords

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

ASJC Scopus subject areas

  • Hematology
  • Transplantation

Cite this

Jacobsohn, D. A., Loken, M. R., Fei, M., Adams, A., Brodersen, L. E., Logan, B. R., Ahn, K. W., Shaw, B. E., Kletzel, M., Olszewski, M., Khan, S., Meshinchi, S., Keating, A., Harris, A., Teira, P., Duerst, R. E., Margossian, S. P., Martin, P. L., Petrovic, A., ... Pulsipher, M. A. (2018). 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. Biology of Blood and Marrow Transplantation, 24(10), 2040-2046. https://doi.org/10.1016/j.bbmt.2018.06.010