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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.

Publication ,  Journal Article
Jacobsohn, DA; Loken, MR; Fei, M; Adams, A; Brodersen, LE; Logan, BR; Ahn, KW; Shaw, BE; Kletzel, M; Olszewski, M; Khan, S; Meshinchi, S ...
Published in: Biol Blood Marrow Transplant
October 2018

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.

Duke Scholars

Published In

Biol Blood Marrow Transplant

DOI

EISSN

1523-6536

Publication Date

October 2018

Volume

24

Issue

10

Start / End Page

2040 / 2046

Location

United States

Related Subject Headings

  • WT1 Proteins
  • Unrelated Donors
  • Transplantation, Homologous
  • Transplantation Conditioning
  • Neoplasm, Residual
  • Male
  • Leukemia, Myeloid, Acute
  • Infant, Newborn
  • Infant
  • Immunology
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Jacobsohn, D. A., Loken, M. R., Fei, M., Adams, A., Brodersen, L. E., Logan, B. R., … 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. Biol Blood Marrow Transplant, 24(10), 2040–2046. https://doi.org/10.1016/j.bbmt.2018.06.010
Jacobsohn, David A., Michael R. Loken, Mingwei Fei, Alexia Adams, Lisa Eidenschink Brodersen, Brent R. Logan, Kwang Woo Ahn, et al. “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 24, no. 10 (October 2018): 2040–46. https://doi.org/10.1016/j.bbmt.2018.06.010.
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 J-AM, Delgado DC, Cheerva A, Gowda M, Ahuja S, Ozkaynak M, Mitchell D, Schultz KR, Fry TJ, Loeb DM, Pulsipher MA. 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 Oct;24(10):2040–2046.
Journal cover image

Published In

Biol Blood Marrow Transplant

DOI

EISSN

1523-6536

Publication Date

October 2018

Volume

24

Issue

10

Start / End Page

2040 / 2046

Location

United States

Related Subject Headings

  • WT1 Proteins
  • Unrelated Donors
  • Transplantation, Homologous
  • Transplantation Conditioning
  • Neoplasm, Residual
  • Male
  • Leukemia, Myeloid, Acute
  • Infant, Newborn
  • Infant
  • Immunology