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 language | English (US) |
|---|---|
| Pages (from-to) | 2040-2046 |
| Number of pages | 7 |
| Journal | Biology of Blood and Marrow Transplantation |
| Volume | 24 |
| Issue number | 10 |
| DOIs | |
| State | Published - Oct 1 2018 |
Fingerprint
Keywords
- Cytogenetics and molecular genetics
- Laboratory hematology
- Measurable residual disease
- Stem cell transplantation
ASJC Scopus subject areas
- Hematology
- Transplantation
Cite this
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. / Jacobsohn, David A.; Loken, Michael R.; Fei, Mingwei; Adams, Alexia; Brodersen, Lisa Eidenschink; Logan, Brent R.; Ahn, Kwang Woo; Shaw, Bronwen E.; Kletzel, Morris; Olszewski, Marie; Khan, Sana; Meshinchi, Soheil; Keating, Amy; Harris, Andrew; Teira, Pierre; Duerst, Reggie E.; Margossian, Steven P.; Martin, Paul L.; Petrovic, Aleksandra; Dvorak, Christopher C.; Nemecek, Eneida; Boyer, Michael W.; Chen, Allen R.; Davis, Jeffrey H.; Shenoy, Shalini; Savasan, Sureyya; Hudspeth, Michelle P.; Adams, Roberta H.; Lewis, Victor A.; Kheradpour, Albert; Kasow, Kimberly A.; Gillio, Alfred P.; Haight, Ann E.; Bhatia, Monica; Bambach, Barbara J.; Haines, Hilary L.; Quigg, Troy C.; Greiner, Robert J.; Talano, Julie An M.; Delgado, David C.; Cheerva, Alexandra; Gowda, Madhu; Ahuja, Sanjay; Ozkaynak, Mehmet; Mitchell, David; Schultz, Kirk R.; Fry, Terry J.; Loeb, David M.; Pulsipher, Michael A.
In: Biology of Blood and Marrow Transplantation, Vol. 24, No. 10, 01.10.2018, p. 2040-2046.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Outcomes of Measurable Residual Disease in Pediatric Acute Myeloid Leukemia before and after Hematopoietic Stem Cell Transplant
T2 - Validation of Difference from Normal Flow Cytometry with Chimerism Studies and Wilms Tumor 1 Gene Expression
AU - Jacobsohn, David A.
AU - Loken, Michael R.
AU - Fei, Mingwei
AU - Adams, Alexia
AU - Brodersen, Lisa Eidenschink
AU - Logan, Brent R.
AU - Ahn, Kwang Woo
AU - Shaw, Bronwen E.
AU - Kletzel, Morris
AU - Olszewski, Marie
AU - Khan, Sana
AU - Meshinchi, Soheil
AU - Keating, Amy
AU - Harris, Andrew
AU - Teira, Pierre
AU - Duerst, Reggie E.
AU - Margossian, Steven P.
AU - Martin, Paul L.
AU - Petrovic, Aleksandra
AU - Dvorak, Christopher C.
AU - Nemecek, Eneida
AU - Boyer, Michael W.
AU - Chen, Allen R.
AU - Davis, Jeffrey H.
AU - Shenoy, Shalini
AU - Savasan, Sureyya
AU - Hudspeth, Michelle P.
AU - Adams, Roberta H.
AU - Lewis, Victor A.
AU - Kheradpour, Albert
AU - Kasow, Kimberly A.
AU - Gillio, Alfred P.
AU - Haight, Ann E.
AU - Bhatia, Monica
AU - Bambach, Barbara J.
AU - Haines, Hilary L.
AU - Quigg, Troy C.
AU - Greiner, Robert J.
AU - Talano, Julie An M.
AU - Delgado, David C.
AU - Cheerva, Alexandra
AU - Gowda, Madhu
AU - Ahuja, Sanjay
AU - Ozkaynak, Mehmet
AU - Mitchell, David
AU - Schultz, Kirk R.
AU - Fry, Terry J.
AU - Loeb, David M.
AU - Pulsipher, Michael A.
PY - 2018/10/1
Y1 - 2018/10/1
N2 - 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.
AB - 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.
KW - Cytogenetics and molecular genetics
KW - Laboratory hematology
KW - Measurable residual disease
KW - Stem cell transplantation
UR - http://www.scopus.com/inward/record.url?scp=85050818070&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85050818070&partnerID=8YFLogxK
U2 - 10.1016/j.bbmt.2018.06.010
DO - 10.1016/j.bbmt.2018.06.010
M3 - Article
C2 - 29933069
AN - SCOPUS:85050818070
VL - 24
SP - 2040
EP - 2046
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
SN - 1083-8791
IS - 10
ER -