Minimal residual disease by either flow cytometry or cytogenetics prior to an allogeneic hematopoietic stem cell transplant is associated with poor outcome in acute myeloid leukemia

Maxim Norkin, Lakshmikanth Katragadda, Fei Zou, Sican Xiong, Myron Chang, Yunfeng Dai, Jack W. Hsu, Jan S. Moreb, Helen Leather, Hemant S. Murthy, Nosha Farhadfar, Ying Li, Robert A Hromas, Randy A. Brown, Christopher R. Cogle, John R. Wingard

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Relapsed acute myeloid leukemia (AML) is a significant challenge after allogeneic hematopoietic cell transplant (HCT). Multiparameter flow cytometry (MFC), conventional cytogenetics (CG), and fluorescence in situ hybridization (FISH) are routinely performed on bone marrow specimens prior to HCT to assess disease status. We questioned the extent by which pre-HCT evidence of minimal residual disease (MRD) detected by these standard assays, corresponded with post-HCT relapse. We conducted a single center, retrospective study of 166 AML patients who underwent HCT. Thirty-eight of one hundred sixty-six (23%) patients in complete remission (CR) or CR with incomplete count recovery (CRi) had MRD detectable by MFC, CG, or FISH. MRD was more frequently seen in patients with poor risk karyotype at diagnosis (P = 0.011). MRD-negative patients (MRDneg) had significantly longer overall survival (OS) and relapse-free survival than patients who were MRD positive (MRDpos) (P = 0.002 and 0.013, respectively). In patients with MRDpos prior to HCT, the presence of acute graft vs. host disease (GVHD) (grade ≥ 2) or chronic GVHD significantly improved progression free survival (PFS) (hazard ratio (HR) = 0.053 (95% confidence interval (CI): 0.01-0.279), P = 0.0005) and OS (HR = 0.211 (95% CI: 0.081-0.547), P = 0.0014).

Original languageEnglish (US)
Article number634
JournalBlood Cancer Journal
Volume7
Issue number12
DOIs
StatePublished - Dec 1 2017
Externally publishedYes

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Residual Neoplasm
Hematopoietic Stem Cells
Acute Myeloid Leukemia
Cytogenetics
Flow Cytometry
Transplants
Fluorescence In Situ Hybridization
Survival
Confidence Intervals
Recurrence
Karyotype
Disease-Free Survival
Retrospective Studies
Bone Marrow

ASJC Scopus subject areas

  • Hematology
  • Oncology

Cite this

Minimal residual disease by either flow cytometry or cytogenetics prior to an allogeneic hematopoietic stem cell transplant is associated with poor outcome in acute myeloid leukemia. / Norkin, Maxim; Katragadda, Lakshmikanth; Zou, Fei; Xiong, Sican; Chang, Myron; Dai, Yunfeng; Hsu, Jack W.; Moreb, Jan S.; Leather, Helen; Murthy, Hemant S.; Farhadfar, Nosha; Li, Ying; Hromas, Robert A; Brown, Randy A.; Cogle, Christopher R.; Wingard, John R.

In: Blood Cancer Journal, Vol. 7, No. 12, 634, 01.12.2017.

Research output: Contribution to journalArticle

Norkin, M, Katragadda, L, Zou, F, Xiong, S, Chang, M, Dai, Y, Hsu, JW, Moreb, JS, Leather, H, Murthy, HS, Farhadfar, N, Li, Y, Hromas, RA, Brown, RA, Cogle, CR & Wingard, JR 2017, 'Minimal residual disease by either flow cytometry or cytogenetics prior to an allogeneic hematopoietic stem cell transplant is associated with poor outcome in acute myeloid leukemia', Blood Cancer Journal, vol. 7, no. 12, 634. https://doi.org/10.1038/s41408-017-0007-x
Norkin, Maxim ; Katragadda, Lakshmikanth ; Zou, Fei ; Xiong, Sican ; Chang, Myron ; Dai, Yunfeng ; Hsu, Jack W. ; Moreb, Jan S. ; Leather, Helen ; Murthy, Hemant S. ; Farhadfar, Nosha ; Li, Ying ; Hromas, Robert A ; Brown, Randy A. ; Cogle, Christopher R. ; Wingard, John R. / Minimal residual disease by either flow cytometry or cytogenetics prior to an allogeneic hematopoietic stem cell transplant is associated with poor outcome in acute myeloid leukemia. In: Blood Cancer Journal. 2017 ; Vol. 7, No. 12.
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abstract = "Relapsed acute myeloid leukemia (AML) is a significant challenge after allogeneic hematopoietic cell transplant (HCT). Multiparameter flow cytometry (MFC), conventional cytogenetics (CG), and fluorescence in situ hybridization (FISH) are routinely performed on bone marrow specimens prior to HCT to assess disease status. We questioned the extent by which pre-HCT evidence of minimal residual disease (MRD) detected by these standard assays, corresponded with post-HCT relapse. We conducted a single center, retrospective study of 166 AML patients who underwent HCT. Thirty-eight of one hundred sixty-six (23{\%}) patients in complete remission (CR) or CR with incomplete count recovery (CRi) had MRD detectable by MFC, CG, or FISH. MRD was more frequently seen in patients with poor risk karyotype at diagnosis (P = 0.011). MRD-negative patients (MRDneg) had significantly longer overall survival (OS) and relapse-free survival than patients who were MRD positive (MRDpos) (P = 0.002 and 0.013, respectively). In patients with MRDpos prior to HCT, the presence of acute graft vs. host disease (GVHD) (grade ≥ 2) or chronic GVHD significantly improved progression free survival (PFS) (hazard ratio (HR) = 0.053 (95{\%} confidence interval (CI): 0.01-0.279), P = 0.0005) and OS (HR = 0.211 (95{\%} CI: 0.081-0.547), P = 0.0014).",
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AU - Norkin, Maxim

AU - Katragadda, Lakshmikanth

AU - Zou, Fei

AU - Xiong, Sican

AU - Chang, Myron

AU - Dai, Yunfeng

AU - Hsu, Jack W.

AU - Moreb, Jan S.

AU - Leather, Helen

AU - Murthy, Hemant S.

AU - Farhadfar, Nosha

AU - Li, Ying

AU - Hromas, Robert A

AU - Brown, Randy A.

AU - Cogle, Christopher R.

AU - Wingard, John R.

PY - 2017/12/1

Y1 - 2017/12/1

N2 - Relapsed acute myeloid leukemia (AML) is a significant challenge after allogeneic hematopoietic cell transplant (HCT). Multiparameter flow cytometry (MFC), conventional cytogenetics (CG), and fluorescence in situ hybridization (FISH) are routinely performed on bone marrow specimens prior to HCT to assess disease status. We questioned the extent by which pre-HCT evidence of minimal residual disease (MRD) detected by these standard assays, corresponded with post-HCT relapse. We conducted a single center, retrospective study of 166 AML patients who underwent HCT. Thirty-eight of one hundred sixty-six (23%) patients in complete remission (CR) or CR with incomplete count recovery (CRi) had MRD detectable by MFC, CG, or FISH. MRD was more frequently seen in patients with poor risk karyotype at diagnosis (P = 0.011). MRD-negative patients (MRDneg) had significantly longer overall survival (OS) and relapse-free survival than patients who were MRD positive (MRDpos) (P = 0.002 and 0.013, respectively). In patients with MRDpos prior to HCT, the presence of acute graft vs. host disease (GVHD) (grade ≥ 2) or chronic GVHD significantly improved progression free survival (PFS) (hazard ratio (HR) = 0.053 (95% confidence interval (CI): 0.01-0.279), P = 0.0005) and OS (HR = 0.211 (95% CI: 0.081-0.547), P = 0.0014).

AB - Relapsed acute myeloid leukemia (AML) is a significant challenge after allogeneic hematopoietic cell transplant (HCT). Multiparameter flow cytometry (MFC), conventional cytogenetics (CG), and fluorescence in situ hybridization (FISH) are routinely performed on bone marrow specimens prior to HCT to assess disease status. We questioned the extent by which pre-HCT evidence of minimal residual disease (MRD) detected by these standard assays, corresponded with post-HCT relapse. We conducted a single center, retrospective study of 166 AML patients who underwent HCT. Thirty-eight of one hundred sixty-six (23%) patients in complete remission (CR) or CR with incomplete count recovery (CRi) had MRD detectable by MFC, CG, or FISH. MRD was more frequently seen in patients with poor risk karyotype at diagnosis (P = 0.011). MRD-negative patients (MRDneg) had significantly longer overall survival (OS) and relapse-free survival than patients who were MRD positive (MRDpos) (P = 0.002 and 0.013, respectively). In patients with MRDpos prior to HCT, the presence of acute graft vs. host disease (GVHD) (grade ≥ 2) or chronic GVHD significantly improved progression free survival (PFS) (hazard ratio (HR) = 0.053 (95% confidence interval (CI): 0.01-0.279), P = 0.0005) and OS (HR = 0.211 (95% CI: 0.081-0.547), P = 0.0014).

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