TY - JOUR
T1 - Minimal residual disease prior to allogeneic hematopoietic cell transplantation in acute myeloid leukemia
T2 - A meta-analysis
AU - Buckley, Sarah A.
AU - Wood, Brent L.
AU - Othus, Megan
AU - Hourigan, Christopher S.
AU - Ustun, Celalettin
AU - Linden, Michael A.
AU - Defor, Todd E.
AU - Malagola, Michele
AU - Anthias, Chloe
AU - Valkova, Veronika
AU - Kanakry, Christopher G.
AU - Gruhn, Bernd
AU - Buccisano, Francesco
AU - Devine, Beth
AU - Walter, Roland B.
N1 - Publisher Copyright:
© 2017 Ferrata Storti Foundation.
PY - 2017/4/30
Y1 - 2017/4/30
N2 - Minimal residual disease prior to allogeneic hematopoietic cell transplantation has been associated with increased risk of relapse and death in patients with acute myeloid leukemia, but detection methodologies and results vary widely. We performed a systematic review and meta-analysis evaluating the prognostic role of minimal residual disease detected by polymerase chain reaction or multipara-metric flow cytometry before transplant. We identified 19 articles published between January 2005 and June 2016 and extracted hazard ratios for leukemia-free survival, overall survival, and cumulative incidences of relapse and non-relapse mortality. Pre-transplant minimal residual disease was associated with worse leukemia-free survival (hazard ratio=2.76 [1.90-4.00]), overall survival (hazard ratio=2.36 [1.73-3.22]), and cumulative incidence of relapse (hazard ratio=3.65 [2.53-5.27]), but not non-relapse mortality (hazard ratio=1.12 [0.81-1.55]). These associations held regardless of detection method, conditioning intensity, and patient age. Adverse cytogenetics was not an independent risk factor for death or relapse. There was more heterogeneity among studies using flow cytometry-based than WT1 polymerase chain reaction-based detection (I2=75.1% vs. <0.1% for leukemia-free survival, 67.8% vs. <0.1% for overall survival, and 22.1% vs. <0.1% for cumulative incidence of relapse). These results demonstrate a strong relationship between pre-transplant minimal residual disease and post-transplant relapse and survival. Outcome heterogeneity among studies using flow-based methods may underscore site-specific methodological differences or differences in test performance and interpretation.
AB - Minimal residual disease prior to allogeneic hematopoietic cell transplantation has been associated with increased risk of relapse and death in patients with acute myeloid leukemia, but detection methodologies and results vary widely. We performed a systematic review and meta-analysis evaluating the prognostic role of minimal residual disease detected by polymerase chain reaction or multipara-metric flow cytometry before transplant. We identified 19 articles published between January 2005 and June 2016 and extracted hazard ratios for leukemia-free survival, overall survival, and cumulative incidences of relapse and non-relapse mortality. Pre-transplant minimal residual disease was associated with worse leukemia-free survival (hazard ratio=2.76 [1.90-4.00]), overall survival (hazard ratio=2.36 [1.73-3.22]), and cumulative incidence of relapse (hazard ratio=3.65 [2.53-5.27]), but not non-relapse mortality (hazard ratio=1.12 [0.81-1.55]). These associations held regardless of detection method, conditioning intensity, and patient age. Adverse cytogenetics was not an independent risk factor for death or relapse. There was more heterogeneity among studies using flow cytometry-based than WT1 polymerase chain reaction-based detection (I2=75.1% vs. <0.1% for leukemia-free survival, 67.8% vs. <0.1% for overall survival, and 22.1% vs. <0.1% for cumulative incidence of relapse). These results demonstrate a strong relationship between pre-transplant minimal residual disease and post-transplant relapse and survival. Outcome heterogeneity among studies using flow-based methods may underscore site-specific methodological differences or differences in test performance and interpretation.
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U2 - 10.3324/haematol.2016.159343
DO - 10.3324/haematol.2016.159343
M3 - Review article
C2 - 28126965
AN - SCOPUS:85018980067
SN - 0390-6078
VL - 102
SP - 865
EP - 873
JO - Haematologica
JF - Haematologica
IS - 5
ER -