Journal
JOURNAL OF HEMATOLOGY & ONCOLOGY
Volume 10, Issue -, Pages -Publisher
BMC
DOI: 10.1186/s13045-017-0404-4
Keywords
Acute promyelocytic leukemia; WT1; FLT3 mutation; Minimal residual disease
Categories
Funding
- Research Fund of Seoul St. Mary's Hospital
- The Catholic University of Korea
- Basic Science Research Program through the National Research Foundation of Korea (NRF) -Ministry of Education [2015R1D1A1A01059819]
- National Research Foundation of Korea [2015R1D1A1A01059819] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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Wilms' tumor gene 1 (WT1) expression is a well-known predictor for relapse in acute myeloid leukemia. We monitored WT1 decrement along the treatment course to identify its significant role as a marker for residual disease in acute promyelocytic leukemia (APL) and tried to suggest its significance for relapse prediction. In this single center retrospective study, we serially measured PML-RARa and WT1 expression from 117 APL patients at diagnosis, at post induction and post consolidation chemotherapies, and at every 3 months after starting maintenance therapy. All 117 patients were in molecular remission after treatment of at least 2 consolidation chemotherapies. We used WT1 ProfileQuant (TM) kit (Ipsogen) for WT1 monitoring. High WT1 expression (>120 copies/104ABL1) after consolidation and at early period (3 months) after maintenance therapy significantly predicted subsequent relapse. All paired PML-RARa RQ-PCR were not detected except for one sample with early relapse. Patients with high WT1 expression at 3 months after maintenance therapy (n =40) showed a significantly higher relapse rate (30.5 vs. 6.9%, P < 0.001) and inferior disease free survival (62.8 vs. 91.4%, P < 0.001). Multivariate analysis revealed that high peak leukocyte counts at diagnosis (HR =6.4, P < 0.001) and high WT1 expression at 3 months after maintenance therapy (HR=7.1, P < 0.001) were significant factors for prediction of relapse. Our data showed high post-remission WT1 expression was a reliable marker for prediction of subsequent molecular relapse in APL. In this high-risk group, early intervention with ATRA +/- ATO, anti-CD33 antibody therapy, and WT1-specific therapy may be used for relapse prevention.
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