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Risk Markers for Significant Bleeding and Thrombosis in Pediatric Acute Promyelocytic Leukemia; Report From the
Madhvi Rajpurkar1, Todd A Alonzo2, Yi-Cheng Wang3
1Carman and Ann Adams Department of Pediatrics, Children's Hospital of Michigan, Wayne State University, Detroit, MI.
Insights
In pediatric acute promyelocytic leukemia (APL), high white blood cell (WBC) counts predict early death. A modified International Society on Thrombosis and Haemostasis (ISTH) score of 6 or higher better predicts coagulopathy events but still requires improved biomarkers.
Area of Science:
- Hematology
- Pediatric Oncology
- Coagulation Disorders
Background:
- Acute promyelocytic leukemia (APL) presents a high risk of coagulopathy, leading to significant morbidity and mortality.
- Predicting early death and coagulopathy in pediatric APL is crucial for timely intervention.
Purpose of the Study:
- To evaluate presenting white blood cell (WBC) count and the International Society on Thrombosis and Haemostasis (ISTH) disseminated intravascular coagulation (DIC) scoring system.
- To identify reliable markers for early death and nonlethal coagulopathy in pediatric APL patients.
Main Methods:
- Analysis of 79 pediatric APL patients from a Children's Oncology Group phase III clinical trial.
- Evaluation of presenting WBC and ISTH DIC scores (thresholds ≥5 and ≥6) against early death and coagulopathy events.
Main Results:
- Elevated presenting WBC was significantly associated with early death (p<0.05).
- An ISTH DIC score ≥6 showed significant association with early death (12% vs. 0%) and coagulopathy events (35% vs. 11%).
- The ISTH DIC score ≥6 had suboptimal sensitivity (70.6%) and specificity (64.5%) for predicting coagulopathy.
Conclusions:
- Presenting WBC count is a valuable marker for early death risk in pediatric APL.
- A modified ISTH DIC score (≥6) improves prediction of coagulopathy but highlights the need for novel biomarkers.
- Further research is needed to identify more accurate biomarkers for APL-associated coagulopathy.
Abstract:
Acute promyelocytic leukemia (APL) is characterized by a heightened risk of coagulopathy with significant morbidity and mortality. Here we report our evaluation of presenting white blood cell (WBC) and the International Society on Thrombosis and Haemostasis (ISTH) disseminated intravascular coagulation (DIC) scoring system as markers for early death and nonlethal coagulopathy in pediatric APL. We evaluated 79 pediatric patients treated on a Children's Oncology Group phase III clinical trial. There were 4 early deaths and 13 nonlethal, clinically significant (grade III to IV) coagulopathy events during induction. Elevated presenting WBC was significantly associated with early death but not with both lethal and nonlethal coagulopathy events. An ISTH DIC score of ≥5 (the original ISTH criteria for overt DIC) was not associated with either early deaths or coagulopathy events. An ISTH DIC score threshold of 6, however, was significantly associated with early death (12% score ≥6 vs. 0% score <6) and with both lethal and nonlethal coagulopathy events (35% score ≥6 vs. 11% score <6). In pediatric APL patients, the presenting WBC is a marker for risk of early death. Although the ISTH score using a cutoff of ≥6 showed improved correlation with adverse coagulation events during induction, the sensitivity was only 70.6% (95% confidence interval, 44.0%-89.7%) and the specificity was 64.5% (95% confidence interval, 51.3%-76.3%). Thus, there is a strong need to identify other biomarkers that can predict APL-associated coagulopathy.