TY - JOUR
T1 - Low-dose cytarabine to prevent myeloid leukemia in children with down syndrome
T2 - TMD prevention 2007 study
AU - Flasinski, Marius
AU - Scheibke, Kira
AU - Zimmermann, Martin
AU - Creutzig, Ursula
AU - Reinhardt, Katarina
AU - Verwer, Femke
AU - De Haas, Valerie
AU - Van Der Velden, Vincent H.J.
AU - Von Neuhoff, Christine
AU - Michel Zwaan, C.
AU - Reinhardt, Dirk
AU - Klusmann, Jan Henning
N1 - Publisher Copyright:
© 2018 by The American Society of Hematology.
PY - 2018/7/10
Y1 - 2018/7/10
N2 - Approximately 5% to 10% of children with Down syndrome (DS) are diagnosed with transient myeloproliferative disorder (TMD). Approximately 20% of these patients die within 6 months (early death), and another 20% to 30% progress to myeloid leukemia (ML-DS) within their first 4 years of life. The aim of the multicenter, nonrandomized, historically controlled TMD Prevention 2007 trial was to evaluate the impact of low-dose cytarabine treatment on survival and prevention of ML-DS in patients with TMD. Patients received cytarabine (1.5 mg/kg for 7 days) in case of TMD-related symptoms at diagnosis (high white blood cell count, ascites, liver dysfunction, hydrops fetalis) or detection of minimal residual disease (MRD) 8 weeks after diagnosis. The 5-year probability of event-free and overall survival of 102 enrolled TMD patients was 72 6 5% and 91 6 3%, respectively. In patients eligible for treatment because of symptoms (n 5 43), we observed a significantly lower cumulative incidence (CI) of early death as compared with symptomatic patients in the historical control (n 5 45) (12 6 5% vs 33 6 7%, PGray 5 .02). None of the asymptomatic patients in the current study suffered early death. However, the treatment of symptomatic or MRD-positive patients did not result in a significantly lower CI of ML-DS (25 6 7% [treated] vs 14 6 7% [untreated], PGray 5 .34 [per protocol analysis]; historical control: 22 6 4%, PGray 5 .55). Thus, low-dose cytarabine treatment helped to reduce TMD-related mortality when compared with the historical control but was insufficient to prevent progression to ML-DS. This trial was registered at EudraCT as #2006-002962-20.
AB - Approximately 5% to 10% of children with Down syndrome (DS) are diagnosed with transient myeloproliferative disorder (TMD). Approximately 20% of these patients die within 6 months (early death), and another 20% to 30% progress to myeloid leukemia (ML-DS) within their first 4 years of life. The aim of the multicenter, nonrandomized, historically controlled TMD Prevention 2007 trial was to evaluate the impact of low-dose cytarabine treatment on survival and prevention of ML-DS in patients with TMD. Patients received cytarabine (1.5 mg/kg for 7 days) in case of TMD-related symptoms at diagnosis (high white blood cell count, ascites, liver dysfunction, hydrops fetalis) or detection of minimal residual disease (MRD) 8 weeks after diagnosis. The 5-year probability of event-free and overall survival of 102 enrolled TMD patients was 72 6 5% and 91 6 3%, respectively. In patients eligible for treatment because of symptoms (n 5 43), we observed a significantly lower cumulative incidence (CI) of early death as compared with symptomatic patients in the historical control (n 5 45) (12 6 5% vs 33 6 7%, PGray 5 .02). None of the asymptomatic patients in the current study suffered early death. However, the treatment of symptomatic or MRD-positive patients did not result in a significantly lower CI of ML-DS (25 6 7% [treated] vs 14 6 7% [untreated], PGray 5 .34 [per protocol analysis]; historical control: 22 6 4%, PGray 5 .55). Thus, low-dose cytarabine treatment helped to reduce TMD-related mortality when compared with the historical control but was insufficient to prevent progression to ML-DS. This trial was registered at EudraCT as #2006-002962-20.
UR - http://www.scopus.com/inward/record.url?scp=85062522199&partnerID=8YFLogxK
U2 - 10.1182/bloodadvances.2018018945
DO - 10.1182/bloodadvances.2018018945
M3 - Article
C2 - 29959152
AN - SCOPUS:85062522199
SN - 2473-9529
VL - 2
SP - 1532
EP - 1540
JO - Blood Advances
JF - Blood Advances
IS - 13
ER -