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A Scoring System To Predict The Risk Of Death During Induction
Chemotherapy For De Novo Acute Myeloid Leukemia.
1David Valcárcel, 2Pau Montesinos, 3Isabel Sánchez-Ortega, 1Salut Brunet, 4Jordi Esteve, 2David M. Cuadrón, 5José M. Ribera, 6Mar Tormo, 7Javier
Bueno, 8Rafael Duarte, 9Andrés Llorente, 10P. Torres, 11Ramón Guardia, 2Miguel A Sanz, and 1Jorge
Sierra; on behalf of the CETLAM Group.
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Background
• Induction chemotherapy of acute myeloid leukemia (AML), the first step to cure this disease, is associated to substantial mortality due to infections, hemorrhages
• up to 10-20% of patients die during induction phase
• the identification of patients at high risk of induction death (ID) may allow the individualization of the chemotherapy regimens and supportive measures 2
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Background
• risk factors associated to higher rates of ID older age, high leukocyte count, and bad performance status
• only few studies designed to build scoring systems to predict accurately the risk of ID
• often including a high number of variables and may not be easy to use in the daily clinical practice
• none has been validated in an external cohort of AML patients
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Objectives
• identify the risk factors for ID in a large cohort of 570 consecutive patients treated between 1999 and 2006 in 20 Spanish centers of the CETLAM group
• Using these risk factors, we aim to build a scoring system to predict ID
• The external validity of the scoring system was tested in an independent set of patients from a single institution
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Performance status / ComorbilidadSuperv. Global
Grupo ECOG Baja
Charlson comorbidity index (CCI) Baja
Hematopoietic cell transplantation comorbidity index (HCT-CI) Baja
Estado general y Pronóstico tras QT intensiva en pacientes mayores de 60-70 años con SMD/LMA
Tasa de RC
Baja
Baja
ND
No. Ptes
998
133
177
Kantarjian H, et al. Cancer 2006; 106:1090-1198.Etienne A, et al. Cancer 2007; 109:1376-1383.Giles FJ, et al. Br J Haematol 2007; 136:624-627.
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SG tras QT intensivaen LMA/SMD según HCT-CI
GilesFJ, et al. Br J Haematol 2007; 136:624-627.
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Methods and Patients
• 570 patients included in two multicenter trials of the CETLAM Group to develop a scoring system (study cohort)
• The scoring system was tested in 209 consecutive patients from an external single institution (validation cohort)
• induction regimens consisted of anthracycline and cytarabine combination with or without etoposide
• ID was defined as death in the first 42 days without evidence of leukemic resistance.
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0
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Days after Start of Induction
Cum
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th
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Days after Start of Induction
Cum
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k of
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th
P<0.001
Low-risk
Intermediate-risk
High-risk
Figure 1Figure 1
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0
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Days after Start of Induction
Cum
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0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42
Days after Start of Induction
Cum
ulat
ive
Ris
k of
Dea
th
P<0.001
Low-risk
Intermediate-risk
High-risk
Figure 2Figure 2
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Conclusions
• our validated scoring system allows easy risk stratification for ID in the clinical setting
• However, our scoring system is not optimal for the risk-adapted implementation of specific supportive measures
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Conclusions
• may be helpful to design risk-adapted induction strategies
• But patient selection depends also on some variables predicting ID (comorbidities, PS, and other)
• leukemic characteristics affecting the chances to achieve a CR (cytogenetics and FLT3-ITD mutations), as well as other circumstances (e.g., patient, family and physician preferences), will also influence the patient selection