Complete remission and early death after intensive chemotherapy in patients aged 60 years or older with acute myeloid leukaemia: a web-based application for prediction of outcomes.
BACKGROUND
About 50% of patients (age ≥60 years) who have acute myeloid leukaemia and are otherwise medically healthy (ie, able to undergo intensive chemotherapy) achieve a complete remission (CR) after intensive chemotherapy, but with a substantially increased risk of early death (ED) compared with younger patients. We verified the association of standard clinical and laboratory variables with CR and ED and developed a web-based application for risk assessment of intensive chemotherapy in these patients.


METHODS
Multivariate regression analysis was used to develop risk scores with or without knowledge of the cytogenetic and molecular risk profiles for a cohort of 1406 patients (aged ≥60 years) with acute myeloid leukaemia, but otherwise medically healthy, who were treated with two courses of intensive induction chemotherapy (tioguanine, standard-dose cytarabine, and daunorubicin followed by high-dose cytarabine and mitoxantrone; or with high-dose cytarabine and mitoxantrone in the first and second induction courses) in the German Acute Myeloid Leukaemia Cooperative Group 1999 study. Risk prediction was validated in an independent cohort of 801 patients (aged >60 years) with acute myeloid leukaemia who were given two courses of cytarabine and daunorubicin in the Acute Myeloid Leukaemia 1996 study.


RESULTS
Body temperature, age, de-novo leukaemia versus leukaemia secondary to cytotoxic treatment or an antecedent haematological disease, haemoglobin, platelet count, fibrinogen, and serum concentration of lactate dehydrogenase were significantly associated with CR or ED. The probability of CR with knowledge of cytogenetic and molecular risk (score 1) was from 12% to 91%, and without knowledge (score 2) from 21% to 80%. The predicted risk of ED was from 6% to 69% for score 1 and from 7% to 63% for score 2. The predictive power of the risk scores was confirmed in the independent patient cohort (CR score 1, from 10% to 91%; CR score 2, from 16% to 80%; ED score 1, from 6% to 69%; and ED score 2, from 7% to 61%).


CONCLUSIONS
The scores for acute myeloid leukaemia can be used to predict the probability of CR and the risk of ED in older patients with acute myeloid leukaemia, but otherwise medically healthy, for whom intensive induction chemotherapy is planned. This information can help physicians with difficult decisions for treatment of these patients.


BACKGROUND
Deutsche Krebshilfe and Deutsche Forschungsgemeinschaft.
Department of Medicine A, Haematology and Oncology, University of Münster, Münster, Germany. utz.krug@ukmuenster.de
Utz
U
Krug
Christoph
C
Röllig
Anja
A
Koschmieder
Achim
A
Heinecke
Maria Cristina
MC
Sauerland
Markus
M
Schaich
Christian
C
Thiede
Michael
M
Kramer
Jan
J
Braess
Karsten
K
Spiekermann
Torsten
T
Haferlach
Claudia
C
Haferlach
Steffen
S
Koschmieder
Christian
C
Rohde
Hubert
H
Serve
Bernhard
B
Wörmann
Wolfgang
W
Hiddemann
Gerhard
G
Ehninger
Wolfgang E
WE
Berdel
Thomas
T
Büchner
Carsten
C
Müller-Tidow
D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003561:Cytarabine / Q000008:administration & dosage; D003630:Daunorubicin / Q000008:administration & dosage; D005260:Female; D005858:Germany; D006801:Humans; D020407:Internet; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D011379:Prognosis; D012044:Regression Analysis; D012074:Remission Induction; D018570:Risk Assessment; D012307:Risk Factors; D011795:Surveys and Questionnaires; D013997:Time Factors
D003561:Cytarabine; D008942:Mitoxantrone; D003630:Daunorubicin