The impact of therapy-related acute myeloid leukemia (AML) on outcome in 2853 adult patients with newly diagnosed AML.
To study the characteristics and clinical impact of therapy-related acute myeloid leukemia (t-AML). 200 patients (7.0%) had t-AML and 2653 de novo AML (93%). Patients with t-AML were older (P < .0001) and they had lower white blood counts (P = .003) compared with de novo AML patients; t-AML patients had abnormal cytogenetics more frequently, with overrepresentation of 11q23 translocations as well as adverse cytogenetics, including complex and monosomal karyotypes, and with underrepresentation of intermediate-risk karyotypes (P < .0001); t-AML patients had NPM1 mutations (P < .0001) and FLT3 internal tandem duplications (P = .0005) less frequently. Younger age at diagnosis of primary malignancy and treatment with intercalating agents as well as topoisomerase II inhibitors were associated with shorter latency periods to the occurrence of t-AML. In multivariable analyses, t-AML was an adverse prognostic factor for death in complete remission but not relapse in younger intensively treated patients (P < .0001 and P = .39, respectively), relapse but not death in complete remission in older, less intensively treated patients (P = .02 and P = .22, respectively) and overall survival in younger intensively treated patients (P = .01). In more intensively treated younger adults, treatment-related toxicity had a major negative impact on outcome, possibly reflecting cumulative toxicity of cancer treatment.
Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany.
Sabine
S
Kayser
Konstanze
K
Döhner
Jürgen
J
Krauter
Claus-Henning
CH
Köhne
Heinz A
HA
Horst
Gerhard
G
Held
Marie
M
von Lilienfeld-Toal
Sibylla
S
Wilhelm
Andrea
A
Kündgen
Katharina
K
Götze
Mathias
M
Rummel
David
D
Nachbaur
Brigitte
B
Schlegelberger
Gudrun
G
Göhring
Daniela
D
Späth
Carina
C
Morlok
Manuela
M
Zucknick
Arnold
A
Ganser
Hartmut
H
Döhner
Richard F
RF
Schlenk
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects; D002869:Chromosome Aberrations; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000209:etiology* / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009381:Neoplasms, Radiation-Induced / Q000209:etiology / Q000235:genetics / Q000401:mortality; D016609:Neoplasms, Second Primary / Q000209:etiology* / Q000235:genetics* / Q000401:mortality; D009687:Nuclear Proteins / Q000235:genetics; D000090243:Nucleophosmin; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D055815:Young Adult; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics
D000970:Antineoplastic Agents; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3