Therapy-related myeloid neoplasms in patients with acute promyelocytic leukemia treated with all-trans-retinoic Acid and anthracycline-based chemotherapy.
OBJECTIVE
We analyzed the incidence, risk factors, and outcome of therapy-related myeloid neoplasms (t-MNs) in patients with acute promyelocytic leukemia (APL) in first complete remission (CR).


METHODS
From 1996 to 2008, 1,025 patients with APL were enrolled onto three sequential trials (LPA96, LPA99, and LPA2005) of the Programa Español para el Tratamiento de Enfermedades Hematológicas and received induction and consolidation therapy with all-trans-retinoic acid (ATRA) and anthracycline-based chemotherapy.


RESULTS
Seventeen of 918 patients who achieved CR developed t-MN (10 with < 20% and seven with > or = 20% of bone marrow blasts) after a median of 43 months from CR. Partial and complete deletions of chromosomes 5 and 7 (nine patients) and 11q23 rearrangements (three patients) were the most common cytogenetic abnormalities. Overall, the 6-year cumulative incidence of t-MN was 2.2%, whereas in low-, intermediate-, and high-risk patients, the 6-year incidence was 5.2%, 2.1%, and 0%, respectively. Multivariate analysis identified age more than 35 years and lower relapse risk score as independent prognostic factors for t-MN. The median overall survival time after t-MN was 10 months.


CONCLUSIONS
t-MN is a relatively infrequent, long-term, and severe complication after first-line treatment for APL with ATRA and anthracycline-based regimens. Therapeutic strategies to reduce the incidence of t-MN are warranted.
Montesinos
Pau
P
Christian Medical College, Vellore, India.
González
José D
JD
González
José
J
Rayón
Chelo
C
de Lisa
Elena
E
Amigo
Maria L
ML
Ossenkoppele
Gert J
GJ
Peñarrubia
María J
MJ
Pérez-Encinas
Manuel
M
Bergua
Juan
J
Debén
Guillermo
G
Sayas
María J
MJ
de la Serna
Javier
J
Ribera
Josep M
JM
Bueno
Javier
J
Milone
Gustavo
G
Rivas
Concha
C
Brunet
Salut
S
Löwenberg
Bob
B
Sanz
Miguel
M
D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000008:administration & dosage / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects*; D019046:Bone Marrow Neoplasms / Q000139:chemically induced* / Q000453:epidemiology; D005260:Female; D006801:Humans; D015994:Incidence; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000139:chemically induced* / Q000453:epidemiology; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D016896:Treatment Outcome; D014212:Tretinoin / Q000008:administration & dosage / Q000009:adverse effects*
D018943:Anthracyclines; D014212:Tretinoin