Therapy-related acute promyelocytic leukemia: observations relating to APL pathogenesis and therapy.
Therapy-related acute promyelocytic leukemia (t-APL) is a well-recognized form of APL for which the underlying etiology has been well characterized. The pathogenesis of de novo (dn-APL) remains unknown; but epidemiologic studies have consistently identified increased body mass index (BMI), younger age, and ethnicity as possible risk factors. We analyzed demographics, clinical features, and treatment responses in a contemporary series of 64 patients treated with all-trans-retinoic acid and anthracycline-based therapy to assess for differences in these two etiologically distinct patient groups. Compared with patients with t-APL (n = 11), those with dn-APL (n = 53) had a greater median BMI (31.33 vs. 28.48), incidence of obesity (60.4% vs. 27.3%) (P = 0.04), and history of hyperlipidemia (45.3% vs. 18.2%) (P = 0.01). Fewer t-APL than dn-APL patients achieved complete remission at 63.6% vs. 92.5% respectively (P = 0.008). This was the result of a higher induction mortality rate of 36.4% vs. 7.5% respectively (P = 0.008). No cases of leukemic resistance were seen in either group. Overall survival (OS) was inferior in t-APL compared with dn-APL at 51% vs. 84%, respectively (P < 0.005), primarily as a result of higher induction mortality. Relapse occurred in nine patients (16.1%) overall, but no relapses occurred in the t-APL cohort. Our observations provide further support for the hypothesis that abnormalities in lipid homeostasis may in some way be of pathogenic importance in dn-APL. Therapy-related APL is sensitive to standard therapy with no cases of resistance or relapse seen. The inferior OS of the t-APL was due to induction mortality, possibly reflecting prior therapy.
Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN 55905, USA. Elliott.michelle@mayo.edu
Michelle A
MA
Elliott
Louis
L
Letendre
Ayalew
A
Tefferi
William J
WJ
Hogan
Christopher
C
Hook
Scott H
SH
Kaufmann
Rajiv K
RK
Pruthi
Animesh
A
Pardanani
Kebede H
KH
Begna
Aneel A
AA
Ashrani
Alexandra P
AP
Wolanskyj
Aref
A
Al-Kali
Mark R
MR
Litzow
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D015331:Cohort Studies; D005260:Female; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000209:etiology* / Q000401:mortality / Q000628:therapy; D008297:Male; D008875:Middle Aged; D011878:Radiotherapy / Q000009:adverse effects; D012008:Recurrence; D012307:Risk Factors; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult
D000970:Antineoplastic Agents