Epidemiologic study on survival of chronic myeloid leukemia and Ph(+) acute lymphoblastic leukemia patients with BCR-ABL T315I mutation.
The BCR-ABL T315I mutation represents a major mechanism of resistance to tyrosine kinase inhibitors (TKIs). The objectives of this retrospective observational study were to estimate overall and progression-free survival for chronic myeloid leukemia in chronic-phase (CP), accelerated-phase (AP), or blastic-phase (BP) and Philadelphia chromosome-positive (Ph)(+) acute lymphoblastic leukemia (ALL) patients with T315I mutation. Medical records of 222 patients from 9 countries were reviewed; data were analyzed using log-rank tests and Cox proportional hazard models. Median age at T315I mutation detection was 54 years; 57% cases were men. Median time between TKI treatment initiation and T315I mutation detection was 29.2, 15.4, 5.8, and 9.1 months, respectively, for CP, AP, BP, and Ph(+) ALL patients. After T315I mutation detection, second-generation TKIs were used in 56% of cases, hydroxyurea in 39%, imatinib in 35%, cytarabine in 26%, MK-0457 in 11%, stem cell transplantation in 17%, and interferon-alpha in 6% of cases. Median overall survival from T315I mutation detection was 22.4, 28.4, 4.0, and 4.9 months, and median progression-free survival was 11.5, 22.2, 1.8, and 2.5 months, respectively, for CP, AP, BP, and Ph(+) ALL patients. These results confirm that survival of patients harboring a T315I mutation is dependent on disease phase at the time of mutation detection.
Hematology Department, E Pavilion, Hôpital Edouard Herriot, 5 place d'Arsonval, 69437 Lyon, Cédex 03, France. franckemmanuel.nicolini@chu-lyon.fr
Franck E
FE
Nicolini
Michael J
MJ
Mauro
Giovanni
G
Martinelli
Dong-Wook
DW
Kim
Simona
S
Soverini
Martin C
MC
Müller
Andreas
A
Hochhaus
Jorge
J
Cortes
Charles
C
Chuah
Inge H
IH
Dufva
Jane F
JF
Apperley
Fumiharu
F
Yagasaki
Jay D
JD
Pearson
Senaka
S
Peter
Cesar
C
Sanz Rodriguez
Claude
C
Preudhomme
Francis
F
Giles
John M
JM
Goldman
Wei
W
Zhou
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D016313:Genes, abl / Q000235:genetics*; D006801:Humans; D053208:Kaplan-Meier Estimate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D012189:Retrospective Studies; D055815:Young Adult