The effect of prior exposure to imatinib on transplant-related mortality.
OBJECTIVE
Imatinib is an effective treatment for chronic myeloid leukemia (CML) and Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). However, relapse is common in patients with advanced or high risk disease. Such patients may be eligible for allogeneic stem cell transplantation (SCT), raising the question whether imatinib therapy may compromise the outcome of subsequent SCT.


METHODS
We retrospectively analyzed 70 patients with CML and 21 with Ph+ ALL who had received imatinib prior to SCT. Data were retrieved by directly contacting centers. Multivariate analysis was used to define factors associated with major outcomes (engraftment, graft-versus-host disease, relapse, non-relapse mortality) in addition to descriptive statistics. For the CML patients major outcomes were compared with those of historical controls drawn from the EBMT registry.


RESULTS
At SCT, 44% of CML patients were in accelerated phase or blast crisis and 40% of ALL patients had active disease compared to 84% and 95% prior to imatinib. At 24 months, estimated transplant-related mortality was 44% and estimated relapse mortality 24%. Factors associated with shorter overall and progression-free survival were advanced disease at SCT and a female donor/male recipient pairing. No unusual organ toxicities were observed. Compared to historical controls, prior imatinib treatment did not influence overall survival, progression-free survival or non-relapse mortality, while there was a trend towards higher relapse mortality and significantly less chronic graft-versus-host disease.


CONCLUSIONS
Within the limits of a heterogeneous and relatively small cohort of patients, we found no evidence that imatinib negatively affects major outcomes after SCT, suggesting that imatinib prior to SCT is safe.
Center for Hematologic Malignancies, Oregon Health & Science University, Portland, OR 97239, USA. deininge@ohsu.edu
Michael
M
Deininger
Michael
M
Schleuning
Hilde
H
Greinix
Herbert Gottfried
HG
Sayer
Thomas
T
Fischer
Jesus
J
Martinez
Richard
R
Maziarz
Eduardo
E
Olavarria
Leo
L
Verdonck
Kerstin
K
Schaefer
Conxa
C
Boqué
Edgar
E
Faber
Arnon
A
Nagler
Enrico
E
Pogliani
Nigel
N
Russell
Liisa
L
Volin
Urs
U
Schanz
Gottfried
G
Doelken
Michael
M
Kiehl
Axel
A
Fauser
Brian
B
Druker
Anna
A
Sureda
Simona
S
Iacobelli
Ronald
R
Brand
Rainer
R
Krahl
Thoralf
T
Lange
Andreas
A
Hochhaus
Alois
A
Gratwohl
Hans
H
Kolb
Dietger
D
Niederwieser
D000293:Adolescent; D000328:Adult; D001549:Benzamides; D002648:Child; D002675:Child, Preschool; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000401:mortality*; D006801:Humans; D000068877:Imatinib Mesylate; D007938:Leukemia / Q000401:mortality / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009026:Mortality; D010879:Piperazines / Q000494:pharmacology* / Q000627:therapeutic use; D011743:Pyrimidines / Q000494:pharmacology* / Q000627:therapeutic use; D012189:Retrospective Studies; D016896:Treatment Outcome
D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate