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.
Deininger
Michael
M
Center for Hematologic Malignancies, Oregon Health & Science University, Portland, OR 97239, USA. deininge@ohsu.edu
Schleuning
Michael
M
Greinix
Hilde
H
Sayer
Herbert Gottfried
HG
Fischer
Thomas
T
Martinez
Jesus
J
Maziarz
Richard
R
Olavarria
Eduardo
E
Verdonck
Leo
L
Schaefer
Kerstin
K
Boqué
Conxa
C
Faber
Edgar
E
Nagler
Arnon
A
Pogliani
Enrico
E
Russell
Nigel
N
Volin
Liisa
L
Schanz
Urs
U
Doelken
Gottfried
G
Kiehl
Michael
M
Fauser
Axel
A
Druker
Brian
B
Sureda
Anna
A
Iacobelli
Simona
S
Brand
Ronald
R
Krahl
Rainer
R
Lange
Thoralf
T
Hochhaus
Andreas
A
Gratwohl
Alois
A
Kolb
Hans
H
Niederwieser
Dietger
D
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