Stem cell transplantation for patients with chronic myeloid leukemia resistant to tyrosine kinase inhibitors with BCR-ABL kinase domain mutation T315I.
BACKGROUND
Resistance to tyrosine kinase inhibitor (TKIs) therapy is associated with the development of kinase domain mutations. Although many imatinib-resistant mutations respond well to second-generation TKIs, the threonine-to-isoleucine mutation at codon 315 of the breakpoint cluster region/v-abl Abelson murine leukemia viral oncogene protein fusion Bcr-Abl (T315I) is insensitive to all currently available TKIs. The outcome in such patients after stem cell transplantation (SCT) is unknown.


METHODS
Eight patients with TKI-resistant CML who had T315I mutations underwent 9 transplantations. At the time of SCT, 2 patients were in chronic phase, 3 patients were in accelerated phase; and 3 patients were in second chronic phase.


RESULTS
The best responses after SCT were a complete molecular response (CMR) in 3 patients, a complete cytogenetic response (CCyR) in 4 patients, and a complete hematologic response (CHR) in 1 patient, and 1 patient had no response. The best outcome was for patients who underwent transplantation in chronic phase, and both of those patients remained alive and in complete molecular remission 14 months and 42 months after SCT. After a median follow-up of 13 months from SCT, 5 patients remained alive, including 3 patients in CMR, 1 patient in CCyR, and 1 patient in CHR.


CONCLUSIONS
The current results indicated that SCT is an effective strategy for patients with CML who have the T315I mutation, particularly in earlier stages.
Velev
Nikolai
N
Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Cortes
Jorge
J
Champlin
Richard
R
Jones
Dan
D
Rondon
Gabriela
G
Giralt
Sergio
S
Borthakur
Gautam
G
Kantarjian
Hagop M
HM
De Lima
Marcos
M
D000328:Adult; D001549:Benzamides; D019008:Drug Resistance, Neoplasm; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000628:therapy*; D008875:Middle Aged; D009154:Mutation; D010879:Piperazines / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D033581:Stem Cell Transplantation; D016896:Treatment Outcome
D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl