[Clonal evolution of abnormal Philadelphia chromosome-negative cells after imatinib mesylate therapy in patients with Philadelphia chromosome-positive chronic myelogenous leukemia].
OBJECTIVE
To investigate clonal evolution of abnormal Philadelphia chromosome-negative cells (Ph- CE) after imatinib mesylate therapy in patients with Philadelphia chromosome-positive chronic myelogenous leukemia (Ph+ CML).


METHODS
Bone marrow cells G-banding karyotype was evaluated every 3 months in 100 patients with Ph+ CML after achieving hematologic responses on the course of imatinib therapy. There were 54 patients in chronic phase (CP), 37 in accelerated phase (AP) and 9 in blast phase (BP).


RESULTS
After a median follow-up of 32 months (ranged 25-34 months), 11 patients, including 5 cases in CP, 5 in AP and 1 in BP, developed transient, interrupted or continuous Ph- CE after 3 - 29 months on imatinib therapy. Ph- CE emerged at the beginning of Ph+ cells decreasing or after Ph+ cells disappearing. The proportion of Ph- CE, was negatively correlated with the proportion of Ph+ cells (P < 0.05). Ph- CE commonly included +8 (45.5%) and +Y (27.3%). Five patients had additional cytogenetic abnormalities besides Ph+ in Ph- CE. Seven of the patients with Ph- CE achieved a major cytogenetic response while 9 of them achieved a complete hematologic response. One patient with Ph- CE in AP progressed to BP 20 months after the initiation of the therapy while the rests remained in hematologic or cytogenetic responses.


CONCLUSIONS
Ph- CE occurred in about 11% of the patients with Ph+ CML who achieved major or minor cytogenetic responses on imatinib therapy. After a median follow-up of more than 2 years, most of the patients with Ph- CE were in a stable status with no disease progression.
Jiang
Qian
Q
Institute of Hematology of People's Hospital, Peking University, Beijing 100044, China.
Chen
Shan-shan
SS
Jiang
Bin
B
Jiang
Hao
H
Lu
Ying
Y
Qiu
Jing-ying
JY
Lu
Dao-pei
DP
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001549:Benzamides; D002999:Clone Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000068877:Imatinib Mesylate; D007621:Karyotyping; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D054438:Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010677:Philadelphia Chromosome; D010879:Piperazines / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate