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Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

Postal Subscription Code 80-967

2018 Impact Factor: 1.847

Front Med    2012, Vol. 6 Issue (2) : 204-211     DOI: 10.1007/s11684-012-0202-x
RESEARCH ARTICLE |
Prognostic analysis of chronic myeloid leukemia in Chinese population in an imatinib era
Haiyan He, Yang Shen, Yongmei Zhu, Saijuan Chen()
Shanghai Institute of Hematology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
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Abstract  

We evaluated the outcomes of chronic myeloid leukemia (CML) patients in three clinical phases, namely, chronic (CP), accelerated (AP), and blast (BP) phases, receiving imatinib treatment. The single-institution treatment experiences of Chinese patients with CML were presented. A total of 275 CML patients (CP, 210; AP, 24; and BP, 41) who received imatinib between February 2001 and April 2008 were enrolled in this study. We evaluated the responses (hematologic, cytogenetic, and molecular), overall survival (OS), treatment event-free survival (EFS), and prognostic factors of outcome. At the cut-off point, the complete cytogenetic response (CCyR) and complete molecular response rates of patients in the CP were 84.7% and 61.9%, respectively, which were significantly higher than those of patients in the AP (50% and 29.1%, respectively, both P<0.001) and BP (24.3% and 9.7%, respectively, both P<0.001). The estimated five-year OS and five-year EFS rates were 93.2% and 86.4% for CP patients, as well as 64.5% and 50.9% for AP patients, which were significantly higher than those for BP patients (P<0.001). In CP patients, univariate analysis revealed that early treatment with imatinib, achieving CCyR within 12 months, additional cytogenetic abnormalities, and kinase domain mutations were associated with the treatment outcome. More patients are needed to carry out multivariate analysis.

Keywords imatinib      chronic myeloid leukemia      complete cytogenetic response     
Corresponding Authors: Chen Saijuan,Email:sjchen@stn.sh.cn   
Issue Date: 05 June 2012
URL:  
http://academic.hep.com.cn/fmd/EN/10.1007/s11684-012-0202-x     OR     http://academic.hep.com.cn/fmd/EN/Y2012/V6/I2/204
Characteristics
Gender, no. of patients (%)MaleFemale156 (56.7)119 (43.3)
Mean age, yearsRange41.5±16.916-80
Clinical phase, no. of patients (%)CPAPBP210 (76.4)24 (8.7)41 (14.9)
Time interval between diagnosis and imatinib initiation, monthsMedianRange60-144
Patients with ACAs*, only for CP patients, no. of patients (%)PretreatmentAcquired during treatment45 (21.4)20 (9.5)25 (11.9)
Tab.1  Demographic data of CML patients ( = 275)
GroupsnCHRMCyRCcyRCMoR
CPAPBP2102441210 (100)23 (95.8)26 (63.4)188 (89.5)12 (50)11 (26.8)178 (84.7)12 (50)10 (24.3)130 (61.9)7 (29.1)4 (9.7)
P value&lt;0.001&lt;0.001&lt;0.001&lt;0.001
Tab.2  Cumulative incidence of treatment response of patients in the three phases
Fig.1  OS and EFS of patients in the three phases.
(A) For CP and AP patients, the 5-year OS rates were 93.2%±2.1% and 64.5%±10.2%, respectively. At 3 years, the probability of OS was 95.9%±1.4% for CP patients, 64.5%±10.2% for AP patients, and 23.7%±6.8% for BP patients. A significant difference was found among the three groups. (B) For CP and AP patients, the 5-year EFS rates were 86.4%±2.7% and 50.9%±10.9%, respectively. At 3 years, the probability of EFS was 91.6%±2.0% for CP patients, 62.2%±10.0% for AP patients, and 13.7%±5.7% for BP patients. A significant difference was found among the three groups.
Fig.2  Landmark analysis based on the cytogenetic response at 12 months.
(A) Patients who achieved CCyR had a better 5-year OS rate than those who did not (97.4% vs. 84.5%, <0.001). (B) Patients who achieved CCyR had a better 5-year EFS rate than those who did not (98% vs. 68.2%, = 0.005).
Fig.3  Landmark analysis according to molecular response at 12 months.
(A) The 5-year OS of patients who achieved MMoR at 12 months or did not were 99% and 94.3%, respectively. No statistical difference was observed in the OS rates ( = 0.252). (B) Patients who achieved MMoR at 12 months had a better 5-year EFS than those who did not (100% vs. 87.6%, = 0.001).
Fig.4  Treatment response of early and late imatinib therapy. Patients treated early with imatinib achieved better treatment response than patients treated late (McyR= 95.0% vs. 82.2%, CCyR= 93.3% vs. 73.3%, and CMoR= 70.0% vs. 51.1%, respectively; = 0.003, <0.001, and = 0.005, respectively).
ACAs acquired pretreatmentnACAs acquired during treatmentn
t(9; 11; 22), t(12;17)t(1; 9; 22)t(2; 9 ; 22)t(7; 9; 22)i(17q), +22, 2Ph1t(4; 16)t(1; 3) +8 +M9q+i(17q)22q+20q+1211111133221t(9; 16; 22)t(9; 20; 22)t(9; 17) +8, t(1;10) +M, 2Ph12Ph1 +8 +M-Y-21 +22 +8, i(17q)i(17q)9q+12p-der221111123521112111
Tab.3  Additional chromosomal abnormalities in CP patients
Fig.5  Effect of additional chromosomal abnormalities on OS. The estimated 5-year OS was 100% for patients who did not have ACAs, 98% for patients with pretreatment ACAs, and 75.9% for patients with during-treatment ACAs. A statistical difference was found in OS ( = 0.001).
PatientsPatient status whenmutations were detectedMonths afterimatinib initiationMutationsOutcome at the last follow-up
CP (1-12)123456789101112CHRCHRCHRCHRCHRCHRCHRPCyRLoss of CCyR-progress to BPProgress to APProgress to BPProgress to BP24181661218162418-25124812F359IM244VT315IG250EG250HG250ET315IG250EM244V/*F317L-*P441L/F317LT315IE255KE255KTherapy changeProgress to APNo CCyRTherapy changeDeathNo CCyRNo CCyRNo CCyRDeathDeathTherapy changeTherapy change
AP (13-15)131415CHRCHRProgress to BP afterachieving CCyR7126F359VE459KE459KTherapy changeTherapy changeDeath
BP (16-21)161718192021CHRCHRCHRCHRCHR-CHR-progress to BPProgress to BP afterachieving CCyR62236-18-2430E459KF359VL324QT315IT315I-F359I-Y253HL273MDeathDeathDeathDeathDeathDeath
Tab.4  Distribution of mutations
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