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Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

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Front. Med.    2015, Vol. 9 Issue (3) : 304-311    https://doi.org/10.1007/s11684-015-0400-4
RESEARCH ARTICLE
Superiority of allogeneic hematopoietic stem cell transplantation to nilotinib and dasatinib for adult patients with chronic myelogenous leukemia in the accelerated phase
Lanping Xu1, Huanling Zhu2, Jianda Hu3, Depei Wu4, Hao Jiang1, Qian Jiang1, Xiaojun Huang1()
1. Peking University People’s Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing 100044, China
2. West China Hospital, Sichuan University, Chengdu 610041, China
3. Fujian Medical University Union Hospital, Fujian Institute of Hematology, Fuzhou 350001, China
4. The First Affiliated Hospital, Soochow University, Suzhou 215006, China
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Abstract

In the tyrosine kinase inhibitor (TKI) era, imatinib is the first-line therapy for patients with chronic myeloid leukemia (CML) in chronic or accelerated phase. Although second-generation TKIs (TKI2), including dasatinib and nilotinib, are appropriate treatment regimens for patients with disease that progressed to accelerated phase following imatinib therapy, allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curative therapy. This study retrospectively analyzed the efficacy of TKI2 and HSCT for treatment of CML in accelerated phase. Ninety-three patients with CML registered in the Chinese CML alliance database from February 2001 to February 2014 were enrolled and divided into the TKI2 (n = 33) and allo-HSCT (n = 60) groups. In the TKI2 group, 26 and 7 patients received nilotinib and dasatinib, respectively, as initial TKI2 and 11 patients transferred to the alternative TKI2 after failure to one TKI2. In the allo-HSCT group, 22 (36.7%), 35 (58.3%), and 3 (10%) patients underwent allo-HSCT from an HLA-matched sibling donor, HLA mismatched/haploidentical donor, and unrelated donor, respectively. All patients in the HSCT group were engrafted. Overall, 69.7%, 48.5%, and 45.5% of patients presented hematological, cytogenetic, and major molecular responses, respectively, to at least one of TKI2. All 60 patients (100%) achieved CHR and cytogenetic response in the HSCT group. Patients in the TKI2 group exhibited lower 5-year overall survival rate (42.9% vs. 86.4%, P = 0.002), 5-year event-free survival rate (14.3% vs. 76.1%, P<0.001), and 5-year progression-free survival (28.6% vs. 78.1%, P<0.001) than those in the allo-HSCT group. Multivariate analysis showed that male sex and TKI2 therapy were predictors of poor overall survival, whereas hemoglobin<100 g/L and TKI2 therapy were predictors of poor event-free survival and progression-free survival. These results indicated that allo-HSCT may be superior to nilotinib and dasatinib for adult patients with CML in accelerated phase.
Keywords chronic myeloid leukemia      imatinib      dasatinib      nilotinib      allogeneic hematopoietic stem cell transplantation     
Corresponding Author(s): Xiaojun Huang   
Online First Date: 23 June 2015    Issue Date: 26 August 2015
 Cite this article:   
Lanping Xu,Huanling Zhu,Jianda Hu, et al. Superiority of allogeneic hematopoietic stem cell transplantation to nilotinib and dasatinib for adult patients with chronic myelogenous leukemia in the accelerated phase[J]. Front. Med., 2015, 9(3): 304-311.
 URL:  
https://academic.hep.com.cn/fmd/EN/10.1007/s11684-015-0400-4
https://academic.hep.com.cn/fmd/EN/Y2015/V9/I3/304
TKI2 group HSCT group P value
n 33 60
Median age (year) 39 (20−65) 36 (18−61) 0.095
Sex (male/female) 25/8 40/20 0.251
CP/AP at first diagnosis of CML 25/8 45/15 0.572
Duration of CML (month) 33 (0−183) 9.5 (2−180) 0.013
Time since first diagnosis of AP (month) 0 (0−60) 4.5 (1−72) 0.003
Features at diagnosis of AP
Splenomegaly diagnosis, n (%) 17 (51.2) 33 (55) 0.350
WBC median (range) (× 109/L) 13.46 (0.99−520) 20.5 (1.0−280) 0.152
BPC median (range) (× 109/L) 322 (40−2201) 900 (28−3000) <0.001
Blasts in peripheral blood (%) 2 (0−13) 2 (0−18) 0.435
Bone marrow blasts (%) 5 (0−19) 6 (0−18) 0.89
PBa (%) 10 (0−43) 7 (0−34) 0.784
Clonal evolution, n (%) 3 (9.1) 5 (8.3) 0.760
Prior TKI therapy, n (%) 31 (93.9) 50 (83.3) 0.144
Duration of imatinib therapy (month) 17 (2−60) 3 (0.3−58) <0.001
Follow-up (month) 22 (2.5−92) 82 (1−160) <0.001
Tab.1  Baseline characteristics (n = 93)
TKI2 group HSCT group P value
n 33 60
Alive, n (%) 21 (63.3%) 50 (83.3%) 0.031
Median (range) survival time (month) 28 (12−91) 89 (13−160) <0.001
CHR, n (%) 15 (71.4%) 50 (100%) <0.001
MCR, n (%) 12 (57.1%) 49 (98%) <0.001
CCR, n (%) 10 (47.2%) 49 (98%) <0.001
MMR, n (%) 9 (42.9%) 49 (98%) <0.001
CMR, n (%) 5 (23.8%) 49 (98%) <0.001
Tab.2  Status at the final follow-up
Fig.1  Effect of different therapies on survival of patients with AP-CML. (A) Overall survival, (B) event-free survival, and (C) progression-free survival of patients with AP-CML with respect to therapy.
Variable n OS EFS PFS
5-year OS P 5-year EFS P 5-year EFS P
Total 93 74.3 57.8 64.4
Age (year)
<40
≥40		 57
36		 65.6
89.8		 0.692 52.0
61.3		 0.232 67.7
58.2		 0.181
Sex
Male
Female		 65
28		 68.3
92.4		 0.029 53.1
67.7		 0.209 54.8
78.6		 0.072
CML duration (month)
<12
12−24
>24		 44
15
34		 58.8
86.7
77.4		 0.375 60.1
72.0
43.5		 0.201 64.3
79.4
52.3		 0.334
IM time (month)
No
0.3−7
>7		 12
44
45		 81.5
80.3
62.9		 0.534 72.9
60.5
42.4		 0.246 0.815
65.3
48.5		 0.273
WBC count (×109/L)
<18
≥18		 44
49		 80.8
57.6		 0.382 57.6
56.7		 0.986 61
67.5		 0.785
Hb (mg/L)
<100
≥100		 33
60		 68.7
80.8		 0.121 47.8
63.7		 0.037 51.5
70.6		 0.020
BPC (×109/L)
100−1000
<100 or>1000		 53
40		 74.0
74.7		 0.981 58.9
56.5		 0.434 69.4
61.1		 0.404
BM blasts (%)
<10
10−19		 72
21		 76.7
71.4		 0.263 54.3
66.7		 0.72 63
58		 0.686
Splenomegaly
No
Yes		 41
52		 79.7
61.3		 0.276 58.1
57.7		 0.887 71.2
59.6		 0.252
Ba in PB (%)
<20
≥20		 74
19		 77.1
69.6		 0.751 56.8
61.5		 0.317 63.5
64.2		 0.342
AP course
≥6 months
<6 months		 33
60		 68.9
80.4		 0.327 49.4
62.4		 0.230 70.8
52.8		 0.323
Therapy group
HSCT
TKI2		 60
33		 86.4
42.9		 0.002 76.1
14.3		 <0.001 78.1
28.6		 <0.001
Tab.3  Univariate analysis of factors associated with OS, EFS and PFS
Variable OS EFS PFS
RR 95% CI P RR 95% CI P RR 95% CI P
TKI2 3.711 1.489−9.247 0.005 5.097 2.532−10.262 <0.001 3.673 1.774−7.605 <0.001
Male sex 3.484 1.016−11.946 0.047 2.237 0.912−5.492 0.071
Hb?<?100?g/L 0.417 0.212−0.821 0.011 0.434 0.214−0.882 0.021
Tab.4  Multivariate analysis of factors associated with OS, EFS and PFS
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