Superiority of allogeneic hematopoietic stem cell transplantation to nilotinib and dasatinib for adult patients with chronic myelogenous leukemia in the accelerated phase

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

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Acknowledgements

The Chinese CML alliance provided the data. This work was partly supported by grants from the Collaborative Innovation Center of Hematology in China, the Key Program of the National Natural Science Foundation of China (81230013), and the Beijing Municipal Science and Technology Commission (Nos. Z121107002812033 and Z121107002612035).

Compliance with ethics guidelines

Lanping Xu, Huanling Zhu, Jianda Hu, Depei Wu, Hao Jiang, Qian Jiang, and Xiaojun Huang declare no conflicts of interest. All procedures followed were performed in accordance with the ethical standards of the committees on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 (5). Informed consent was obtained from all patients who were included in the study.

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2015 Higher Education Press and Springer-Verlag Berlin Heidelberg