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Superiority of allogeneic hematopoietic stem cell transplantation to nilotinib and dasatinib for adult

Lanping Xu,Huanling Zhu,Jianda Hu,Depei Wu,Hao Jiang,Qian Jiang,Xiaojun Huang

Frontiers of Medicine 2015, Volume 9, Issue 3, Pages 304-311 doi: 10.1007/s11684-015-0400-4

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 TKI₂therapy 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.