In our study, 6 of 9 patients started dasatinib therapy at < 100 mg daily. Caocci et al reported that 5 of 8 patients who underwent allo-SCT started dasatinib at < 100 mg daily (50 mg in 5 and 100 mg in 3),23 whereas in the report of Teng et al, all 10 patients started dasatinib at 100 mg daily.24 These 2 reports emphasized the safety and efficacy of the dasatinib therapy after allo-SCT (Table 3). However, in our study, 7 of 9 patients discontinued dasatinib because of AEs. In particular, there was a trend toward an increased incidence of PE, which is one of immune-mediated and nonhematological toxicity, in the group with LGL increase compared with that in the group without LGL increase (P = .17; Table 2). Therefore, the incidence and severity of AEs after dasatinib therapy after transplantation might be more closely associated with the appearance of LGLs than the dosage of dasatinib. In our study, 3 of 6 patients with increased LGLs after dasatinib therapy have maintained molecular CR for a long time; 2 patients (Case 1 and 2) with increased LGLs have maintained CR under a relatively low dosage of dasatinib therapy (40 mg and 50 mg daily, respectively). Moreover, Case 5 has persistent LGL lymphocytosis even after the discontinuation of dasatinib therapy, and she has maintained molecular CR. These results also suggest that outcomes of dasatinib therapy after allo-SCT might be primarily affected by its induction of LGL lymphocytosis, which does not always depend on the dosage of dasatinib.
Conclusion
Our results revealed dasatinib therapy can induce immunostimulation in the form of a marked expansion of LGLs in a proportion of patients with relapsed Ph+ALL after allo-SCT. This phenomenon is associated with favorable outcomes in some of the patients. However, it remains unclear which patients are the most suitable candidates for dasatinib treatment of relapsed Ph+ALL after allo-SCT because of the small number of cases treated. Therefore, further large-scale, prospective, and randomized studies are required to assess efficacy and safety of dasatinib therapy for relapsed Ph+ALL after allo-SCT.