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S. Chiaretti et al.
A
Figure 6. Impact of genetic lesions on survival. (A) Disease-free survival (DFS) and (B) overall survival (OS) of IKZF1 deletion with or without other
abnormalities. CI:
Interval; CHR: complete hematologic remission; yrs: years.
Confidence
B
T315I mutation. Although mutations were not systemati- cally screened in this trial, ten patients in hematologic relapse were evaluated and seven indeed harbored a muta- tion, with T315I being the most frequent (n=4). These results are in line with our previous experience16 and with Rousselot and colleagues who reported a high incidence of T315I mutations (18 of 24 relapsing patients, 75%).32 Importantly, three cases were screened and proved positive for ABL1 mutations at MRD increase and none of them relapsed, thus corroborating the notion that an earlier detec- tion can better drive therapeutic decisions. A 7.5% increase in OS was observed in the current study compared to the results of the LAL0904 protocol, from 48.8% to 56.3%.
Our results compare favorably also with other studies based on a combination of dasatinib plus chemotherapy, which were also aggravated by toxicities and treatment dis- continuations.27,32 The European Working Group on Adult ALL used dasatinib in combination with low-dose chemotherapy in elderly patients with Ph+ ALL: 61 patients
were enrolled (median age 69 years), 96% of patients achieved CR after induction, but three patients died. Overall, the 5-year OS was 36%, suggesting that a propor- tion of patients may experience long-term survival without intensive therapies.32 Ravandi et al.27 published the final results of their phase II study with dasatinib plus HyperCVAD in 72 adult Ph+ ALL patients: they reported CHR of 96% with 83% of complete cytogenetic responses after induction with three early deaths. Overall, the 5-years DFS and OS were 44% and 46%, respectively. The US Intergroup reported the results of a multicenter trial for Ph+ ALL patients aged 18-60 years treated with dasatinib plus HyperCVAD and allo-SCT for eligible patients.33 The over- all complete remission/complete remission with incom- plete hematologic recovery (CR-CRi) rate was 88% and the 3-year OS and DFS were 69% and 62%, respectively. The shorter follow-up does not allow a direct comparison with our study. In addition, a sizable proportion of patients (n=34) had received one course of therapy prior to enroll-
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