These findings suggest that discontinuation of second- or subsequent-line dasatinib after a sustained DMR of ≥ 1 year is feasible, especially for patients with no history of imatinib resistance. In addition, the natural killer cell count was associated with the TFR.

No abstract

3759 Imatinib treatment dramatically improves survival in chronic myeloid leukemia (CML) patients, but whether its effects of imatinib can be considered a cure remains controversial. This is because primitive, quiescent, Philadelphia-positive stem cells from patients with CML are insensitive to imatinib in vitro. Nonetheless, it was recently recognized that some patients with a complete molecular response (CMR) could sustain that response after discontinuation of imatinib. In a non-randomized prospective study, Mahon et al. reported that among patients with CMR lasting at least 2 years, CMR was sustained in 41% after discontinuation of imatinib. To characterize the clinical outcomes and profiles of chronic phase CML patients who discontinued imatinib, we conducted a nationwide survey in Japan. Among 3,242 imatinib-treated CML patients, 50 (1.5%) were identified who discontinued imatinib therapy for at least 6 months; of those, 43 were analyzed further. Molecular recurrence was detected in 19 patients, and the complete molecular response (CMR) rate was estimated to be 47% following imatinib discontinuation. Notably, the durations of imatinib therapy and CMR before cessation of therapy were significantly longer, and imatinib dose intensity and the frequency of prior IFN-a administration were significantly higher, in patients sustaining CMR for 12 months after cessation than in those with molecular recurrence. No significant correlations were detected between molecular recurrence and age, sex, Sokal risk, imatinib daily dose, combination with IFN-a, or time to achieve CMR. Moreover, we found a significant difference in estimated CMR rate following discontinuation between patients who had sustained CMR for greater than 24 months prior to imatinib discontinuation and those with less than 24 months (78% vs. 15%, p =0.0002 by Log-rank test, Figure). Based on multivariate regression analysis, only imatinib dose intensity and prior IFN-a administration were independently predictive of molecular recurrence within 12 months (p =0.0035, p =0.0060). The identified prediction formula was: Y= −0.0061 x dose intensity of imatinib(g)-3.17171 x prior IFN-a(Yes=1/No=0) +4.0124. If 1/(1+exp(-1 × Y)) > 0.5, molecular recurrence was predicted; the total accuracy rate of the formula was 82.5%. Although the depth of the molecular response should be a factor influencing long-term sustained CMR after discontinuation of imatinib, other factors, for example an immunological mechanism modified by IFN-a, might control quiescent CML stem cells. To increase the “cure” rate among CML patients, it will be necessary to establish a treatment strategy on the basis of large prospective study of imatinib discontinuation. This should entail the use of a highly sensitive and strict method for monitoring minimal residual disease over the course of a long follow-up period. Disclosures: No relevant conflicts of interest to declare.

No abstract

We conducted a phase II clinical study to evaluate the therapeutic efficacy of cladribine (2-chlorodeoxyadenosine [2-CdA]) in the treatment of Japanese patients with hairy cell leukemia (HCL). Seven patients with classic HCL and 3 with a prolymphocytic HCL variant were administered 2-CdA (0.09 mg/kg per day) by continuous intravenous infusion for 7 days. Seven patients responded to this therapy, with 5 patients achieving a complete response (CR). After a median follow-up of 792 days (range, 599-1253 days), there were no cases of clinical relapse, and the median duration of the response in the responders was 670+ days (range, 470+ to 1121+ days). The median duration of the CR in the CR patients was 953+ days (range, 480+ to 1121+ days). At treatment initiation, most patients had hematologic impairment as a manifestation of HCL. During the early stage after administration, further hematologic impairment occurred, but subsequent peripheral blood counts gradually recovered as 2-CdA treatment showed antitumor activity. Infections occurred at a high incidence at this time, but all cases could be controlled with appropriate treatment. 2-CdA was surmised to represent a useful therapeutic approach for Japanese patients with HCL.