ATRA plus arsenic trioxide is at least not inferior and may be superior to ATRA plus chemotherapy in the treatment of patients with low-to-intermediate-risk APL. (Funded by Associazione Italiana contro le Leucemie and others; ClinicalTrials.gov number, NCT00482833.).

In patients with Myelofibrosis (MF) treated with ruxolitinib (RUX), the response is unpredictable at therapy start. We retrospectively evaluated the impact of clinical/laboratory factors on responses in 408 patients treated with RUX according to prescribing obligations in 18 Italian Hematology Centers. At 6 months, 114 out of 327 (34.9%) evaluable patients achieved a spleen response. By multivariable Cox proportional hazard regression model, pre-treatment factors negatively correlating with spleen response were: high/intermediate-2 IPSS risk (p=0.024), large splenomegaly (p=0.017), transfusion dependency (p=0.022), platelet count <200×109/l (p=0.028), and a time-interval between MF diagnosis and RUX start >2 years (p=0.048). Also, patients treated with higher (≥10 mg BID) average RUX doses in the first 12 weeks achieved higher response rates (p=0.019). After adjustment for IPSS risk, patients in spleen response at 6 months showed only a trend for better survival compared to non-responders. At 6 months, symptoms response was achieved by 85.5% of 344 evaluable patients; only a higher (>20) Total Symptom Score significantly correlated with lower probability of response (p<0.001). Increased disease severity, a delay in RUX start and titrated doses <10 mg BID were associated with patients achievinglower response rates. An early treatment and higher RUX doses may achieve better therapeutic results.

The APL0406 study showed that arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) are not inferior to standard ATRA and chemotherapy (CHT) in newly diagnosed, low-intermediaterisk acute promyelocytic leukaemia (APL). We analysed the kinetics of promyelocytic leukaemia-retinoic acid receptor-α (PML-RARα) transcripts by real-time quantitative PCR (RQ-PCR) in bone marrow samples from 184 patients and assessed the prognostic impact of fms-related tyrosine kinase 3-internal tandem duplication (FLT3-ITD) in 159 patients enrolled in this trial in Italy. After induction therapy, the reduction of PML-RARα transcripts was significantly greater in patients receiving ATRA-CHT as compared with those treated with ATRA-ATO (3.4 vs 2.9 logs; P=0.0182). Conversely, at the end of consolidation, a greater log reduction of PML-RARα transcripts was detected in the ATRA-ATO as compared with the ATRA-CHT group (6.3 vs 5.3 logs; P=0.0024). FLT3-ITD mutations had no significant impact on either event-free survival (EFS) or cumulative incidence of relapse in patients receiving ATRA-ATO, whereas a trend for inferior EFS was observed in FLT3-ITD-positive patients receiving ATRA-CHT. Our study shows at the molecular level that ATRA-ATO exerts at least equal and probably superior antileukaemic efficacy compared with ATRA-CHT in low-intermediaterisk APL. The data also suggest that ATRA-ATO may abrogate the negative prognostic impact of FLT3-ITD.

Background Stopping tyrosine kinase inhibitor (TKI) treatment has become a realistic and safe objective for patients who have chronic myeloid leukemia (CML). Both a sustained deep molecular response (sDMR) and the lack of a molecular recurrence after TKI discontinuation are required to reach a durable treatment‐free remission (TFR). Methods The potential predictive role of BCR‐ABL transcripts in attaining an sDMR and a TFR was analyzed in a strictly consecutive, unselected series of 194 patients who were diagnosed and treated with TKIs at the authors’ center. Results Of 173 fully evaluable patients, 67 (38.7%) had the e13a2 transcript, and 106 (61.3%) had the e14a2 transcript. Complete cytogenetic and major molecular remissions were not affected, whereas the achievement of both a DMR (P = .008) and an sDMR (P = .004) was favored significantly in patients who had the e14a2 transcript. After a median of 68 months, the sDMR rate was 39.6% in those with the e14a2 transcript and 19.4% in those with the e13a2 transcript. In addition to transcript type, both the early achievement of a molecular response and starting treatment with a second‐generation TKI positively affected the attainment of an sDMR in multivariate analysis. The use of a second‐generation TKI as frontline treatment increased the sDMR rate in both transcript types. However, in patients who had the e13a2 transcript, the probability of attaining an sDMR was 37% after 60 months and did not increase further despite continuing therapy. Among 51 of 60 patients who attained an sDMR after discontinuing TKIs, 24 experienced a molecular relapse, but all regained molecular remission after resuming TKI treatment. Again, transcript type influenced TFR maintenance (P = .005), because only 2 patients (3%) with the e13a2 transcript enjoyed a durable TFR compared with 25 (23.5%) of those with the e14a2 transcript. Conclusions The e13a2 transcript hinders the achievement of deep responses and the possibility of stopping TKI treatment in patients with CML.

Overall, current HRQOL findings further support the use of ATRA plus arsenic trioxide as preferred first-line treatment in patients with low- or intermediate-risk APL.