The combination of all--retinoic acid (ATRA) plus arsenic trioxide (ATO) has been shown to be superior to ATRA plus chemotherapy in the treatment of standard-risk patients with newly diagnosed acute promyelocytic leukemia (APL). A recent study demonstrated the efficacy of this regimen with added gemtuzumab ozogamicin (GO) in high-risk patients. We examined the long-term outcome of patients with newly diagnosed APL treated at our institution on 3 consecutive prospective clinical trials, using the combination of ATRA and ATO, with or without GO. For induction, all patients received ATRA (45 mg/m daily) and ATO (0.15 mg/kg daily) with a dose of GO (9 mg/m on day 1) added to high-risk patients (white blood cell count, >10 × 10/L), as well as low-risk patients who experienced leukocytosis during induction. Once in complete remission, patients received 4 cycles of ATRA plus ATO consolidation. One hundred eighty-seven patients, including 54 with high-risk and 133 with low-risk disease, have been treated. The complete remission rate was 96% (52 of 54 in high-risk and 127 of 133 in low-risk patients). Induction mortality was 4%, with only 7 relapses. Among low-risk patients, 60 patients (45%) required either GO or idarubicin for leukocytosis. Median duration of follow-up was 47.6 months. The 5-year event-free, disease-free, and overall survival rates are 85%, 96%, and 88%, respectively. Late hematological relapses beyond 1 year occurred in 3 patients. Fourteen deaths occurred beyond 1 year; 12 were related to other causes. This study confirms the durability of responses with this regimen.

Background The long-term efficacy of combination of chemotherapy with dasatinib in patients with Philadelphia-chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) is not well-established. Methods Patients received dasatinib with 8 cycles of alternating hyperCVAD and high dose cytarabine and methotrexate. Patients in complete remission (CR) continued maintenance dasatinib, vincristine and prednisone for 2 years followed by dasatinib indefinitely. Patients eligible for allogeneic stem cell transplant (SCT) received it in first CR. Results 72 patients with a median age of 55 years (range 21 – 80) were treated; 69 (96%) achieved CR. Among them, 57 (83%) achieved cytogenetic (CG) CR after 1 cycle and 64 (93%) achieved a major molecular response (MMR) at a median of 4 weeks (range, 2 – 38 weeks). Minimal residual disease by flow cytometry was negative in 65 (94 %) patients at a median of 3 weeks (range, 2–37). Dasatinib-related grade 3 and 4 adverse events included bleeding, pleural/pericardial effusions, and elevated transaminases. With a median follow-up of 67 months (range, 33–97), 33 patients (46%) are alive and 30 (43%) are in CR; 12 underwent an allogeneic SCT. Thirty nine patients have died (3 at induction, 19 after relapse, 7 post SCT performed in CR1, and 10 in CR). The median disease free and overall survival are 31 months (range, 0.3 to 97) and 47 months (range, 0.2 to 97). Seven relapsed patients had ABL mutations including 4 T315I. Conclusion Combination of chemotherapy with dasatinib is effective in achieving long-term remissions in patients with newly diagnosed Ph+ ALL.

A B S T R A C T PurposeTo evaluate the safety and efficacy of the combination of the histone deacetylase inhibitor vorinostat with idarubicin and ara-C (cytarabine) in patients with acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS). Patients and MethodsPatients with previously untreated AML or higher-risk MDS age 15 to 65 years with appropriate organ function and no core-binding factor abnormality were candidates. Induction therapy was vorinostat 500 mg orally three times a day (days 1 to 3), idarubin 12 mg/m 2 intravenously (IV) daily ϫ 3 (days 4 to 6), and cytarabine 1.5 g/m 2 IV as a continuous infusion daily for 3 or 4 days (days 4 to 7). Patients in remission could be treated with five cycles of consolidation therapy and up to 12 months of maintenance therapy with single-agent vorinostat. The study was designed to stop early if either excess toxicity or low probability of median event-free survival (EFS) of more than 28 weeks was likely. ResultsAfter a three-patient run-in phase, 75 patients were treated. Median age was 52 years (range, 19 to 65 years), 29 patients (39%) were cytogenetically normal, and 11 (15%) had FLT-3 internal tandem duplication (ITD). No excess vorinostat-related toxicity was observed. Induction mortality was 4%. EFS was 47 weeks (range, 3 to 134 weeks), and overall survival was 82 weeks (range, 3 to 134 weeks). Overall response rate (ORR) was 85%, including 76% complete response (CR) and 9% in CR with incomplete platelet recovery. ORR was 93% in diploid patients and 100% in FLT-3 ITD patients. Levels of NRF2 and CYBB were associated with longer survival. ConclusionThe combination of vorinostat with idarubicin and cytarabine is safe and active in AML.

SUMMARY The prognostic value of minimal residual disease (MRD) assessed by multi-parameter flow cytometry (MFC) was investigated among 340 adult patients with B-cell acute lymphoblastic leukaemia (B-ALL) treated between 2004 and 2014 using regimens including the hyperCVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone, methotrexate, cytarabine) backbone. Among them, 323 (95%) achieved complete remission (CR) and were included in this study. Median age was 52 years (range, 15-84). Median white blood cell count (WBC) was 9.35 × 109/l (range, 0.4-658.1 ×109/l). MRD by MFC was initially assessed with a sensitivity of 0.01%, using a 15-marker, 4-colour panel and subsequently a 6-colour panel on bone marrow specimens obtained at CR achievement and at approximately 3 month intervals thereafter. MRD negative status at CR was associated with improved disease-free survival (DFS) and overall survival (OS)(P=0.004 and P=0.04, respectively). Similarly, achieving MRD negative status at approximately 3 and 6 months was associated with improved DFS (P=0.002 and P<0.0001, respectively) and OS (P=0.003 and P<0.0001, respectively). Multivariate analysis including age, WBC at presentation, cytogenetics (standard vs. high risk) and MRD status at CR, 3 months and 6 months, indicated that MRD negative status at CR was an independent predictor of DFS (P<0.05). Achievement of an MRD negative state assessed by MFC is an important predictor of DFS and OS in adult patients with ALL

Adherence to oral chemotherapy regimens maximizes their effectiveness and minimizes any potential toxicities. Factors specifically related to the treatment, patient, and health care provider may influence medication adherence. Treatment‐related factors include the complexity of the regimen, the cost of therapy, the possibility of side effects, and the delay in treatment benefits. Meanwhile, patients may not have an adequate support system or an understanding of the need for the medication, and providers may not fully succeed in communicating the importance of adherence and the types of side effects that may occur. Nonadherence may lead to an increased risk of toxicity, decreased effectiveness, and increased utilization of health care resources. Although various methods for measuring adherence are available, self‐reporting is the most widely used. Studies describing adherence in a broad range of cancers are reviewed. Treatment of chronic myeloid leukemia has been revolutionized by the development of oral tyrosine kinase inhibitors that are highly effective in managing the disease when taken consistently. However, nonadherence is relatively common and can lead to reduced rates of response and increased medical costs. Similar effects of nonadherence on outcome and cost have also been observed in patients with various other hematologic malignancies and solid tumors. Interventions to improve adherence to oral chemotherapy regimens include communication about the importance of adherence and the potential consequences of nonadherence, simplification of the patient's medication schedule (if possible), and inclusion of a caregiver or family member in the conversation. Written materials should always be provided to accompany verbal instructions. This review summarizes factors influencing medication adherence, impact of nonadherence on patient outcomes, methods for measuring adherence, previous studies of nonadherence in patients with cancer, common barriers to access, and interventions to improve adherence in the community setting.