A phase 1/2 study of gilteritinib in combination with chemotherapy in newly diagnosed patients with AML in Asia.

Objective: This interim analysis of a phase 1/2, open-label, single-arm study assessed the safety, efficacy, and pharmacokinetics of gilteritinib plus chemotherapy in adults with newly diagnosed FLT3 mutation-positive acute myeloid leukemia.

Methods: In sequential phase 1 and 2 studies, induction and consolidation therapy with gilteritinib 120 mg/day plus chemotherapy (induction: idarubicin/cytarabine once daily; consolidation: cytarabine twice daily) was followed by maintenance gilteritinib 120 mg/day monotherapy. Endpoints included maximum tolerated dose (MTD), recommended expansion dose (RED), and dose-limiting toxicity (phase 1), and complete remission (CR) rate following induction therapy (primary endpoint), overall survival (OS), safety, and pharmacokinetics (phase 2).

An fMRI study examining the role of the extended amygdala and amygdala in emotion and inhibitory control in native versus second language processing.

The role of the extended amygdala and amygdala in mediating emotion and inhibitory control in native language versus second language processing is currently not well understood. The current study examined activity in the extended amygdala and amygdala when twelve healthy young adults were exposed to emotional-linguistic stimuli in either their native language (i.e.

Nilotinib vs dasatinib in achieving MR4.5 for de novo chronic myeloid leukemia: the randomized JALSG CML212 study.

Deep molecular response (DMR) is a prerequite for treatment-free remission (TFR) in chronic myeloid leukemia in chronic phase (CML-CP). The JALSG (Japan Adult Leukemia Study Group) conducted a prospective randomized phase 3 CML212 study for de novo CML-CP to compare the cumulative achievement of molecular response 4.5 (MR4.

Glasdegib with intensive/nonintensive chemotherapy in Japanese patients with untreated acute myeloid leukemia or high-risk myelodysplastic syndromes.

Glasdegib is a potent, selective, oral inhibitor of the hedgehog signaling pathway. In this phase I study, previously untreated Japanese patients with acute myeloid leukemia (AML) or high-risk myelodysplastic syndromes were treated with glasdegib (100 mg once daily) combinations: low-dose cytarabine (20 mg twice daily; cohort 1, n = 6; expansion cohort, n = 15); daunorubicin and cytarabine (60 mg/m i.v.

Immunoreactivity to WT1 peptide vaccine is associated with prognosis in elderly patients with acute myeloid leukemia: follow-up study of randomized phase II trial of OCV-501, an HLA class II-binding WT1 polypeptide.

We previously conducted a randomized phase II trial of OCV-501, a WT1 peptide presented by helper T cells, in elderly AML (acute myeloid leukemia) patients in first remission, indicating no difference in 2-year disease-free survival (DSF) between the OCV-501 and placebo groups. Here, we analyzed 5-year outcome and biomarkers. Five-year DFS was 36.

Postazacitidine clone size predicts long-term outcome of patients with myelodysplastic syndromes and related myeloid neoplasms.

Azacitidine is a mainstay of therapy for myelodysplastic syndrome (MDS)-related diseases. The purpose of our study is to elucidate the effect of gene mutations on hematological response and overall survival (OS), particularly focusing on their posttreatment clone size. We enrolled a total of 449 patients with MDS or related myeloid neoplasms.

Clinical outcomes of second-generation tyrosine kinase inhibitors versus imatinib in older patients with CML.

Age and comorbidities are important factors to be considered in the selection of tyrosine kinase inhibitors (TKIs) for first-line treatment in patients with chronic myeloid leukemia in chronic phase (CML-CP). However, it is yet unclear whether TKI selection, particularly, imatinib versus second-generation TKIs (2GTKIs), impacts treatment outcomes in the clinical practice. To address this, we compared the clinical outcomes of prospectively registered 452 patients with CML-CP treated with imatinib and 2GTKIs, taking into consideration their age and/or comorbidities.

Phase 3 trial of gilteritinib plus azacitidine vs azacitidine for newly diagnosed FLT3mut+ AML ineligible for intensive chemotherapy.

Treatment results for patients with newly diagnosed FMS-like tyrosine kinase 3 (FLT3)-mutated (FLT3mut+) acute myeloid leukemia (AML) ineligible for intensive chemotherapy are disappointing. This multicenter, open-label, phase 3 trial randomized (2:1) untreated adults with FLT3mut+ AML ineligible for intensive induction chemotherapy to receive gilteritinib (120 mg/d orally) and azacitidine (GIL + AZA) or azacitidine (AZA) alone. The primary end point was overall survival (OS).

Prospective comparison of 5- and 7-day administration of azacitidine for myelodysplastic syndromes: a JALSG MDS212 trial.

The hypomethylating agent azacitidine (AZA) significantly extends overall survival (OS) in patients with higher risk myelodysplastic syndromes (MDS), when compared with other conventional care regimens, including supportive care and low-dose and intensive chemotherapy. However, the effects of 5- and 7-day treatment schedules of AZA (AZA-5 and AZA-7, respectively) on the OS of MDS patients had not been compared prospectively. We started a phase 3 trial comparing the effects of AZA-7 and AZA-5 on MDS patients with refractory anemia with excess blasts (RAEB) and RAEB in transformation (RAEB-T).

A phase II randomized study evaluating azacitidine versus conventional care regimens in newly diagnosed elderly Japanese patients with unfavorable acute myeloid leukemia.

A multicenter phase II study was conducted in 44 elderly (≥ 65 years) Japanese patients with newly diagnosed acute myeloid leukemia (AML) to evaluate whether azacitidine is also effective and feasible in Japanese AML patients. The 28 patients with AML with poor-risk cytogenetics and/or myelodysplasia-related changes (unfavorable AML) were randomly assigned to receive either azacitidine or conventional care regimens (CCR), and the other 16 patients without unfavorable AML received azacitidine alone. The primary endpoint was overall survival.

Two novel high-risk adult B-cell acute lymphoblastic leukemia subtypes with high expression of CDX2 and IDH1/2 mutations.

The genetic basis of leukemogenesis in adults with B-cell acute lymphoblastic leukemia (B-ALL) is largely unclear, and its clinical outcome remains unsatisfactory. This study aimed to advance the understanding of biological characteristics, improve disease stratification, and identify molecular targets of adult B-ALL. Adolescents and young adults (AYA) (15 to 39 years old, n = 193) and adults (40 to 64 years old, n = 161) with Philadelphia chromosome-negative (Ph-) B-ALL were included in this study.

Efficacy and safety of Wilms' tumor 1 helper peptide OCV-501 in elderly patients with acute myeloid leukemia: a multicenter, randomized, double-blind, placebo-controlled phase 2 trial.

Purpose: Complete remission (CR) of acute myeloid leukemia (AML) in elderly patients has a short duration, and there is no suitable post-remission therapy. We explored the role of the Wilms' tumor 1 helper peptide OCV-501 to prevent recurrence after remission.

Methods: This placebo-controlled phase 2 study was designed to evaluate accurately the efficacy and immunogenicity of OCV-501 in elderly AML patients.

Adjunctive Volasertib in Patients With Acute Myeloid Leukemia not Eligible for Standard Induction Therapy: A Randomized, Phase 3 Trial.

In this phase 3 trial, older patients with acute myeloid leukemia ineligible for intensive chemotherapy were randomized 2:1 to receive the polo-like kinase inhibitor, volasertib (V; 350 mg intravenous on days 1 and 15 in 4-wk cycles), combined with low-dose cytarabine (LDAC; 20 mg subcutaneous, twice daily, days 1-10; n = 444), or LDAC plus placebo (P; n = 222). Primary endpoint was objective response rate (ORR); key secondary endpoint was overall survival (OS). Primary ORR analysis at recruitment completion included patients randomized ≥5 months beforehand; ORR was 25.

Prognostic effect of comorbidities in patients with chronic myeloid leukemia treated with a tyrosine kinase inhibitor.

Comorbidities at diagnosis among patients with chronic myeloid leukemia in chronic phase (CML-CP) may affect their overall survival (OS) rate even in the tyrosine kinase inhibitor (TKI) era. However, the prognostic impact of comorbidities in patients with CML-CP treated with a second-generation TKI (2GTKI) has not been elucidated. We evaluated the effect of comorbidities on survival using the Charlson Comorbidity Index (CCI) in patients with CML-CP treated with imatinib or a 2GTKI (nilotinib and dasatinib).

In vivo tracking of transplanted macrophages with near infrared fluorescent dye reveals temporal distribution and specific homing in the liver that can be perturbed by clodronate liposomes.

Macrophages play an indispensable role in both innate and acquired immunity, while the persistence of activated macrophages can sometimes be harmful to the host, resulting in multi-organ damage. Macrophages develop from monocytes in the circulation. However, little is known about the organ affinity of macrophages in the normal state.

Predictors of early death, serious hemorrhage, and differentiation syndrome in Japanese patients with acute promyelocytic leukemia.

Significant advancements have been achieved with regard to the outcomes of acute promyelocytic leukemia (APL) patients through the introduction of all-trans retinoic acid; however, early hemorrhagic death and differentiation syndrome remain the major causes of remission induction failure in patients with APL. To investigate early death, serious hemorrhage, and differentiation syndrome during remission induction therapy in terms of incidence, risk factors, influence on outcomes, and prophylactic effects of several new anticoagulants, the results of 344 patients enrolled in the Acute Promyelocytic Leukemia 204 study conducted by the Japan Adult Leukemia Study Group were analyzed. Early death was observed in 16 patients (4.

＜Editors' Choice＞ How to improve outcomes of elderly patients with acute myeloid leukemia: era of excitement.

Among elderly patients with acute myeloid leukemia (AML), especially those who are unfit for intensive chemotherapy, a policy of reduced-intensity chemotherapy or conservative observation has been chosen, resulting in unmet medical needs. Clinical trials using anticancer drugs including antimetabolites or drugs targeted to cell cycle-related molecules failed to show superiority over conventional treatments. Recently, drugs targeted to Bcl-2, SMO, FLT3, and IDH1/2 have been shown to prolong overall survival alone or in combination with reduced-intensity chemotherapy.

Impact of CD56 Continuously Recognizable as Prognostic Value of Acute Promyelocytic Leukemia: Results of Multivariate Analyses in the Japan Adult Leukemia Study Group (JALSG)-APL204 Study and a Review of the Literature.

Background: After long-term analysis of the JALSG-APL204 study we recently reported that maintenance therapy with tamibarotene was more effective than all-trans retinoic acid (ATRA) by reducing relapse in APL patients. Here, the clinical significance of other important prognostic factors was evaluated with multivariate analyses.

Patients And Methods: Newly diagnosed acute promyelocytic leukemia (APL) patients were registered with the study.

Allogeneic hematopoietic stem cell transplantation at the first remission for younger adults with FLT3-internal tandem duplication AML: The JALSG AML209-FLT3-SCT study.

In this phase II multicenter study (JALSG AML209-FLT3-SCT), we aimed to prospectively elucidate the role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) at first complete remission (CR1) for FLT3-internal tandem duplication (ITD)-positive AML. Newly diagnosed de novo AML patients with FLT3-ITD were enrolled at the achievement of CR1 and received allo-HSCT as soon as possible after the first consolidation therapy. Mutations of 57 genes in AML cells at diagnosis were also analyzed.

Treatment outcomes of chronic-phase chronic myeloid leukemia with resistance and/or intolerance to a 1st-line tyrosine kinase inhibitor in Japan: the results of the New TARGET study 2nd-line.

We herein report the results of the New TARGET study 2nd-line, which collected data on patients with chronic-phase (CP) chronic myeloid leukemia (CML) who received a 2nd-line tyrosine kinase inhibitor (TKI) because of resistance and/or to a 1st-line TKI. A total of 98 patients were enrolled intolerance between April 2010 and March 2013, and 82 patients were analyzed. The median age was 54 years (range 22-88 years).

Development of tissue conditioner containing cetylpyridinium chloride montmorillonite as new antimicrobial agent: Pilot study on antimicrobial activity and biocompatibility.

Purpose: The mechanical properties, antimicrobial activity, and biocompatibility of a novel antimicrobial tissue conditioner containing cetylpyridinium chloride with montmorillonite (CPC-Mont) were evaluated.

Methods: To examine the mechanical properties of the novel material, hardness, consistency, and penetration tests were conducted. Antimicrobial activity against Candida albicans (C.