Phase 1 dose escalation multicenter trial of pracinostat alone and in combination with azacitidine in patients with advanced hematologic malignancies.

Background: Pracinostat is a potent histone deacetylase inhibitor with antitumor activity in both solid tumor and acute myeloid leukemia (AML) cell lines. Pracinostat is reported to have modest clinical activity in patients with advanced solid tumors. Given the higher preclinical sensitivity of hematologic malignancies to pracinostat, the authors conducted a phase 1 study to assess the safety, maximum tolerated dose, recommended phase 2 dose, efficacy, pharmacokinetics, and pharmacodynamics of pracinostat in patients with advanced hematological malignancies.

Clonal chromosomal abnormalities appearing in Philadelphia chromosome-negative metaphases during CML treatment.

Clonal chromosomal abnormalities in Philadelphia chromosome-negative (CCA/Ph) metaphases emerge as patients with chronic phase chronic myeloid leukemia (CP-CML) are treated with tyrosine kinase inhibitors (TKIs). We assessed the characteristics and prognostic impact of 598 patients with CP-CML treated on clinical trials with various TKIs. CCA/Ph occurred in 58 patients (10%); the most common were -Y in 25 (43%) and trisomy 8 in 7 patients (12%).

Treatment of adult acute lymphoblastic leukemia with inotuzumab ozogamicin.

Treatment of adult acute lymphoblastic leukemia (ALL) has largely relied on cytotoxic chemotherapy agents borrowed from successful treatment regimens of pediatric ALL. However, the high cure rates seen in pediatric ALL have not been replicated in adults. In recent years, the development of monoclonal antibodies targeting cell surface antigens, such as CD19 and CD20, have significantly improved outcomes when used alone or in combination with cytotoxic chemotherapy.

Randomized phase 2 study of low-dose decitabine vs low-dose azacitidine in lower-risk MDS and MDS/MPN.

Hypomethylating agents (HMAs) improve survival in patients with higher-risk myelodysplastic syndromes (MDS) but are less well-studied in lower-risk disease. We compared the safety and efficacy of low-dose decitabine vs low-dose azacitidine in this group of patients. Adults with low- or intermediate 1-risk MDS or MDS/myeloproliferative neoplasm (MPN), including chronic myelomonocytic leukemia, according to the International Prognostic Scoring System, were randomly assigned using a Bayesian adaptive design to receive either azacitidine 75 mg/m intravenously/subcutaneously daily or decitabine 20 mg/m intravenously daily for 3 consecutive days on a 28-day cycle.

Prognostic factors and survival outcomes in patients with chronic myeloid leukemia in blast phase in the tyrosine kinase inhibitor era: Cohort study of 477 patients.

Background: Outcomes in patients with chronic myeloid leukemia in blast phase (CML-BP) are historically dismal. Herein, the authors sought to analyze the characteristics, prognostic factors, and survival outcomes in patients with CML-BP in the tyrosine kinase inhibitor (TKI) era.

Methods: A total of 477 patients with CML-BP were treated with a TKI at some point during the course of their CML.

Vosaroxin in combination with decitabine in newly diagnosed older patients with acute myeloid leukemia or high-risk myelodysplastic syndrome.

Vosaroxin is an anti-cancer quinolone-derived DNA topoisomerase II inhibitor. We investigated vosaroxin with decitabine in patients ≥60 years of age with newly diagnosed acute myeloid leukemia (n=58) or myelodysplastic syndrome (≥10% blasts) (n=7) in a phase II non-randomized trial. The initial 22 patients received vosaroxin 90 mg/m on days 1 and 4 with decitabine 20 mg/m on days 1-5 every 4-6 weeks for up to seven cycles.

A phase I/II randomized trial of clofarabine or fludarabine added to idarubicin and cytarabine for adults with relapsed or refractory acute myeloid leukemia.

The purine nucleoside analogues clofarabine and fludarabine are active in acute myeloid leukemia (AML). We conducted a phase I/II randomized study of idarubicin and cytarabine with either clofarabine (CIA) or fludarabine (FIA) for relapsed or refractory AML. Clofarabine 15 mg/m was identified as the recommended phase II dose.

A randomized phase 2 study of idarubicin and cytarabine with clofarabine or fludarabine in patients with newly diagnosed acute myeloid leukemia.

Background: Fludarabine and clofarabine are purine nucleoside analogues with established clinical activity in patients with acute myeloid leukemia (AML).

Methods: Herein, the authors evaluated the efficacy and safety of idarubicin and cytarabine with either clofarabine (CIA) or fludarabine (FIA) in adults with newly diagnosed AML. Adults with newly diagnosed AML who were deemed suitable for intensive chemotherapy were randomized using a Bayesian adaptive design to receive CIA (106 patients) or FIA (76 patients).

The effect of patient death on medical students in the emergency department.

Background: The emotional consequences of patient deaths on physicians have been studied in a variety of medical settings. Reactions to patient death include distress, guilt, and grief. Comparatively, there are few studies on the effects of patient death on physicians and residents in the Emergency Department (ED).

Hepatic adverse event profile of inotuzumab ozogamicin in adult patients with relapsed or refractory acute lymphoblastic leukaemia: results from the open-label, randomised, phase 3 INO-VATE study.

Background: The INO-VATE study demonstrated efficacy and safety of inotuzumab ozogamicin versus standard care in adults with relapsed or refractory B-cell acute lymphoblastic leukaemia. Here, we report the frequency of, and potential risk factors for, hepatotoxicity in patients in this trial and after treatment and subsequent haemopoietic stem-cell transplantation (HSCT).

Methods: In this open-label, phase 3, multicentre, international study, adults with relapsed or refractory, CD22-positive, Philadelphia chromosome (Ph)-positive or Ph-negative B-cell acute lymphoblastic leukaemia who were due to receive first or second salvage treatment were randomly assigned (1:1) via an interactive voice response system to receive inotuzumab ozogamicin (starting dose 1·8 mg/m per cycle [0·8 mg/m on day 1; 0·5 mg/m on days 8 and 15 of a 21-28 day cycle for ≤6 cycles]) or standard care (either fludarabine plus cytarabine plus granulocyte colony-stimulating factor, mitoxantrone plus cytarabine, or high-dose cytarabine).

New Tool for Monitoring Molecular Response in Patients With Chronic Myeloid Leukemia.

Objective: Chronic myeloid leukemia treatment monitoring using polymerase chain reaction-based peripheral blood testing of t9;22 BCR-ABL1 provides improved test sensitivity over cytology but suffers from inadequate standardization in most laboratories due to variations inherent in the existing polymerase chain reaction methodologies. We performed the initial analytic performance evaluation of a novel competitive template-based peripheral blood b2a2/b3a2 transcript abundance method, called standardized nucleic acid quantification (SNAQ) test, with hypothesis that this will produced more consistent results with less frequent interlaboratory variations.

Materials And Methods: Thirty-six chronic myeloid leukemia patients treated at our institution were enrolled.

Evaluation of healthcare resource utilization and incremental economic burden of patients with chronic myeloid leukemia after disease progression to blast phase.

Aims: To evaluate healthcare resource utilization and economic burden of patients with chronic myeloid leukemia (CML) progression to the blast phase.

Methods: Patients (≥ 18 years) with ≥1 inpatient or ≥2 outpatient CML diagnoses were identified from the MarketScan Commercial and Medicare databases (January 1, 2007-June 30, 2015). CML patients were grouped into two study cohorts, those with evidence of disease progression to the blast phase and those without.

Clonal evolution and outcomes in myelofibrosis after ruxolitinib discontinuation.

Despite significant improvements in the signs and symptoms of myelofibrosis (MF), and possible prolongation of patients' survival, some have disease that is refractory to ruxolitinib and many lose their response over time. Furthermore, patients with ≥3 mutations are less likely to respond to ruxolitinib. Here we describe outcomes after ruxolitinib discontinuation in MF patients enrolled in a phase 1/2 study at our center.

Bone marrow pathologic abnormalities in familial platelet disorder with propensity for myeloid malignancy and germline RUNX1 mutation.

A subset of patients with familial platelet disorder with propensity to myeloid malignancy and germline mutation develops hematological malignancies, often myelodysplastic syndrome/acute myeloid leukemia, currently recognized in the 2016 WHO classification. Patients who develop hematologic malignancies are typically young, respond poorly to conventional therapy, and need allogeneic stem cell transplant from non-familial donors. Understanding the spectrum of bone marrow morphologic and genetic findings in these patients is critical to ensure diagnostic accuracy and develop criteria to recognize the onset of hematologic malignancies, particularly myelodysplastic syndrome.

TP53 mutation does not confer a poor outcome in adult patients with acute lymphoblastic leukemia who are treated with frontline hyper-CVAD-based regimens.

Background: Tumor protein 53 (TP53) mutations are uncommon in adult patients with acute lymphoblastic leukemia (ALL) and predict a poor outcome.

Methods: TP53 mutation analysis was performed in 164 newly diagnosed adult patients with ALL using a combination of targeted amplicon-based next-generation sequencing and Sanger sequencing.

Results: TP53 mutations were detected in 25 patients (15%), with a median allelic frequency of 42.

Treatment of acute lymphoblastic leukemia in older adults: now and the future.

Acute lymphoblastic leukemia (ALL) is an uncommon disease with poor outcomes in older patients. Although intensive chemotherapy can induce complete responses in older patients, the mortality rate is unacceptably high. The 5-year survival rate for patients achieving a remission ranges from 17% to 23%.

Factors associated with risk of central nervous system relapse in patients with non-core binding factor acute myeloid leukemia.

Central nervous system (CNS) relapse is uncommon in patients with acute myeloid leukemia (AML) with the use of high-dose cytarabine containing chemotherapy regimens. The clinical and molecular features associated with a higher risk of CNS relapse are not well defined. We assessed the incidence and outcome of CNS relapses among 1245 patients with relapsed/refractory AML referred to our institution between 2000 and 2014.

Feasibility of Lenalidomide Therapy for Persistent Chronic Lymphocytic Leukemia after Allogeneic Transplantation.

In patients with chronic lymphocytic leukemia (CLL), persistence of disease after allogeneic stem cell transplantation (alloSCT) can result in poor outcomes. In an effort to improve these outcomes, patients with persistent CLL who were 90 to 100 days beyond alloSCT with no evidence of graft-versus-host-disease (GVHD) were randomized to receive lenalidomide or standard care (withdrawal of immunosuppression followed by donor lymphocyte infusion). Lenalidomide was initiated at 5 mg every other day and increased to 10 mg daily, if tolerated, in each patient.