. Autologous T cell activation fosters ABT-199 resistance in chronic lymphocytic leukemia: rationale for a combined therapy with SYK inhibitors and anti-CD20 MoAbs.

No abstract

The prognosis of the primary refractory anaplastic lymphoma kinase (ALK+) anaplastic T large cell lymphoma is ominous. The identification of molecular targets with potential to drive oncogenesis remains a cornerstone for the designing of new selective cancer therapies. Crizotinib is a selective ATP-competitive inhibitor for ALK, approved for its use in lung cancer with rearrangements on ALK gene. The reported cases describe the use of crizotinib as a bridging strategy prior to allotransplantation; there are no reported prolonged survivals under monotherapy with Crizotinib. We report a case of a primary refractory ALK+ anaplastic large-cell lymphoma that sustains complete response after 3 years of crizotinib monotherapy.

The kinematic and dynamic flow behavior of granular material on a transfer chute whose main feature is that it can adapt to different operating conditions while maintaining its configuration is studied. As a result, a geometry is obtained that can fulfill some design criteria such as minimum wear of the linings; easy change of the geometry for different configurations, minimize the probability of plugging; fast return to normal operating conditions after a jam; prevent spillage loss of material; and minimum dimensions. The design is obtained by a simulation based on the discrete element method (DEM), considering the mechanical properties of all the materials involved, with a particle size distribution in line with normal operating conditions, incorporating the distribution of the material’s size and moisture related to friction, cohesion and adhesion phenomena. The LIGGGHTS open source program is used to calculate the movement of the material, and the ParaView program to process the results.

Case series Patients: Male, 72-year-old • Female, 59-year-old • Female, 62-year-old Final Diagnosis: Multiple myeloma Symptoms: Anemia • hypercalcemia • lytic bone lesions Medication: Selinexor Clinical Procedure: — Specialty: Hematology Objective: Unusual setting of medical care Background: Numerous treatment options are available for patients with multiple myeloma (MM). Because of the course of the disease, most patients will experience serial relapse or the MM will become refractory to most of these treatments, leaving patients with few or no treatment options over time. Selinexor, a treatment with a novel mechanism of action, is an oral selective inhibitor of nuclear export (SINE) compound that blocks exportin 1, the major nuclear exporter of tumor suppressor proteins. Case Reports: In this case series, we report on treatment with the weekly oral administration of selinexor combined with bortezomib and dexamethasone (XVd) in 3 patients from Argentina who were heavily treated (5–7 prior therapies) for MM that relapsed or was refractory to each previous treatment. Two patients had the high-risk cytogenetic abnormality del(17p). All 3 patients experienced efficacy with XVd reaching a best response of partial response or very good partial response. These responses were consistent with those of patients from the BOSTON study who were treated with XVd but were less heavily pretreated (1–3 prior therapies) and had a shorter median time since diagnosis of MM (7 years vs 3.7 years). The 3 patients experienced adverse events (AEs) that included nausea, thrombocytopenia, asthenia, and fatigue, which were similar to the most commonly reported AEs associated with selinexor treatment. Conclusions: With its oral administration, novel mechanism of action, and responses in heavily pretreated patients, selinexor may help to address an important clinical need in the treatment of patients with relapsed/refractory MM.