Understanding Immune Evasion and Therapeutic Targeting Associated with PD-1/PD-L1 Pathway in Diffuse Large B-cell Lymphoma

In tumor microenvironment, the programmed death 1 (PD-1) immune checkpoint has a crucial role of mechanism of T cell exhaustion leading to tumor evasion. Ligands of PD-1, programmed death ligand 1/2 (PD-L1/L2) are over-expressed in tumor cells and participate in prolonged tumor progression and survivals. Recently, clinical trials for patients who failed to obtain an optimal response prior to standardized chemotherapy in several solid cancers have been focused on targeting therapy against PD-1 to reduce disease progression rates and prolonged survivals. Since various inhibitors targeting the immune checkpoint in PD-1/PD-L1 pathway in solid cancers have been introduced, promising approach using anti-PD-1 antibodies were attempted in several types of hematologic malignances. In diffuse large B cell lymphoma (DLBCL) as the most common and aggressive B cell type of non-Hodgkin’s lymphoma, anti-PD-1 and anti-PD-L1 antibodies were studies in various clinical trials. In this review, we summarized the results of several studies associated with PD-1/PD-L1 pathway as an immune evasion mechanism and described clinical trials about targeting therapy against PD-1/PD-L1 pathway in DLBCL

Mycophenolate-based graft versus host disease prophylaxis is not inferior to methotrexate in myeloablative-related donor stem cell transplantation

We retrospectively reviewed 242 patients who received related donor myeloablative peripheral blood hematopoietic cell transplantation. We compared patients who received mycophenolate (MMF)/cyclosporine (CSA) (n=71), to historical controls who received methotrexate (MTX)/CSA (n=172). There were no differences in overall survival, nonrelapse mortality, and relapse. The MMF/CSA group had significantly faster neutrophil and platelet engraftment: medians of 13 versus 18 days and 10 versus 14 days, respectively (P=0.001). The cumulative incidence of acute graft versus host disease (GVHD) (Grades, 2-4) was significantly lower in the MMF/CSA group (45.1 vs. 74.4%,

Characterization and capacitive modeling of target concentration-dependent subthreshold swing in silicon nanoribbon biosensors

The effect of streptavidin concentration as a target molecule on the subthreshold swing (SS) of biotin-functionalized silicon nanoribbon sensors was investigated for a configuration of field effect transistors. The increasing concentration of conjugated target molecules was modeled as a degradation of the coupling capacitance between the electrolyte and the sensor surface. A binding factor for the ratio of conjugation between targets and receptors was modeled as a coupled capacitance and experimentally determined to be from 0.65 (streptavidin at 1 pM) to 1 (1 nM). This result suggests that SS is potentially a good indicator of the target concentration.close0

A comparison of long-term outcomes of donor lymphocyte infusions and tyrosine kinase inhibitors in patients with relapsed CML after allogeneic hematopoietic cell transplantation

Background Donor lymphocyte infusion (DLI) and tyrosine kinase inhibitors (TKIs) are the 2 standard treatment options in chronic myeloid leukemia (CML) that relapses after hematopoietic cell transplantation (HCT), but reports comparing long-term outcomes of these modalities are rare. Patients and Methods A total of 46 patients were treated with either DLI (n = 28) or TKIs (n = 18) during a first relapse of CML after HCT between 1993 and 2012. The stage of relapse was the chronic phase in 37 patients and the advanced phase in 9 patients. All patients had myeloablative conditioning without T-cell depletion during HCT. The median interval between HCT and treatment for relapse was 34 (range, 2-197) months. Results At a median follow-up of 146 and 70 months, respectively, 32% of the DLI group and 33% of the TKI group had died. Six (21%) patients initially treated with DLI received TKIs during a second relapse. In multivariable analyses, DLI was associated with inferior overall survival (OS) (hazard ratio [HR], 37.4; 95% confidence interval [CI], 2.2-625.4; P =.01), shorter failure-free survival (FFS) (HR, 21.15; 95% CI, 1.8-251; P =.02), higher cumulative incidence of failure (CIF) (HR, 19.5; 95% CI, 1.6-236.5; P =.02), and increased incidence of treatment-induced graft vs. host disease (GVHD) (68% vs. 6%; P =.001). Conclusion TKIs appear better than DLI in chronic-phase relapses after myeloablative non-T-cell-depleted HCT. Outcomes were poor in advanced-phase relapses irrespective of treatment modality

Outcomes of Hematopoietic Cell Transplantation in Adult Patients with Acquired Aplastic Anemia Using Intermediate-Dose Alemtuzumab-Based Conditioning

AbstractGraft-versus-host disease (GVHD) has no therapeutic benefit after hematopoietic cell transplantation (HCT) for patients with acquired aplastic anemia (AA), and its prevention is highly desirable. We designed a conditioning regimen using an intermediate dose of alemtuzumab (50 to 60 mg) and describe our institutional experience of 41 patients who underwent HCT for AA. The median age at HCT was 37 years (range, 17 to 59). The conditioning regimen was high-dose cyclophosphamide (n = 9) or fludarabine based (n = 32). Additional GVHD prophylaxis was with cyclosporine. With a median follow-up of 3.6 years, overall survival at 3 years was 85%. Survival in patients <40 years and ≥40 years was 96% and 67%, respectively (P = .04). Graft failure occurred in 4 (10%) patients; 2 primary and 2 secondary. The cumulative incidences of acute (grades 1 to 2) and chronic GVHD were 27% and 15%, respectively. No patients developed grade 3 to 4 acute GVHD or severe chronic GVHD. The following viral complications were frequent: cytomegalovirus reactivation (79%), herpes simplex (18%), varicella zoster (25%), and BK virus hemorrhagic cystitis (8%). The majority of patients had no significant long-term health issues. This intermediate-dose alemtuzumab-based conditioning regimen results in excellent survival with a favorable impact on GVHD and long-term health outcomes, but close monitoring for viral complications is important