Inotuzumab Ozogamicin and Low-Intensity Chemotherapy in Older Patients With Newly Diagnosed CD22 Philadelphia Chromosome-Negative B-Cell Precursor Acute Lymphoblastic Leukemia.

Purpose: The use of inotuzumab ozogamicin (InO), a conjugated anti-CD22 monoclonal antibody, is becoming a promising frontline treatment for older patients with ALL.

Patients And Methods: EWALL-INO is an open-label prospective multicenter phase II trial (ClinicalTrials.gov identifier: NCT03249870).

Significance of Measurable Residual Disease in Adult Philadelphia Chromosome-Positive ALL: A GRAAPH-2014 Study.

Purpose: quantification is widely regarded as the standard for monitoring measurable residual disease (MRD) in Philadelphia chromosome-positive (Ph+) ALL. However, recent evidence of multilineage involvement questions the significance of MRD. We aimed to define the prognostic role of MRD as assessed by or lymphoid-specific immunoglobulin/T-cell receptor () gene markers.

Faster clinical decisions in B-cell acute lymphoblastic leukaemia: A single flow cytometric 12-colour tube improves diagnosis and minimal residual disease follow-up.

Assessing minimal residual disease (MRD) in B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) is essential for adjusting therapeutic strategies and predicting relapse. Quantitative polymerase chain reaction (qPCR) is the gold standard for MRD. Alternatively, flow cytometry is a quicker and cost-effective method that typically uses leukaemia-associated immunophenotype (LAIP) or different-from-normal (DFN) approaches for MRD assessment.

Chemically diverse activity-based probes with unexpected inhibitory mechanisms targeting trypsin-like serine proteases.

Activity-based probes (ABP) are molecules that bind covalently to the active form of an enzyme family, making them an attractive tool for target and biomarker identification and drug discovery. The present study describes the synthesis and biochemical characterization of novel activity-based probes targeting trypsin-like serine proteases. We developed an extensive library of activity-based probes with "clickable" affinity tags and a diaryl phosphonate warhead.

The immune contexture of primary central nervous system diffuse large B cell lymphoma associates with patient survival and specific cell signaling.

Primary central nervous system diffuse large B-cell lymphoma (PCNSL) is a rare and aggressive entity that resides in an immune-privileged site. The tumor microenvironment (TME) and the disruption of the immune surveillance influence lymphoma pathogenesis and immunotherapy resistance. Despite growing knowledge on heterogeneous therapeutic responses, no comprehensive description of the PCNSL TME is available.

Integrative analysis of a phase 2 trial combining lenalidomide with CHOP in angioimmunoblastic T-cell lymphoma.

Angioimmunoblastic T-cell lymphoma (AITL) is a frequent T-cell lymphoma in the elderly population that has a poor prognosis when treated with cyclophosphamide, doxorubicin, vincristine, and prednisone  (CHOP) therapy. Lenalidomide, which has been safely combined with CHOP to treat B-cell lymphoma, has shown efficacy as a single agent in AITL treatment. We performed a multicentric phase 2 trial combining 25 mg lenalidomide daily for 14 days per cycle with 8 cycles of CHOP21 in previously untreated AITL patients aged 60 to 80 years.

Treatment and outcome of Philadelphia chromosome-positive acute lymphoblastic leukemia in adults after relapse.

Introduction: Despite the significant progress that has been made over the last years in the front-line treatment of Philadelphia (Ph) chromosome-positive acute lymphoblastic leukemia (ALL), relapses are frequent and their treatment remains a challenge, especially among patients with resistant mutations.

Areas Covered: This manuscript reviews available data for the treatment of adult patients with relapsed/refractory Ph-positive ALL, with a focus on the role of tyrosine kinase inhibitors (TKIs), monoclonal antibodies, and immunotherapy.

Expert Opinion: Although a majority of patients with first relapsed Ph-positive ALL respond to subsequent salvage chemotherapy plus TKI combination, their outcomes remain poor.

and atypical/unbalanced gene rearrangements in diffuse large B-cell lymphoma are indicators of an aggressive clinical course.

Aims: Diffuse large B-cell lymphoma (DLBCL) is the most common type of aggressive non-Hodgkin's lymphoma that represents a heterogeneous group of disease that is differentially characterised by clinical, molecular and cytogenetic features. , and gene rearrangements have been identified as prognostic factors in DLBCL, especially for . Nevertheless the frequency and effect of atypical/unbalanced and translocations in DLBCL is not fully documented.

A Retrospective Comparison of DLI and gDLI for Post-Transplant Treatment.

Donor lymphocyte infusion (DLI) is used to prevent or treat haematological malignancies relapse after allogeneic stem cell transplantation (allo-SCT). Recombinant human granulocyte colony-stimulated factor primed DLI (gDLI) is derived from frozen aliquots of the peripheral blood stem cell collection. We compared the efficacy and safety of gDLI and classical DLI after allo-SCT.

Thromboembolism prophylaxis in adult patients with acute lymphoblastic leukemia treated in the GRAALL-2005 study.

Patients undergoing treatment of acute lymphoblastic leukemia (ALL) are at risk for thrombosis, caused in part by the use of l-asparaginase (L-ASP). Antithrombin (AT) replacement has been suggested to prevent venous thromboembolism (VTE) and thus may increase exposure to ASP. We report herein the results of the prophylactic replacement strategy in the pediatrics-inspired prospective GRAALL-2005 study.

The molecular landscape and microenvironment of salivary duct carcinoma reveal new therapeutic opportunities.

: Salivary duct carcinoma (SDC) is a rare and aggressive salivary gland cancer subtype with poor prognosis. The mutational landscape of SDC has already been the object of several studies, however little is known regarding the functional genomics and the tumor microenvironment despite their importance in oncology. Our investigation aimed at describing both the functional genomics of SDC and the SDC microenvironment, along with their clinical relevance.

Characterisation of tumour microenvironment and immune checkpoints in primary central nervous system diffuse large B cell lymphomas.

Primary central nervous system diffuse large B cell lymphoma (PCNS-DLBCL) is a rare and aggressive entity of diffuse large B cell lymphoma (DLBCL). Elements of the tumour microenvironment (TME) including tumour-infiltrating lymphocytes (TILs) and tumour-associated macrophages (TAMs) have been associated with survival in DLBCL but their composition and prognostic impact in PCNS-DLBCL are unknown. Programmed cell death-1 (PD1)/programmed death-ligand 1 (PD-L1) immune checkpoint may represent a therapeutic option.

Human herpesvirus 6 infection after autologous stem cell transplantation: A multicenter prospective study in adult patients.

Objectives: to prospectively evaluate the incidence and the clinical relevance on hematopoietic reconstitution of HHV-6 infection in autologous hematopoietic stem cell transplantation (ASCT) recipients.

Methods: HHV-6 DNA load was measured in whole blood specimens once during the 7 days before stem cell re-infusion and once a week after transplantation until hematopoietic recovery. Active HHV-6 infection was defined by 2 consecutive positive DNA loads.

Generation of induced pluripotent stem cells (iPSCs) IRMBi002-A from an Alzheimer's disease patient carrying a D694N mutation in the APP gene.

Induced pluripotent stem cells (iPSC) were generated from skin fibroblasts obtained from a 58 year-old woman suffering from Alzheimer's disease and carrying a D694N mutation on Amyloid precursor protein (APP). Fibroblasts were reprogrammed into iPSC using the integration-free Sendai Virus which allows the expression of the Yamanaka factors. Verification of their pluripotency was achieved by demonstrating the expression of pluripotency markers and their differentiation potential into the three primary germ layers.

Systemic, primary cutaneous, and breast implant-associated ALK-negative anaplastic large-cell lymphomas present similar biologic features despite distinct clinical behavior.

Despite distinct clinical presentation and outcome, systemic, primary cutaneous, and breast implant-associated anaplastic large cell lymphomas (S-, PC-, BI-ALCL) ALK-negative (ALK-) show similar histopathological features including the presence of the "hallmark" cells with horseshoe-shaped nuclei and CD30 protein expression. The purpose was to better characterize these three entities using immunohistochemistry and FISH (Fluorescent in situ hybridization) to identify biomarkers differently expressed and that might be involved in their pathogenesis. Twenty-two S-ALCL ALK-, 13 PC-ALCL, and 2 BI-ALCL were included.

Generation of induced pluripotent stem cells (IRMBi001-A) from an Alzheimer's disease patient carrying a G217D mutation in the PSEN1 gene.

Induced pluripotent stem cells (iPSC) were generated from skin fibroblasts obtained from a 50 year-old patient suffering from Alzheimer's disease and carrying a G217D causal mutation on presenilin 1 (PSEN1). iPSCs were obtained following reprogramming using the integration-free Sendai Virus system which allows expression of the Yamanaka factors. Verification of their pluripotency was achieved by demonstrating the expression of pluripotency markers and their differentiation potential into the three primary germ layers.

Diagnostic value of STMN1, LMO2, HGAL, AID expression and 1p36 chromosomal abnormalities in primary cutaneous B cell lymphomas.

Aims: Distinction between primary cutaneous follicular lymphoma (PCFL) and primary cutaneous marginal zone lymphoma (PCMZL) is challenging, as clear-cut immunophenotypical and cytogenetic criteria to segregate both entities are lacking.

Methods And Results: To characterize PCFL and PCMZL more clearly and to define criteria helpful for the differential diagnosis, we compared expression of immunohistochemical markers [LIM-only transcription factor 2 (LMO2), human germinal centre-associated lymphoma (HGAL), stathmin 1 (STMN1), activation-induced cytidine deaminase (AID), myeloid cell nuclear differentiation antigen (MNDA)] and the presence of cytogenetic abnormalities described previously in nodal follicular lymphoma [B cell lymphoma 2 (BCL2) and BCL6 breaks, 1p36 chromosomal region deletion (del 1p36)] in a series of 48 cutaneous follicular and marginal zone lymphomas [cutaneous follicular lymphoma (CFL) and cutaneous marginal zone lymphoma (CMZL)]. Immunostaining for STMN1, LMO2, HGAL and AID allowed the distinction between CFL and CMZL, and STMN1 was the most sensitive marker (100% CFL, 0% CMZL).

Personalized genome sequencing coupled with iPSC technology identifies GTDC1 as a gene involved in neurodevelopmental disorders.

The cellular and molecular mechanisms underlying neurodevelopmental conditions such as autism spectrum disorders have been studied intensively for decades. The ability to generate patient-specific induced pluripotent stem cells (iPSCs) now offers a novel strategy for modelling human diseases. Recent studies have reported the derivation of iPSCs from patients with neurological disorders.