The European landscape on allogeneic haematopoeietic cell transplantation in Chronic Lymphocytic Leukaemia between 2009 and 2019: a perspective from the Chronic Malignancies Working Party of the EBMT.

Allogeneic transplantation (allo-HCT) is a curative treatment in CLL whose efficacy including the most severe forms had led to the 2006 EBMT recommendations. The advent after 2014 of targeted therapies has revolutionized CLL management, allowing prolonged control to patients who have failed immunochemotherapy and/or have TP53 alterations. We analysed the pre COVID pandemic 2009-2019 EBMT registry.

Effect of transtibial prosthesis weight on the contralateral knee joint in relation to the risk of osteoarthritis.

Background: Individuals with transtibial amputation place more load on the contralateral lower extremity. A higher adduction moment at the knee joint has been shown to have an effect on the risk of osteoarthritis.

Objective: The aim of this study was to investigate the effect of weight-bearing of lower-limb prosthesis on the biomechanical parameters associated with the risk of contralateral knee osteoarthritis.

Definition and Clinical Significance of the Monoclonal Gammopathy of Undetermined Significance-Like Phenotype in Patients With Monoclonal Gammopathies.

Purpose: The existence of patients with multiple myeloma (MM) and light-chain (AL) amyloidosis who present with a monoclonal gammopathy of undetermined significance (MGUS)-like phenotype has been hypothesized, but methods to identify this subgroup are not standardized and its clinical significance is not properly validated.

Patients And Methods: An algorithm to identify patients having MGUS-like phenotype was developed on the basis of the percentages of total bone marrow (BM) plasma cells (PC) and of clonal PC within the BM PC compartment, determined at diagnosis using flow cytometry in 548 patients with MGUS and 2,011 patients with active MM. The clinical significance of the algorithm was tested and validated in 488 patients with smoldering MM, 3,870 patients with active MM and 211 patients with AL amyloidosis.

Large cell calcifying Sertoli cell tumour: molecular and immunohistochemical assessment of a series comprising non-metastasising and metastasising neoplasms.

Large cell calcifying Sertoli cell tumour (LCCSCT) is a type of testicular sex cord-stromal tumour that may occur sporadically or in the context of Carney complex and other genetic syndromes. A subset is clinically malignant, and the molecular mechanisms that drive such aggressive behaviour remain unknown. METHODS AND RESULTS: We analysed 21 samples from 20 patients with LCCSCT (12 non-metastasising and eight metastasising) using PRKAR1A immunohistochemistry (IHC) and next-generation sequencing.

Biphenotypic sinonasal sarcoma with PAX3::MAML3 fusion transforming into high-grade rhabdomyosarcoma: report of an emerging rare phenomenon.

We report a case of a 67-year-old male patient with a sinonasal tumor that showed areas of classic biphenotypic sinonasal sarcoma (BSNS) which in some sections sharply transitioned into high-grade rhabdomyosarcoma. Immunohistochemically, the conventional BSNS parts showed S100 protein, SMA, PAX7, and focal MyoD1 expression, whereas desmin and myogenin were negative. In contrast, the cells in high-grade areas expressed desmin, MyoD1, myogenin, and PAX7, while being negative for S100 protein and SMA.

Real-world evidence of efficacy and safety of pomalidomide and dexamethasone in relapsed/refractory multiple myeloma patients: Czech registry data.

We assessed the outcomes of pomalidomide and dexamethasone treatment in relapsed/refractory multiple myeloma (RRMM) patients with ≥1 prior line of therapy. We analyzed the data of all RRMM patients treated with pomalidomide and dexamethasone at nine Czech centers between 2013 and 2018. The source of the data was the Registry of Monoclonal Gammopathies of the Czech Republic.

The role of HIV/hepatitis B virus/hepatitis C virus RNA+ triple infection in end-stage liver disease and all-cause mortality in Europe.

Background: There are limited data on end-stage liver disease (ESLD) and mortality in people with HIV (PWH) coinfected with both hepatitis B virus (HBV) and hepatitis C virus (HCV).

Methods: All PWH aged greater than 18 under follow-up in EuroSIDA positive for HBsAg (HBV), and/or HCVRNA+, were followed from baseline (latest of 1 January 2001, EuroSIDA recruitment, known HBV/HCV status) to ESLD, death, last visit, or 31 December 2020. Follow-up while HCVRNA- was excluded.

Ixazomib, Lenalidomide and Dexamethasone in Relapsed and Refractory Multiple Myeloma in Routine Clinical Practice: Extended Follow-Up Analysis and the Results of Subsequent Therapy.

Background: We confirmed the benefit of addition of ixazomib to lenalidomide and dexamethasone in patients with relapsed and refractory multiple myeloma (RRMM) in unselected real-world population. We report the final analysis for overall survival (OS), second progression free survival (PFS-2), and the subanalysis of the outcomes in lenalidomide (LEN) pretreated and LEN refractory patients.

Methods: We assessed 344 patients with RRMM, treated with IRD (N  =  127) or RD (N  = 217).

Unexpected Heterogeneity of Newly Diagnosed Multiple Myeloma Patients with Plasmacytomas.

In multiple myeloma (MM), malignant plasma cells infiltrate the bone marrow. In some cases, plasma cells migrate out of the bone marrow creating either para-skeletal plasmacytomas (PS) or infiltrating soft tissues as extramedullary plasmacytomas (EMD). The aim of this study was to define risk groups in newly diagnosed MM (NDMM) patients with PS and EMD plasmacytomas.

MonoMAC syndrome with GATA2 novel mutation: A case report.

GATA2 deficiency was first identified in 2011 and have been reported over 500 individuals with GATA2 mutations. The onset of symptoms ranges from early childhood to late adulthood but very often the diagnosis is made between adolescence and early adulthood. These patients can be relatively asymptomatic or have life threatening diseaseas (myelodysplastic syndrome, acute leukemia).

Impact of Cytogenetic Risk on Outcomes of Non-T-Cell-Depleted Haploidentical Hematopoietic Cell Transplantation in Patients with Relapsed or Refractory Acute Myeloid Leukemia.

Baseline cytogenetics and disease status are key factors predicting the outcomes of allogeneic hematopoietic cell transplantation (HCT) in patients with acute myeloid leukemia (AML). The importance of cytogenetic risk in patients with primary refractory or relapsed (R/R) AML undergoing haploidentical (Haplo) HCT is unknown. We studied the impact of cytogenetic risk in patients with R/R de novo AML with active disease who underwent non-T-cell-depleted Haplo-HCT with post-transplantation cyclophosphamide from 2010 to 2020.

Comparison of HLA-mismatched unrelated donor transplantation with post-transplant cyclophosphamide versus HLA-haploidentical transplantation in patients with active acute myeloid leukemia.

HLA-haploidentical allogeneic hematopoietic stem cell transplantation (Haplo-HCT) is frequently used as treatment for patients with active acute myeloid leukemia (AML). Here, we investigated whether 9/10 HLA-mismatched unrelated donor transplantation (MMUD-HCT) with post-transplant cyclophosphamide (PTCy) is an adequate alternative. Inclusion criteria in this retrospective registry study consisted of adult patients, first HCT with a Haplo donor or MMUD between 2010 and 2020 using PTCy as graft-versus-host disease (GVHD) prophylaxis, and primary refractory or relapsed disease.

Whole blood samples for faster real-time PCR analysis of thrombophilic mutations in SARS-CoV-2 virus positive patients.

High incidence of thrombosis and venous thromboembolism was reported in patients with COVID-19. In this study, we focused on analysis of thrombophilic mutations performed without a standard DNA extraction step. In one hundred of COVID-19 positive outpatients, real-time PCR for Leiden mutation in the FV gene and G20210A mutation in the FII gene was carried out from DNA extracts and modified whole blood samples, and their cycle threshold (Ct) values were evaluated.

Genomics Driving Diagnosis and Treatment of Inborn Errors of Immunity With Cancer Predisposition.

Inborn errors of immunity (IEI) are genetically and clinically heterogeneous disorders that, in addition to infection susceptibility and immune dysregulation, can have an enhanced cancer predisposition. The increasing availability of upfront next-generation sequencing diagnostics in immunology and oncology have uncovered substantial overlap of germline and somatic genetic conditions that can result in immunodeficiency and cancer. However, broad application of unbiased genetics in these neighboring disciplines still needs to be deployed, and joined therapeutic strategies guided by germline and somatic genetic risk factors are lacking.

Granulomas associated with renal neoplasms: A multi-institutional clinicopathological study of 111 cases.

Aims: Formal depiction of granulomatous inflammation associated with renal neoplasms has mainly consisted of case reports. Herein, we investigate the clinicopathological features and potential significance of granulomas associated with renal tumours from a large multi-institutional cohort.

Methods And Results: One hundred and eleven study cases were collected from 22 institutions, including 57 partial nephrectomies and 54 radical nephrectomies.

Guideline for the diagnosis and treatment of Faecal Incontinence-A UEG/ESCP/ESNM/ESPCG collaboration.

Introduction: The goal of this project was to create an up-to-date joint European clinical practice guideline for the diagnosis and treatment of faecal incontinence (FI), using the best available evidence. These guidelines are intended to help guide all medical professionals treating adult patients with FI (e.g.

Impact of in vivo T-cell depletion in patients with myelodysplastic syndromes undergoing allogeneic hematopoietic stem cell transplant: a registry study from the Chronic Malignancies Working Party of the EBMT.

While in vivo T-cell depletion (TCD) is widely used, its benefit in patients with MDS still remains a matter of debate. This study evaluates the impact of TCD on outcomes, and compares ATG and alemtuzumab, in patients with MDS. 1284 patients from the EBMT registry were included in this study with 470 patients in the no-TCD group and 814 in the TCD group (alemtuzumab N = 168; ATG N = 646).

Clinical value of ALK and CD30 expression in mature systemic T cell lymphomas: analysis from the Czech Lymphoma Study Group database (NIHIL).

Mature T cell lymphomas (MTCLs) have worse prognosis, and in contrast to B cell lymphomas, there is no universal marker like CD20 with exception of ALK and CD30, which are present in proportion of MTCL only. Up to now, ALK is traditionally associated with good prognosis in ALCLs, and there are some evidences that CD30-positive T cell or B cell lymphomas have better prognosis. In our retrospective, population-based analysis, we analyzed the real clinical value of ALK and CD30 in the most frequent MTCL subtypes.

Measurable residual disease, FLT3-ITD mutation, and disease status have independent prognostic influence on outcome of allogeneic stem cell transplantation in NPM1-mutated acute myeloid leukemia.

Nucleophosmin-1 (NPM1) mutations in acute myeloid leukemia (AML) confer a survival advantage in the absence of FLT3-internal tandem duplication (FLT3-ITD). Here, we investigated the main predictors of outcome after allogeneic hematopoietic stem cell transplantation (allo-HCT). We identified 1572 adult (age ≥ 18 year) patients with NPM1-mutated AML in first complete remission (CR1:78%) or second complete remission (CR2:22%) who were transplanted from matched sibling donors (30.

Melflufen or pomalidomide plus dexamethasone for patients with multiple myeloma refractory to lenalidomide (OCEAN): a randomised, head-to-head, open-label, phase 3 study.

Background: Melphalan flufenamide (melflufen), an alkylating peptide-drug conjugate, plus dexamethasone showed clinical activity and manageable safety in the phase 2 HORIZON study. We aimed to determine whether melflufen plus dexamethasone would provide a progression-free survival benefit compared with pomalidomide plus dexamethasone in patients with previously treated multiple myeloma.

Methods: In this randomised, open-label, head-to-head, phase 3 study (OCEAN), adult patients (aged ≥18 years) were recruited from 108 university hospitals, specialist hospitals, and community-based centres in 21 countries across Europe, North America, and Asia.

20-Year Steady Increase in Survival of Adult Patients with Relapsed Philadelphia-Positive Acute Lymphoblastic Leukemia Post Allogeneic Hematopoietic Cell Transplantation.

Purpose: Relapse after allogeneic hematopoietic cell transplantation (allo-HCT) remains the first cause of transplant failure in patients with Philadelphia-positive (Ph+) acute lymphoblastic leukemia (ALL). In other hematologic malignancies, therapeutic advances resulted in significant improvement over time in survival of patients relapsing after transplant.

Experimental Design: We compared outcomes at European Society for Blood and Marrow Transplantation (EBMT) participating centers of 899 adult patients with Ph+ ALL who relapsed between 2000 and 2019 after allo-HCT performed in first complete remission.