Hematopoietic stem cell (HSC) aging, which is accompanied by reduced self-renewal ability, impaired homing, myeloid-biased differentiation, and other defects in hematopoietic reconstitution function, is a hot topic in stem cell research. Although the number of HSCs increases with age in both mice and humans, the increase cannot compensate for the defects of aged HSCs. Many studies have been performed

Abstract This case–control study investigated immune thrombocytopenic purpura (ITP) risk following live, inactivated, and simultaneous vaccination, with a focus on infants aged < 2 years. We matched case patients with ITP to one or two control patients with other diseases by institution, hospital visit timing, sex, and age. We calculated McNemar’s pairwise odds ratios (ORs [95% confidence interval])

Abstract Terminal deoxynucleotidyl transferase (TdT) is expressed on precursor lymphoblastic neoplasms and some acute myeloid leukemia (AML) cells. The clinical impact of TdT expression on AML outcomes remains unclear. Here, we conducted a retrospective analysis to identify prognostic implications of TdT expression in AML with an intermediate-risk karyotype. Forty-eight cases of intermediate-risk AML

Abstract Advances in the molecular biology of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and development of molecularly targeted therapies have resulted in treatment innovations. Therapeutic approaches for previously untreated CLL/SLL patients are changing from chemoimmunotherapy (CIT) to molecularly targeted drugs. The aim of therapy for CLL patients has been to control the

Abstract We report a case of acquired dysfibrinogenemia with monoclonal gammopathy of undetermined significance presenting λ-type IgA M protein. The patient showed lower functional (0.4 g/dL) and normal immunological fibrinogen (2.9 g/dL). To examine the cause of the false lower value of fibrinogen, we performed experiments using the patient’s purified fibrinogen and IgA. Fibrinogen was purified from

Abstract A 70-year-old male was referred to our hospital for marked thrombocytosis without anemia. The patient simultaneously presented with an MPL W515L mutation, one of the major driver mutations in essential thrombocythemia (ET), and deletion of 5q, a characteristic cytogenetic abnormality in myelodysplastic syndrome (MDS). Bone marrow examination showed a combination of both mature hyperlobulated

Abstract Acute graft-versus-host disease (aGVHD) of the lower gastrointestinal (GI) tract is the major cause of non-relapse mortality (NRM) in allogeneic hematopoietic stem cell transplantation (alloHSCT). This study aimed to identify variables associated with corticosteroid response and NRM in patients who developed lower GI aGVHD. We retrospectively analyzed the clinical data of patients treated

Abstract Separase, a cysteine endopeptidase, is a key player in mitotic sister chromatid separation, replication fork dynamics, and DNA repair. Aberrant expression and/or altered separase proteolytic activity are associated with aneuploidy, tumorigenesis, and disease progression. Since genomic instability and clonal evolution are hallmarks of progressing chronic myeloid leukemia (CML), we have comparatively

Abstract These are the results of phase II study of bortezomib-melphalan-prednisolone (VMP) induction therapy followed by lenalidomide-dexamethasone (Rd) consolidation and lenalidomide maintenance in transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM). The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS), overall response

Minimal residual disease (MRD) in chronic lymphocytic leukemia (CLL) has prognostic and predictive significance. One of the approaches to detect MRD by flow cytometry (FC) is the use of dry antibody reagents such as DuraClone® RE CLB (Beckman Coulter—BC). The aim of this study was to evaluate the performance of the DuraClone® RE CLB in detecting MRD in CLL compared to liquid reagents.

Large B‐cell lymphoma with IRF4 rearrangement, and Burkitt‐like lymphoma with 11q aberration are two provisional lymphoma entities in the 2017 revision of the WHO classification of lymphoid neoplasms. Despite being more frequent in young patients, knowledge regarding their true incidence and clinical features in unselected cohorts of paediatric and adolescent patients is limited. We screened for both

Leukaemic stem cells (LSC) have been experimentally defined as the leukaemia‐propagating population and are thought to be the cellular reservoir of relapse in acute myeloid leukaemia (AML). Therefore, LSC measurements are warranted to facilitate accurate risk stratification. Previously, we published the composition of a one‐tube flow cytometric assay, characterised by the presence of 13 important membrane

Exposure to acute, high-dose, high dose-rate whole-body ionizing radiations damages the bone marrow resulting in rapid decreases in concentrations of blood cells, especially lymphocytes, granulocytes and platelets with associated risks of infection and bleeding. In several experimental models including non-human primate radiation exposure models giving molecularly cloned haematopoietic growth factor

Myelodysplastic syndromes (MDS) are a heterogeneous group of myeloid disorders characterized by cytopenias and increased risk of acute leukemia transformation. Prognosis of MDS patients can be assessed by various scoring systems, the most common being the International Prognostic Scoring System (IPSS) now refined by the revised version (IPSS-R). Genomic information at baseline, that is currently not

The Complement 1 trial investigated the efficacy and safety of ofatumumab + chlorambucil with chlorambucil monotherapy in patients with previously untreated chronic lymphocytic leukaemia (CLL). On long‐term follow‐up in the chemoimmunotherapy arm vs. the chemotherapy arm there was an estimated 12% (not significant) and 39% risk reduction in overall survival and progression‐free survival, respectively

Abstract Real-world data on regimens for relapsed/refractory multiple myeloma (RRMM) represent an important component of therapeutic decision-making. This multi-centric, retrospective, observational study conducted by the treating physicians evaluated the effectiveness and safety of ixazomib-lenalidomide-dexamethasone (IRd) in 155 patients who received ixazomib via early access programs in Greece,

Advances in genomics have deepened our understanding of the biology of acute lymphoblastic leukemia (ALL), defined novel molecular leukemia subtypes, discovered new prognostic biomarkers and paved the way to emerging molecularly targeted therapeutic avenues. Since its discovery, IKZF1 has generated significant interest within the leukemia scientific community. IKZF1 plays a critical role in lymphoid

We studied the efficacy and safety of humanized CAR‐T therapy following intensive chemotherapy for refractory/relapsed (R/R) acute lymphoblastic leukaemia (B‐ALL). Twenty‐three patients with R/R B‐ALL were pretreated with intensive chemotherapy (fludarabine combined with medium‐dose cytarabine) 12 days before CAR‐T therapy. Adverse events (AEs), curative effects, infection indicators and cytokine release

Data on older patients with primary central nervous system lymphoma (PCNSL) are scarce. Comorbidities and performance status frequently compromise outcomes in this group. Medical records for consecutive patients ≥65 years (n = 244) with PCNSL diagnosed 2012–2017 from 14 UK centres were retrospectively reviewed. Of these 192 patients received methotrexate (MTX)‐based treatment. Patients were categorised

Despite the availability of guidelines for the management of chronic myeloid leukaemia (CML), various issues may prevent their successful implementation. The TARGET survey examined real‐world management of CML patients compared with international recommendations. This online survey was completed in 2017. Results were discussed by a Steering Committee (SC) of eight international haematologists, challenges

Exomic rare variant polymorphisms (c. 300 000) were analysed in the Scripps Venous Thrombosis (VTE) registry (subjects aged <55 years). Besides coagulation factor V (F5) single nucleotide polymorphisms (SNPs), family with sequence similarity 134, member B (FAM134B; rs78314670, Arg127Cys) and myosin heavy chain 8 (MYH8; rs111567318, Glu1838Ala) SNPs were associated with recurrent VTE (n = 34 cases)

Future progress in the treatment of multiple myeloma (MM) requires both the characterisation of key drivers of the disease and novel, innovative approaches to tackle these vulnerabilities. The present study focussed on the pre‐clinical evaluation of a novel drug class, BMI‐1 modulators, in MM. We demonstrate potent activity of PTC‐028 and PTC596 in a comprehensive set of in vitro and in vivo models

Protein-protein interactions (PPIs) are central to a variety of biological processes, and their dysfunction is implicated in the pathogenesis of a range of human diseases, including cancer. Hence, the inhibition of PPIs has attracted significant attention in drug discovery. Covalent inhibitors have been reported to achieve high efficiency through forming covalent bonds with cysteine or other nucleophilic

Previous reports suggest a benefit associated with haploidentical donor transplantation (HIDT) compared to matched sibling donor transplantation (MSDT) in certain contexts, and the choice of optimal candidates warrants further investigation. We designed a prospective genetically randomized study to evaluate donor options between acute lymphoblastic leukemia (ALL) patients positive for measurable residual

Acute myeloid leukemia (AML) remains difficult to treat: despite multiagent chemotherapy, allogeneic hematopoietic cell transplantation, and several newly approved agents, many patients will not be alive and in remission 3 years after diagnosis. However, with more agents available there are more options and a corresponding need to choose among them. Doing so is complicated by the molecular diversity

Allogeneic hematopoietic cell transplant (HCT) is often the only curative therapy for patients with non-malignant diseases; however, many patients do not have a human leukocyte antigen (HLA)-matched donor. Historically, poor survival was seen following HLA-haploidentical HCT due to poor immune reconstitution, increased infections, graft-versus-host disease (GVHD), and graft failure. Encouraging results

During malignant transformation, accumulated somatic mutations endow cancer cells with increased invasiveness and immunogenicity. Under selective pressure, these highly immunogenic cancer cells develop multiple strategies to evade immune attack. It has been well established that cancer cells could downregulate the expression of major histocompatibility complex, acquire alterations in interferon pathway

Magnesium is an important element that has essential roles in the regulation of cell growth, division, and differentiation. Mounting evidence in the literature suggests an association between hypomagnesemia and all-cause mortality. In addition, epidemiologic studies have demonstrated that a diet poor in magnesium increases the risk of developing cancer, highlighting its importance in the field of hematology

Late relapse [>3 years from complete remission (CR)] in acute lymphoblastic leukaemia (ALL), is unusual. Data from the MRC UKALLXII/ECOG E2993 trial are presented to evaluate the incidence and characteristics of late relapse in adult ALL. Of 1,909 patients, 1,752 (92%) achieved CR and among these 757 (43·2%) relapsed; 691 (91·3%) within three years and 66 (8·7%) beyond. Among these 66 patients, median

Aerobic glycolysis is a hallmark of metabolic reprogramming that contributes to tumor progression. However, the mechanisms regulating expression of glycolytic genes in neuroblastoma (NB), the most common extracranial solid tumor in childhood, still remain elusive. Crucial transcriptional regulators and their downstream glycolytic genes were identified by integrative analysis of a publicly available

Abstract Treatment outcomes in pediatric lymphoma have improved substantially over the past 2 decades; however, the prognosis for patients with high risk or relapsed disease remains poor. We evaluated outcomes of high-dose chemotherapy (HDC) and autologous stem cell transplantation (auto-SCT) in 56 pediatric lymphoma patients. Patients received nitrosourea (51 BCNU; 5 ACNU), etoposide, and cyclophosphamide

Sickle cell disease is a life-threatening inherited condition designated as a public health priority by WHO. Increased longevity of patients with sickle cell disease in high-income, middle-income, and low-income countries present unprecedented challenges for all settings; however, a globally standardised solution for patient transition from paediatric to adult sickle cell disease health care is unlikely

For decades intravenous iron was considered dangerous. Newer formulations with carbohydrate cores binding elemental iron more tightly allow complete iron replacement within 15–60 min in one visit. Meta-analyses and prospective comparisons of different formulations support equivalent safety to placebo with less toxicity than oral iron. Of the available formulations, the preponderance of published evidence

Background Multiple myeloma is an incurable haematological malignancy, representing over 10% of haematological cancers in the USA. We did a phase 1–2 study of melflufen and dexamethasone in patients with relapsed and refractory multiple myeloma to determine the maximum tolerated dose of melflufen and to investigate its safety and efficacy. Methods We did a multicentre, international, dose-confirmation

Background Intravenous daratumumab for treatment of patients with multiple myeloma involves a lengthy infusion that affects quality of life, and infusion-related reactions are common. Subcutaneous daratumumab is thought to be easier to administer and to cause fewer administration-related reactions. In this study (COLUMBA), we tested the non-inferiority of subcutaneous daratumumab to intravenous daratumumab

Detection of circulating tumor cells (CTC) by techniques based on epithelial cell adhesion molecule (EpCAM) is suboptimal in urothelial carcinoma (UC). As HER2 is thought to be broadly expressed in UC, we explored its utility for CTC detection.

Inhibitor development is a major complication of treatment with factor VIII concentrates in nonsevere haemophilia A. It has been suggested that plasma‐derived factor VIII (FVIII) concentrates elicit fewer inhibitors than recombinant FVIII concentrates, but studies in severe haemophilia A patients have shown conflicting results. We designed a case‒control study to investigate the clinical and genetic

Abstract Immunoglobulin light chain amyloidosis (AL) is a plasma cell disorder characterized by accumulation of misfolded proteins, which can induce organ damage. Venetoclax is active in multiple myeloma patients, in particular those with t(11;14) translocation. t(11;14) translocation is the most common cytogenetic abnormality in AL patients; venetoclax may thus be a useful additional treatment option

Abstract Transfusion-associated iron overload may lead to increased risk of infection, but its role in myelofibrosis (MF) has been scarcely explored. We evaluated 106 consecutive patients with primary or secondary MF. Up to 38% of patients were transfusion-dependent (TD) with a median of 14 RBC units received. Median observation time was 36 months (range 3–203). Forty-five percent of patients experienced

Abstract Various central nervous system (CNS) complications may occur after allogeneic hematopoietic stem cell transplantation (allo-HSCT), which can result in severe clinical problems. Diagnosis is often difficult, as distinctive clinical symptoms may be absent and different neurological disorders may exhibit similar symptoms. Despite the fact that antibodies responding to brain cell surface antigens

NK cells have killing activity against leukemic cells and solid cancer cells that escape from T cell recognition because of the low expression level of HLA class I molecules. This characteristic feature of NK cell recognition of target cells in contrast to T cells provides a strategy to overcome tolerance in cancer and leukemia patients. A strong alloreactive NK cell-mediated anti-leukemia effect can

Myelofibrosis is an enigmatic myeloproliferative neoplasm, despite noteworthy strides in understanding its genetic underpinnings. Driver mutations involving JAK2, CALR or MPL in 90% of patients mediate constitutive JAK‐STAT signaling which, in concert with epigenetic alterations (ASXL1, DNMT3A, SRSF2, EZH2, IDH1/2 mutations), play a fundamental role in disease pathogenesis. Aberrant immature megakaryocytes

Langerhans cell histiocytosis (LCH) is a rare protean disease that usually affects children. Few data are available for management of adult‐onset cases. A complete picture of the efficacy and safety of 2CdA (2‐chlorodeoxyadenosine, cladribine) is lacking. We report a retrospective multicentre study of 23 adult LCH (a‐LCH) patients who received single‐agent 2CdA and a systematic literature review. All

Objectives Chronic hepatitis E virus (HEV) infection in hematopoietic stem cell transplant (HSCT) recipients is an emerging threat. The aim of this study was to provide data on HEV burden in an Italian cohort of HSCT recipients and analyze risk factors for HEV seropositivity. Methods This retrospective study reports data from 596 HSCT recipients from years 2010-2019. It included patients transplanted

Background Potentially curative but high-risk trials of gene therapy or stem cell transplantation (PBSCT) for Sickle Cell Disease (SCD) pose new opportunities for adults with SCD, many of whom experience significant disease burden and complications with few treatment options, as well as stigma and disparities in care. We explored motivations and decision-making processes of enrollees and decliners

Pulmonary complications are fatal adverse events after allo-HCT. On the other hand, smoking is a well-known risk factor for various pulmonary diseases and also increases the incidence of pulmonary complications and overall mortality in allo-HCT recipients. In this study, we retrospectively assessed the impact of smoking intensity on survival outcomes. This study included consecutive allo-HCT recipients

Introduction Haematopoietic stem cell transplantation (HSCT) is the only curative option available for patients with thalassaemia major in India with increasing access to alternate donor transplantation for patients with no matched family donor. We aimed to analyse the impact of family and alternate donor HSCT on morbidity and mortality post-HSCT Methods We conducted a retrospective study in the department

Background Latent tuberculosis infection (LTBI) affects one-fourth of the world´s population. Hematopoietic Stem Cell Transplant (HSCT) recipients are at a higher risk of developing active tuberculosis infection (ATBI). Our aim was to determine LTBI prevalence, ATBI incidence, and describe diagnostic and therapeutic strategies in an HSCT population in an endemic region. Methods Retrospective study