The Latest Haemato-Oncology Journal Articles

Keep up to date with the latest in haemato-oncology. Check out the latest haemato-oncology articles from leading medical journals in a single view, helping you discover relevant articles quickly and easily

• CC-90009, a novel cereblon E3 ligase modulator targets acute myeloid leukemia blasts and leukemia stem cells.16th November 2020
  A number of clinically validated drugs have been developed by repurposing the CUL4-DDB1-CRBN-RBX1 (CRL4CRBN) E3 ubiquitin ligase complex with molecular glue degraders to eliminate disease-driving proteins. Here, we present the identification of a first-in-class GSPT1-selective cereblon E3 ligase modulator, CC-90009. Biochemical, structural and molecular characterization demonstrates that CC-90009 co-opts the CRL4CRBN to selectively target GSPT1 […]
• Enhanced IL-9 secretion by p66Shc-deficient CLL cells modulates the chemokine landscape of the stromal microenvironment.12th November 2020
  The stromal microenvironment is central to chronic lymphocytic leukemia (CLL) pathogenesis. How leukemic cells condition the stroma to enhance its chemoattractant properties remains elusive. Here we show that mouse and human CLL cells promote the contact-independent stromal expression of homing chemokines. This function was strongly enhanced in leukemic cells from Em-TCL1 mice lacking the pro-oxidant […]
• Networking for advanced molecular diagnosis in acute myeloid leukemia patients is possible: the PETHEMA NGS-AML project.12th November 2020
  Next-Generation Sequencing has recently been introduced to efficiently and simultaneously detect genetic variations in acute myeloid leukemia. However, its implementation in the clinical routine raises new challenges focused on the diversity of assays and variant reporting criteria. To overcome this challenge, the PETHEMA group established a nationwide network of reference laboratories aimed to deliver molecular […]
• The LEukemia Artificial Intelligence Program (LEAP) in Chronic Myeloid Leukemia in Chronic Phase: A Model to Improve Patient Outcomes.12th November 2020
  Extreme gradient boosting methods outperform conventional machine-learning models. Here, we have developed the LEukemia Artificial intelligence Program (LEAP) with the extreme gradient boosting decision tree method for the optimal treatment recommendation of tyrosine kinase inhibitors (TKIs) in patients with chronic myeloid leukemia in chronic phase (CML-CP).A cohort of CML-CP patients was randomly divided into training/validation […]
• UTX maintains functional integrity of murine hematopoietic system by globally regulating aging-associated genes.11th November 2020
  Epigenetic regulation is essential for the maintenance of the hematopoietic system, and its deregulation is implicated in hematopoietic disorders. Here, we show that UTX, a demethylase for lysine 27 on histone H3 (H3K27) and a component of Compass-like and SWI/SNF complexes, plays an essential role in the hematopoietic system by globally regulating aging-associated genes. Utx-deficient […]
• Minimal Residual Disease Quantification in Ovarian Tissue Collected in Patients in Complete Remission of Acute Leukemia.10th November 2020
  Ovarian tissue cryopreservation (OTC) is offered to women treated for acute leukemia to preserve their fertility before hematopoietic stem cell transplantation. The risk of leukemic infiltration in ovarian samples harvested before administration of chemotherapy limits ovarian tissue transplantations. We assessed the minimal residual disease (MRD) by sensitive quantitative polymerase chain reaction in cryopreserved ovarian cortex […]
• How I diagnose and treat NPM1-mutated AML.10th November 2020
  Mutations of the nucleophosmin (NPM1) gene, encoding for a nucleolar multifunctional protein, occur in about one-third of adult acute myeloid leukemia (AML). NPM1-mutated AML exhibits unique molecular, pathological and clinical features, that led to its recognition as distinct entity in the 2017 World Health Organization (WHO) classification of myeloid neoplasms. Although WHO criteria for the […]
• The treatment of Burkitt lymphoma in adults.10th November 2020
  Burkitt lymphoma (BL) is a highly aggressive, B-cell, non-Hodgkin lymphoma (NHL) categorized into endemic, sporadic and immunodeficiency-associated subtypes. BL has distinct pathologic and clinical features, characterized by rapidly progressive tumors with high rates of extranodal involvement. Next generation sequencing (NGS) analyses have further characterized the genomic landscape of BL and our understanding of disease pathogenesis, […]
• miR-29 Modulates CD40 Signaling in Chronic Lymphocytic Leukemia by Targeting TRAF4: an Axis Affected by BCR inhibitors.10th November 2020
  B cell receptor (BCR) signaling and T cell interactions play a pivotal role in chronic lymphocytic leukemia (CLL) pathogenesis and disease aggressiveness. CLL cells can utilize microRNAs (miRNAs) and their targets to modulate microenvironmental interactions in the lymph node niches. To identify miRNA expression changes in the CLL microenvironment, we performed complex profiling of short […]
• Chronic lymphocytic leukemia and second primary nonlymphoid malignancies: cytopathologic study of 17 cases.10th November 2020
  Second primary nonlymphoid malignancies (SPNLM) have long been recognized as a complication of chronic lymphocytic leukemia (CLL).A search was made of our cytopathology database for cases of CLL that also contained a SPNLM.Seventeen cases from 13 known CLL patients [M:F = 2.3:1; age range: 47-77 years, x = 67 years] met criteria for this study. […]
• A fixed-duration, measurable residual disease-guided approach in CLL: follow-up data from the phase 2 ICLL-07 FILO trial.9th November 2020
  Trials assessing first-line, fixed-duration approaches in chronic lymphocytic leukemia (CLL) are yielding promising activity, but few long-term data are available. We report follow-up data from a phase 2 trial (ICLL-07 FILO; NCT02666898) in previously untreated, medically-fit patients (N=135). Patients underwent obinutuzumab-ibrutinib induction for 9 months; then, following evaluation (N=130 evaluable), those in complete remission and […]
• Relapse risk following truncation of PEG-asparaginase in childhood acute lymphoblastic leukemia.5th November 2020
  Truncation of asparaginase treatment due to asparaginase related toxicities or silent inactivation (SI) is common and may increase relapse risk in acute lymphoblastic leukemia (ALL). We investigated relapse risk following suboptimal asparaginase exposure among 1401 children aged 1-17 years, diagnosed with ALL between July 2008 and February 2016, and treated according to the NOPHO ALL2008 […]
• Progression signature underlies clonal evolution and dissemination of multiple myeloma.5th November 2020
  Clonal evolution drives tumor progression, dissemination and relapse in multiple myeloma (MM), with most patients dying of relapsed disease. This multi-stage process requires tumor cells to enter the circulation, extravasate and colonize distant bone marrow (BM) sites. Here, we developed a fluorescent or DNA-barcode clone-tracking system on MM PrEDiCT (Progression through Evolution and Dissemination of […]
• Chemotherapy or Allogeneic Transplantation in High-Risk Philadelphia Chromosome-Negative Adult Lymphoblastic Leukemia.5th November 2020
  The need for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in adults with Philadelphia chromosome-negative (Ph-neg) acute lymphoblastic leukemia (ALL) with high-risk (HR) features and adequate measurable residual disease (MRD) clearance remains unclear. The aim of the ALL-HR-11 trial was to evaluate the outcomes of HR Ph-neg adult ALL patients following chemotherapy or allo-HSCT administered based […]
• Expression of the chemokine receptor CCR1 promotes the dissemination of multiple myeloma plasma cells in vivo.5th November 2020
  Multiple myeloma (MM) disease progression is dependent on the ability of MM plasma cells (PCs) to egress from the bone marrow (BM), enter the circulation and disseminate to distal BM sites. Expression of the chemokine CXCL12 by BM stromal cells is crucial for MM PC retention within the BM. However, the mechanisms which overcome CXCL12-mediated […]
• PVRIG is a novel NK cell immune checkpoint receptor in acute myeloid leukemia.5th November 2020
  This study explored the novel immune checkpoint poliovirus receptor-related immunoglobulin domain-containing (PVRIG) in acute myeloid leukemia (AML). We showed that AML patient blasts consistently expressed the PVRIG ligand (poliovirus receptor-related 2, PVRL2). Furthermore, PVRIG blockade significantly enhanced NK cell killing of PVRL2+, poliovirus receptor (PVR)lo AML cell lines, and significantly increased NK cell activation and […]
• Multiclonal complexity of pediatric acute lymphoblastic leukemia and the prognostic relevance of subclonal mutations.5th November 2020
  Genomic studies of pediatric acute lymphoblastic leukemia (ALL) have shown remarkable heterogeneity in initial diagnosis, with multiple (sub)clones harboring lesions in relapse-associated genes. However, the clinical relevance of these subclonal alterations remains unclear. We assessed the clinical relevance and prognostic value of subclonal alterations in the relapse-associated genes IKZF1, CREBBP, KRAS, NRAS, PTPN11, TP53, NT5C2, […]
• Standardization of 18F-FDG-PET/CT According to Deauville Criteria for Metabolic Complete Response Definition in Newly Diagnosed Multiple Myeloma.5th November 2020
  18F-Fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) is currently the standard technique to define minimal residual disease (MRD) status outside the bone marrow (BM) in patients with multiple myeloma (MM). This study aimed to define criteria for PET complete metabolic response after therapy, jointly analyzing a subgroup of newly diagnosed transplantation-eligible patients with MM […]
• -Active AKT signaling triggers CLL towards Richter’s transformation via over-activation of Notch1.3rd November 2020
  Richter’s transformation (RT) is an aggressive lymphoma which occurs upon progression from chronic lymphocytic leukemia (CLL). Transformation has been associated with genetic aberrations in the CLL-phase involving TP53, CDKN2A, MYC, and NOTCH1, however a significant proportion of RT cases lack CLL-phase associated events. Here, we report that high levels of AKT phosphorylation occurs both in […]
• CRM1 inhibitor anti-tumor activity is enhanced with salicylates by S-phase arrest and impaired DNA-damage repair.3rd November 2020
  Chromosome region maintenance protein1 (CRM1) mediates protein export from the nucleus and is a new target for anti-cancer therapeutics. Broader application of KPT-330 (selinexor), a first in class CRM1 inhibitor recently approved for relapsed multiple myeloma and diffuse large B-cell lymphoma, have been limited by substantial toxicity. We discovered that salicylates markedly enhance the anti-tumor […]
• Intermittent schedules of the oral RAF-MEK inhibitor CH5126766/VS-6766 in patients with RAS/RAF-mutant solid tumours and multiple myeloma: a single-centre, open-label, phase 1 dose-escalation and basket dose-expansion study.1st November 2020
  CH5126766 (also known as VS-6766, and previously named RO5126766), a novel MEK-pan-RAF inhibitor, has shown antitumour activity across various solid tumours; however, its initial development was limited by toxicity. We aimed to investigate the safety and toxicity profile of intermittent dosing schedules of CH5126766, and the antitumour activity of this drug in patients with solid […]
• Venetoclax or placebo in combination with bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma (BELLINI): a randomised, double-blind, multicentre, phase 3 trial.1st November 2020
  Venetoclax is a highly selective, potent, oral BCL-2 inhibitor, which induces apoptosis in multiple myeloma cells. Venetoclax plus bortezomib and dexamethasone has shown encouraging clinical efficacy with acceptable safety and tolerability in a phase 1 trial. The aim of this study was to evaluate venetoclax plus bortezomib and dexamethasone in patients with relapsed or refractory […]
• The IL1-IL1RAP axis plays an important role in the inflammatory leukemic niche that favors acute myeloid leukemia proliferation over normal hematopoiesis.30th October 2020
  Upregulation of the plasma membrane receptor IL1RAP in Acute Myeloid Leukemia (AML) has been reported but its role in the context of the leukemic bone marrow niche is unclear. Here, we studied the signaling events downstream of IL1RAP in relation to leukemogenesis and normal hematopoiesis. High IL1RAP expression was associated with a leukemic GMP-like state, […]
• Venetoclax plus bendamustine-rituximab or bendamustine-obinutuzumab in chronic lymphocytic leukemia: final results of a phase 1b study (GO28440).30th October 2020
  Venetoclax (Ven), an orally administered, potent BCL-2 inhibitor, has demonstrated efficacy in chronic lymphocytic leukaemia (CLL) in combination with rituximab (R) or obinutuzumab (G). Our aim was to investigate the addition of bendamustine (B) to these Ven-containing regimens in relapsed/refractory (R/R) or first-line (1L) CLL. This multi-arm, non-randomized, open-label, phase 1b study was designed to […]
• SF3B1-mutated chronic lymphocytic leukemia shows evidence of NOTCH1 pathway activation including CD20 downregulation.30th October 2020
  Chronic lymphocytic leukemia (CLL) is characterized by a low CD20 expression, in part explained by an epigenetic-driven downregulation triggered by mutations of the NOTCH1 gene. In the present study, by taking advantage of a wide and well-characterized CLL cohort (n=537), we demonstrate that CD20 expression is downregulated in SF3B1-mutated CLL in an extent similar to […]
• A phase 1b study of once-weekly carfilzomib combined with lenalidomide and dexamethasone in patients with newly diagnosed multiple myeloma.30th October 2020
  Twice-weekly carfilzomib with lenalidomide-dexamethasone (Rd) is an effective regimen for newly diagnosed multiple myeloma (NDMM). Here we evaluated once-weekly carfilzomib with Rd (once-weekly KRd) in NDMM patients. NDMM patients were enrolled regardless of transplant eligibility. Patients received carfilzomib on days 1, 8, and 15; lenalidomide 25 mg on days 1-21; and dexamethasone 40 mg on […]
• Absence of a common founder mutation in patients with co-occurring myelodysplastic syndrome and plasma cell disorder.29th October 2020
  Epidemiological studies have demonstrated an increased incidence of MDS in patients with plasma cell disorder (PCD) i.e. multiple myeloma (MM) or MGUS and several case reports / series of co-occurring MDS and PCD have been published. The underlying pathogenesis for this condition, and if the two diseases share a common genetic lesion remains unknown. Here, […]
• Venetoclax with azacitidine or decitabine in patients with newly diagnosed acute myeloid leukemia: long term follow-up from a Phase 1b study.29th October 2020
  This analysis represents the longest-term follow-up for patients with acute myeloid leukemia (AML) treated with 400 mg of venetoclax plus azacitidine or decitabine. Adults with newly diagnosed AML ineligible for intensive chemotherapy were enrolled in an open-label, non-randomized, multicenter phase 1b trial of venetoclax with azacitidine (AZA; 75 mg/m2 ; days 1-7) or decitabine (DEC; […]
• Mutant Isocitrate Dehydrogenase 1 Inhibitor Ivosidenib in Combination With Azacitidine for Newly Diagnosed Acute Myeloid Leukemia.29th October 2020
  Ivosidenib is an oral inhibitor of the mutant isocitrate dehydrogenase 1 (IDH1) enzyme, approved for treatment of IDH1-mutant (mIDH1) acute myeloid leukemia (AML). Preclinical work suggested that addition of azacitidine to ivosidenib enhances mIDH1 inhibition-related differentiation and apoptosis.This was an open-label, multicenter, phase Ib trial comprising dose-finding and expansion stages to evaluate safety and efficacy […]
• Tumor and microenvironment response but no cytotoxic T-cell activation in classic Hodgkin lymphoma treated with anti-PD1.28th October 2020
  Classic Hodgkin lymphoma (cHL) is the cancer type most susceptible to anti-programmed-death-receptor-1 (PD1) treatment and characterized by scarce Hodgkin and Reed-Sternberg cells (HRSC) perpetuating a unique tumor microenvironment (TME). Whilst in solid tumors anti-PD1 effects appear largely mediated by cytotoxic CD8+ T-cells, HRSC frequently lack major histocompatibility complex expression and the mechanism of anti-PD1 efficacy […]
• Effect of rhG-CSF Combined With Decitabine Prophylaxis on Relapse of Patients With High-Risk MRD-Negative AML After HSCT: An Open-Label, Multicenter, Randomized Controlled Trial.27th October 2020
  Relapse is a major cause of treatment failure after allogeneic hematopoietic stem-cell transplantation (allo-HSCT) for high-risk acute myeloid leukemia (HR-AML). The aim of this study was to explore the effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) combined with minimal-dose decitabine (Dec) on the prevention of HR-AML relapse after allo-HSCT.We conducted a phase II, open-label, […]
• CLEC12A and CD33 co-expression as preferential target on pediatric AML for combinatorial immunotherapy.23rd October 2020
  Emerging immunotherapies such as chimeric antigen receptor T cells have advanced the treatment of acute lymphoblastic leukemia. In contrast, long-term control of acute myeloid leukemia (AML) cannot be achieved by single lineage-specific targeting while sparing benign hematopoiesis. In addition, heterogeneity of AML warrants combinatorial targeting and several suitable immunotargets (HAVCR2/CD33 or HAVCR2/CLEC12A) were identified in […]
• A probable case of multiple myeloma from Bronze Age China.22nd October 2020
  Paleopathological evidence of cancer from past populations is rare, especially outside of Europe and North Africa. This study expands upon the current temporal and spatial distribution of cancer by presenting a probable case of multiple myeloma from Bronze Age China.The human skeletal remains of an adult male from the Qijia culture horizon (1750-1400 BCE) of […]
• Emerging epigenetic therapeutics for myeloid leukemia: modulating demethylase activity with ascorbate.22nd October 2020
  The past decade has seen a proliferation of drugs that target epigenetic pathways. Many of these drugs were developed to treat acute myeloid leukemia, a condition in which dysregulation of the epigenetic landscape is well established. While these drugs have shown promise, critical issues persist. Specifically, patients with the same mutations respond quite differently to […]
• Dasatinib-Blinatumomab for Ph-Positive Acute Lymphoblastic Leukemia in Adults.21st October 2020
  Outcomes in patients with Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL) have improved with the use of tyrosine kinase inhibitors. Molecular remission is a primary goal of treatment.We conducted a phase 2 single-group trial of first-line therapy in adults with newly diagnosed Ph-positive ALL (with no upper age limit). Dasatinib plus glucocorticoids were administered, followed […]
• Endoscopic and clinicopathological characteristics of colorectal T/NK cell lymphoma.21st October 2020
  Colorectal T/natural killer (NK)-cell lymphomas (TNKCL) are very rare. Endoscopic and clinicopathological characteristics of colorectal TNKCL have not been clearly demonstrated. In this study, we demonstrated the clinical characteristics of colorectal TNKCL.Endoscopic and clinicopathological characteristics were investigated in 27 patients with colorectal monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), adult T-cell leukemia/lymphoma (ATLL), and other types […]
• Updated Breast Cancer Surveillance Recommendations for Female Survivors of Childhood, Adolescent, and Young Adult Cancer From the International Guideline Harmonization Group.20th October 2020
  As new evidence is available, the International Late Effects of Childhood Cancer Guideline Harmonization Group has updated breast cancer surveillance recommendations for female survivors of childhood, adolescent, and young adult cancer.We used evidence-based methods to apply new knowledge in refining the international harmonized recommendations developed in 2013. The guideline panel updated the systematic literature review, […]
• Isatuximab as monotherapy and combined with dexamethasone in patients with relapsed/refractory multiple myeloma.20th October 2020
  This Phase 2 study evaluated isatuximab as monotherapy or combined with dexamethasone in relapsed/refractory multiple myeloma (RRMM). Patients had RRMM refractory to an immunomodulatory drug (IMiD) and a proteasome inhibitor (PI) or had received ≥3 prior lines of therapy incorporating an IMiD and PI. Patients received isatuximab either as monotherapy (20 mg/kg on days 1, […]
• Del17p without TP53 mutation confers poor prognosis in intensively treated newly diagnosed multiple myeloma patients.20th October 2020
  Despite tremendous improvements in the outcome of patients with multiple myeloma (MM) in the past decade, high-risk patients have not benefited from the approval of novel drugs. The most important prognostic factor is the loss of parts of the short arm of chromosome 17, known as deletion 17p (del(17p)). A recent publication (on a small […]
• How I treat Adult T-cell leukemia/lymphoma.19th October 2020
  Adult T-cell Leukaemia/lymphoma (ATL) is a highly aggressive T-cell malignancy that arises in a proportion of individuals who are long-term carriers of human T-lymphotropic virus type 1 (HTLV-1). The median survival of aggressive subtypes is 8-10 months, and with chemotherapy-based approaches, the overall survival has remained largely unchanged in ~35 years since first described. Through […]
• A Phase I study of inotuzumab ozogamicin in pediatric relapsed/refractory acute lymphoblastic leukemia (ITCC-059 study).17th October 2020
  This Phase I study investigated the recommended Phase II dose (RP2D) of inotuzumab ozogamicin (InO), a CD22-directed antibody-drug conjugate, in pediatric patients with multiple-relapsed/refractory (R/R) CD22-positive acute lymphoblastic leukemia (ALL). Patients (≥1-<18 years) received three InO doses (Days 1, 8, 15) per course. Dose-escalation was based on dose-limiting toxicities (DLT) during Course 1 . Dose […]
• An epitope-based approach to use of HLA matched platelets for transfusion: a noninferiority, cross-over, randomised trial.17th October 2020
  Platelet transfusion refractoriness results in adverse outcomes and increased healthcare costs. Managing refractoriness due to HLA alloimmunization necessitates the use of HLA antigen matched platelets, but requires a large platelet donor pool, and does not guarantee full matching. We report the first ever randomized, double-blind, non-inferiority, cross-over trial comparing HLA epitope-matched (HEM) platelets with HLA […]
• Quantification of Thioguanine in DNA Using Liquid Chromatography-Tandem Mass Spectrometry for Routine Thiopurine Drug Monitoring in Patients With Pediatric Acute Lymphoblastic Leukemia.16th October 2020
  We developed an assay to measure DNA-incorporated 6-thioguanine (DNA-TG) and validated its clinical applicability in Korean pediatric patients with acute lymphoblastic leukemia (ALL) in order to improve individualized thiopurine treatment and reduce the life-threatening cytotoxicity.The DNA-TG assay was developed based on liquid chromatography-tandem mass spectrometry, with isotope-labeled TG-d3 and guanine-d3 as internal standards. This method […]
• Discontinuation of tyrosine kinase inhibitors in chronic myeloid leukemia: when and for whom?15th October 2020
  Treatment discontinuation is considered one of the main goals of therapy for patients with chronic myeloid leukemia. Several criteria are felt to be necessary to consider discontinuation, while others may predict a better chance of achieving treatment-free remission. Criteria for discontinuation include patients in chronic phase chronic myeloid leukemia, a minimum duration of tyrosine kinase […]
• Pediatric acute lymphoblastic leukemia.15th October 2020
  The last decade has witnessed great advances in our understanding of the genetic and biological basis of childhood acute lymphoblastic leukemia (ALL), the development of experimental models to probe mechanisms and evaluate new therapies, and the development of more efficacious treatment stratification. Genomic analyses have revolutionized our understanding of the molecular taxonomy of ALL, and […]
• Pediatric-inspired chemotherapy incorporating pegaspargase is safe and results in high rates of minimal residual disease negativity in adults up to age 60 with Philadelphia chromosome-negative acute lymphoblastic leukemia.15th October 2020
  Administration of pediatric-inspired chemotherapy to adults up to age 60 with acute lymphoblastic leukemia (ALL) is challenging in part due to toxicities of asparaginase as well as myelosuppression. We conducted a multicenter phase II clinical trial (NCT01920737) investigating a pediatric-inspired regimen, based on the augmented arm of the Children’s Cancer Group 1882 protocol, incorporating 6 […]
• Plasmacytoid dendritic cells proliferation associated with acute myeloid leukemia: phenotype profile and mutation landscape.15th October 2020
  Neoplasms involving plasmacytoid Dendritic Cells (pDCs) include Blastic pDC Neoplasms (BPDCN) and other pDC proliferations, where pDCs are associated with myeloid malignancies: most frequently Chronic MyeloMonocytic Leukemia (CMML) but also Acute Myeloid Leukemia (AML), hereafter named pDC-AML. We aimed to determine the reactive or neoplastic origin of pDCs in pDC-AML, and their link with the […]
• Hodgkin lymphoma arising in patients with chronic lymphocytic leukemia: outcomes from a large multi-center collaboration.15th October 2020
  Chronic lymphocytic leukemia (CLL) patients who develop Hodgkin lymphoma (HL) have limited survival. No current therapeutic standard of care exists. We conducted a multi-center retrospective study of patients with Hodgkin Transformation (HT) of CLL. Clinicobiologic characteristics, treatment type, and survival outcomes were analyzed and compared with historic case series. Ninety-four patients were identified. Median age […]
• Zanubrutinib monotherapy for patients with treatment naïve chronic lymphocytic leukemia and 17p deletion.15th October 2020
  Patients with chronic lymphocytic leukemia or small lymphocytic lymphoma whose tumors carry deletion of chromosome 17p13.1 [del(17p)] have an unfavorable prognosis and respond poorly to standard chemoimmunotherapy. Zanubrutinib is a selective next-generation Bruton tyrosine kinase inhibitor. We evaluated the safety and efficacy of zanubrutinib 160 mg twice daily in treatment-naïve patients with del(17p) disease enrolled […]
• The effect of eltrombopag in managing thrombocytopenia associated with tyrosine kinase therapy in patients with chronic myeloid leukemia and myelofibrosis.15th October 2020
  Approximately 20-50% patients with chronic phase chronic myeloid leukemia (CML-CP) treated with tyrosine kinase inhibitors (TKIs) or with myelofibrosis (MF) treated with ruxolitinib develop grade ≥3 thrombocytopenia needing treatment interruptions and dose reductions. We conducted a non-randomized, phase II, single-arm study to determine the efficacy of eltrombopag for patients with CML or MF with persistent […]
• Differentiation therapy of myeloid leukemia: four decades of development.15th October 2020
  Acute myeloid leukemia is characterized by arrested differentiation, and agents that overcome this block are therapeutically useful, as shown by the efficacy of all-trans retinoic acid in acute promyelocytic leukemia. However, the early promise of differentiation therapy did not translate into clinical benefit for other subtypes of acute myeloid leukemia, in which cytotoxic chemotherapeutic regimens […]
• Engineered type 1 regulatory T cells designed for clinical use kill primary pediatric acute myeloid leukemia cells.15th October 2020
  Type 1 regulatory (Tr1) T cells induced by enforced expression of IL-10 (LV-10) are being developed as a novel treatment for chemotherapy-resistant myeloid leukemias. In vivo, LV-10 cells do not cause graft vs host disease while mediating graft vs leukemia (GvL) effect against adult acute myeloid leukemia (AML). Since pediatric AML (pAML) and adult AML […]
• Transducin β-like protein 1 controls multiple oncogenic networks in diffuse large B-cell lymphoma.15th October 2020
  Diffuse large B-cell lymphoma (DLBCL) is the most common Non-Hodgkin’s lymphoma and is characterized by a remarkable heterogeneity with diverse variants that can be identified histologically and molecularly. Large-scale gene expression profiling studies have identified the germinal center B-cell (GCB-) and activated B-cell (ABC-) subtypes. Standard chemo-immunotherapy remains standard front line therapy, curing approximately two […]
• Relapse After Early-Stage, Favorable Hodgkin Lymphoma: Disease Characteristics and Outcomes With Conventional or High-Dose Chemotherapy.15th October 2020
  We evaluated disease and treatment characteristics of patients with relapse after risk-adapted first-line treatment of early-stage, favorable, classic Hodgkin lymphoma (ES-HL). We compared second-line therapy with high-dose chemotherapy and autologous stem cell transplantation (ASCT) or conventional chemotherapy (CTx).We analyzed patients with relapse after ES-HL treated within the German Hodgkin Study Group HD10+HD13 trials. We compared, […]
• Why is it critical to achieve a deep molecular response in chronic myeloid leukemia?15th October 2020
  The primary goal of tyrosine kinase inhibitor (TKI) therapy for patients with chronic myeloid leukemia is survival, which is achieved by the vast majority of patients. The initial response to therapy provides a sensitive measure of future clinical outcome. Measurement of BCR-ABL1 transcript levels using real-time quantitative polymerase chain reaction standardized to the international reporting […]
• First-in-Human Phase I Study of Iadademstat (ORY-1001): A First-in-Class Lysine-Specific Histone Demethylase 1A Inhibitor, in Relapsed or Refractory Acute Myeloid Leukemia.14th October 2020
  Iadademstat is a novel, highly potent, and selective inhibitor of LSD1 (KDM1A), with preclinical in vitro and in vivo antileukemic activity. This study aimed to determine safety and tolerability of iadademstat as monotherapy in patients with relapsed/refractory acute myeloid leukemia (R/R AML).This phase I, nonrandomized, open-label, dose-escalation (DE), and extension-cohort (EC) trial included patients with […]
• Targeting GCK pathway: a novel and selective therapeutic strategy against RAS mutated multiple myeloma.9th October 2020
  In multiple myeloma (MM), frequent mutations of NRAS, KRAS, or BRAF are found in up to 50% of newly diagnosed patients. The majority of the NRAS, KRAS, and BRAF mutations occur in hotspots causing constitutive activation of the corresponding proteins. Thus targeting RAS mutation in MM will increase therapeutic efficiency and potentially overcome drug-resistance. We […]
• HIGHER ORDER IMMUNOGLOBULIN REPERTOIRE RESTRICTIONS IN CLL: THE ILLUSTRATIVE CASE OF STEREOTYPED SUBSETS #2 AND #169.9th October 2020
  Chronic lymphocytic leukemia (CLL) major stereotyped subset #2 (IGHV3-21/IGLV3-21, ~2.5% of all CLL) is an aggressive disease variant, irrespective of the somatic hypermutation (SHM) status of the clonotypic IGHV gene. Minor stereotyped subset #169 (IGHV3-48/IGLV3-21, ~0.2% of all CLL) is related to subset #2 as it displays a highly similar variable antigen-binding site. We further […]
• Germline PAX5 mutation predisposes to familial B acute lymphoblastic leukemia.9th October 2020
  In recent years, through whole genome analyses, convincing evidence for the contribution of genetic predisposition to childhood B-cell precursor – acute lymphoblastic leukemia (BCP-ALL) due to altered PAX5 has been provided. A recurrent mutation p.Gly183Ser affecting the octapeptide domain has been described in three unrelated families and a p.Arg38His mutation affecting the DNA-binding paired domain […]
• Tazemetostat for patients with relapsed or refractory follicular lymphoma: an open-label, single-arm, multicentre, phase 2 trial.9th October 2020
  Activating mutations of EZH2, an epigenetic regulator, are present in approximately 20% of patients with follicular lymphoma. We investigated the activity and safety of tazemetostat, a first-in-class, oral EZH2 inhibitor, in patients with follicular lymphoma.This study was an open-label, single-arm, phase 2 trial done at 38 clinics or hospitals in France, the UK, Australia, Canada, […]