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Glucose-6-phosphate dehydrogenase (G6PD) deficient individuals are at increased risk of developing haemolysis following treatment with various antimalarial drugs. Reliable field tests for G6PD deficiency are thus needed in chemotherapy studies and their validity has to be assessed. In two phase II clinical trials on methylene blue (MB) antimalarial therapy in rural Burkina Faso, paediatric and adult participants were tested for G6PD deficiency. The results of a haemoglobin-adjusted nicotinamide adenine dinucleotide phosphate (NADPH) fluorescence test on paper (NFP test) were compared with polymerase chain reaction (PCR)-based G6PD genotyping also using blood samples on filter papers. This is the first study comparing sensitivity and specificity of the two methods. There was good agreement between the NFP test results and the PCR findings. The estimate of the sensitivity of the NFP test was 98·2% (95·8–99·6%) and the specificity was 97·1% (94·2–99·2%). In conclusion, the NFP assay is a reliable and inexpensive method for large-scale G6PD deficiency screening in rural West Africa. [ABSTRACT FROM AUTHOR]

Dysregulation of fibroblast growth factor receptor 3 ( FGFR3) by the translocation t(4;14)(p16;q32) occurs in 15% of multiple myeloma (MM) patients and confers a growth and survival advantage to malignant plasma cells. As FGFR3 is a molecular target, we assessed the therapeutic potential of the FGFR-specific tyrosine kinase inhibitors SU5402 and SU10991 in MM. SU5402 inhibited FGFR3 phosphorylation in vitro and in murine MM tumour models. B cells dependent on FGFR3 for survival were specifically sensitive to SU5402. A panel of 11 human myeloma cell lines was studied, five bearing the t(4;14) translocation. The KMS11 human myeloma cell line, which expresses constitutively active mutant FGFR3, displayed an 85% decrease in S-phase cells, a 95% increase in G0/G1 cells, and 4·5-fold increase in apoptotic cells after 72 h treatment with 10 μmol/l SU5402. Activated extracellular signal-regulated kinases  1 and 2 and signal transducer and activator of transcription 3 were rapidly down-regulated after SU5402 treatment. In human myeloma cell lines expressing wild-type FGFR3 the stimulating effect of aFGF ligand was abrogated by SU5402 treatment. Myeloma cells lacking the t(4;14) or with the t(4;14) and a secondary RAS mutation did not respond to therapy. These findings support the development of clinical trials of early intervention with FGFR3 inhibitors in t(4;14) myeloma. [ABSTRACT FROM AUTHOR]

Primary plasma cell leukaemia (PCL) is a rare plasma cell malignancy, which is related to multiple myeloma (MM) and is characterized by a poor prognosis. In a previous study we demonstrated that PCL plasma cells display a high expression of CD27, in contrast to MM plasma cells. The present study was set out to assess the functional properties of CD27 expressed on PCL plasma cells by triggering with its ligand CD70. Using CD27-expressing purified plasma cells from a PCL patient we demonstrated that CD27-triggering modestly inhibited spontaneous and dexamethasone-induced apoptosis. In vitro stimulation and Western blotting showed that activation of p38 and extracellular-regulated kinase 1/2 (ERK1/2) mitogen-activated protein kinases (MAPK) was associated with CD27-mediated signal transduction. Specific inhibition of p38 and ERK1/2 MAPK abolished the anti-apoptotic effects of CD27-triggering. Interestingly, simultaneous inhibition of p38 and ERK1/2 strongly sensitized PCL cells for dexamethasone-induced apoptosis. Finally, in dexamethasone-treated PCL cells, CD27-triggering was associated with persistent DNA-binding activity of activator protein 1 (AP-1) but not of nuclear factor- κB. These findings suggest that, in primary PCL, specific anti-apoptotic pathways exist that might provide novel therapeutic targets. [ABSTRACT FROM AUTHOR]

The article lists the studies to be published in forthcoming issues on topics including bowel perforation while on thalidomide treatment, imatinib treatment for leukemia patients, and ruxolitinib for myelofibrosis treatment.

The article lists several research papers to be published in 2017 issue which include topics like selective neutralization of the serpin Protease Nexin-1 by a specific monoclonal antibody; Heavy menstrual bleeding on rivaroxaban; and Monoclonal B cell lymphocytosis and hypogammaglobulinemia.

Summary: Mesenchymal stromal cells (MSCs) are non‐haematopoietic cells found in fetal and adult organs, that play important roles in tissue repair, inflammation and immune modulation. MSCs residing in the bone marrow interact closely with haematopoietic cells and comprise an important component of the microenvironment supporting haematopoiesis, in both health and disease states. Since their identification in 1970, basic scientific and preclinical research efforts have shed light on the role of MSCs in the regulation of haematopoiesis and evoked interest in their clinical application in haematopoietic stem cell transplantation (HSCT) and malignant haematology. Over the last two decades, these research efforts have led to numerous clinical trials, which have established the safety of MSC therapy; however, the optimal mode of administration and the benefit remain inconclusive. In this paper, we will review the clinical experience with use of MSCs in HSCT for enhancement of engraftment, prevention and treatment of graft‐versus‐host disease and haemorrhagic cystitis. Then, we will discuss the contradictory evidence regarding tumour‐promoting versus tumour‐suppressing effects of MSCs in haematological malignancies, which may have relevance for future clinical applications. [ABSTRACT FROM AUTHOR]

Lists several research articles related to hematology. "Tumour Lysis Syndrome: New Therapeutic Strategies and Classification," by M. S. Cario and M. Bishop; "Dose and Response in Haemophilia - Optimisation of Factor Replacement Therapy," by A. Srivastava; "Secondary Haemophagocytic Lymphohistiocytosis (SHLH) Occurring in Chronic Myelomonocytic Leukaemia," by A. Marmont and F. Gualandi.

The article focuses on a research which aims to evaluate the efficacy of bendamustine, dexamethasone and thalidomide in relapsed or refractory multiple myeloma patients following lenalidomide and bortezomib therapy or who were ineligible to receive such drugs as measured by the rate of response in terms of overall response rate. It also aims to assess the tolerability and toxicity and evaluate the time to treatment failure, overall survival, and disease-free survival.

Patient-specific primers from 10 children/adolescents with Burkitt leukaemia (BL) ± central nervous system disease who were treated with French-British-American/Lymphome Malins de Burkitt 96 C1 plus rituximab were developed from diagnostic blood/bone marrow. Minimal residual disease ( MRD) was assessed by real-time polymerase chain reaction at the end of induction ( EOI) and consolidation ( EOC). Seventy per cent (7/10) and 71% (5/7) were MRD-positive at EOI and EOC, respectively, with no disease recurrences. MRD after induction and consolidation did not predict relapse and subsequent therapy appeared to eliminate MRD. Thus, assessing MRD at a later time point is warranted in future trials to determine its clinical significance. [ABSTRACT FROM AUTHOR]

T-cell lymphomas (TCLs) are characterised by poor responses to therapy with brief durations of remissions. An early phase study of pralatrexate has demonstrated dramatic activity in patients with relapsed/refractory disease. Of the first 20 lymphoma patients treated, 16 had B-cell lymphoma and four had refractory aggressive TCL. All four patients with TCL achieved a complete remission. Patients with B-cell lymphoma achieved stable disease at best. For each TCL patient, the response was more durable than their best response with chemotherapy. This early experience is the first to document this unique activity of pralatrexate in TCL. [ABSTRACT FROM AUTHOR]

Inhibition of the mechanistic target of rapamycin (mTOR) pathway has clinical activity in lymphoma. The mTOR inhibitor sirolimus has been used in the prevention and treatment of graft-versus-host disease ( GVHD) after allogeneic haematopoietic stem cell transplantation ( HSCT). A retrospective study suggested that patients with lymphoma undergoing reduced intensity conditioning ( RIC) HSCT who received sirolimus as part of their GVHD prophylaxis regimen had a lower rate of relapse. We therefore performed a multicentre randomized trial comparing tacrolimus, sirolimus and methotrexate to standard regimens in adult patients undergoing RIC HSCT for lymphoma in order to assess the possible benefit of sirolimus on HSCT outcome. 139 patients were randomized. There was no difference overall in 2-year overall survival, progression-free survival, relapse, non-relapse mortality or chronic GVHD. However, the sirolimus-containing arm had a significantly lower incidence of grade II-IV acute GVHD (9% vs. 25%, P = 0·015), which was more marked for unrelated donor grafts. In conclusion, the addition of sirolimus for GVHD prophylaxis in RIC HSCT is associated with no increased overall toxicity and a lower risk of acute GVHD, although it does not improve survival; this regimen is an acceptable option for GVHD prevention in RIC HSCT. This trial is registered at clinicaltrials.gov ( NCT00928018). [ABSTRACT FROM AUTHOR]

Chemoimmunotherapy followed by autologous stem cell transplantation ( ASCT) is a standard therapy for transplant-eligible patients with newly diagnosed mantle cell lymphoma ( MCL). The achievement of complete remission ( CR) and minimal residual disease ( MRD) negativity are associated with better outcomes. We tested an induction regimen of rituximab/bendamustine followed by rituximab/high-dose cytarabine ( RB/ RC). This phase 2 study ( NCT01661881) enrolled 23 transplant-eligible patients aged 42-69, of whom 70% were MCL international prognostic index low-risk. Patients received three cycles of RB followed by three cycles of RC. The primary endpoint of the trial was the rate of CR after six cycles of therapy, with a rate of 75% considered promising. 96% of patients achieved a CR/unconfirmed CR after treatment, meeting the primary objective. One patient progressed on study, one declined ASCT in CR, and the remaining 21 underwent successful stem cell collection and ASCT. After a median follow-up of 13 months, the progression-free survival rate was 96%. Among 15 MRD -evaluable patients who completed treatment, 93% achieved MRD negativity after RB/ RC. In conclusion, RB/ RC achieves very high CR and MRD negativity rates in transplant-eligible patients, with a favourable safety profile. RB/ RC warrants further comparative studies, and may become a useful alternative to RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone)-based induction regimens in this patient population. [ABSTRACT FROM AUTHOR]

The article focuses on a study related to treatment of Bing-Neel Syndrome (BNS) with oral fludarabine which occurs due to neurologic complication of Waldenström macroglobulinemia (WM). Topics discussed include good responses for high dose systemic chemotherapy using methotrexate (MTX) and cytarabine; treatment with rituximab-fludarabine that resulted in a second haematological and neurological partial remission (PR); and effectiveness of radiotherapy for reversing neurological symptoms.

The article focuses on the antiprogrammed cell death 1 (PD-1) inhibitor-related pneumonitis in lymphoma patients treated with single-agent pembrolizumab therapy. It mentions the U.S. Food and Drug Administration (FDA) approval granted to nivolumab for the treatment of classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous haematopoietic stem-cell transplantation (HSCT). It also mentions treatment with immune-checkpoint inhibitors associated with toxicities.

The article discusses research which examined the effect of regulated automated red cell exchange transfusion (ARCET) in male patients with sickle cell disease (SCD) and recurrent stuttering priapism (SP), an unwanted erection. Topics discussed include management measures for SP, evolution of SP into acute major priapism (MP) which carries a risk of erectile dysfunction (ED), patient characteristics and haematological parameters and improvement experienced by patients after undergoing ARCET.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is incurable with conventional therapies. Limited retrospective data have shown durable remissions after haematopoietic cell transplantation (HCT) [allogeneic (allo) or autologous (auto)]. We conducted a multicentre retrospective study in BPDCN patients treated with allo-HCT and auto-HCT at 8 centres in the United States and Canada. Primary endpoint was overall survival (OS). The population consisted of 45 consecutive patients who received an allo-HCT (n = 37) or an auto-HCT (n = 8) regardless of age, pre-transplant therapies, or remission status at transplantation. Allo-HCT recipients were younger (50 (14–74) vs. 67 (45–72) years, P = 0·01) and had 1-year and 3-year OS of 68% [95% confidence interval (CI) = 49–81%] and 58% (95% CI = 38–75%), respectively. Allo-HCT in first complete remission (CR1) yielded superior 3-year OS (versus not in CR1) [74% (95% CI = 48–89%) vs. 0, P < 0·0001]. Allo-HCT outcomes were not impacted by regimen intensity [3-year OS for myeloablative conditioning = 61% (95% CI = 28–83%) vs. reduced-intensity conditioning = 55% (95% CI = 28–76%)]. One-year OS for auto-HCT recipients was 11% (95% CI = 8–50%). These results demonstrate efficacy of allo-HCT in BPDCN, especially in patients in CR1. Pertaining to auto-HCT, our results suggest lack of efficacy against BPDCN, but this observation is limited by the small sample size. Larger prospective studies are needed to better define the role of HCT in BPDCN. [ABSTRACT FROM AUTHOR]

The article reports on a study which investigated the impact of telomere length on the outcome of allogeneic stem cell transplantation (SCT) for patients with poor risk chronic lymphocytic leukaemia (CLL) based on the German CLL3X trial which included 100 patients. Topics covered include association of telomere length with clinical characteristics, and analysis of telomere length using quantitative polymerase chain reaction.

The article discusses the first-line treatment of patients with peripheral T-cell lymphoma (PTCL) via high-dose chemotherapy followed by autologous stem cell transplant (HDC-ASCT). Topics discussed include the response rate, progression-free survival and overall survival of patients, treatment-related mortality, and the common histological subtypes of PTCL including PTCL-not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL) and anaplastic large cell lymphoma (ALCL).

The article presents information on etanercept treatment in fanconi anaemia. Fanconi Anaemia (FA) is an autosomal recessive disease with the characteristics of progressive bone marrow failure, variable congenital abnormalities and a predisposition to malignancy. Etanercept was effective in disease modification in adults and children with arthritis, colitis and psoriasis.

Summary: Intravenous Anti‐Rhesus‐D immunoglobulin (Anti‐D) is a first‐line treatment option for immune thrombocytopenia in non‐splenectomised and RhD‐positive patients. In this report, we retrospectively review our experience with intramuscular (IM) Anti‐D treatment in 74 adult patients between 1990 and 2018. We found that 73% of patients showed a response; almost all of them had complete responses (68.9%), and 26% achieved complete responses sustained at least 6 months after treatment discontinuation. [Correction added on 02 December 2022, after first online publication: In the preceding sentence, '(68.89%)' has been corrected to '(68.9%)' in this version.] No significant side effects were observed with no cases of acute haemolysis or anaemia reported. We conclude from this study that IM Anti‐D is an effective and safe treatment for immune thrombocytopenia. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 38-year-old female with abdominal bleeding during and after surgery of ovarian cyst and blood coagulation defect caused by the use of thrombomodulin. Topics discussed include use of red blood cell transfusions, desmopressin, laparotomy undertaken for surgical control of the bleeding and clot removal.

Keywords: early assessment; flow cytometry; measurable residual disease; multiple myeloma; outcome EN early assessment flow cytometry measurable residual disease multiple myeloma outcome e82 e85 4 06/14/22 20220615 NES 220615 Multiple myeloma (MM) treatment has evolved remarkably with the introduction of new agents such as proteasome inhibitors, immunomodulatory drugs (IMIDS) and therapeutic antibodies. The level of minimal residual disease in the bone marrow of patients with multiple myeloma before high-dose therapy and autologous blood stem cell transplantation is an independent predictive parameter. The 26 patients with persistent positive MRD had worse PFS compared to the negative MRD post- and pre-ASCT cases (24 months vs 45 months vs 68 months, I p i < 0.0001). [Extracted from the article]

The article discusses an exploratory study of the protective effect of transfusion therapy on the loss of brain volume and concomitant cognitive function of children with sickle cell anemia. Standard treatment and transfusion therapy were found to have no significant differences in brain volumetric change and have both showed rates of atrophy.

The article discusses a study which assessed the proportion of chronic myeloid leukemia patients treated front line with imatinib outside clinical trials who could achieve a durable molecular response (MR) and maintain after treatment discontinuation. Topics covered include the reason for therapy restart, characteristics of patients who discontinued imatinib, and comparison of dasatinib and nilotinib with imatinib.

Summary: Historically, understanding of the human mast cell (MC) compartment has lagged behind the appreciation of other cell lineages. MCs exist in vascularised tissues but do not under normal circumstances circulate in blood, and there has been no pharmacological agent identified that totally and selectively inhibits human MC function. There are no substantiated accounts of an apparently healthy individual who is severely lacking in MCs. Thus, some of the approaches employed to understand the function of a specific immune cell are not available to the MC biologist. The disease categories that have provided the greatest insight into MC biology have been monoclonal and IgE‐mediated MC disorders. This has led to the categorisation of MC diseases as intrinsic or extrinsic to the MC compartment and to the recognition of the role of mediators in MC activation disorders. Mastocytosis as a clonal disorder not only impacts the MC compartment through changes intrinsic to the MC, but also by the effects of episodes of significant release of MC mediators. The availability of newer therapeutic approaches developed to treat monoclonal MC disorders offer insights into how to more selectively approach management of MC centric diseases. [ABSTRACT FROM AUTHOR]

Although several parameters are useful for risk stratification of patients with acute myeloid leukaemia (AML), there are no firm criteria for predicting response to induction treatment of individual patients. Daily flow cytometry (FC) analysis, carried out during induction treatment in 30 AML patients, showed that the clearance of blasts from peripheral blood (PBC) correlated closely with response, as assessed by bone marrow FC on day 14, and by morphologic analysis at haematopoietic recovery. Therefore, a major treatment outcome can be predicted very early in AML patients, thus providing an opportunity for tailoring treatment modalities from the outset. [ABSTRACT FROM AUTHOR]

Dosing and monitoring of argatroban for treatment of heparin‐induced thrombocytopenia (HIT) remain uncertain. Marchetti and colleagues critically and systematically reviewed their institutional experience using this direct thrombin inhibitor to treat patients with laboratory‐confirmed HIT, and have formulated several practical recommendations for managing this challenging clinical situation. Commentary on: Marchetti et al. Managing argatroban in heparin‐induced thrombocytopenia: A retrospective analysis of 729 treatment days in 32 patients with confirmed heparin‐induced thrombocytopenia. Br J Haematol. 2022;197:766‐790 [ABSTRACT FROM AUTHOR]

Summary: Data on non‐Hodgkin lymphoma (NHL) after classical Hodgkin lymphoma (cHL) are scarce. We therefore performed a retrospective analysis comprising 11·841 cHL patients who had first‐line treatment within the randomized German Hodgkin Study Group (GHSG) HD7–HD15 studies. After a median follow‐up of 106 months, 175 patients (1·5%) had developed NHL. The median time to NHL was 44 months, the median age at NHL diagnosis was 54 years. The five‐year event‐free survival and overall survival estimates from the diagnosis of NHL were 36·9% and 44·2%, respectively. Thus, NHL after cHL is a rare event primarily affecting older individuals and often resulting in the patient´s death. [ABSTRACT FROM AUTHOR]

The article discusses a study on immunoglobulin D associated AL amyloidosis in context of clinical profiles and outcomes. It informs that the study performed treatment with cyclophosphamide-thalidomide-dexamethasone (CTD) and vincristine-adriamycin-dexamethasone (VAD) with routine screening for the presence of immunoglobulin D monoclonal protein. The study revealed that factors such as clonal resistance and higher plasma cell burden play a vital role in the immunoglobulin D-AL amyloidosis.

The article presents case study of a 29-year-old pregnant female with high‐titre inhibitor to Type 3 von Willebrand disease (VWF), managed by caesarean delivery, high dose rFVIII and rFVIIa infusions. It mentions that recurrent musculoskeletal bleeding throughout childhood of the patient and subsequent menorrhagia required prophylaxis with an intermediate purity FVIII concentrate. It presents information on use of hydrocortisone and chlorphenamine for treatment of the patient.

Summary: T‐cell large granular lymphocytic leukaemia (T‐LGLL) is an incurable leukaemia characterised by clonal proliferation of abnormal cytotoxic T cells that can result in severe neutropenia, transfusion‐dependent anaemia and pancytopenia requiring treatment. The most commonly used agents, methotrexate (MTX), cyclophosphamide (Cy) and cyclosporine primarily produce partial remissions (PRs), with few complete responses (CRs). We evaluated the clinical course and treatment response of 60 consecutive patients with T‐LGLL to evaluate clinical outcomes and future potential treatment directions. Impaired overall survival was noted among male patients, patients with elevated lactate dehydrogenase, and those without rheumatoid arthritis. Cy was the most efficacious second‐line agent, with a 70% overall response rate (ORR; three CR, four PR). All patients who failed frontline MTX responded to second‐line Cy. In the relapsed or Cy‐refractory setting, alemtuzumab (n = 4) and pentostatin (n = 3) had an ORR of 50% and 66%, respectively, while duvelisib induced a long‐term response in one patient. In this large, retrospective analysis, our results suggest Cy is a highly effective therapy for second‐line treatment in T‐LGLL and should be considered a strong candidate for up‐front therapy in select high‐risk patients. Prospective studies evaluating pentostatin, alemtuzumab and novel agents, such as duvelisib, are needed for patients with relapsed/refractory T‐LGLL. [ABSTRACT FROM AUTHOR]

The article offers information on the use of acyclovir prophylaxis for herpes zoster induced during bortezomib treatment of multiple myeloma. It mentions a retrospective study of 169 patients treated with bortezomib-based regimens and analysis is carried in two groups, patients receiving or not receiving 200 mg acyclovir. It adds that patients with prophylaxis did not have herpes zoster reactivation and those treated with bortezomib without prophylaxis is at risk of infection.

Summary: Splenectomy is considered therapeutic in various non‐malignant haematologic diseases. Adverse events ‒ specifically infections and thromboembolism ‒ are not extensively documented in the paediatric population, maintaining the concern over risks‐versus‐benefits of the procedure. We studied a cohort of paediatric haematology patients undergoing splenectomy between 1977 and 2015 to determine short‐ and long‐term complications. We summarised all the patients of the haematology clinic in our major Israeli tertiary centre undergoing splenectomy for therapeutic reasons, capturing infectious and thromboembolic events. The data of 103 patients, comprising 1657 follow‐up years, were analysed. The cohort included 33 patients with transfusion‐dependent thalassaemia, seven with non‐transfusion‐dependent thalassaemia, four with sickle‐thalassaemia, 41 with hereditary spherocytosis, and 18 with immune thrombocytopenia. Standard presplenectomy vaccinations were noted in most. No typical cases of overwhelming postsplenectomy infection (OPSI) were identified, nor were typical OPSI bacteria isolated. Thalassaemics with central lines were most prone to infection and thrombosis. Beyond this subgroup, thrombotic events were anecdotal. This is the largest study to date to comprehensively analyse infectious and thrombotic complications of childhood splenectomy for the treatment of haematologic diseases. The use of splenectomy appears to be a relatively safe therapeutic option in paediatric patients with proper preoperative vaccination and follow‐up care; use of central venous lines or catheters increase the risk in thalassaemic patients and should be avoided if possible. [ABSTRACT FROM AUTHOR]

Comments on an article about the management of low-risk patients with primary thrombocythemia (PT). Increase in thrombotic risk in patients with PT; Clinical behavior of PT patients; Conditions associated with PT.

Presents a reply to comments from Mehta on an article about the comparison of liposomal and lipid complexed amphotericin B preparations in hematological oncology. Predisposing factor for fungal infection; Probability that patients are neutropenic.

Summary: Molecular genetic studies of lymphoma have led to refinements in disease classification in the most recent World Health Organization update. Nevertheless, a 'one‐size‐fits‐most' treatment strategy based on morphology remains widely used for lymphoma despite significant molecular heterogeneity within histopathologically‐defined subtypes. Precision medicine aims to improve patient outcomes by leveraging disease‐ and patient‐specific information to optimise treatment strategies, but implementation of precision medicine strategies is challenged by the biological diversity and rarity of lymphomas. In this review, we explore existing and emerging real‐world data sources that can be used to facilitate the development of precision medicine strategies in lymphoma. We provide illustrative examples of the use of real‐world analyses to refine treatment strategies, provide comparators for clinical trials, improve risk‐stratification to identify patients with unmet clinical needs and describe long‐term and rare toxicities. [ABSTRACT FROM AUTHOR]

Summary: Haemophilia is a serious inherited bleeding disorder resulting from a deficiency of coagulation factor VIII (haemophilia A) or coagulation factor IX (haemophilia B). While effective therapies have been developed to replace the missing factor and restore normal coagulation, they can lead to the development of neutralizing anti‐drug antibodies, termed inhibitors, which significantly worsen morbidity and quality of life. While advancements have been made to improve the management of patients, and particularly for this review, children with inhibitors, there remain significant unmet needs including inhibitor prevention, inhibitor eradication and, when those fail, more effective bleed prevention and a reduction in the treatment burden. This review will discuss current treatment options including the recently licensed bispecific antibody, emicizumab, and provide insights into how I treat children with inhibitors. [ABSTRACT FROM AUTHOR]

Summary: Intravascular large B‐cell lymphoma (IVLBCL) is a rare entity, with a generally aggressive course that may vary based on geographic presentation. While a United States (US) registry study showed relatively good outcomes with IVLBCL, clinicopathological and treatment data were unavailable. We performed a detailed retrospective review of cases identified at 8 US medical centres, to improve understanding of IVLBCL and inform management. We compiled data retrieved via an Institutional Review Board‐approved review of IVLBCL cases identified from 1999 to 2015 at nine academic institutions across the US. We characterized the cohort's clinical status at time of diagnosis, presenting diagnostic and clinical features of the disease, treatment modalities used and overall prognostic data. Our cohort consisted of 54 patients with varying degrees of clinical features. Adjusting for age, better performance status at presentation was associated with increased survival time for the patients diagnosed in vivo (hazard ratio: 2·12, 95% confidence interval 1·28, 3·53). Based on the data we have collected, it would appear that the time interval to diagnosis is a significant contributor to outcomes of patients with IVLBCL. [ABSTRACT FROM AUTHOR]

Summary: The question of which chemotherapy induction provides the best results for indolent lymphoma patients is yet unanswered. Different regimens have been compared, none of which has been shown to improve overall survival. The use of bendamustine is growing. A number of trials evaluated its efficacy for patients with indolent B‐cell lymphoid neoplasms, including chronic lymphocytic leukaemia (CLL). To evaluate the efficacy of bendamustine in that population we performed a systematic review and meta‐analysis of 9 randomised controlled trials (2726 patients). Bendamustine was compared to fludarabine‐containing regimens, CVP (cyclophosphamide, vincristine, prednisolone), CHOP (CVP+ doxorubicin) and chlorambucil. Due to insufficient reported data, six of the nine trials were included in analysis of overall survival. Bendamustine was associated with a prolonged overall survival, (hazard ratio 0·79, 95% confidence interval 0·65–0·95). Data regarding quality of life was reported for two trials, therefore too scarce to pool. The risk of neutropenia was reduced with bendamustine treatment compared to other chemotherapy. Bendamustine induction is an efficacious option for patients with indolent lymphoma, and CLL. Maintenance therapy was not evaluated after bendamustine induction, and potentially there is an interaction between the two. Chemotherapy‐free approach was shown to be efficacious for patients with CLL, while toxicity with that approach is not negligible. [ABSTRACT FROM AUTHOR]

Summary: Sickle cell disease (SCD) affects over 2 million people worldwide with high morbidity and mortality in underdeveloped countries. Therapeutic interventions aimed at reactivating fetal haemoglobin (HbF) is an effective approach for improving survival and ameliorating the clinical severity of SCD. A class of agents that inhibit DNA methyltransferase (DNMT) activity show promise as HbF inducers because off‐target effects are not observed at low concentrations. However, these compounds are rapidly degraded by cytidine deaminase when taken by oral administration, creating a critical barrier to clinical development for SCD. We previously demonstrated that microRNA29B (MIR29B) inhibits de novo DNMT synthesis, therefore, the goal of our study was to determine if MIR29 mediates HbF induction. Overexpression of MIR29B in human KU812 cells and primary erythroid progenitors significantly increased the percentage of HbF positive cells, while decreasing the expression of DNMT3A and the HBG repressor MYB. Furthermore, HBG promoter methylation levels decreased significantly following MIR29B overexpression in human erythroid progenitors. We subsequently, observed higher MIR29B expression in SCD patients with higher HbF levels compared to those with low HbF. Our findings provide evidence for the ability of MIR29B to induce HbF and supports further investigation to expand treatment options for SCD. [ABSTRACT FROM AUTHOR]

Summary: Lymphoblastic lymphoma (LBL) is the second most common type of Non‐Hodgkin Lymphoma (NHL) in childhood and adolescence, accounting for 25–35% of all cases. The majority, 70–80%, is of T‐lymphoblastic origin while 20–25% arise from B lymphoblasts. With current therapy, the event‐free and overall survivals for paediatric LBL patients now exceeds 80%. Therapy, especially in T‐LBL with large mediastinal tumours, is challenging, with both significant morbidity and late sequela. An additional challenge is the dismal prognosis of patients with refractory or relapsed disease. This review article will focus on the growing knowledge of the pathogenesis and biology of LBL, recent advances and challenges in the therapy of LBL, and ongoing and future efforts and opportunities in optimizing therapy and developing novel targeted treatment approaches. [ABSTRACT FROM AUTHOR]

Summary: Paediatric non‐Hodgkin lymphomas (pNHL) are a diverse group of malignancies characterised by nodal and/or extranodal involvement. Less common pNHL forms include those derived from mature T‐ and natural killer (NK) cells. Much of our current understanding of paediatric mature (non‐anaplastic) T/NK‐cell lymphomas with respect to pathogenesis, diagnosis and treatment is extrapolated from adult literature. At the Sixth International Symposium on Childhood, Adolescent and Young Adult Non‐Hodgkin Lymphoma, convened September 26–29, 2018 in Rotterdam, The Netherlands, some important aspects on diagnosis and outcomes of mature (non‐anaplastic) T/NK‐cell lymphoma in children and adolescents were discussed and will be reviewed in here. [ABSTRACT FROM AUTHOR]

Summary: Optimal treatment for transformed follicular lymphoma (tFL) is not fully defined. Clinical characteristics and treatments that impact on post‐transformation outcome of 176 biopsy‐proven tFL were analysed. Transformation occurred at initial diagnosis in 52% (Group 1) and after a FL diagnosis in 48% (Group 2). Five‐year overall survival was 84% for Group 1 and 51% for Group 2 (P < 0·001). In Group 1, 5‐year progression‐free survival was superior after rituximab maintenance compared to observation only (94% vs. 53%, P = 0·024). In Group 2, an inverse trend was found between survival and both a higher number of pre‐transformation treatment lines and a short time‐to‐transformation. [ABSTRACT FROM AUTHOR]

Summary: In a prospective phase II trial, pentostatin combined with cyclophosphamide and rituximab (PCR) induced strong responses and was well‐tolerated in previously untreated patients with advanced‐stage, indolent non‐Hodgkin lymphoma (iNHL). After a median patient follow‐up of more than 108 months, we performed an intent‐to‐treat analysis of our 83 participants. Progression‐free survival (PFS) rates at 108 months for follicular lymphoma (FL), marginal zone lymphoma (MZL) and small lymphocytic lymphoma (SLL) were 71%, 67% and 15%, respectively, and were affected by clinicopathological characteristics. Ten‐year PFS rates for those with beta‐2‐microglobulin levels <2·2 and ≥2·2 mg/l prior to treatment were 71% and 21%, respectively. Patients without bone marrow involvement had 10‐year PFS rates of 72% vs. 29% for those with involvement. At time of analysis, the median overall survival (OS) had not been reached. The OS rate was 64% at 10 years and differed significantly based on histology: 94% for FL, 66% for MZL and 39% for SLL. Long‐term toxicities included 18 (21·7%) patients with second malignancies and 2 (2·4%) who developed myelodysplastic syndrome after receiving additional lines of chemotherapy. Our 10‐year follow‐up analysis confirms that PCR is an effective, robust and tolerable treatment regimen for patients with iNHL. [ABSTRACT FROM AUTHOR]

Summary: Erythropoiesis‐stimulating agents (ESAs) were combined with ruxolitinib in 59 anaemic myelofibrosis patients (93% with Dynamic International Prognostic Scoring System [DIPSS] intermediate‐2/high risk; 52·5% transfusion‐dependent). Anaemia response (AR) rate was 54% and 76% of patients responded at 5 years. A further 15% displayed minor improvement in anaemia and 78% of patients reduced spleen size. Endogenous erythropoietin levels <125 u/l correlated with a higher AR rate (63% vs. 20%, P = 0·008). No thrombotic events or other toxicities occurred. Overall survival was 62% at 4 years, influenced by DIPSS and transfusion dependency. ESAs seem effective in improving anaemia in ruxruxolitinib‐treated myelofibrosis patients. [ABSTRACT FROM AUTHOR]

Summary: The inherited platelet glycoprotein deficiencies, Glanzmann thrombasthenia (GT) and Bernard Soulier syndrome (BSS) are rare but important long‐term bleeding disorders. Once diagnosed, affected patients should be referred to a specialist centre for bleeding disorders for general advice and ongoing management. Patients do not require prophylactic treatment and so the management of GT and BSS focuses around prophylactic treatment prior to high risk procedures and treatment in response to non‐surgical bleeding events and, in women, the management of menorrhagia and pregnancy. There is no consistent approach to the treatment or prevention of bleeding complications. Management must be tailored for each individual and the approach may not be the same for different events, even for the same patient, depending on the type of accident or invasive procedure, the extent of bleeding and the presence or not of platelet refractoriness. [ABSTRACT FROM AUTHOR]

Summary: Phosphatidylserine (PS) exposure increases as red cells age, and is an important signal for the removal of senescent cells from the circulation. PS exposure is elevated in red cells from sickle cell anaemia (SCA) patients and is thought to enhance haemolysis and vaso‐occlusion. Although precise conditions leading to its externalisation are unclear, high intracellular Ca2+ has been implicated. Red cells from SCA patients are also exposed to an increased oxidative challenge, and we postulated that this stimulates PS exposure, through increased Ca2+ levels. We tested four different ways of generating oxidative stress: hypoxanthine and xanthine oxidase, phenazine methosulphate, nitrite and tert‐butyl hydroperoxide, together with thiol modification with N‐ethylmaleimide (NEM), dithiothreitol and hypochlorous acid (HOCl), in red cells permeabilised to Ca2+ using bromo‐A23187. Unexpectedly, our findings showed that the four oxidants significantly reduced Ca2+‐induced PS exposure (by 40–60%) with no appreciable effect on Ca2+ affinity. By contrast, NEM markedly increased PS exposure (by about 400%) and slightly but significantly increased the affinity for Ca2+. Dithiothreitol modestly reduced PS exposure (by 25%) and HOCl had no effect. These findings emphasise the importance of thiol modification for PS exposure in sickle cells but suggest that increased oxidant stress alone is not important. [ABSTRACT FROM AUTHOR]