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The rarity of severe complications of this disease in children makes randomized clinical trials in immune thrombocytopenia (ITP) unfeasible. Therefore, the current management recommendations for ITP are largely dependent on clinical expertise and observations. As part of its discussions during the Intercontinental Cooperative ITP Study Group Expert Meeting in Basel, the Management working group recommended that the decision to treat an ITP patient be individualized and based mainly on bleeding symptoms and not on the actual platelet count number and should be supported by bleeding scores using a validated assessment tool. The group stressed the need to develop a uniform validated bleeding score system and to explore new measures to evaluate bleeding risk in thrombocytopenic patients—the role of rituximab as a splenectomy-sparing agent in resistant disease was also discussed. Given the apparently high recurrence rate to rituximab therapy in children and the drug's possible toxicity, the group felt that until more data are available, a conservative approach may be considered, reserving rituximab for patients who failed splenectomy. More studies of the effectiveness and side effects of drugs to treat refractory patients, such as TPO mimetics, cyclosporine, mycophenolate mofetil, and cytotoxic agents are required, as are long-term data on post-splenectomy complications. In the patient with either acute or chronic ITP, using a more personalized approach to treatment based on bleeding symptoms rather than platelet count should result in less toxicity and empower both physicians and families to focus on quality-of-life.

Myelofibrosis (MF) is a myeloproliferative neoplasm (MPN) with a poor prognosis, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only treatment with curative potential. Ruxolitinib, a JAK1/2 inhibitor, has shown promising results in improving patients' symptoms, overall survival, and quality of life, and can be used as a bridging therapy to HSCT that increases the proportion of transplantable patients. However, the effect of this and similar drugs on HSCT outcomes is unknown, and the reports on their efficacy and safety in the peri-transplantation period vary widely in the published literature. This paper reviews clinical data related to the use of JAK inhibitors in the peri-implantation phase of hematopoietic stem cell transplantation for primary myelofibrosis and discusses their efficacy and safety. [ABSTRACT FROM AUTHOR]

Ferroptosis is a form of cell death that is regulated by iron and characterized by the buildup of lipid peroxides (LPO) and subsequent rupture of the cell membrane. The molecular mechanisms of ferroptosis involve metabolic pathways related to iron, lipids, and amino acids, which contribute to the production of lipid reactive oxygen species (ROS). In recent years, there has been increasing attention on the occurrence of ferroptosis in various diseases. Ferroptosis has been found to play a crucial role in cardiovascular diseases, digestive diseases, respiratory and immunological diseases, and particularly in malignancies. However, there is still a lack of studies on ferroptosis in acute myeloid leukemia (AML). This paper provides a comprehensive review of the mechanism of ferroptosis and its regulatory molecules and therapeutic agents in AML. It also evaluates the relationship between ferroptosis-related genes (FRGs), non-coding RNAs (ncRNAs), and prognosis to develop prognostic molecular models in AML. The study also explores the association between ferroptosis and immune infiltration in AML, to identify novel potential target regimens for AML. [ABSTRACT FROM AUTHOR]

Diagnosis and classification of acute myeloid leukemia (AML) are based on morphology and genetics. An increasing number of gene mutations have been found, and some are used for risk classification in AML patients with normal karyotype (cytogenetically normal (CN)-AML). In this systematic review and meta-analysis, we examined three frequent mutations in CN-AML: mutations of fms-related tyrosine kinase 3 ( FLT3-ITD), mutated nucleophosmin ( NPM1), and mutations of the CCAAT enhancer-binding protein alpha ( CEBPA) gene. A systematic literature search of publications listed in the electronic databases (Embase, Pubmed, Healthstar, BIOSIS, ISI Web of Knowledge and Cochrane) from 2000 up to March 2012 was performed (Fig. 1). Nineteen studies were included and qualitatively analyzed. Two to four studies entered the quantitative meta-analysis incorporating 1,378 to 1,942 patients with CN-AML. Meta-analysis for overall survival (OS) and relapse-free survival (RFS) showed FLT3-ITD to predict an unfavorable prognosis, with hazard ratios (HR) of 1.86 and 1.75, respectively. In contrast, meta-analysis of the impact of NPM1 and CEBPA mutations on OS yielded an HR of 0.56 for each mutation, while analysis of impact on RFS produced HRs of 0.37 and 0.42, respectively. This systematic review and meta-analysis aimed to evaluate the prognostic value of mutations in the NPM1, CEBPA, and FLT3 genes. FLT3-ITD was associated with worse prognosis, whereas mutations in NPM1 and CEBPA genes were associated with a favorable prognosis. [ABSTRACT FROM AUTHOR]

Anti CD-19 chimeric antigen receptor T (CAR-T) cells demonstrate effective early anti-tumor response; however, impaired hematopoietic recovery is observed in about 30% of patients with prolonged cytopenia appearing as an unmet need for optimal treatment. All adult patients given commercially available anti CD-19 CAR-T for diffuse large B cell lymphoma (DLBCL) were screened at 21–28 days after CAR-T infusion for cytopenia. In case of severe persistent cytopenia, patients were given TPO receptor agonists. Initial dose of eltrombopag was 50 mg/day and gradually increased to a maximal dose of 150 mg/day. Romiplostim was given as subcutaneous injection once a week for 2 doses (125 mcg). Response was defined as transfusion independency along with resolution of severe neutropenia (ANC > 500 /microL) and/or platelets > 20,000/microL for three consecutive values on different days. TPO receptor agonists were tapered down when response was met. From May 2019 to December 2021, 93 patients were eligible (74%, tisagenlecleucel and 26%, axicabtagene ciloleucel). The median age was 69 (range, 19–85) years. Six patients (6.5%) (tisagenlecleucel, n = 4 or axicabtagene ciloleucel, n = 2) demonstrated prolonged severe cytopenia and were treated with TPO receptor agonists (eltrombopag, n = 4; romiplastim, n = 1, both drugs, n = 1). Median time from CAR-T infusion to initiation of TPO receptor agonist was 43 (range, 21–55) days. All patients were transfusion-dependent and were given daily GCSF prior to TPO receptor agonist administration. Response to TPO receptor agonists was seen in all 6 patients. Median time from TPO receptor agonist initiation to resolution of cytopenia was 22 (range, 8–124) days for Hb, 27 (range, 6–38) days for platelets, and 29 (range, 7–61) days for neutrophils. A complete resolution of all blood counts (ANC > 500 /microL and platelets > 20,000/microL and hemoglobin > 8 gr/dL) was seen in 5/6 patients. No toxicity was observed during the therapy course. This paper supports further investigation of TPO receptor agonists in the treatment of persistent cytopenia following CAR-T cell therapy. [ABSTRACT FROM AUTHOR]

Idelalisib in combination with rituximab is an efficacious treatment for patients suffering from chronic lymphocytic leukemia (CLL) with known limitations due to toxicities. However, the benefit after prior Bruton tyrosine kinase inhibitor (BTKi) therapy remains unclear. For this analysis, 81 patients included in a non-interventional registry study of the German CLL study group (registered at www.clinicaltrials.gov as # NCT02863692) meeting the predefined criteria of a confirmed diagnosis of CLL and being treated with idelalisib containing regimens outside clinical trials were considered. 11 patients were treatment naïve (13.6%) and 70 patients (86.4%) pretreated. Patients had median of one prior therapy line (range 0–11). Median treatment duration with idelalisib was 5.1 months (range 0–55.0 months). Of 58 patients with documented treatment outcome, 39 responded to idelalisib containing therapy (67.2%). Patients treated with the BTKi ibrutinib as last prior treatment prior to idelalisib responded in 71.4% compared to a response rate of 61.9% in patients without prior ibrutinib. Median event free survival (EFS) was 15.9 months with a 16 versus 14 months EFS in patients with ibrutinib as last prior treatment or not, respectively. Median overall survival was 46.6 months. In conclusion, treatment with idelalisib appears to have a valuable impact in patients being refractory to prior ibrutinib therapy even though there are limitations in our analysis due to the low number of patients included. [ABSTRACT FROM AUTHOR]

B Correction to: Annals of Hematology b https://doi.org/10.1007/s00277-023-05189-3 In the published paper, almost all the figures and tables of the article (Table 1, table 2, figure 3, figure 4, figure 5 and figure 6 are incompatible with its current captions. Correction to: Real-world imatinib mesylate treatment in patients with chronic myeloid leukemia: The importance of molecular monitoring and the early molecular response The original article can be found online at https://doi.org/10.1007/s00277-023-05189-3. [Extracted from the article]

The affiliations now read: SP 1 sp Department of Infectious Diseases, St. Joseph Hospital Berlin-Tempelhof, Germany SP 2 sp Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin SP 3 sp Department of Hematology and Oncology, Red Cross Hospital, Munich, Germany The authors now read: Pascal Migaud SP 1,2 sp ; Markus Müller SP 1 sp ; Keikawus Arastéh SP 1,2 sp ; Marcus Hentrich SP 3 sp ; Hartmut Stocker SP 1 sp Publisher's note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. The original article can be found online at https://doi.org/10.1007/s00277-022-04944-2 B Correction to: Annals of Hematology b https://doi.org/10.1007/s00277-022-04944-2 After publication of this paper, the affiliation: "Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin" for Pascal Migaud and Keikawus Arastéh was missed. [Extracted from the article]

Previous studies have shown the reproducibility of the 2008 World Health Organization (WHO) classification in myelodysplastic syndromes (MDS), especially when multilineage dysplasia or excess of blasts are present. However, there are few data regarding the reproducibility of MDS with unilineage dysplasia. The revised International Prognostic Scoring System R-IPSS described two new morphological categories, distinguishing bone marrow (BM) blast cell count between 0-2 % and >2- < 5 %. This distinction is critical for establishing prognosis, but the reproducibility of this threshold is still not demonstrated. The objectives of our study were to explore the reliability of the 2008 WHO classification, regarding unilineage vs. multilineage dysplasia, by reviewing 110 cases previously diagnosed with MDS, and to study whether the threshold of ≤2 % BM blasts is reproducible among different observers. We used the same methodology as in our previous paper [Font et al. (2013) Ann Hematol 92:19-24], by encouraging investigators to include patients with <5 % BM blasts. Samples were collected from 11 hospitals and were evaluated by 11 morphologists. Each observer evaluated 20 samples, and each sample was analyzed independently by two morphologists. Discordance was observed in 36/108 suitable cases (33 %, kappa test 0.503). Diagnosis of MDS with unilineage dysplasia (refractory cytopenia with unilineage dysplasia (RCUD), refractory anemia with ring sideroblasts (RARS) or unclassifiable MDS) was assessed in 33 patients, by either of the two observers. We combined this series with the cases with RCUD or RARS included in our 2013 paper, thus obtaining 50 cases with unilineage dysplasia by at least one of the observers. The whole series showed very low agreement regarding RCUD (5/23, 21 %) and RARS (5/28, 18 %). Regarding BM blast count, the threshold of ≤2 % was not reproducible (discordance rate 32/108 cases, kappa test 0.277). Our study shows that among MDS WHO 2008 categories, interobserver discordance seems to be high in cases with unilineage dysplasia. We also illustrate that the threshold of ≤2 % BM blasts as settled by the R-IPSS may be not easy to reproduce by morphologists in real practice. [ABSTRACT FROM AUTHOR]

1 Pre-treatment TEP SCAN (a) and after 3 months of treatment (b) A PET scan was performed after the third cycle of association showing a complete metabolic remission (Fig. 1:CAS:528:DC%2BD1MXmvFyjur0%3D. 10.1111/j.1365-2141.2009.07679.x 2 Garnache-Ottou F, Vidal C, Biichlé S, Renosi F, Poret E, Pagadoy M. How should we diagnose and treat blastic plasmacytoid dendritic cell neoplasm patients? Recent papers [[6]-[8]] showed that venetoclax combined with decitabine or 5-Aza in treatment-naive elderly patients with AML was effective and well tolerated, leading this association to become a standard of treatment in this indication. [Extracted from the article]

Skin lesions have been reported in about 10–12% of hairy cell leukemia (HCL) patients. Most are etiologically related to autoimmune or infectious processes, although secondary cutaneous neoplasms and drug-induced lesions are also reported. However, leukemia cutis with the direct infiltration of the skin by leukemic cells is extremely rare in HCL patients. This paper reviews the epidemiology, pathogenesis, clinical symptoms, diagnosis, and approach to treating skin lesions in HCL. A literature review of the MEDLINE database for articles in English concerning hairy cell leukemia, skin lesions, leukemia cutis, adverse events, infectious, cutaneous, drug reactions, neutrophilic dermatoses, secondary neoplasms, and vasculitis was conducted via PubMed. Publications from January 1980 to September 2020 were scrutinized. Additional relevant publications were obtained by reviewing the references from the chosen articles. [ABSTRACT FROM AUTHOR]

B Correction to: Annals of Hematology b https://doi.org/10.1007/s00277-023-05196-4 Following the online publication of this paper I , i the authors have learned that the National Comprehensive Cancer Network (NCCN) requires some editorial changes relating to how their guidelines are referenced within the paper. The original article can be found online at https://doi.org/10.1007/s00277-023-05196-4. Correction to: RE-MIND2: comparative effectiveness of tafasitamab plus lenalidomide versus polatuzumab vedotin/bendamustine/rituximab (pola-BR), CAR-T therapies, and lenalidomide/rituximab (R2) based on real-world data in patients with relapsed/refractory diffuse large B-cell lymphoma. [Extracted from the article]

We believe that early and aggressive treatment of detrimental acute inflammation is essential, covering all aspects of sepsis management, and that tocilizumab is only one piece of the puzzle that can be aid recovery of patients with hyper-inflammatory response. The majority of authors still restrict the use of tocilizumab only for patients suffering from COVID-19 related Adult Respiratory Distress Syndrome (ARDS) explaining this by the lack of randomized controlled trials (RCTs) conducted in humans [[2]]. Dear Editor, We've read with great interest the paper by Dr. Wang and co-workers, regarding the effective use of tocilizumab, an interleukin-6 inhibitor, in septic patients with hematologic malignancies [[1]]. [Extracted from the article]

Wider use of clozapine, one of the most effective antipshychotic drugs, is precluded by its propensity to cause agranulocytosis. Currently, clozapine is used for treatment-resistant schizophrenia, with mandatory blood count monitoring for the duration of treatment. Agranulocytosis occurs in up to 0.8% of patients and presents a significant medical challenge, despite decreasing mortality rates. In this paper, we review the epidemiology of clozapine-induced agranulocytosis (CLIA), advances in identifying genetic risk factors, and the preventive measures to reduce the risk of CLIA. We discuss the pathogenesis of CLIA, which, despite receiving considerable scientific attention, has not been fully elucidated. Finally, we address the clinical management and suggest the approach to clozapine re-challenge in patients with a previous episode of neutropenia. With a significant proportion of clozapine recipients in Western hemisphere being Black, we comment on the importance of recognizing benign ethnic neutropenia as a potential impediment to clozapine administration. This review aims to aid haematologists and psychiatrists to jointly manage neutropenia and agranulocytosis caused by clozapine. [ABSTRACT FROM AUTHOR]

Therapeutic plasma exchange (TPE) has dramatically improved the prognosis of acquired thrombotic thrombocytopenic purpura (TTP), and TPE and corticosteroids are the mainstays of treatment of acquired TTP. However, a subset of patients may remain refractory to this treatment modality, or have an initial response but relapse after the discontinuation of TPE during the follow-up. While managing patients with relapsed/refractory acquired TTP, there are several therapeutic maneuvers, which can be considered. Recently, there came some papers regarding the use of bortezomib in relapsed or refractory acquired TTP, and in this review, this indication of bortezomib was evaluated along with the current data available. In seven published papers, 12 patients with relapsed/refractory acquired TTP received bortezomib, of which 11 survived the acute episodes and maintained remission. Bortezomib may serve as an adjunct treatment, but prospective trials are needed to determine the dosing, administration route, and the treatment schedule of this treatment option in patients with relapsed/refractory TTP. [ABSTRACT FROM AUTHOR]

The wave of coronavirus disease 2019 (COVID-19) with Omicron variant reached its first peak in Beijing, China in December 2022. We delineated characteristics and factors associated with adverse outcome of patients with plasma cell dyscrasias (PCDs) and COVID-19 during the first month of the wave. A total of 104 patients with a median age of 65 years were included in the study, with multiple myeloma (74%, n=77) and primary Immunoglobulin light chain amyloidosis (16.3%, n=17) being the two most common disease. Overall, severe or critical COVID-19 was developed in 18 (17.3%) patients, with a total all-cause mortality rate of 4.8% (n=5). The vaccination coverage was 41% and 48.1%, before and during the upsurge of Omicron, respectively, calling for the improvement of vaccination in PCD patients. Multivariable analysis revealed that age was the only independent risk factors (OR=1.14, 95% CI: 1.06-1.26, p = 0.002) associated with the development of severe or critical disease. Among patients with severe or critical group, low levels of albumin (HR=18.29; 95% CI: 1.82-183.44, p = 0.013) and high levels of lactic dehydrogenase (LDH) (HR=0.08; 95% CI: 0.01-0.65, p = 0.018) were associated with longer time to negative conversion of COVID-19., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Thalassemia is characterized by a defect in the synthesis of one or more of the globin subunits of hemoglobin. This defect results in imbalance in the α/β-globin chain ratio, ineffective erythropoiesis, chronic hemolytic anemia, and iron overload. With advances in diagnosis, treatment, and transfusion support, the prognosis of patients with thalassemia has improved over the past few decades. An increasing number of patients with thalassemia is living with long-term complications, including cardiomyopathy, chronic liver disease, endocrinopathy, and infections. In this paper, we review common complications that bring the patient with thalassemia to urgent or emergent medical attention. We also discuss the aspects of emergency care that are most relevant while caring for the patient with thalassemia in the emergency department. [ABSTRACT FROM AUTHOR]

Lenalidomide is an integral, yet evolving, part of current treatment pathways for both transplant-eligible and transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM). It is approved in combination with dexamethasone as first-line therapy for transplant-ineligible patients with NDMM, and as maintenance treatment following autologous stem cell transplantation (ASCT). Although strong clinical trial evidence has supported the integration of lenalidomide into current treatment paradigms for NDMM, applying those paradigms to individual patients and determining which patients are most likely to benefit from lenalidomide treatment are more complex. In this paper, we utilize the available clinical trial evidence to provide recommendations for patient selection and lenalidomide dosing in both the first-line setting in patients ineligible for ASCT and the maintenance setting in patients who have undergone ASCT. In addition, we provide guidance on management of those adverse events that are most commonly associated with lenalidomide treatment, and consider the optimal selection and sequencing of next-line agents following long-term frontline or maintenance treatment with lenalidomide. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor (CAR)-based immunotherapy has achieved dramatic success in the treatment of B cell malignancies, based on the summary of current research data, and has shown good potential in early phase cancer clinical trials. Modified constructs are being optimized to recognize and destroy tumor cells more effectively. By targeting the proper B-lineage-specific antigens such as CD19 and CD20, adoptive immunotherapy has demonstrated promising clinical results and already plays a role in the treatment of several lymphoid malignancies, which highlights the importance of target selection for other CAR therapies. The high efficacy of CAR-T cells has resulted in the approval of anti-CD19-directed CAR-T cells for the treatment of B cell malignancies. In this review, we focus on the basic structure and current clinical application of CAR-T cells, detail the research progress of CAR-T for different antigenic targets in hematological malignancies, and further discuss the current barriers and proposed solutions, investigating the possible mechanisms of recurrence of CAR-T cell therapy. A summary of the paper is also given to overview as the prospects for this therapy. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) is a new human infectious disease. The etiology for this outbreak is a novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Thus far, related research on COVID-19 is still in preliminary stage. This paper summarized the latest outcomes of corresponding study from Chinese centers and clarified the hematopoietic abnormality caused by SARS-CoV-2 and potential mechanism. Lymphopenia was common in the early stage after the onset of COVID-19. A significant decrease was observed in peripheral CD4+ and CD8+ T lymphocytes. As the illness progressed, neutrophilia emerged in several cases, and patients with severe critical pulmonary conditions showed higher neutrophils than common type. Thrombocytopenia was resulting from the consumption and/or the reduced production of platelets in damaged lungs. Anemia was not observed notably, but the decrease in hemoglobin was frequent. The activation of monocyte-macrophage system aggravates the immune damage of lung and other tissues, which leads to the increase of D-dimer, prothrombin time, and platelet consumption. [ABSTRACT FROM AUTHOR]