European Hematology Association Research Articles

Establishment and Characterization of in Vitro Model of X-Linked Sideroblastic Anemia

(Background) Congenital sideroblastic anemia (CSA) is an inherited microcytic anemia characterized by the presence of bone marrow ring sideroblasts. The most common form of CSA is X-linked sideroblastic anemia (XLSA), which is attributed to mutations in the X-linked gene erythroid-specific 5-aminolevulinate synthase (ALAS2) . ALAS2 encodes the enzyme that catalyzes the first and rate-limiting steps in the heme biosynthesis pathway in erythroid cells. This pathway converts glycine and acetyl-CoA to 5-aminolevulinic acid (ALA), which requires pyridoxal 5'-phosphate (PLP) as a cofactor. Although PLP has been used for treating XLSA, a marked proportion of patients with XLSA remain refractory to treatment. Therefore, to elucidate the details of the underlying molecular mechanisms that contribute to ring sideroblast formation for XLSA, we succeeded to induce ALAS2 gene mutation in human induced pluripotent stem cell-derived erythroid progenitor (HiDEP) cells by CRISPR/Cas9 (European Hematology Association 2017). Recently we have further extended the study; we succeeded to establish ring sideroblast by newly optimized in vitro co-culture system and conducted its molecular characterization.(Method) We targeted the GATA-1-binding region of intron 1 of the human ALAS2 gene in HiDEP cells. The mutation diminished the binding of transcription factor GATA-1, which lead to decreased transcription of the ALAS2 gene, thereby causing XLSA (Kaneko et al . Haematologica 2014). Co-culture with OP9 stromal cells (ATCC) was conducted with IMDM medium supplemented with FBS, erythropoietin, dexamethasone, doxycycline, MTG, Insulin-Transferrin-Selenium, and L-ascorbic acid. Prussian blue staining and electron microscopy were used to assess iron deposition in erythroblasts. For transcription profiling, Human Oligo chip 25K (Toray) was used. Apoptotic cell was determined with annexin V.(Results) The established XLSA clone harbored 19-bp deletion within the intron 1 enhancer region of ALAS2, including GATA binding domain. The XLSA clone appeared pink/pale color, accompanied by the decreased intracellular heme concentration. Quantitative ChIP analysis demonstrated that the chromatin occupancies of GATA-1 and its cofactor TAL1 were significantly abrogated at the ALAS2 intron 1 loci in the XLSA clone. Quantitative RT-PCR analysis demonstrated significant downregulation of ALAS2 as well as globin genes in the XLSA clone. Microarray analysis revealed >2-fold up- and down-regulation of 619 and 274 genes caused by the 19-bp deletion, respectively. The downregulated gene ensemble included globins as well as genes involved in iron/heme metabolism (ALAS2, TFRC, CPOX, and MFRN1). GO analysis revealed significant enrichment of genes involved in cellular iron ion homeostasis, regulation of transcription, and regulation of apoptosis. In support of the observation, the apoptotic cell frequency was increased in the XLSA clone than the wild-type cells.When the XLSA clone was induced to undergo erythroid differentiation by co-culture with OP9 cells in the medium supplemented with 100 uM sodium ferrous citrate (SFC), a majority of the erythroblasts exhibited aberrant mitochondrial iron deposition (Figure). Intriguingly, the co-culture without SFC nor even with transferrin-loaded iron did not induce ring sideroblasts. By the co-culture with SFC, ALAS2 as well as globin mRNA levels in the XLSA clone was obviously induced to the level comparable to the wild-type cells. Quantitative ChIP-based mechanistic analysis at the ALAS2 locus demonstrated that GATA-1 occupancy was still abrogated at intron 1, while it was significantly increased at intron 8, in the XLSA clone-derived ring sideroblasts. Noticeably, when SFC was supplemented to induce ring sideroblasts, the apoptotic cell frequency was significantly reduced as compared with the XLSA clone co-cultured without SFC. Also, microarray analysis identified upregulation of anti-apoptotic genes (i.e. HSP70) in the ring sideroblast, implying that ring sideroblast formation might be a consequence of cytoprotective reaction. Finally, ALA treatment significantly improved the consequences compromised heme synthesis in the XLSA clone, implying that ALA may represent a therapeutic option for XLSA.(Conclusion) Further characterization of the XLSA model would help to clarify its molecular etiology as well as to establish novel therapeutic strategies. [Display omitted] DisclosuresFukuhara:Eisai, Janssen, Takeda, Ono and Zenyaku Kogyo: Honoraria; Nihon Ultmarc, Astellas, AbbVie, Alexionpharma, Bayer Yakuhin, Bristol-Myers Squibb, Baxalta, Celgene, Chugai, Daiichi-Sankyo, Toehringer Ingelheim, Eisai, GlaxoSmithKline, Janssen, Japan Blood Products Organization, Kyowa Hakko Kirin, Mitsubishi Tanabe, : Research Funding.

FLT3 Tyrosine Kinase Inhibitors for the Treatment of Fit and Unfit Patients with FLT3-Mutated AML: A Systematic Review.

FLT3-mutated acute myeloid leukemia accounts for around 30% of acute myeloid leukemia (AML). The mutation carried a poor prognosis until the rise of tyrosine kinase inhibitors (TKIs). New potent and specific inhibitors have successfully altered the course of the disease, increasing the complete response rate and the survival of patients with FLT3-mutated AML. The aim of this article is to review all the current knowledge on these game-changing drugs as well as the unsolved issues raised by their use for fit and unfit FLT3-mutated AML patients. To this end, we analyzed the results of phase I, II, III clinical trials evaluating FLT3-TKI both in the first-line, relapse monotherapy or in combination referenced in the PubMed, the American Society of Hematology, the European Hematology Association, and the Clinicaltrials.gov databases, as well as basic science reports on TKI resistance from the same databases. The review follows a chronological presentation of the different trials that allowed the development of first- and second-generation TKI and ends with a review of the current lines of evidence on leukemic blasts resistance mechanisms that allow them to escape TKI.

Patient-reported outcomes in clinical trials for multiple myeloma: Where we are.

e18615 Background: It is recommended to include patient-reported outcomes (PROs) in cancer trials to ensure clinical benefit based on patients’ perceptions. For multiple myeloma patients, PRO measurement is essential to understand the impact of treatment on their physical and psychosocial functional behaviour. However, it is unclear which PRO instruments are utilized in multiple myeloma trials, how often they are used and whether results are consistently reported. The aim of this project was to explore the use and frequency of PRO instruments in randomized controlled trials for multiple myeloma and to assess the consistency of their reporting. Methods: Within the European Hematology Association (EHA) project to develop guidelines for the use of PROs in adult patients with hematological malignancies, MEDLINE and CENTRAL were systematically searched for randomized controlled trials investigating multiple myeloma between 2015 and 2020. Study design, disease and treatment characteristics, the primary outcome and used PRO instrument(s) were extracted using a pre-defined template. To assess the consistency of PRO reporting, study registries were compared with publications, study protocol and Health Technology Assessment (HTA) reports where available. Results: Overall, 10,707 records were found. Following screening for randomized-controlled trials, 283 ongoing, completed or published studies were included for review. 118 studies planned the use of PROs. The most frequently used PRO instrument (92 studies) was the EORTC QLQ-30, an instrument that measures health-related quality-of-life (HRQoL) in cancer patients. The disease-specific questionnaire EORTC-MY20 was also frequently used (50 studies). Likewise, the HRQoL instrument EQ-5D was used in 50 studies. Overall, 38 different PRO instruments were reported. In 39 studies for which a study protocol was found, only 19 reported PRO instruments consistently with the trial registry for the study. In addition, in 30 studies, for which a publication reported PRO results (58 overall), the information on PRO instruments differed between publication and the trial registry. For example, PRO instruments mentioned in the registry were omitted in the respective publications. Additionally, information on PRO in HTA reports was available for 26 studies, of which 18 reports were consistent with the trial registries. Conclusions: The results show that measurement of PROs still remain under-utilized in multiple myeloma research. While most PRO instruments identified in this review comply with the recommendations for incorporating PROs into clinical research in adult oncology, they are often inconsistently reported. Thus, reporting standards for the use of PROs are needed to ensure consistency in the use and reporting of PROs.

Hodgkin lymphoma. ASCO, EHA and ASH 2020 news

The review shows the most interesting and promising studies presented at major international conferences of the American Society of Clinical Oncology, the European Hematology Association, and the American Society of Hematology in 2020. The main aim of the therapy for Hodgkin lymphoma (HL), which have been formulated over the past 20 years, is the highly effective therapy and high quality of life, and the main possibility to solve this task is positron emission tomography (PET). The studies presented at conferences this year have shown that PET-adapted therapy has become the basis of modern HL therapy. The second equally interesting direction presented at the conferences this year is the widespread use of targeted (brentuximab vedotin) therapy and immunotherapy (nivolumab, pembrolizumab) in combination with standard chemotherapy not only in patients with relapsed/refractory HL, but also as first-line therapy, including the patients of an elderly section. The combination of brentuximab vedotin and immunotherapy during all lines of HL treatment, as well as brentuximab vedotin and immunotherapy consolidation after high-dose chemotherapy and autologous stem cell transplantation are another direction to improve the efficacy of therapy in patients with HL.

Selecting β-thalassemia Patients for Gene Therapy: A Decision-making Algorithm.

This expert opinion originally developed by a panel of the Italian Society of Thalassemias and Hemoglobinopathies (SITE), reviewed and adopted by the European Hematology Association (EHA) through the EHA Scientific Working Group on Red Cells and Iron, has been developed as priority decision-making algorithm on evidence and consensus with the aim to identify which patients with transfusion-dependent beta-thalassemia (TDT) could benefit from a gene therapy (GT) approach. Even if the wide utilized and high successful allogeneic hematopoietic stem-cell transplantation provides the possibility to cure several patients a new scenario has been opened by GT. Therefore, it is important to establish the patients setting for whom it is priority indicated, particularly in the early phase of the diffuse use outside experimental trials conducted in high selected centers. Moreover, actual price, limited availability, and resources disposal constitute a further indication to a rational and progressive approach to this innovative treatment. To elaborate this algorithm, the experience with allogeneic transplantation has been used has a predictive model. In this large worldwide experience, it has been clearly demonstrated that key for the optimal transplant outcome is optimal transfusion and chelation therapy in the years before the procedure and consequently optimal patient’s clinical condition. In the document, different clinical scenarios have been considered and analyzed for the possible impact on treatment outcome. According to the European Medicine Agency (EMA) for the GT product, this expert opinion must be considered as a dynamic, updatable, priority-based indications for physicians taking care of TDT patients.

Management of patients with difficult-to-treat multiple myeloma.

Newer treatments for multiple myeloma (MM) have improved response rates and survival for many patients. However, MM remains challenging to treat due to the propensity for multiple relapses, cumulative and emergent toxicities from prior therapies and increasing genomic complexity that arises due to clonal evolution. In particular, patients with relapsed/refractory MM often require increased complexity of treatment, yet still experience poorer outcomes compared with patients who are newly diagnosed. Additionally, several patient subgroups, including those with extramedullary disease and patients who are frail and/or have multiple comorbidities, have an unfavorable prognosis and remain undertreated. This review (based on an Updates-in-Hematology session at the 25th European Hematology Association Annual Congress2020) discusses the management of these difficult-to-treat patients with MM.

Changes in the diagnostic and treatment strategies of patients with hematological diseases during the COVID-19 pandemic with reference to recommendations from American Society of Hematology and European Hematology Association

The novel coronavirus (COVID-19) pandemic has affected all aspects of human life worldwide. Under this situation, the American Society of Hematology and European Hematology Association have provided resources and recommendations for the management of hematologic diseases during the COVID-19 pandemic. This review aims to summarize these recommendations and provide helpful, accurate, and up-to-date information for Japanese hematologists.

Efficacy and Safety of CAR-T Therapy for Relapse or Refractory Multiple Myeloma: A systematic review and meta-analysis.

Background: Multiple myeloma (MM) is incurable in spite of recent treatment improvements, highlighting the development of new therapies. Chimeric antigen receptor (CAR) T-cell therapy has dramatically changed the therapeutic effectiveness in high-risk B-cell malignancies. For relapsed/refractory multiple myeloma (RRMM), preclinical evaluations of CAR-T therapy have shown promising efficacy, thus various active clinical trials are under way. Herein, we conducted this review to summarize efficacy and safety of CAR-T therapy and provide more evidence to guide clinical treatments.Method: We systematically searched literature based on databases (PubMed, EMBASE, Cochrane Central Register of Controlled Trials), and conference abstracts reported from American Society of Hematology (ASH), European Hematology Association (EHA) and American Society of Clinical Oncology (ASCO), in addition to other sources (www.clinicaltrials.gov, article citations). Data assessed efficacy and safety of CAR-T therapy in patients with RRMM were extracted and evaluated, and then systematically analyzed by Comprehensive Meta-analysis 3.0 (CMA 3.0).Results: A total of 23 studies including 350 participants from different countries, diagnosed as RRMM and treated with CAR-T therapy (containing 7 antigens targeted by CARs) were combined. In summary, we discovered the pooled overall response rate (77%), complete response rate (37%) and minimal residual disease (MRD) negativity rate within responders (78%). Furthermore, the pooled relapse rate of responders was 38% and median progression-free survival was 8 months. The pooled survival rate was 87% at last follow-up (median, 12 months). In addition, the pooled grade 3-4 rates of cytokine release syndrome (CRS) and neurologic toxicities (NT) were 14% and 13%, respectively.Conclusion: Our study suggests that CAR-T therapy has demonstrated efficacy and safety in RRMM patients. BCMA-targeted CAR-T and anti-BCMA contained regimen have shown better efficacy.

Longitudinal Immunogenomic Profiling of Tumor and Immune Cells for Minimally-Invasive Monitoring of Smoldering Multiple Myeloma (SMM): The Immunocell Study

Longitudinal Immunogenomic Profiling of Tumor and Immune Cells for Minimally-Invasive Monitoring of Smoldering Multiple Myeloma (SMM): The Immunocell Study

FGF/FGFR Axis-Blockade Leads to Anti-Tumor Activity in Waldenstrom's Macroglobulinemia By Silencing MYD88

The human fibroblast growth factor/fibroblast growth factor-receptor (FGF/FGFR) axis deregulation is largely involved in supporting the pathogenesis of hematologic malignancies, including Waldenstrom's Macroglobulinemia (WM). Therefore, novel therapeutics designed to specifically target deregulated signaling pathways in WM are required. We investigated the role of FGF/FGFR system blockade in WM by using a pan-FGF trap molecule, NSC12, a small molecule identified using pharmacophore modeling of the interaction of a minimal PTX3-derived FGF-binding pentapeptide with FGF2. By interrogating the transcriptome signature of patients' BM-derived CD19-positive cells (GEO9656, GEO6691), we found a significant enrichment of FGF/FGFR-driven signaling cascades, including PI3K-AKT, MAPK and STAT3 pathways (FDR<0.25; P<0.05); coupled with higher expression of FGFs (FGF2, FGF7, FGF12, FGF18; P<0.05) in WM cells as compared to their normal cellular counterpart. FGFRs are also shown to be overexpressed in WM. We performed transcriptome profiling of NSC12-treated WM cells, confirming the blockade of the FGFR-signaling blockade; and, importantly, we discovered the efficacious silencing of MYD88 and MYD88-dopwnstream target HCK in WM cells. These findings were confirmed at protein level, showing inhibition of MYD88-driven pathways, such as BTK-, and SYK-phosphorylation. As a further demonstration of the functional impact of NSC12-dependent targeting of MYD88, we could confirm the inhibition of both canonical and non-canonical NF-kB in NSC12-treated WM cells, as assessed at nuclear protein level by WB and by using the NFkB activity assay. In addition, the NSC12-dependent inhibition of MYD88 resulted in silencing of the MAPK-ERK signaling cascade, thus leading to NSC12-induced Myc-silencing in WM cells. We next confirmed the efficacy of NSC12 in silencing bone marrow stromal cell (BMSC)-induced FGFR3 phosphorylation; paralleled by inhibition of of pro-survival pathways, including pAKT, the AKT-downstream pGSK3β; p-ERK; and p-STAT3. Functional sequelae of the FGF/FGFR blockade in WM cells were studied, demonstrating inhibition of WM cell growth, induction of apoptosis, enhanced ER stress and initiation of UPR. Of note, anti-WM activity of NSC12 was also documented using primary bone marrow-derived CD19+ cells isolated from patients with WM. In contrast, NSC12 did not show cytotoxicity on PBMC-derived CD19+ cells isolated from healthy donors. The anti-WM activity exerted by NSC12 was confirmed also within the context of the supportive bone marrow milieu, as shown both in vitro and in vivo. BCWM.1, MWCL1 cells were cultured with NSC12 in the presence or absence of primary WM BMSCs: adherence of WM cells to BMSCs triggered a significant increase in the proliferation, which was inhibited by NSC12in a dose-dependent manner (P<0.05). Using a disseminated humanized WM model, BCWM.1 M-Cherry-Luc tumor-bearing mice were treated with either NSC12 or vehicle control. NSC12-treated mice presented with a significant inhibition of WM tumor growth as demonstrated by bioluminescence imaging analysis. NSC12-dependent reduction of WM tumor cell BM infiltration was confirmed by IHC performed on harvested femurs, in comparison to vehicle-treated mice. Importantly, we assessed MYD88-mRNA expression using harvested bone marrow femurs; and found a significant reduction of MYD88- and MYD88-downstream target HCK in NSC12-treated mice was confirmed ex vivo (P<0.05). Overall, our studies are reporting on the use of NSC12, as a novel potential therapeutic strategy to specifically halt the FGF/FGFR axis in WM; and demonstrate how the observed anti-WM activity exerted by NSC12 may be driven, at least in part, by inhibition of MYD88. Disclosures Motta: Roche: Honoraria; Janssen: Honoraria. Rossi:Alexion: Membership on an entity's Board of Directors or advisory committees; Novartis: Other: Advisory board; Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Consultancy, Honoraria; Amgen: Honoraria; Sanofi: Honoraria; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Jazz: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees. Roccaro:Amgen: Other; AstraZeneca: Research Funding; Celgene: Other; Janssen: Other; Italian Association for Cancer Research (AIRC): Research Funding; Transcan2-ERANET: Research Funding; European Hematology Association: Research Funding.

Waldenström’s Macroglobulinemia (WM) Is Preceded By Clonal Lymphopoiesis Including MYD88 L265P in Progenitor B Cells

Waldenström’s Macroglobulinemia (WM) Is Preceded By Clonal Lymphopoiesis Including MYD88 L265P in Progenitor B Cells

A Phase 1 Study of Tasquinimod in Patients with Relapsed or Refractory Multiple Myeloma

Background Multiple myeloma (MM) is a hematologic malignancy resulting from clonal proliferation of plasma cells in the bone marrow (BM). The BM tumor microenvironment confers therapeutic resistance through survival and growth signals to myeloma cells and suppression of anti-tumor immune responses. A population of myeloid-derived suppressor cells (MDSCs), abundantly producing the pro-inflammatory S100A9 protein, promotes myeloma progression. Tasquinimod (TASQ) is an investigational drug that targets MDSCs via the S100A9 protein. In pre-clinical models of MM, TASQ has significant anti-tumor effects as a single agent and in combination with bortezomib, a proteasome inhibitor (PI) and lenalidomide, an immunomodulator (IMiD) (Lin C, et al. 25th Annual Meeting of European Hematology Association June 11-21 2020: EP896). TASQ has previously been studied as a novel, once-daily oral anti-cancer agent, including in a phase-3 randomized trial in patients (pts) with metastatic prostate cancer that showed improvement in radiographic progression-free survival (Sternberg C, et al. JCO 2016; 34(22): 2636-43). The side effect profile of TASQ is well-characterized based on this previous experience. We therefore designed a phase 1 trial (NCT04405167) to establish the maximum tolerated dose (MTD) and optimal schedule for TASQ in MM and then investigate the MTD of TASQ in combination with a standard oral myeloma regimen of ixazomib, lenalidomide, and dexamethasone (IRd). For both single agent TASQ and the combination of TASQ with IRd, exploratory expansion cohorts will be enrolled to preliminarily characterize the antimyeloma activity of each regimen. Study Design Enrolled pts must have MM relapsed or refractory after at least one prior line of anti-MM therapy. Other key inclusion criteria include measurable disease and Eastern Cooperative Oncology Group performance status ≤2. Key exclusion criteria include failure to have fully recovered from clinically significant adverse effects of prior chemotherapy; active graft versus host disease; treatment with cytotoxic chemotherapy within 3 weeks prior to initiation of study treatment; treatment with PIs, IMiDs, or monoclonal antibodies within 2 wks, experimental therapy or plasmapheresis within 4 wks, or systemic corticosteroids or radiotherapy within 7 days; known central nervous system involvement by myeloma; or a diagnosis of smoldering MM or POEMS syndrome, active plasma cell leukemia, symptomatic primary amyloidosis, or myelodysplastic or myeloproliferative syndrome. Single agent TASQ and the combination of TASQ with IRd will be investigated in two parts. Part A will start with dose-escalation of single agent TASQ using a standard 3+3 design, with 3 to 6 pts evaluable for dose-limiting toxicity at each dose-level (see table). In the subsequent expansion cohort, additional pts will enroll at the MTD/optimal schedule, so that 12 pts total evaluable for response will have received the MTD/optimal schedule of single agent TASQ. Part B combines TASQ with standard-dose IRd: 28-day cycles of ixazomib 4 mg on days 1, 8, and 15, lenalidomide 25 mg on days 1-21, and dexamethasone 40 mg on days 1, 8, 15, and 22. The part B dose-escalation starts at the lower of either dose-level 1 or one dose-level below the single agent MTD. Additional pts with disease refractory to their most recent PI/IMiD combination will enroll into a part B expansion cohort, so that 12 pts total who are both evaluable for response and PI/IMiD refractory will have received the MTD/optimal schedule of TASQ in combination with IRd. Treatment will continue until unacceptable toxicity or myeloma progression. The primary study endpoint is the MTD of TASQ as single agent and in combination with IRd. Key secondary endpoints include toxicity (treatment-emergent grade 3/4 adverse events using the National Cancer Institute Common Toxicity Criteria for Adverse Events, version 5), preliminary antimyeloma activity (using the response criteria of the International Myeloma Working Group), changes in the BM microenvironment, and systemic TASQ exposure during therapy with single-agent TASQ and during therapy with TASQ in combination with IRd. These results will determine whether TASQ, alone or combined with standard anti-MM therapy, represents a promising novel treatment strategy in MM. Table 1 Disclosures Vogl: Active Biotech: Consultancy, Research Funding; Janssen: Consultancy; Karyopharm: Consultancy; Takeda: Consultancy; Celgene: Consultancy; Oncopeptides: Consultancy; MorphoSys: Consultancy. Nefedova:Active Biotech: Consultancy, Research Funding. Bondesson:Active Biotech: Current Employment. Eriksson:Active Biotech: Current Employment. Tuvesson:Active Biotech: Current Employment. OffLabel Disclosure: Tasquinimod for multiple myeloma

Prophylaxis of thromboembolism during therapy with asparaginase in adults with acute lymphoblastic leukaemia.

Prophylaxis of thromboembolism during therapy with asparaginase in adults with acute lymphoblastic leukaemia.

Report from the Virtual Edition of the 25th European Hematology Association (EHA), Annual Congress 11th –21st June 2020

Report from the Virtual Edition of the 25th European Hematology Association (EHA), Annual Congress 11th –21st June 2020

PNH Clones for Aplastic Anemia with Immunosuppressive Therapy: A Systematic Review and Meta-Analysis

Objectives: PNH clones, also aptly called “escape clones,” are evidence of acquired immune-mediated bone marrow failure and have a high prevalence in patients with aplastic anemia (AA). Several studies have reported contradictory results regarding the impact of PNH clones on AA patients with immunosuppression treatment, and PNH clones have not been confirmed as positive predictors of response in the AA guidelines of the British Society for Standards in Haematology. Methods: We performed a meta-analysis to address this issue by searching for articles in PubMed, EMBASE, The Coch­rane Library, Web of Science, and ClinicalTrials.gov, and for abstracts from the annual meetings of the American Society of Hematology and the European Hematology Association. We included 1,236 participants from 11 cohort-controlled studies. Our primary outcome was the 6-month hematologic response with a secondary outcome of the mortality rate within 3 months. Results: A better response rate was observed in the PNH+ group than in the PNH– group (odds ratio [OR] 2.85; 95% confidence interval [CI] 2.17–3.75; p < 0.00001), and further subgroup analysis strengthened the outcome, with minor heterogeneity in non-Asian countries. In contrast, the early mortality was not significantly different between the PNH+ and PNH– groups (OR 0.54; 95% CI 0.26–1.10; p = 0.09). Conclusions: The meta-analysis suggested an evidence-based role for PNH clones in predicting a better response in AA patients with immunosuppression.

Editorial introductions

Editorial introductions

Venetoclax in AML: Where We Are and Where We Are Headed

The developmental path for venetoclax in acute myeloid leukemia (AML) has been rapid and stands in stark contrast to the incremental progress that has characterized the field in previous decades. For perspective, on December 31, 2013, the first AML patient was enrolled into a study using venetoclax; 59 months later, on November 21, 2018, venetoclax received accelerated approval by the FDA for use in AML. In June 2020, Dr. DiNardo presented the results of the required confirmatory study at the European Hematology Association meeting, showing that venetoclax with azacitidine resulted in a superior response rate and overall survival compared to azacitidine alone for older, newly diagnosed AML patients. This swift progress has provided a welcome and potent new therapy for patients with AML; with it come questions about how its role can be expanded, and how its use can be optimized.

Recommendations for Pregnancy in Rare Inherited Anemias

Rare inherited anemias are a subset of anemias caused by a genetic defect along one of the several stages of erythropoiesis or in different cellular components that affect red blood cell integrity, and thus its lifespan. Due to their low prevalence, several complications on growth and development, and multi-organ system damage are not yet well defined. Moreover, during the last decade there has been a lack of proper understanding of the impact of rare anemias on maternal and fetal outcomes. In addition, there are no clear-cut guidelines outlining the pathophysiological trends and management options unique to this special population. Here, we present on behalf of the European Hematology Association, evidence- and consensus-based guidelines, established by an international group of experts in different fields, including hematologists, gynecologists, general practitioners, medical geneticists, and experts in rare inherited anemias from various European countries for standardized and appropriate choice of therapeutic interventions for the management of pregnancy in rare inherited anemias, including Diamond-Blackfan Anemia, Congenital Dyserythropoietic Anemias, Thalassemia, Sickle Cell Disease, Enzyme deficiency and Red cell membrane disorders.

Prevalence and mortality in β‐thalassaemias due to outbreak of novel coronavirus disease (COVID‐19): the nationwide Iranian experience

In late December 2019, an ongoing outbreak of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection that was termed Coronavirus Disease 2019 (COVID‐19), was reported in Wuhan, China (Zhu, et al 2020).

Abstract Book: 25th Congress of the European Hematology Association Virtual Edition, 2020

Abstract Book: 25th Congress of the European Hematology Association Virtual Edition, 2020