Search

Background: Based on the new data from the primary analysis of the OPTIC (Optimizing Ponatinib Treatment in CP-CML) trial on dose optimization of ponatinib in patients with chronic phase (CP)-CML, the German consensus paper on ponatinib published in 2020 (Saussele S et al., Acta Haematol. 2020) has been updated in this addendum. Summary: Focus is on the update of efficacy and safety of ponatinib, reflecting the new data set, as well as the update of the benefit-risk assessment and recommendations for ponatinib starting dose in CP-CML – provided that the decision to use ponatinib has already been made. Furthermore, based on OPTIC and additional empirical data, the expert panel collaborated to develop a decision tree for ponatinib dosing, specifically for intolerant and resistant patients. The recommendations on cardiovascular management have also been updated based on the most recent 2021 guidelines of the European Society of Cardiology (ESC) on cardiovascular disease prevention in clinical practice. Key Messages: The OPTIC data confirm the high efficacy of ponatinib in patients with CP-CML and provide the basis for individualized dose adjustment during the course of treatment. [ABSTRACT FROM AUTHOR]

Chronic myelogenous leukemia at blast crisis with a T-cell phenotype (T-ALL CML-BC) at diagnosis, without any prior history of CML is extremely rare. After the introduction of tyrosine kinase inhibitors (TKIs), CML patients have a median survival comparable to general population and accelerated/blast crisis are rarely encountered. Most CML patients (80%) transform into acute myeloid leukemia and the rest into B-ALL. Anecdotal cases of Ph+ T-ALL, either de novo or in the context of CML-BC have been reported. Left shift in the blood, the presence of splenomegaly/extramedullary infiltration and the occurrence of BCR::ABL1 rearrangement in both the blastic population, as well as in the myeloid cell compartment are key points in differentiating de novo Ph+ T-ALL from T-ALL CML-BC. The latter is a rare entity, characterized by extramedullary disease, p210 transcript and clonal evolution. Lack of preceding CML does not rule out the diagnosis of T-ALL CML-BC. Prompt TKI treatment with ALL-directed therapy followed by allogeneic stem cell transplantation may offer long-term survival in this otherwise poor prognosis entity. In this paper, we describe a patient with T-ALL CML-BC at presentation, still alive 51 months after diagnosis and we offer a review of the literature on this rare subject. All clinical and laboratory features are provided in order to distinguish de novo Ph+ T-ALL from T-ALL CML-BC, underscoring the prognostic and therapeutic significance of such a differentiation. [ABSTRACT FROM AUTHOR]

Background: Acute myeloid leukemia (AML) is a heterogeneous hematological malignancy characterized by uncontrolled proliferation and impaired differentiation of myeloid cells in the bone marrow. The tumor suppressor gene TP53 plays a crucial role in maintaining genomic integrity and preventing the development of cancer. TP53 mutations are frequently observed in AML (∼10% of patients) and are associated with aggressive disease behavior, resistance to therapy, and poor prognosis. Summary: Recent changes in classification of TP53-mutated myelodysplastic syndrome (MDS) have occurred related to the allelic status of TP53 and more importantly to harmonize MDS/AML patients as a homogeneous hematological malignancy. Current treatment regimens involve hypomethylating agents +/− venetoclax or intensive chemotherapy although unfortunately independent of treatment regimen the overall survival (OS) of this patient cohort is around 6 months with poor long-term outcomes after allogeneic stem-cell transplantation. Recent developments geared toward the treatment of TP53-mutated MDS/AML have focused on immunotherapies. Key Messages: Notably, there is optimism surrounding these new therapies that could provide breakthroughs with improving outcomes either as monotherapy or combined with established nonimmune therapies. This paper aims to provide an overview of TP53-mutated MDS/AML, including the underlying mechanisms, clinical implications, and emerging therapeutic strategies targeting this hematologic malignancy. [ABSTRACT FROM AUTHOR]

We describe a case of acute myeloid leukemia with NPM1 mutation and disseminated leukemia cutis in a very old patient, who achieved a long-lasting response to the azacitidine/venetoclax combination with molecular complete remission, given the potential value of this rarely observed clinical outcome. [ABSTRACT FROM AUTHOR]

Background: The level of minimal residual disease (MRD), often binarized into detectable or undetectable MRD according to certain thresholds, is strongly associated with long-term outcomes after chemo- and chemoimmunotherapy. Summary: Driven by our improved understanding of the biology of chronic lymphocytic leukemia (CLL), the recent decade has shown a shift from chemotherapy-based regimens to regimens based on targeted agents that exploit distinct biological vulnerabilities of CLL. These targeted agents can be broadly classified into inhibitors of Bruton tyrosine kinase (BTK) and BCL2 as well as CD20-directed antibodies. Depending on which agent and which combination of agents is used, the levels or status of MRD can have varying clinical relevance. This has implications on the prognosis after therapy as well as on possible strategies to guide treatment duration and intensity. Key Messages: This review summarizes the main discoveries related to MRD in the context of targeted therapies. Furthermore, it provides an overview on current hurdles and caveats related to the implementation of MRD in regular clinical care and summarize open research questions that need to be addressed with future clinical studies. [ABSTRACT FROM AUTHOR]

Background: The treatment landscape of chronic lymphocytic leukemia (CLL) has tremendously evolved in the last decades, thanks to the introduction of more effective therapies. Summary: Frontline therapy for patients with CLL includes chemoimmunotherapy (CIT) and pathway inhibitors (PIs) (i.e., bruton tyrosine kinase inhibitors and BCL2 inhibitors); the latter has proved to be more effective than CIT mainly in patients with high-risk features (e.g., TP53 aberrations and unmutated IGHV) with acceptable toxicity. Combinations of PIs are playing the protagonist role as frontline therapy for CLL. Key Messages: In this article, the management of treatment-naïve patients with CLL is discussed. [ABSTRACT FROM AUTHOR]

Background: Chronic lymphocytic leukemia (CLL) is a prevalent hematological malignancy (HM) characterized by inherent immunodeficiency, which is further pronounced by disease-directed therapy. The COVID-19 pandemic has had devastating outcomes, and although its impact has diminished over time, it continues to be a cause of significant morbidity and mortality, particularly among immunodeficient patients. Summary: In this review, we describe mechanisms of immune dysfunction in CLL in relation to COVID-19, provide an overview of the clinical outcomes of the disease in this patient population, and identify risk factors associated with severe morbidity and mortality. Additionally, we acknowledge the influence of the rapidly evolving landscape of new disease variants. The review further delineates the humoral and cellular responses to vaccination and their clinical efficacy in preventing COVID-19 in CLL patients. Moreover, we explore potential approaches to enhance these immune responses. Pre- and post-exposure prophylaxis strategies are discussed, along with description of common agents in the treatment of the disease in both outpatient and inpatient setting. Throughout the review, we emphasize the interplay between novel therapies for CLL and COVID-19 outcomes, prevention, and treatment and describe the impact of COVID-19 on the utilization of these novel agents. This information has the potential to guide clinical decision making in the management CLL patients. Key Messages: CLL patients are at risk for severe COVID-19 infection. Vaccinations and COVID-19 directed therapy have improved outcomes in patients with CLL, yet clinical challenges persist. [ABSTRACT FROM AUTHOR]

Background: Chronic lymphocytic leukemia (CLL) is a hematological malignancy characterized by immune dysfunction, which significantly contributes to increased morbidity and mortality due to infections. Summary: Advancement in therapeutic strategies based on combination chemoimmunotherapy and targeted treatment have increased life expectancy for patients affected by CLL. However, mortality and morbidity due to infection showed no improvement over the last decades. Although therapy options are highly efficient in targeting leukemic cells, several studies highlighted the interactions of different treatments with the tumor microenvironment immune components, significantly impacting their clinical efficacy and fostering increased risk of infections. Key Messages: Given the profound immune dysfunction caused by CLL itself, treatment can thus represent a double-edged sword. Thus, it is essential to increase our understanding and awareness on how conventional therapies affect the disease-microenvironment-infection axis to ensure the best personalized strategy for each patient. This requires careful consideration of the advantages and disadvantages of efficient treatments, whether chemoimmunotherapy or targeted combinations, leading to risk of infectious complications. To this regard, our machine learning-based algorithm CLL Treatment-Infection Model, currently implemented into the local electronic health record system for Eastern Denmark, aims at early identification of patients at high risk of serious infections (PreVent-ACaLL; NCT03868722). We here review strategies for management of immune dysfunction and infections in CLL. [ABSTRACT FROM AUTHOR]

Introduction: Haemato-oncologic patients are more susceptible to severe infections with SARS-CoV-2. We aimed to assess the clinical outcomes of SARS-CoV-2 infection among patients with Mycosis Fungoides and Sezary Syndrome (MF/SS). Methods: The data were retrieved from anonymized electronic medical records of Maccabi Healthcare Services (MHS), the second-largest healthcare organization in Israel. Patients diagnosed with MF/SS were included in the study. COVID-19 PCR test results together with sociodemographic and clinical data were extracted and analyzed to evaluate the association of COVID-19 with clinical outcomes. Results: In the period of 2020–2022, 1,472 MF/SS patients were included in the study. Among them, 768 (52%) had SARS-CoV-2 infection. The hospitalization rate was 2.9% and infection by the Delta variant was associated with the highest hospitalization rate (7.7%). The hospitalization rate was lower among fully vaccinated patients (p = 0.032) but higher for patients older than 65 (p < 0.001) and patients with SS (vs. MF) (p < 0.001) or COPD (p = 0.024) diagnosis. There was a tendency for decreased hospitalization among patients treated with nirmatrelvir + ritonavir within 5 days of infection, with a 79% risk reduction, although it was not statistically significant (p = 0.164). Conclusion: Patients with MF/SS do not necessarily have worse COVID-19 outcomes compared to the general population. [ABSTRACT FROM AUTHOR]

Introduction: Median duration of therapy with the first JAK1/2 inhibitor ruxolitinib (RUX) approved for patients with intermediate or high-risk myelofibrosis (MF) is about 3 years. Methods: In this retrospective study, we aimed to evaluate clinical features, predictive factors, and outcome of patients presenting to our institution who were able to remain on RUX for ≥5 years (RUX ≥5y, n = 73). Results: Comparing baseline demographics of patients who remained on RUX ≥5y (n = 73) with patients who were on RUX for 6 months to 3 years (n = 203), we confirmed that patients on RUX ≥5y lacked advanced clinical features at the start of therapy, such as anemia, neutropenia, thrombocytopenia, higher blasts or monocytes. Predictive independent factors for staying on RUX ≥5y were hemoglobin >10 g/dL, circulating blasts <1%, platelets >150 × 109/L, neutrophils >70%, and having primary MF. Age over 65 years remained significant for outcome in patients on RUX ≥5y. Conclusion: In this retrospective study, we report on the relevance of absence of advanced clinical features for long RUX therapy and confirm the role of age on outcome despite therapy. [ABSTRACT FROM AUTHOR]

Introduction: Influenza virus causes significant global annual morbidity and mortality. Thrombocytopenia is recognized as a poor prognostic factor in sepsis and is associated with mortality, while lymphopenia has been established as a poor prognostic factor in other viral infections. We aimed to assess the incidence of thrombocytopenia and lymphopenia in seasonal influenza and their effect on clinical outcomes. Methods: This single-center, retrospective, cohort study included consecutive adult patients, hospitalized in Rabin Medical Center between October 2017 and April 2018, with laboratory-confirmed influenza. Patients were grouped according to blood counts on admission: (1) thrombocytopenia (<150 K/mL), (2) lymphopenia (<0.5 K/mL), and (3) both thrombocytopenia and lymphopenia. Patients without thrombocytopenia and lymphopenia were designated as controls. The primary outcome was 30-day all-cause mortality. Risk factors were identified by univariable and multivariable analyses, using logistic regression and reported as odds ratios (ORs) and 95% confidence intervals (CIs). Results: A total of 625 patients were included, 112 (18%) had thrombocytopenia, 98 (15.6%) had lymphopenia, and 107 (17%) had both. The crude 30-day all-cause mortality was 7.6% (48/625). Mortality rates were 7.1% (8/112) for the thrombocytopenia group, 11.2% (11/98) for the lymphopenia group, and 14.9% (16/107) for patients with both versus 4.2% (13/308) in the control (p = 0.000 for all). In a multivariable regression model, significant thrombocytopenia (<100 K/μL) [OR 5.07 (95% CI 1.5–16.2)], age [OR 1.07 (95% CI 1.02–1.11)], time to oseltamivir [OR 1.006 (95% CI 1.002–1.11)], and significant respiratory support [OR 8.85 (3.4–22.6)] were associated with 30-day all-cause mortality. Conclusion: Patients hospitalized with seasonal influenza and thrombocytopenia <100 K/mL on admission, have an increased 30-day all-cause mortality. [ABSTRACT FROM AUTHOR]

Background: Acute myeloid leukemia (AML) is a disease of the hematopoietic system that remains a therapeutic challenge despite advances in our understanding of the underlying cancer biology in the past decade. It is also an affliction of the elderly that predominantly affects patients over 60 years of age. Standard therapy involves intensive chemotherapy that is often difficult to tolerate in older populations. Fortunately, recent developments in molecular targeting have shown promising results in treating leukemia, paving the way for novel treatment strategies that are easier to tolerate. Summary: Venetoclax, a BCL-2 inhibitor, when combined with a hypomethylating agent, has proven to be a highly effective and well-tolerated drug and established itself as a new standard for treating AML in patients who are unfit for standard intensive therapy. Other targeted therapies include clinically proven and FDA-approved agents, such as IDH1/2 inhibitors, FLT3 inhibitors, and Gemtuzumab, as well as newer and more experimental drugs such as magrolimab, PI-kinase inhibitors, and T-cell engaging therapy. Some of the novel agents such as magrolimab and menin inhibitors are particularly promising, providing therapeutic options to a wider population of patients than ever before. Determining who will benefit from intense or novel low-intense therapy remains a challenge, and it requires careful assessment of individual patient's fitness and disease characteristics. Key Messages: This article reviews past and current treatment strategies that harness various mechanisms of leukemia-targeting agents and introduces novel therapies on the horizon aimed at exploring therapeutic options for the elderly and unfit patient population. It also provides a strategy to select the best available therapy for elderly patients with both newly diagnosed and relapsed/refractory AML. [ABSTRACT FROM AUTHOR]

Introduction: In response to the increasing complexity of care for patients with bleeding disorders, we established new clinical teams for our hemophilia treatment center (HTC). Aims: We undertook a quality improvement project to improve the coordination and communication with our patients by establishing primary assignments of clinical staff to individual patients (primary teams). Methods: A quality improvement project group was formed that established the goals and assignment of primary teams. Patients were surveyed for their knowledge of their primary teams as well as their ability to schedule and contact their primary providers. As a measure of the effects on clinical staff, a balancing survey was also conducted among providers impacted by the clinical assignment of teams. Results: Our results demonstrate improvements across both coordination and communication as reported by patients. Additionally, the assignment of primary teams was met with high satisfaction and improvement in coordination and communication as reported by the clinical staff members of the HTC. Conclusions: Initiation of a quality improvement project and the creation of a primary team system were feasible at a large HTC and resulted in improvements in both patient-reported and staff-reported outcomes of coordination and communication of care. [ABSTRACT FROM AUTHOR]

Daratumumab, an anti-CD38 monoclonal antibody, is worldwide approved for treatment of newly diagnosed and relapsed/refractory multiple myeloma (MM) patients and is available as intravenous or subcutaneous formulations. Intravenous daratumumab is associated with frequent infusion-related reactions, while eye complications, especially refractive shifts, are very rare, with only previously reported cases. Here, we described a rare case of multi-refractory MM who developed transient myopic shift during intravenous daratumumab infusion successfully treated only with cycloplegic collyrium not requiring infusion rate lowering or drug discontinuation. This conservative therapeutic approach allowed termination of induction therapy and autologous hematopoietic stem-cell transplantation resulting in durable complete remission. [ABSTRACT FROM AUTHOR]

Photon counting detector (PCD) computed tomography (CT) is a paradigm-shifting innovation in CT imaging which was recently granted approval for clinical use by the US Food and Drug Administration. PCD-CT allows the generation of multi-energy images with increased contrast and scanning speed or ultra-high spatial resolution (UHR) images with lower radiation doses, compared to the currently used energy integrating detector (EID) CT. Since the recognition of bone disease related to multiple myeloma is important for the diagnosis and management of patients, the advent of PCD-CT heralds a new era in superior diagnostic evaluation of myeloma bone disease. In a first-in-human pilot study, patients with multiple myeloma were imaged with UHR-PCD-CT to validate and establish the utility of this technology in routine imaging and clinical care. We describe 2 cases from that cohort to highlight the superior imaging performance and diagnostic potential of PCD-CT for multiple myeloma compared to clinical standard EID-CT. We also discuss how the advanced imaging capabilities from PCD-CT enhances clinical diagnostics to improve care and overall outcomes for patients. [ABSTRACT FROM AUTHOR]

Successful management of surgery in severe coagulation disorders depends on adequate replacement of the deficient factors from intervention until wound healing. Extended half-life (EHL) recombinant factor IX (rFIX) has been increasingly used in hemophilia B (HB) patients. Monitoring of blood levels of EHL rFIX allows to obtain pharmacokinetic (PK) parameters in order to optimize and personalize therapeutic scheme. We describe a case of a young male with severe HB who successfully underwent aortic valve repair. This is the first reported open-heart surgery in a patient with severe HB using EHL rFIX. The success was based on accurate PK evaluation and on meticulous preoperative planning and close cooperation among surgeons, hemophilia specialists, and laboratory team despite the long distance between hemophilia center and surgical clinic. [ABSTRACT FROM AUTHOR]

The imatinib-sensitive fusion gene FIP1L1::PDGFRA is the most frequent molecular abnormality identified in patients with eosinophilic myeloid neoplasms. Rapid recognition of this mutation is essential given the poor prognosis of PDGFRA-associated myeloid neoplasms prior to the availability of imatinib therapy. We report a case of a patient in whom delayed diagnosis resulted in cardiac transplantation for eosinophilic endomyocardial fibrosis. The delay in diagnosis was due, in part, to a false-negative result in fluorescence in situ hybridization (FISH) testing for FIP1L1::PDGFRA. To explore this further, we examined our cohort of patients presenting with confirmed or suspected eosinophilic myeloid neoplasms and found 8 additional patients with negative FISH results despite a positive reverse-transcriptase polymerase chain reaction test for FIP1L1::PDGFRA. More importantly, false-negative FISH results delayed the median time to imatinib treatment by 257 days. These data emphasize the importance of empiric imatinib therapy in patients with clinical features suggestive of PDGFRA-associated disease. [ABSTRACT FROM AUTHOR]

Introduction: Both microenvironmental signals from surrounding cells and changes in the genome of leukemic cells play essential role in the development of chronic lymphocytic leukemia. Nurse-like cells (NLCs) are one of the important elements of the microenvironment of CLL cells. The key role in the interactions of leukemic cells with NLCs is played by chemokines, which may interfere with the programmed cell death process in the leukemic lymphocytes. The aim of our study was analysis of selected microenvironmental factors having a potential impact on the leukemic cells survival, as well as their association with clinical, cytogenetic, and molecular parameters. For this study, we selected three types of molecules which can modulate microenvironment: chemokines IL-8 and CCL3 (which are classically secreted to extracellular matrix), soluble forms of adhesion molecules JAG1 and CD163, and secreted form of endogenous protein BIRC5. We assessed their expression in the serum of CLL patients as well as in medium of long-term NLCs cultures. Methods: Long-term cell culture was prepared from mononuclear cells derived from the blood of 34 patients with CLL. Number of NLCs cells was evaluated, under a light inverted microscope. The concentration of IL-8, CCL3, sBIRC5, sCD163, and sJAG1 in culture medium and serum was assessed by enzyme-linked immunosorbent assays. Results: There were significant differences in the concentration of IL-8, sBIRC5, CCL3, sCD163, and sJAG1 between the patient's blood serum and the culture medium. The concentrations of IL-8, CCL3, and JAG1 were higher in the culture medium, which confirmed the role of the microenvironment in the production of these proteins. In addition, the concentration of CCL3 chemokine in both patient's blood serum and in the culture medium correlated with the number of NLCs and with known prognostic factors in the course of CLL, e.g., Rai stage, WBC, expression of ZAP-70, CD38, and CD5/19. Conclusion: The microenvironment of CLL cells, which includes NLCs, plays an important role in the pathogenesis of CLL. The CCL3 chemokine seems to be a good factor representing microenvironment of CLL cells. Chronic lymphocytic leukemia is a complex and very heterogeneous disease; therefore, its progress should be considered both in the context of genetic changes and the interaction with microenvironmental cells. [ABSTRACT FROM AUTHOR]

Large single mitochondrial DNA (mtDNA) deletion syndrome is a rare inborn error of metabolism with variable heteroplasmy levels and clinical phenotype among affected individuals. Chronic progressive external ophthalmoplegia (CPEO) is the most common phenotype in adults with this form of mitochondrial disease [J Intern Med. 2020;287(6):592–608 and Biomed Rep. 2016;4(3):259–62]. The common CPEO clinical manifestations are ptosis and ophthalmoplegia. More variable phenotypic manifestations of CPEO (CPEO plus) include involvement of the peripheral nervous system and myopathy. Here, we describe a 62-year-old female with CPEO and the major mtDNA deletion present at 40% heteroplasmy, who had a coexistent previously undescribed CPEO phenotypic feature of persistent unexplained macrocytosis without anemia. Building on this case, we reviewed other major mtDNA deletion cases seen in our Adult Metabolic Diseases Clinic (AMDC) at the University of British Columbia, Vancouver, Canada, from 2016 to 2022. The major mtDNA deletion cases (n = 26) were compared with mtDNA missense variants identified in the clinic over the same period who acted as the comparison group (n = 16). Of these, the most frequent diagnosis was maternally inherited diabetes and deafness and mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes. Ten out of 26 (38%) of mtDNA deletion patients had macrocytosis with elevated mean corpuscular volume (MCV), median (interquartile range) of 108 fL (102–114 fL). Seven of the patients with macrocytosis had no pertinent etiology. None of the comparison group had macrocytosis. There was a significant difference (p = 0.000) between the MCV and MCH in the mtDNA deletion group compared to the comparison group. This communication sheds light on the association of macrocytosis with the mtDNA deletion syndrome. It would be of great interest to determine if the association is found in other mitochondrial disease clinic populations. [ABSTRACT FROM AUTHOR]

Cardiac amyloidosis, the majority of cases of which are due to immunoglobulin light chain amyloidosis (AL) and transthyretin amyloidosis (ATTR), affects different aspects of the heart and cardiovascular system. Amyloid-induced cardiomyopathy, clinically manifesting with heart failure and electrophysiological abnormalities, has distinct characteristics compared to non-amyloid cardiomyopathies. Accordingly, specific management strategies are required. This paper will review the cardiovascular manifestations of patients with cardiac amyloidosis and their suggested treatment strategies, emphasizing the importance of multidisciplinary care. [ABSTRACT FROM AUTHOR]

Introduction: Myeloid malignancies are a heterogeneous group of clonal bone marrow disorders that are complex to manage in the community and therefore often referred to subspecialists at tertiary oncology referral centers. Many patients do not live in close proximity to tertiary referral centers and are unable to commute long distances due to age, comorbidities, and frailty. Interventions that minimize the travel time burden without compromising quality of care are an area of unmet need. We describe a cancer care delivery model for patients with myeloid malignancies that is built around telehealth and enables this vulnerable population access to care at an NCI-designated cancer center while receiving majority of their care close to home. Methods and Materials: We report on a cohort of patients with myeloid malignancies who were co-managed by a general community oncologist and an academic leukemia subspecialist at Montefiore Einstein Cancer Center in New York. Patients were initially referred to our institute for a second opinion by community practices that are in partnership with Montefiore Health System, and initial visits were in-person or via telehealth. Treatment plans were made after discussion with patient's local community oncologist. Patients then continued to receive majority of their treatment and supportive care including transfusion support with their local oncologist, and follow-up visits were mainly via telehealth with the academic leukemia subspecialist. Results: Our cohort of 12 patients had a median age of 81 years (range, 59–88 years). Patients remained on active treatment for a median time of 357 days (range, 154–557 days). Most of our patients had a performance status of ECOG 2 or higher. Three patients had myelodysplastic syndromes, 7 patients had acute myeloid leukemia, and 2 patients had myelofibrosis. The median number of hospitalizations over the total treatment time period was one. Conclusion: We demonstrate a shared academic and community care co-management model for the treatment of myeloid malignancies in elderly, frail patients using telehealth as a backbone with a very low hospitalization rate. [ABSTRACT FROM AUTHOR]

Introduction: Coronavirus disease 2019 (COVID-19) disease is associated with coagulopathy and an increased risk of thrombosis. An association between thrombin generation (TG) capacity, disease severity, and outcomes has not been well described. Methods: We assessed the correlation of TG with sequential organ failure assessment (SOFA) and sepsis-induced coagulopathy (SIC) scores and clinical outcomes by analysis of plasma samples obtained from hospitalized COVID-19 patients. Results: 32 patients (68.8% male), whose median age was 69 years, were assessed, of whom only 3 patients did not receive anticoagulant therapy. D-dimers were uniformly increased. During hospitalization, 2 patients suffered thrombosis, 3 experienced bleeding, and 12 died. TG parameters from anticoagulated COVID-19 patients did not significantly differ from the values obtained from non-anticoagulated healthy controls. Patients who received higher than prophylactic doses of anticoagulant therapy had increased lag time (p = 0.003), lower endogenous thrombin potential (ETP) (p = 0.037), and a reduced peak height (p = 0.006). ETP correlated with the SIC score (p = 0.038). None of the TG parameters correlated with the SOFA score or were associated with mortality. Conclusion: TG was not associated with disease severity among patients hospitalized with COVID-19. However, a correlation between ETP and the SIC score was noted and deserves attention. [ABSTRACT FROM AUTHOR]

Background: Although the use of cord blood transplantation (CBT) is becoming more frequent in acute leukemia, considering the relationship between the low stem cell dose and graft failure, whether use of CBT for adolescents and young adults (AYAs) is appropriate remains uncertain. Methods: A retrospective registry-based analysis of clinical outcomes and immune reconstitution was conducted for 105 AYAs and 187 children with acute leukemia who underwent single-unit CBT using myeloablative conditioning (MAC) without antithymocyte globulin (ATG). Results: Outcomes were similar between AYAs and children, except for nonrelapse mortality (NRM) and recovery rates of neutrophils and platelets. The 30-day cumulative incidence of neutrophil engraftment was similar between AYAs and children, but children had faster rates of neutrophil and platelet recovery than AYAs. The median time to neutrophil engraftment was earlier in children than in AYAs (AYAs, 19 days, 95% confidence interval [CI] 17.3–21.7; children, 16 days, 95% CI 13.1–19.5, p = 0.00003). The incidence of platelet recovery on day 120 was higher in children than in AYAs (AYAs, 80%, 95% CI 71–81%; children, 88%, 95% CI 82–92%, p = 0.037). CD34+ cell dose was the only independent factor influencing both neutrophil and platelet recovery. The cumulative incidence of NRM at 2 years was higher among AYAs than among children (AYAs, 27.5%, 95% CI 20–37%; children, 15%, 95% CI 10–21%, p = 0.008). Conditioning regimen was an independent factor influencing NRM. With respect to immune reconstitution, natural killer cell counts quickly recovered to normal levels 1-month post-CBT in both children and AYAs. CD8+ T-cell counts were higher in children than in AYAs at 1 and 3 months post-CBT. CD4+ T-cell counts were similar in both children and AYAs after CBT. Conclusion: AYAs with acute leukemia have outcomes of single-unit CBT using MAC without ATG that are as good as those of children. Thus, single-unit CBT using modified MAC without ATG is an acceptable choice for both AYAs and children who do not have a suitable donor. [ABSTRACT FROM AUTHOR]

Cancer-related anemia (CRA) is a commonly occurring problem for patients with cancer regardless of whether they are receiving treatment with chemotherapy or immunotherapy. It may result from one or more processes (decreased production, increased destruction, or increased loss of red blood cells, RBC). Perturbations in iron availability form the primary basis for anemia in many patients with cancer-related anemia. Functional iron deficiency (FID) anemia is a condition in which the patient has adequate or increased iron stores, but this iron pool is not available for erythropoiesis. Erythropoiesis-stimulating agents (ESAs) were the original treatment for FID; over time, however, if the supply of iron cannot keep pace with increased RBC synthesis driven by ESAs, FID may eventually lead to the lack or loss of ESA responsiveness. Subsequent clinical trials reported that intravenous (IV) iron could enhance the erythropoietic response to ESAs. This chapter reviews the pathogenesis of FID and summarizes the literature on the treatment of cancer- and chemotherapy-induced anemia. Clinical trials using IV iron with or without ESAs are reviewed in addition to the currently available IV iron products. The consensus conclusions from these trials, as well as guideline recommendations, support the use of IV iron in these patients to enhance ESA responsiveness, decrease ESA dosage, and reduce RBC transfusions. Little data have been published on the long-term safety of IV iron or its impact on tumor growth. This paper also briefly explores novel approaches for the treatment of FID anemia, which has relevance in treating not only cancer patients but also patients with benign inflammatory disorders. [ABSTRACT FROM AUTHOR]

Progressive multifocal leukoencephalopathy (PML) is a rare neurological disease caused by the reactivation of latent John Cunningham polyomavirus. Hematological disorders associated with immunomodulatory monoclonal antibodies and hematopoietic stem cell transplantation (HSCT) are risk factors for PML. Blinatumomab is a novel antileukemic immunomodulatory agent and more effective for relapsed and refractory acute lymphoblastic leukemia (ALL) than conventional chemotherapy. But, blinatumomab suppresses humoral immunity due to long-lasting B-cell depletion during and after the treatment. The development of PML involves cellular immunity and impairment of humoral immunity. Although few cases of blinatumomab-related PML have been reported, the use of blinatumomab after allogeneic HSCT may increase the risk of developing PML. The current case report presents a patient of Philadelphia chromosome-positive ALL wherein PML developed after cord blood stem cell transplantation and administrating blinatumomab. [ABSTRACT FROM AUTHOR]

Introduction: Data regarding the prevalence of paraproteinemia in patients with chronic myeloid leukemia (CML) are lacking. Methods: To evaluate for the prevalence of paraproteinemia, we undertook this cross-sectional study among consecutive chronic-phase CML patients. Complete blood count, chemistry, immunoglobulins, serum-free light chains, serum-protein electrophoresis and immunofixation were collected. Further analyses evaluated whether various patient-, disease-, and treatment-related variables are associated with paraproteinemia. Results: One hundred patients, median age 63.5 (IQR 48.1–72) years were recruited. Median time from CML diagnosis to enrollment was 6.3 (IQR 2.3–11.3) years. Monoclonal protein was detected in 8 patients (8%), diagnosed with smoldering multiple myeloma (SMM, n = 2) and low-risk monoclonal gammopathy of undetermined significance (MGUS, n = 6). Six patients were on tyrosine kinase inhibitor treatment, 2 were in treatment-free remission. The only covariate associated with paraproteinemia was the presence of anemia, albeit with borderline statistical significance in univariate analysis (p = 0.053) and when adjusted for age (p = 0.056). Conclusions: In this largest study so far describing the prevalence of paraproteinemia among CML patients, we found MGUS prevalence to be higher than the 3.2% expected prevalence in the general population above 50 years and a non-negligible prevalence of SMM (2%). Screening for paraproteinemia in CML patients, especially in the presence of anemia, should be considered. [ABSTRACT FROM AUTHOR]

Introduction: The safety and efficacy of blinatumomab, a CD19/CD3 bispecific T-cell engager (BiTE®) molecule, was evaluated in an expansion cohort of the phase 1b/2 study (NCT02412306) in Japanese adult (n = 14) and pediatric (n = 17) patients with relapsed/refractory Philadelphia-negative B-cell precursor (BCP) acute lymphoblastic leukemia (ALL). Materials and methods: Globally recommended blinatumomab doses were administered to adult (9–28 μg/day) and pediatric (5–15 μg/m2/day) patients. Primary endpoint was the incidence of treatment-emergent adverse events (TEAEs) and treatment-related AEs. Results: All adult and pediatric patients experienced ≥1 TEAE. Grade ≥3 TEAEs were observed in 11 (79%) adult and 15 (88%) pediatric patients. Blinatumomab was discontinued in 1 (6%) pediatric patient due to treatment-related grade 4 cytokine release syndrome. Fatal AEs such as disease progression and multiple-organ dysfunction syndrome, which were not treatment-related, were reported in 2 (12%) pediatric patients. Eleven (79%) adults achieved complete remission (CR)/CR with partial hematological recovery (CRh) within the first two blinatumomab cycles. Nine of 10 adult patients with CR/CRh and evaluable minimal residual disease (MRD) achieved MRD response. CR/CRh was achieved by 5 (29%) pediatric patients, of which two had MRD response. Conclusion: In conclusion, blinatumomab was safe and efficacious in Japanese patients with relapsed/refractory BCP ALL. [ABSTRACT FROM AUTHOR]

Background: Long-term treatment with direct oral anticoagulants (DOAC) is required for the majority of patients with nonvalvular atrial fibrillation (AF) to prevent ischemic stroke and systemic embolism. Adherence to therapy may impact clinical outcomes. Therefore, the purpose of this study was to assess the potential impact of structured follow-up on long-term adherence to DOAC therapy compared to standard care. Methods: This is a cross sectional study on the implementation phase of medication adherence to DOACs, comparing patients with AF following completion of structured follow-up of minimally 1 year with those who received standard care. All patients used DOACs for more than 2 years and completed a questionnaire on adherence. Adherence was measured with the Morisky Medication Adherence Scale-8 (MMAS-8) score and assessed via an online web portal. Results: A total of 212 patients were included. The mean MMAS-8 score was 7.55 (SD 0.93) after structured follow-up and 7.25 (SD 1.01) for standard care; p = 0.045. Following structured follow-up 64.1% of patients had a high adherence (MMAS score of 8) compared to 50% receiving standard care; p = 0.05. Patients following structured follow-up on a once daily DOAC regime had higher MMAS-8 scores compared to those on a twice daily regime; 7.74 (SD 0.74) versus 7.00 (SD 1.22); p < 0.001. The rates of minor bleedings were 10.6% versus 21.4% respectively, p = 0.038. Conclusion: In patients on long-term DOAC treatment, adherence to therapy was significantly increased after receiving an initial period of structured follow-up compared to standard care. Additionally, adherence to DOAC therapy was higher with once-daily treatment regimen. Significant more minor bleedings were reported in the standard care group. These results indicate that implementation of structured follow-up of patients with AF using DOACs merits further evaluation. [ABSTRACT FROM AUTHOR]

Extramedullary relapse of acute myeloid leukemia (AML) is not a rare event, and the FMS-like tyrosine kinase 3 (FLT3) mutation is a well-known risk factor. Gilteritinib is approved for relapsed/refractory FLT3+ AML, but its efficacy in extramedullary relapse is still undefined. Here, we present the case of a 69-year-old woman with therapy-related nucleophosmin-1 and FLT3-internal tandem duplication (FLT3-ITD) positive AML treated with induction and consolidation with CPX-351 (liposomal daunorubicin plus cytarabine) followed by off-label azacitidine maintenance who obtained a complete remission (CR) with persistent measurable residual disease. After 19 months of CR, she experienced an isolated breast relapse of FLT3-ITD+ AML. She was started on single-agent gilteritinib, resulting in a rapid and persistent complete regression of the breast nodule. Targeted therapy with gilteritinib for relapsed/refractory FLT3-ITD+ AML can be effective in isolated extramedullary relapse. [ABSTRACT FROM AUTHOR]

Introduction: Venous thromboembolism (VTE) is a common cardiovascular disease. MicroRNAs (miRNAs) play a key role in VTE; however, the role of exosomal miRNAs in VTE remains unknown. Therefore, we aimed to identify key exosomal miRNAs and their potential mechanisms in VTE. Methods: We collected 31 samples from unprovoked VTE patients and 25 samples from healthy individuals. Exosomal miRNA sequencing was performed on 11 unprovoked VTE samples and 9 normal samples, and the remaining samples were used to verify the expression level of candidate 9 miRNAs in VTE and normal samples. The sequencing data were used to analyze exosomal miRNA expression. Meanwhile, gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed to determine the potential biological functions of differentially expressed miRNA target genes. Results: A total of 32 differentially expressed miRNAs were identified by sequencing. Among the 32 miRNAs, 23 miRNAs were upregulated (72%), and 9 miRNAs were downregulated (28%). In addition, we found that the biological functions and metabolic pathways of the target genes were related to hemostatic factors involved in VTE, indicating the regulation of differentially expressed miRNAs. We identified key miRNAs by constructing a miRNA-messenger RNA regulatory network and found that the target genes were related to VTE. We finally determined that the abnormal expression of 9 miRNAs is closely related to VTE, and the expression level between VTE and normal was verified through other samples. Conclusion: Our study identified a set of key miRNAs for future research on the molecular mechanisms of VTE. [ABSTRACT FROM AUTHOR]

Objective: To study the molecular basis of hereditary antithrombin (AT) deficiency in a Chinese family. It will help us understand the pathogenesis of this type of disease. Method: AT activity (AT:A) and the AT antigen (AT:Ag) level were tested by chromogenic substrate and immunoturbidimetry, respectively. To identify the novel mutations, SERPINC1 gene sequencing was carried out. The possible impact of the mutations was analyzed by model and bioinformatic analyses. Results: AT:A and the AT:Ag level of the proband were 43% and 113 mg/L (normal range: 98–119% and 250–360 mg/L), respectively. Sequencing analysis revealed compound heterozygous mutations, including a frameshift mutation (c.318_319insT) resulting in Asn75stop and a missense mutation (c.922G>T) resulting in Gly276Cys. The bioinformatic and model analyses indicated that these mutations may disrupt the function and structure of the AT protein. Conclusion: We detected 2 novel heterozygous mutations (c.318_319insT and c.922G>T) in the proband, and these were associated with decreased AT:A. [ABSTRACT FROM AUTHOR]

An introduction to the journal is presented that focuses on the use of oral iron, including the safety of oral and intravenous formulations, the role of iron replacement in cancer- and chemotherapy-induced anemia, and the significance of proactive diagnosis and interventions that decrease morbidity.

Moyamoya syndrome increases the risk of stroke in sickle cell disease, but revascularization surgery can modify this risk. Collaborative management between hematology and neurosurgery offers effective strategies to reduce stroke risk in these patients. We describe a challenging case where a patient with sickle cell disease undergoing standard of care management as prescribed by the Stroke Prevention Trial in Sickle Cell Anemia and revascularization with pial synangiosis subsequently developed rapidly progressive disease in other cerebral vessels and suffered ischemic hemispheric stroke. This case not only demonstrates the success of management in accordance with the American Heart Association (AHA) and American Stroke Association (ASA) guidelines but also demonstrates critical areas where we lack understanding of disease progression. [ABSTRACT FROM AUTHOR]

Background: The use of unmanipulated haploidentical hematopoietic stem cell transplantations (haplo-HSCT) with post-transplant cyclophosphamide (PTCY) in children has emerged as an acceptable alternative to the patients without a matched donor. However, the timing of calcineurin inhibitors (CNIs) used in combination with PTCY is increasingly becoming a topic of controversy. Method: We evaluated 49 children with acute leukemia who underwent unmanipulated haplo-HSCT with PTCY according to the initiation day of CNIs (pre- or post-cyclophosphamide [CY]). Results: There were no significant differences in the overall survival analysis between the 2 groups. The cumulative incidence of relapse at 2 years was 21.2% in the pre-CY group and 38.9% in the post-CY group (p = 0.33). Cytokine release syndrome (CRS) was observed more frequently in the post-CY group (p = 0.04). The overall survival and event-free survival at 2 years in patients with and without CRS in the pre-CY group were 42.9% versus 87.5% (p = 0.04) and 38.1% versus 87.5% (p = 0.04), respectively. Conclusion: Our study shows that the argument for starting CNI administration after CY is tenuous, and the rationale for not starting CNIs before CY needs to be reconsidered. [ABSTRACT FROM AUTHOR]

Background: Leg ulcers are a frequent complication in patients with the inherited hemoglobin disorders. In thalassemia, the literature is limited, and factors associated with the development of leg ulcers in hemoglobin E (HbE) beta thalassemia, the most common form of severe beta-thalassemia worldwide, have not previously been reported. Methods: We reviewed all available medical records of patients with HbE beta thalassemia to document the onset of leg ulcers at the 2 largest treatment centers in Sri Lanka. We reviewed the literature to identify studies reporting outcomes of interventions for ulcers in severe thalassemia. Results: Of a total of 255 actively registered patients with HbE thalassemia in the 2 centers, 196 patient charts were evaluable. A leg ulcer with a documented date of onset was recorded in 45 (22%) of 196 evaluable patients, aged (mean ± SEM) 22.2 ± 1.4 years. Most had been irregularly transfused; steady-state hemoglobin was 6.4 ± 0.2 g/dL. Treatment achieving healing in 17 patients included transfusions, antibiotics, oral zinc, wound toileting, and skin grafting. Conclusion: Leg ulcers may be more common in HbE beta thalassemia than in other forms of thalassemia. A systematic approach to treatment will be needed to document the prevalence and factors placing such patients at risk for leg ulcers. Controlled trials to evaluate the optimal treatment of this common complication are indicated. [ABSTRACT FROM AUTHOR]

Splenic micronodular T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) is derived from diffuse large B-cell lymphoma N.O.S., perhaps with some affinity with nodal THRLBCL. Of note, in contrast with the latter, the only lymph nodes involved in association with the splenic micronodular pattern of the disease are the splenic hilar lymph nodes. The possibility that corticosteroids, when prescribed prior to splenectomy, cause histopathological and functional modulations, apoptosis, necrosis, tissue shrinkage, which may obscure the diagnostic morphological features of this variant lymphoma and cause an underdiagnosis of this condition. The indications for glucocorticoid therapy are either related to the lymphoma itself, or else to other comorbidities, like asthma and autoimmune disorders. We propose that patients with the splenic subset of the disease are likely to have been prescribed corticosteroids prior to histopathologic examination of the involved spleen, causing disparate morphologies. However, a reviewer might accidentally dismiss the corticosteroid pretreatment which is thus overlooked. Apoptosis, induced by corticosteroids, is hypothesized as the major mechanism initiating the histopathological and functional changes in the splenic micronodular variant of the lymphoma. [ABSTRACT FROM AUTHOR]

Background:BCR/ABL1-like acute lymphoblastic leukemia is a newly recognized high-risk subtype of ALL, characterized by the presence of genetic alterations activating kinase and cytokine receptor signaling. This subtype is associated with inferior outcomes, compared to other B-cell precursor ALL. Summary: The recognition of BCR/ABL1-like ALL is challenging due to the complexity of underlying genetic alterations. Rearrangements of CRLF2 are the most frequent alteration in BCR/ABL1-like ALL and can be identified by flow cytometry. The identification of BCR/ABL1-like ALL can be achieved with stepwise algorithms or broad-based testing. The main goal of the diagnostic analysis is to detect the underlying genetic alterations, which are critical for the diagnosis and targeted therapy. Key Messages: The aim of the manuscript is to review the available data on BCR/ABL1-like ALL characteristics, diagnostic algorithms, and novel, molecularly targeted therapeutic options. [ABSTRACT FROM AUTHOR]

Background: Bibliometric analyses are a tool employed by researchers and funding agencies to establish the most important areas of research in a particular field, and to determine which foci need increased research attention. Such analyses have been published in a variety of clinical specialties; however, a detailed literature search showed that no such study has been done for "myeloid neoplasms." In order to bridge this gap, we conducted a citation analysis of the 100 most influential articles on myeloid neoplasms. Methods: Two independent researchers extracted relevant articles from the Scopus database. These articles were then ranked in descending order of citations and a list of the top 100 original articles was made. A further, more detailed list was created containing significant discriminating characteristics. Results: The top cited articles were published over a period of 47 years, with most of them being published in the 5-year interval of 2001–2005. The citations ranged from 636 to 4,039. The articles originated from 28 different countries. Most of the articles were published in high-impact journals. Conclusion: Our analysis sheds light on the quality of work and driving trends, listing the most cited and impactful guideline articles within this field and aiding clinicians. [ABSTRACT FROM AUTHOR]

Neurolymphomatosis (NL) is a rare condition caused by the lymphomatous or leukemic infiltration of nerves and manifests as neuropathy. Most often, NL is associated with B-lineage non-Hodgkin lymphoma (NHL) and only infrequently occurs in conjunction with T- or NK-lineage NHL. Extranodal NK/T-cell lymphoma (ENKTL)-associated NL is exceedingly unusual, with only 9 cases described in the English language literature, in addition to our case. Diagnosis of NL is challenging, as the entity can mimic neuropathies of more common etiologies, and an adequate biopsy may be difficult to obtain. Timely diagnosis demands a high index of suspicion, especially for patients without a history of hematologic malignancy. We expand upon a unique case of NL exclusively involving cranial nerves and cauda equina nerve roots, as the initial manifestation of ENKTL, and contextualize our findings within the framework of previously reported NK/T-lineage NL cases. [ABSTRACT FROM AUTHOR]

Introduction: Patient blood management (PBM) is a clinical and multidisciplinary, 3-pillar concept. The aim of this study was to detect the subjective increase in physician's awareness towards perioperative anaemia, patient's blood resource, and transfusion after the implementation of PBM in German hospitals. Material and Methods: A survey among 56 hospitals from the German PBM Network group was conducted from October 27 to December 19, 2020. An electronic questionnaire with 28 questions was sent to the local PBM coordinator for the distribution at the hospital level. For assessment of the physician's subjective increase in awareness, numeric rating scales (0 [no increase] – 10 [maximum increase]) were used. Results: In total, 404 clinicians from 56 hospitals completed the survey. The mean (±standard deviation) time of an existing PBM program was 4.8 (±2.2) years. The physician's subjective increase in awareness towards anaemia (8.2 [±2.0]), patient's blood resource (7.6 [±2.5]), and transfusion (8.1 [±1.9]) was the highest in physicians from hospitals with ≥21 implemented PBM measures. In addition, a subjective increase in awareness towards anaemia (6.6 [±3.3]), patient's blood resource (7.0 [±3.3]), and transfusion (6.6 [±3.4]) was the highest in physicians with daily PBM contact. Conclusion: Results suggest that physician's awareness towards perioperative anaemia, patient's blood resource, and transfusion has increased, depending on the hospital's number of implemented PBM measures and physician's PBM contact in everyday clinical practice. [ABSTRACT FROM AUTHOR]

Development of post-chemotherapy histiocyte-rich pseudotumor (PHP) is an underrecognized event following therapy in lymphoma patients and may mimic residual tumor using current therapy monitoring protocols. We report a series of 5 patients with PHP along with a review of the literature. In our series, we describe 3 patients with persistent hypermetabolic masses by positron emission tomography-computed tomography, one with persistent terminal ileal nodules on endoscopy, and one with bone marrow involvement, a site not associated with mass-like disease. Twenty-three patients with long-term follow-up were identified from our series and review of the literature. Forty-four percent of patients received additional therapy, and only 4% of patients died of lymphoma. This study illustrates that PHPs are not identified using current lymphoma therapy monitoring algorithms and may result in overtreatment with risk for additional therapy-related complications. The need for confirmatory tissue biopsy in this setting is recommended. [ABSTRACT FROM AUTHOR]