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International audience; Purpose: Infertility in adolescents and young adult (AYA) survivors of malignant disease remains a major long-term adverse effect, but semen collection for fertility preservation in fertility centers is not always feasible and makes AYAs uncomfortable. We evaluated the feasibility of collecting sperm samples on the ward versus in fertility centers. Methods: Consecutive hospitalized AYA-aged male patients in the Hematology AYA unit (Saint-Louis Hospital, France) between August 2010 and June 2016 with hematological disease and indication of semen collection (n = 95) were included in this retrospective study. Semen quality was analyzed according to World Health Organization guidelines and was compared according to semen collection place: on the ward (n = 46) or in fertility center (n = 49). Results: The median age was median age 19.1 years (range: 13.7-33.3; interquartile range: 17.1-22.8) and 85 patients successfully collected semen. Sperm collection failure was ∼11% and was comparable between the two modalities as were main sperm quality characteristics (semen volume, sperm concentration, total sperm count, progressive motility and vitality, sperm morphology, and multiple anomalies index). Oligospermia was significantly higher in the samples obtained in fertility center (47.7%) than on the ward (26.8%), p = 0.047. Average frozen straws were comparable, 12.2 ± 6.4 on the ward versus 11.9 ± 6.3 in fertility center. Conclusion: Semen collection on the ward is feasible and would be particularly interesting for AYA male patients without altering semen quality characteristics.

BACKGROUND Blood donors with high Hb are often deferred for the presumed risk of polycythemia vera (PV). However, adequate data to substantiate or refute this hypothesis is lacking. METHODOLOGY We conducted an observational study on blood donors found to have high hemoglobin (Hb ≥18 g/dl) during the pre-donation screening process using a portable hemoglobinometer at our blood center for four months. We adopted a cost effective methodology wherein a questionnaire was used to elicit the secondary causative factors of high hemoglobin and a complete blood count test to observe the blood cell parameters and JAK2V617F mutation test was performed in a subset of donors lacking secondary erythrocytosis (SE) history. RESULTS Of the total 7076 donors enrolled 112 male donors (1.58%) had high hemoglobin. The majority (70.4%) were repeat donors with mean age of 31.4 years. About 61% of the donors had attributable factors for SE like smoking, occupational exposure to carbon-monoxide. The mean hemoglobin value of capillary and venous hemoglobin demonstrated a statistically significant difference (p

Purpose To explore parents' experience in the decision-making process for children with haematological diseases receiving haematopoietic stem cell transplantation (HSCT) based on genograms. Design and methods A qualitative study based on genogram was conducted. Seven pairs of parents completed their genogram and a semi-structured interview. Two related donors were interviewed to discuss their experiences in the decision-making process of donating bone marrow to their loved ones. Interviews were transcribed verbatim and analysed using interpretative phenomenological analysis. Results The genogram presents the complete family structure, family member relationships and incident-related conflicts. Two superordinate themes emerged from the data analysis. The first theme was transplantation decision motivations, including four subthemes: the values of life priority, empathy based on kinship, inheritance of family blood, trust in doctors and medical science. The second theme was transplantation decision conflicts, including four subthemes: decision-making conflicts among family members, related-donor decision-making conflicts, risk-benefit game, blind optimism and insufficient cognition conflict. Conclusions Genogram can show the hidden resources and conflicts of each family and help the care providers better understand parents' experience and the decision-making dilemmas in the decision-making process for children with haematological diseases receiving HSCT. The needs of transplant families for treatment-related information were not fully met. Practice implications It is necessary for medical staff to increase psychological and informational support for donors and their families when the parents of patients make bone marrow transplant decisions. Medical staff should engage in family-focused systematic interventions to reduce the psychological burden and conflicts of decision makers.

The Kaposi sarcoma herpesvirus (KSHV), also known as human herpesvirus 8 (HHV-8), is the causal agent of Kaposi sarcoma (KS), but is also pathogenetically related to several lymphoproliferative disorders, including primary effusion lymphoma (PEL)/extra-cavitary (EC)-PEL, KSHV-associated multicentric Castleman disease (MCD), KSHV-positive diffuse large cell lymphoma (DLBCL) and germinotropic lymphoproliferative disorder (GLPD). These different KSHV-associated diseases may co-occur and can have overlapping features. KSHV, similar to the Epstein-Barr virus (EBV), is a lymphotropic gamma herpesvirus which is preferentially present in abnormal lymphoid proliferations occurring in immune compromised individuals. Notably, both KSHV and EBV can infect and transform the same B cell, which is frequently seen in the KSHV-positive, EBV-positive PEL/EC-PELs. The mechanisms by which KSHV leads to lymphoproliferative disorders is thought to be related to the expression of a few transforming viral genes that can affect cellular proliferation and survival. There are critical differences between KSHV-MCD and PEL/EC-PEL, the two most common KSHV-associated lymphoid proliferations, including the viral associations, the patterns of viral gene expression and the cellular differentiation stage reflected by the phenotype and genotype of the infected abnormal B cells. Advances in treatment have improved outcomes, but mortality rates remain high. Our deepening understanding KSHV biology, the clinical features of KSHV-associated diseases, and newer clinical interventions should lead to improved and increasingly targeted therapeutic interventions.

Key Points Severe bone marrow failure was primarily observed in early childhood in children with biallelic SBDS mutations.Absolute neutrophil counts were positively associated with age (P < .0001) in patients with biallelic SBDS mutations., Visual Abstract, Shwachman-Diamond syndrome (SDS) is an inherited bone marrow failure syndrome with leukemia predisposition. An understanding of the hematologic complications of SDS with age could guide clinical management, but data are limited for this rare disease. We conducted a cohort study of 153 subjects from 143 families with confirmed biallelic SBDS mutations enrolled on the North American Shwachman Diamond Registry or Bone Marrow Failure Registry. The SBDS c.258 + 2T>C variant was present in all but 1 patient. To evaluate the association between blood counts and age, 2146 blood counts were analyzed for 119 subjects. Absolute neutrophil counts were positively associated with age (P < .0001). Hemoglobin was also positively associated with age up to 18 years (P < .0001), but the association was negative thereafter (P = .0079). Platelet counts and marrow cellularity were negatively associated with age (P < .0001). Marrow cellularity did not correlate with blood counts. Severe marrow failure necessitating transplant developed in 8 subjects at a median age of 1.7 years (range, 0.4-39.5), with 7 of 8 requiring transplant prior to age 8 years. Twenty-six subjects (17%) developed a myeloid malignancy (16 myelodysplasia and 10 acute myeloid leukemia) at a median age of 12.3 years (range, 0.5-45.0) and 28.4 years (range, 14.4-47.3), respectively. A lymphoid malignancy developed in 1 patient at the age of 16.9 years. Hematologic complications were the major cause of mortality (17/20 deaths; 85%). These data inform surveillance of hematologic complications in SDS.

SARS-CoV-2 has rapidly spread across the globe and infected hundreds of millions of people worldwide. As our experience with this virus continues to grow, our understanding of both short-term and long-term complications of infection with SARS-CoV-2 continues to grow as well. Just as there is heterogeneity in the acute infectious phase, there is heterogeneity in the long-term complications seen following COVID-19 illness. The purpose of this review article is to present the current literature with regards to the epidemiology, pathophysiology, and proposed management algorithms for the various long-term sequelae that have been observed in each organ system following infection with SARS-CoV-2. We will also consider future directions, with regards to newer variants of the virus and their potential impact on the long-term complications observed.

The global burden of dengue is increasing against a background of rising global prevalence of chronic noncommunicable diseases (NCDs) and an epidemiological shift of dengue toward older age groups. The contribution of NCDs toward risk for adverse clinical and healthcare utilization outcomes was assessed in a national linked-database study. About 51,433 adult dengue cases between 2014 and 2015 were assessed for outpatient and inpatient claims data in Taiwan’s National Health Insurance Research Database for the 30 days after their dengue diagnosis. A multivariable logistic regression with generalized estimating equations was used to estimate the probability of adverse dengue outcomes in patients with NCDs compared with dengue patients without underlying diseases. Rheumatoid arthritis and related disease were associated with the highest risk of hospitalization after dengue diagnosis (odds ratio: 1.78; 95% CI: 1.37–2.30), followed by stroke, chronic kidney disease (CKD), liver cirrhosis, asthma, coronary artery disease, chronic obstructive pulmonary disease, diabetes, congestive heart failure, hypertension, and malignancy. Chronic kidney disease and diabetes were associated with higher risks of hospitalization, intensive care unit (ICU) use, and all-cause mortality. After adjusting for socioeconomic status and other variables, the number of coexisting chronic diseases was associated with increasing risk of adverse dengue outcomes. Specific NCDs were associated with longer hospitalizations, ICU admission, and higher healthcare costs. Quantifying the risks of adverse dengue outcomes and health expenditures among dengue patients with preexisting NCDs provides insights for improved clinical management and essential inputs for health economic analyses on the cost-benefit of risk-based routine or catch-up immunization programs.

Kabuki syndrome (KS) is a disease characterized by distinctive facial features, skeletal anomalies and delay in neuromotor development. KS 1 is an autosomal dominant condition caused by mutations in the KMT2D gene, whereas KS 2 is an X-linked disorder caused by mutations in the KDM6A gene. In the majority of KS patients who present with hypoglycemia, KDM6A is the defective gene. A 9-month old girl was admitted to our emergency department due to a seizure. On physical examination, hypotonia, mild facial dysmorphism, brachydactyly of the 5th finger, prominent finger pads and pansystolic murmur were detected. A fasting glucose tolerance test was performed the next day due to her history of hypoglycemia, but she had convulsions at the fifth hour of the test. Her serum glucose was 24 mg/dL, insulin 1.94 mIU/L, C-peptide 0.94 ng/mL, growth hormone 11 ng/mL, anti-insulin antibody 4.2 IU/mL, cortisol 19.8 μg/dL, and adrenocorticotropic hormone 9.3 pg/mL. A diagnosis of hyperinsulinemic hypoglycemia was considered. Given the abnormalities, genetic analysis for congenital hyperinsulinism, including the genes causing KS was performed. A heterozygous frameshift mutation (c.2579del, p.Leu860Argfs*70) was detected in the KMT2D gene. Epilepsy and other neurological symptoms may be seen in KS patients and in some of these the neurological symptoms are the result of hypoglycemia. In such cases, the detection and prevention of hypoglycemia can help prevent the progression of neurological symptoms. We suggest considering the diagnosis of KS for patients with hypoglycemia and dysmorphic features, even if the patient does not manifest all features of KS.

Publisher Copyright: © 2021 The Authors. Vox Sanguinis published by John Wiley & Sons Ltd on behalf of International Society of Blood Transfusion. Background and Objectives: Deferral of blood donors due to low haemoglobin (Hb) is demotivating to donors, can be a sign for developing anaemia and incurs costs for blood establishments. The prediction of Hb deferral has been shown to be feasible in a number of studies based on demographic, Hb measurement and donation history data. The aim of this paper is to evaluate how state-of-the-art computational prediction tools can facilitate nationwide personalized donation intervals. Materials and Methods: Using donation history data from the last 20 years in Finland, FinDonor blood donor cohort data and blood service Biobank genotyping data, we built linear and non-linear predictors of Hb deferral. Based on financial data from the Finnish Red Cross Blood Service, we then estimated the economic impacts of deploying such predictors. Results: We discovered that while linear predictors generally predict Hb relatively well, they have difficulties in predicting low Hb values. Overall, we found that non-linear or linear predictors with or without genetic data performed only slightly better than a simple cutoff based on previous Hb. However, if any of our deferral prediction methods are used to assign temporary prolongations of donation intervals for females, then our calculations indicate cost savings while maintaining the blood supply. Conclusion: We find that even though the prediction accuracy is not very high, the actual use of any of our predictors in blood collection is still likely to bring benefits to blood donors and blood establishments alike.

Introduction Kabuki syndrome is a rare congenital condition characterized clinically by unique facial features, abnormalities in the skeleton, finger pad abnormalities, and developmental delays, as well as a range of other health issues. Existing research lacks information on the daily burden of living with Kabuki syndrome. Methods A survey collected caregiver- and patient-reported data about the experience of living with Kabuki syndrome in order to better understand its presentation and effect on patients and their psychosocial well-being. Results A total of 68 participants (n = 57 caregivers and n = 11 adolescents) were recruited from the USA and Canada. Caregiver survey participants reported developmental delays and lower IQ in individuals with Kabuki syndrome compared to the general population, as well as difficulty with cognitive-related tasks, need for educational accommodations, and difficulty with particular school subjects and with daily tasks. Additionally, participants reported significant emotional, social, and communication-related impacts of Kabuki syndrome. Adolescent data largely corroborated the information collected from caregivers, with the exception of adolescents reporting the emotional and social impacts as occurring less frequently. Conclusions Kabuki syndrome is a multidimensional disease which has substantial negative effects on physical, mental, emotional, and social aspects of health-related quality of life. This research adds to the limited existing body of literature on the clinical presentation of Kabuki syndrome and provides a novel perspective into the caregiver and adolescent perception of the burden of Kabuki syndrome.

Polymerase chain reaction (PCR) tests cannot always detect the SARS-CoV-2 virus, possibly due to differences in sensitivity between sample types. Under these circumstances, immunochromatography may serve as an alternative method to detect anti-SARS-CoV-2 IgG antibodies that indicate a history of infection. In our analysis of patients with severe COVID-19 infection, we found that 14 of 19 serum samples were positive for IgG antibodies, whereas 6 of 10 samples from patients with asymptomatic or mild cases were negative. Two patients with immune thrombocytopenia who were treated with prednisolone experienced aggressive COVID-19-related respiratory failure and eventually died. Patients not in remission and those who received steroid-based chemotherapy had a higher risk of death, and patients with lymphoid malignancies including lymphoma and myeloma died in larger numbers than those with myeloid malignancies. A stricter cohorting strategy based on repeat PCR tests or isolation to a private room should be adopted in routine care in hematology departments to prevent viral spread to the environment.

BACKGROUND Canine stomatocytosis is a well-recognized rare erythrocyte disorder characterized by nonsyndromic forms with selective erythroid involvement, syndromic forms with extra-hematologic disease, and acquired forms. OBJECTIVES We describe serial clinicopathologic changes in two dogs with stomatocytosis of breeds that are different from those previously reported. METHODS Blood samples were obtained from a 12-year-old female neutered Australian Cattle Dog and a 12-year-old male neutered Beagle for hematologic and biochemical analyses, including a morphologic examination of peripheral blood films. Serial clinicopathologic data were reviewed, including CBCs performed by the referring veterinary surgeons. RESULTS Serial CBC data in both cases reported a variable decrease in RBC numbers commonly associated with a normal hematocrit, macrocytosis, hypochromasia, changes in red cell distribution width parameters including marked histogram abnormalities in volume distribution of the RBC population, and mildly increased or normal reticulocyte counts. Morphologic examination of peripheral blood films identified variable numbers of stomatocytes, knizocytes (Case 1, Day 1, Day 4), mild anisocytosis, mild macrocytosis, and mild polychromasia. CONCLUSIONS In both cases, the changes exhibited in the erythrogram raise suspicion for an RBC membrane disorder with cell volume dysregulation and stomatocytosis, although they did not appear to cause clinically relevant hemolysis.

Background Prior studies comparing the efficacy of laparoscopic (LHR) and open hepatic resection (OHR) have not evaluated inpatient costs. Methods We conducted a retrospective cohort study using the Healthcare Cost and Utilization Project State Inpatient Databases to identify patients undergoing hepatic resection between 2010 and 2014. Results 10,239 patients underwent hepatic resection. 865 (8%) underwent LHR and 9374 (92%) underwent OHR. On adjusting for hospital volume, patients undergoing LHR had a lower risk of respiratory (OR 0.64, 95% CI [0.52, 0.78]), wound (OR 0.48; 95% CI [0.29, 0.79]) and hematologic (OR 0.57; 95% CI [0.44, 0.73]) complication as well as a lower risk of being in the highest quartile of cost (0.58; 95% CI [0.43, 0.77]) than those undergoing OHR. Patients undergoing LHR in very high volume (>314 hepatectomies/year) centers had lower risk-adjusted 90-day aggregate costs of care than those undergoing OHR (-$8022; 95% CI [-$11,732, -$4311). Discussion Laparoscopic partial hepatectomy is associated with lower risk of postoperative complication than OHR. This translates to lower aggregate costs in very high-volume centers.

Purpose of Review Social media-based scientific journal clubs provide an opportunity to promote published literature to a broader audience and allow robust multi-disciplinary and inter-professional discussion. Hematopathology Journal Club (#HemepathJC) on Twitter has successfully conducted monthly sessions since November 2019, covering topics related to lymphoma and leukemia. Recent Findings To enhance connectivity, multitasking, and productivity, we present our experience of leveraging the voice-based platform Clubhouse concurrent with Twitter. Summary The Twitter and Clubhouse partnership for #hemepathJC holds the potential to increase dissemination of scientific knowledge and further promote journal club format discussion.

Introduction Indications for therapeutic plasma exchange (TPE) have expanded over the years, and the number of procedures is expected to have been increased. Apheresis registries can be difficult to sustain due to workload and privacy issues. This study aimed to analyze national claims data to characterize the use of TPE. Materials and methods Patients who underwent TPE were retrospectively identified between January 2008 and December 2017 from the Korean Health Insurance Review and Assessment Service database. Data of patients' characteristics, primary diagnosis, hospitalization, treatment, and procedures were analyzed. Results A total of 9944 patients underwent 62 606 TPE procedures. The median number of TPE procedures performed per patient was 5 (interquartile range, 3-7). Fresh frozen plasma (71.4%) was most commonly used as the replacement fluid. The most common indication was renal diseases (36.8%), followed by hepato-biliary (17.6%) and hematological (15.2%) diseases. Increased frequency of renal diseases was the most remarkable change, which increased from 529 (21.2%) procedures in 2008 to 4107 (44.5%) procedures in 2017, reflecting the widespread implementation of ABO-incompatible kidney transplantation. The top five hospitals conducted 59.6% of the procedures, which showed a centralized distribution. Conclusions The most common indication was renal diseases. The number of TPE procedures performed annually increased by approximately 3.7 times from 2008 to 2017. This study shows that other than a registry, claims data can be successfully used to analyze various aspects of TPE procedures on a nationwide scale. This approach could be used by other countries, especially those that have national health insurance.

Pre‐clinical haematopoietic cell transplantation (HCT) studies in canines have proven to be invaluable for establishing HCT as a highly successful clinical option for the treatment of malignant and non‐malignant haematological diseases in humans. Additionally, studies in canines have shown that immune tolerance, established following HCT, enabled transplantation of solid organs without the need of lifelong immunosuppression. This progress has been possible due to multiple biological similarities between dog and mankind. In this review, the hurdles that were overcome and the methods that were developed in the dog HCT model which made HCT clinically possible are examined. The results of these studies justify the question whether HCT can be used in the veterinary clinical practice for more wide‐spread successful treatment of canine haematologic and non‐haematologic disorders and whether it is prudent to do so., Pre‐clinical haematopoietic cell transplantation (HCT) studies in canines were essential to the establishment of HCT as a treatment option for haematological malignant and non‐malignant diseases in man, and a proven method to induce tolerance towards solid organ transplantation. With recent advancements in mind, it is time to assess whether HCT can be applied in a more routine manner in the veterinary clinical practice for treating dogs with similardisorders.

Recognition of distinct phenotypic features is an important component of genetic diagnosis. Although CHARGE syndrome, Kabuki syndrome, and a recently delineated KMT2D Ex 38/39 allelic disorder exhibit significant overlap, differences on neuroimaging may help distinguish these conditions and guide genetic testing and variant interpretation. We present an infant clinically diagnosed with CHARGE syndrome but subsequently found to have a de novo missense variant in exon 38 of KMT2D, the gene implicated in both Kabuki syndrome and a distinct KMT2D allelic disorder. We compare her brain and inner ear morphology to a retrospective cohort of 21 patients with classic Kabuki syndrome and to typical CHARGE syndrome findings described in the literature. Thirteen of the 21 Kabuki syndrome patients had temporal bone imaging (5/13 CT, 12/13 MRI) and/or brain MRI (12/13) which revealed findings distinct from both CHARGE syndrome and the KMT2D allelic disorder. Our findings further elucidate the spectrum of inner ear dysmorphology distinguishing Kabuki syndrome and the KMT2D allelic disorder from CHARGE syndrome, suggesting that these three disorders may be differentiated at least in part by their inner ear anomalies.

The Vulnerable Elders Survey-13 (VES-13) is a well-studied simplified frailty screening tool for elderly patients in the oncology setting. We conducted a prospective clinical trial to evaluate the efficacy and safety of dose-adjusted treatment based on the VES-13 in transplant-ineligible patients with newly diagnosed multiple myeloma (MM). In the Fit group (VES-13

Objectives Kabuki syndrome (KS) is a genetic disorder characterized by intellectual disability, facial dysmorphism and congenital anomalies. We aim to investigate the prenatal features of fetuses with KS and to provide a comprehensive review of the literature on prenatal sonographic abnormalities associated with KS. Methods We retrospectively reviewed the prenatal ultrasound findings of all mothers of children with molecularly confirmed KS in Hong Kong, between 1991 and 2019. We also performed systematic review of the literature to identify studies on the prenatal findings in KS. Results We identified 11 cases with KS with detectable fetal ultrasound findings ranging from no detectable abnormalities to a variety of non-specific findings including increased nuchal translucency, pleural effusion, cardiac anomalies, renal anomalies, intrauterine growth restriction, polyhydramnios, oligohydramnios and single umbilical artery. In combining our cases with the 77 cases published, 42 (50.6%) of them had more than one abnormal antenatal ultrasound finding. The most frequent ultrasound features observed were cardiac anomalies (49.4%), followed by polyhydramnios (28.9%), genitourinary anomalies (26.5%), single umbilical artery (15.7%), intrauterine growth restriction (14.5%) and hydrops fetalis/pleural effusion/ascites (12.0%). Conclusions These cases demonstrate the prenatal phenotypic heterogeneity associated with KS. Although the ultrasound abnormalities are non-specific, KS should be considered in the differential diagnosis when these fetal findings following normal microarray analysis/karyotyping.

The extraordinary advances in clinical hematology, biology, and oncology in the last decades would not have been possible without discovering how to identify and count the cells circulating in the blood. For centuries, scientists have used slides, counting chambers (hemocytometers), and diluting and staining solutions for this task. Then, automated hemocytometry began. This science, now linked to the daily routine of laboratory hematology, has completed an overwhelming path over a few decades. Our laboratories today operate with versatile multiparameter systems, ranging from complex single-channel instruments to bulky continuous flow machines. In terms of clinical information obtained from a simple routine blood test, the full exploitation of their potential depends on the operators' imagination and courage. A comprehensive review of the scientific publications that have accompanied the development of hemocytometry from the 1950s to today would require entire volumes. More than seven hundred contributions that authors worldwide have published in Clinical and Laboratory Haematology until 2007 and then the International Journal of Laboratory Hematology are summarized. Such journals have represented and hopefully will continue to represent the privileged place of welcome for future scientific research in hemocytometry. Improved technologies, attention to quality, new reagents and electronics, information technology, and scientist talent ensure a more profound and deeper knowledge of cell properties: current laboratory devices measure and count even minor immature or pathological cell subpopulations. Full-field hemocytometry includes the analysis of nonhematic fluids, digital adds to the microscope, and the development of effective point-of-care devices.

Chemotherapy-induced myelosuppression is an acute, dose-limiting toxicity of chemotherapy regimens used in the treatment of extensive-stage small cell lung cancer (ES-SCLC). Trilaciclib protects haematopoietic stem and progenitor cells from chemotherapy-induced damage (myeloprotection). To assess the totality of the myeloprotective benefits of trilaciclib, including analysis of several clinically relevant but low-frequency events, an exploratory composite endpoint comprising five major adverse haematological events (MAHE) was prospectively defined: all-cause hospitalisations, all-cause chemotherapy dose reductions, febrile neutropenia (FN), prolonged severe neutropenia (SN) and red blood cell (RBC) transfusions on/after week 5. MAHE and its individual components were assessed in three randomised, double-blind, placebo-controlled Phase 2 trials in patients receiving a platinum/etoposide or topotecan-containing chemotherapy regimen for ES-SCLC, and in data pooled from the three trials. A total of 242 patients were randomised across the three trials (trilaciclib, n = 123; placebo, n = 119). In the individual trials and the pooled analysis, administering trilaciclib prior to chemotherapy resulted in a statistically significant reduction in the cumulative incidence of MAHE compared with placebo. In the pooled analysis, the cumulative incidences of all-cause chemotherapy dose reductions, FN, prolonged SN and RBC transfusions on/after week 5 were significantly reduced with trilaciclib versus placebo; however, no significant difference was observed in rates of all-cause hospitalisations. Additionally, compared with placebo, trilaciclib significantly extended the amount of time patients remained free of MAHE. These data support the myeloprotective benefits of trilaciclib and its ability to improve the overall safety profile of myelosuppressive chemotherapy regimens used to treat patients with ES-SCLC. This article is protected by copyright. All rights reserved.

Kabuki syndrome (KS) is a well-recognized disorder characterized by postnatal growth deficiency, dysmorphic facial features, skeletal anomalies, and intellectual disability. The syndrome is caused by KMT2D gene mutations or less frequently KDM6A gene mutations or deletions. We report a systematic evaluation of KS patients from Campania region of Italy; data were also compared with literature ones. We collected data of 15 subjects (8 males and 7 females with age range 10–26 years; mean age 16.9 years) with confirmed diagnosis of KS, representing the entire cohort of patients from Campania Region. Each patient performed biochemical testing and instrumental investigation. Neuro-intellectual development, cranio-facial dysmorphisms, and multisystem involvement data were collected retrospectively. For each category, type of defects and frequency of the anomalies were analyzed. Our observation shows that KS patients from Campania region have some particular and previously underscored, neurological and immunological findings. We found high prevalence of EEG’s abnormalities (43%) and MRI brain abnormalities (60%). Microcephaly resulted more common in our series (33%), if compared with major cohorts described in literature. Biochemical features of immunodeficiency and autoimmune diseases including thyroid autoimmunity, polyserositis, and vitiligo were observed with high prevalence (54.5%). Low immunoglobulins levels were a frequent finding. Lymphocyte class investigation showed significantly reduced CD8 levels in one patient.Conclusions: These data confirm great heterogeneity of clinical manifestations in KS and suggest to introduce further clinical diagnostic criteria in order to perform a correct and precocious diagnosis. What is Known• Kabuki syndrome is characterized by growth deficiency, dysmorphic facial features, skeletal anomalies, and intellectual disability• Immune dysfunction is a common finding but autoimmune diseases are rarely seen• Neurological features are common What is New• Some particular facial features could help gestalt diagnosis (hypertelorism, broad nasal bridge, micrognathia, tooth agenesis, cutaneous haemangiomas and strabismus)• Higher prevalence of autoimmune disorders than previously reported• Particular neurological features are present in this cohort (EEG and MRI brain abnormalities)

Since the SARS‐CoV‐2 pandemic began, countries across the globe have seen repeated periods of government‐enforced social distancing to restrict transmission in response to rises in COVID‐19 incidence1. Social distancing in the UK was first introduced in March 2020, and for 6 of the following 12 months the population was under strict national restrictions. This led to substantially reduced contact between different households2, with mass gatherings prohibited.

Background Fatal hemorrhagic pneumonia is one of the most severe manifestations of Stenotrophomonas maltophilia (SM) infections. Here, we aimed to investigate the clinical characteristics of SM bacteremia and to identify the risk factors of hemorrhagic pneumonia caused by SM in patients with hematologic diseases. Methods The clinical records of 55 patients diagnosed with hematologic diseases and SM bacteremia were retrospectively reviewed. We compared patients’ clinical characteristics and outcomes between the hemorrhagic pneumonia group and non-hemorrhagic pneumonia group. Results Twenty-seven (49.1%) patients developed hemorrhagic pneumonia. The overall mortality rate of SM bacteremia was 67.3%. Hemorrhagic pneumonia (adjusted HR 2.316, 95% CI 1.140–4.705; P = 0.020) was an independent risk factor of 30-day mortality in hematological patients with SM bacteremia. Compared with the non-hemorrhagic pneumonia group, patients in the hemorrhagic pneumonia group were older and showed clinical manifestations as higher proportions of isolated SM in sputum culture, neutropenia and elevated procalcitonin (PCT). Multivariate analysis showed that neutropenia, high levels of PCT, prior tigecycline therapy within 1 month were independent risk factors associated with hemorrhagic pneumonia. Conclusions Neutropenia, high level of PCT and prior tigecycline therapy within 1 month were significant independent predictors of hemorrhagic pneumonia in hematologic patients with SM bacteremia. Due to no effective antibiotics to prevent hemorrhagic pneumonia, prophylaxis of SM infection and its progression to hemorrhagic pneumonia is particularly important.

Patients with cancer are considered at high risk of acquiring coronavirus disease (COVID-19). To identify patients who are likely to be diagnosed with severe COVID-19, we analyzed the risk factors for mortality in patients admitted to the hematology department at our institute. The mortality rate of all patients was as high as 62% (21 of the 34 patients), and most of these patients had malignant malignancies. Patients before an achievement of remission had a 10.8-fold higher risk of death than those in remission. The group receiving chemotherapy with steroids had a shorter survival time and had an 8.3-fold higher risk of death than that receiving chemotherapy without steroids. During the COVID-19 pandemic, it is necessary to carefully monitor or follow-up patients with active diseases and patients receiving steroid-containing chemotherapy.

Kabuki syndrome is characterized by multiple systemic anomalies and intellectual disability. It is complicated with immunodeficiencies and autoimmune disorders. The syndrome is caused by a mutation in the KMT2D gene. We herein report a case of a Kabuki syndrome with developing immune thrombocytopenic purpura (ITP) and progressive splenomegaly. Laparoscopic splenectomy was performed and the patients' symptoms quickly disappeared with platelet recovery. After this operation, the patient had no severe complications. A sequence analysis of the KMT2D gene identified a pathogenic mutation frequently associated with ITP. Laparoscopic splenectomy is therefore considered to be a good therapeutic option for recurrent ITP and symptomatic splenomegaly with Kabuki syndrome.

The extrafollicular immune response is essential to generate a rapid but transient wave of protective antibodies during infection. Despite its importance, the molecular mechanisms controlling this first response are poorly understood. Here, we demonstrate that enhanced Cxcr4 signaling caused by defective receptor desensitization leads to exacerbated extrafollicular B-cell response. Using a mouse model bearing a gain-of-function mutation of Cxcr4 described in 2 human hematologic disorders, warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome and Waldenström macroglobulinemia, we demonstrated that mutant B cells exhibited enhanced mechanistic target of rapamycin signaling, cycled more, and differentiated more potently into plasma cells than wild-type B cells after Toll-like receptor (TLR) stimulation. Moreover, Cxcr4 gain of function promoted enhanced homing and persistence of immature plasma cells in the bone marrow, a phenomenon recapitulated in WHIM syndrome patient samples. This translated in increased and more sustained production of antibodies after T-independent immunization in Cxcr4 mutant mice. Thus, our results establish that fine-tuning of Cxcr4 signaling is essential to limit the strength and length of the extrafollicular immune response.

Allogeneic hematopoietic stem cell transplantation (AHSCT) is a potentially curative treatment of choice for many hematological diseases. However, there are some transplantation-related risks. Predicting the risk-benefit ratio prior to AHSCT facilitates the choice of conditioning regimens and posttransplant follow-up. Hence, many risk models have been developed. The aim of the present study was to compare 6 different risk models that are clinically used.A total of 259 patients were enrolled in this study. The European Society for Blood and Marrow Transplantation (EBMT), Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI), Age-Adjusted Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI-Age), revised Pretransplant Assessment of Mortality (rPAM), Acute Leukemia-EBMT (AL-EBMT), and Disease Risk Index (DRI) risk models were applied retrospectively.The AL-EBMT, HCT-CI, and HCT-CI-Age scoring systems were found to be predictive for 2-year overall survival (OS) and 2-year non-relapse mortality (NRM) (2-year OS: AL-EBMT, reference vs. score 8.5-10, HR: 1.3, p=0.035; AL-EBMT, reference vs. score10, HR: 3.8, p=0.001; HCT-CI: reference vs. score 1-2, HR: 1.4, p=0.018; HCT-CI: reference vs. score ≥3, HR: 2.5, p0.001; HCT-CI-Age: reference vs. score 1-2, HR: 1.3, p0.001; HCT-CI-Age: reference vs. score ≥3, HR: 3.2, p0.001) (2-year NRM: AL-EBMT: reference vs. score 8.5-10, HR: 1.61, p0.001; AL-EBMT: reference vs. score10, HR: 3.3, p0.001; HCT-CI: reference vs. score 1-2, HR: 1.3, p=0.028; HCT-CI: reference vs. score ≥3, HR: 2.3, p=0.011; HCT-CI-Age: reference vs. score 1-2, HR: 1.3, p=0.01; HCT-CI-Age: reference vs. score ≥3, HR: 2.4, p=0.003). In terms of the Kaplan-Meier estimates of 2-year OS and 2-year NRM, the risk scoring system with the highest predictive power was found to be AL-EBMT (2-year AUC: 0.59 and 0.60, respectively). The other scores were not found to be predictive for 2-year OS and NRM.In the present study at our bone marrow and stem cell transplant center, it has been demonstrated that the HCT-CI, HCT-CI-Age, and AL-EBMT are good predictors of 2-year NRM and OS.Allojeneik hematopoetik kök hücre nakli (AHKHN) birçok hematolojik hastalıkta kullanılan potansiyel küratif bir tedavi seçeneğidir. Bununla birlikte nakil ilişkili bazı riskler bulunmaktadır. AHKHN öncesi risk-fayda oranının belirlenmesi, kullanılacak hazırlık rejimlerinin seçimi ve nakil sonrası hasta takibini kolaylaştırmaktadır. Bu nedenle birçok risk modeli geliştirilmiştir. Bu çalışmanın amacı, klinik kullanımı olan 6 farklı risk modelini karşılaştırılmasıdır.Bu çalışmaya çeşitli hematolojik nedenlerle AHKHN yapılan 259 hasta alınmıştır. Avrupa Kan ve Kemik iliği Nakli Derneği (EBMT), Hematopoetik Hücre Transplantasyon Komorbidite İndeksi (HCT-CI), yaşa göre düzenlenmiş Hematopoetik Hücre Transplantasyon Komorbidite İndeksi (HCT-CI-Yaş), düzenlenmiş nakil öncesi mortalite değerlendirme skoru (rPAM), akut lösemi-EBMT skoru (AL-EBMT) ve hastalık risk indeksi (DRI) risk modelleri geriye dönük olarak uygulanmıştır.HCT-CI, HCT-CI-Age ve AL-EBMT risk modelleri 2 yıllık genel sağkalım (OS) ve 2 yıllık NRM için prediktif bulundu (2 yıllık OS; AL-EBMT: referans vs skor 8,5-10 HR: 1,3 p=0,035 referans vs skor10 HR: 3,8 p=0,001, HCT-CI: referans vs score 1-2 HR: 1,4 p=0,018 referans vs skor ≥3 HR: 2,5 p0.001, HCT-CI-Age referans vs skor 1-2 HR: 1,3 p0,001 referans vs skor ≥3 HR: 3,2 p0,001 2 yıllık NRM: AL-EBMT: referans vs skor 8,5-10 HR: 1,61 p0,001 referans vs skor10 HR: 3,3 p0,001 HCT-CI: referans vs skor 1-2 HR: 1,3 p=0,028 referans vs skor ≥3 HR: 2,3 p=0,011 HCT-CI-Age referance vs skor 1-2 HR: 1,3 p=0,01 referans vs skor ≥3 HR: 2,4 p=0,003). İki yıllık OS ve 2 yıllık NRM için, prediktif gücü en yüksek olan test AL-EBMT idi (sırasıyla 2 yıllık AUC; 0,59-0,60). Diğer modeller 2 yıllık OS ve NRM için prediktif değildi.Referans nakil merkezimizde yapılan bu çalışmada, HCT-CI, HCT-CI-Yaş ve AL-EBMT risk modellerinin 2 yıllık NRM ve OS için iyi birer belirteç olduğu gösterilmiştir.

Objectives To evaluate the frequency and findings of dry eye associated with ocular graft-versus-host disease (GVHD) in pediatric hematopoietic stem cell transplantation (HSCT) patients. Materials and methods Retrospectively the records of pediatric patients with ocular GVHD were evaluated and ophthalmologic examination findings as well as Schirmer test results, tear film break-up time, and corneal staining grades were recorded. In severe dry eye patients topical cyclosporine-A was prescribed and the results were evaluated. Results GVHD was detected in 51 (23.4%) of 218 HSCT patients, 4 of whom died during follow-up. Thirty (63.8%) of the remaining 47 patients had chronic ocular GVHD and 4 patients with severe dry eye were treated with topical cyclosporine-A with a median follow-up of 12.1 months. Severe dry eye symptoms and findings significantly improved in 2 patients. However, 1 patient had to stop treatment due to side effects. Conclusion In children, chronic ocular GVHD is a common finding of GVHD after HSCT. Therefore, these patients should be examined periodically for dry eye.

This perspective article discusses the various practices classified as complementary and alternative medicine (CAM) and reviews the benefits and uncertainties with respect to nutritional supplements in patients with hematological disease. It considers the high prevalence of CAM use especially among cancer survivors, particularly patients with hematologic malignancies and allogeneic stem cell transplant survivors, many of whom believe (because of extensive advertising) that supplements are anticancer/antitoxic agents, despite the paucity of evidence to support any benefit and the enormous cost to the individual. CAM constitutes various practices and nutritional behaviors including prayers, relaxation, spiritual healing, nutritional supplements, meditation, religious counseling, massage, and support groups. We highlighted the current literature regarding CAM practices and focused our discussion on the omnipresent nutritional supplements in particular to further expound on their benefits and adverse effects. As the number of survivors after HSCT increases over the next several years along with prevalence of CAM use, it becomes imperative to ascertain any beneficial potential, as well as toxicities associated with CAM use in this population.