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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.

This study is the first to analyse the prevalence of oral candidiasis in onco-haematological patients by physical and oral cytopathological examinations.This is a cross-sectional and observational study with a retrospective sample composed of participants hospitalised in the haematology clinic, who were diagnosed with haematological diseases. All participants received an oral mucosal examination and scraping from oral mucosa.Of the 62 participants, 56.5% were male and 82.3% were white, with mean age of 57 years. Lymphoma was the most common haematological disease (24.2%). In total, 48.4% of the sample was diagnosed with oral candidiasis. Of the participants with oral candidiasis, 13 (21.0%) had a clinical diagnosis. Cytopathological analysis revealed 17 more (27.4%) cases without oral lesions indicative of candidiasis. Erythematous candidiasis (P = 0.02), pseudomembranous candidiasis (P lt; 0.001), clinical candidiasis (P lt; 0.001), fibrous hyperplasia (P = 0.032), and coated tongue (P = 0.012) showed a correlation with a candidiasis cytopathological diagnosis.Oral candidiasis is common among patients with haematological disease, and the cytopathological examination proved to be a useful tool, confirming clinical diagnosis of candidiasis and identifying subclinical cases. These data are of great relevance considering the possible complications that these patients may develop, such as longer hospitalisations, worsening of the general condition or even death due to candidemia.

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

Objective Acute pulmonary lesions (APLs), defined as an acute infiltrate or nodular lung field, are a major complication in patients with haematological diseases. Recently, endobronchial ultrasonography with a guide-sheath (EBUS-GS) was established as a useful technique for diagnosing pulmonary lesions. This study aimed to evaluate the efficacy and safety of EBUS-GS for managing APLs in patients with haematological diseases. Methods Our single-centre, retrospective, observational, single-arm, descriptive study enrolled 22 consecutive adult (20-year-old) patients with haematological diseases and concomitant APL who underwent EBUS-GS between January 2011 and June 2016 at Kameda Medical Center, Chiba, Japan. The primary endpoint was the contribution of EBUS-GS to clinical decision-making. Secondary endpoints were an adequate tissue collection rate, diagnostic yield, complication rate, and 30-day mortality. Results The median patient age was 70 years old, and 63.6% were men. Acute myeloid leukaemia was the most frequent underlying disease, accounting for 54.5% of patients. The contribution of EBUS-GS to clinical decision-making was recognised in 11 (50.0%) patients. Adequate tissue collection was achieved in 21 (95.5%) patients. The aetiology of the APL was identified in 9 (40.9%) patients. No complications, including severe haemorrhaging and pneumothorax, were observed in any patients, and the 30-day mortality rate was 0%. Conclusion EBUS-GS may be a suitable diagnostic option for APL in patients with haematological diseases. Further larger-scale and randomised controlled trials are needed to confirm our results.

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.

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.

BackgroundSARS-CoV2 vaccination efficiently prevents severe COVID-19, although hematological patients, particularly under therapy, respond less well. Besides vaccine efficacy, adherence to vaccination is essential for ensuring adequate protection of this vulnerable population.MethodsWe evaluated the impact of a program aimed at maximizing patient adherence by comparing the rate of SARS-CoV2 vaccination of our hematological patients and a matched sample of the general population.ResultsVaccination rates were 88.9% among 2,156 patients, aged 65.2 ± 15.8 years (M ± SD, range 19-86 years). Rates differed considerably with age, i.e. 84.2% between 18-64 years and 92.4% above 65 years (pConclusionsVaccination rates were significantly higher in hematological patients compared to the general population regardless of age, sex and municipality. Acceptance of Covid vaccines by hematological patients may be improved by targeted information campaigns carried out by trusted health care professionals.

In the last 10 years, numbers of donors in the case of Polish potential unrelated hematopoietic stem cells (HSC) have increased dynamically, reaching 1,900,000 in 2020 (including donors presented in World Marrow Donor Association as PL6). On the world scale, the share of Polish donors in the global registry increased from 1% in 2010 to about 5% in 2020. The level and range of typing of potential donors has also been improving steadily toward the international "gold standard." At the end of 2020, 92% of Polish resources were at least HLA-A, B, C, DR, DQ high- or intermediate-resolution typed, mostly by way of genomic typing techniques, mostly by way of genomic typing techniques. The Central Bone Marrow Donor Registry (CBMDR) also stands out in terms of the young ages of potential donors. As of 2020, 27.2% of those registered were younger than 30 years of age, and 36.3% were aged between 30 and 40 years. Sixty percent of registered donors were female. The data in question were presented at the World Marrow Donor Association SearchMatch Service, ensuring their visibility and accessibility to Polish and international search units and registries. In 2020, donors in Poland were the subject of almost 18,000 search requests from 40 countries, with 271 extended typing requests and more than 7600 confirmatory typing requests. The total number of donations from Polish donors also increased. In 2020, HSC of bone marrow, peripheral blood, or lymphocytes were collected from 1391 donors, as opposed to 94 donors in 2010. The growing number of donors available in the CBMDR means a better chance of a donor being found among Polish resources, without any need to resort to international registers. Although in 2010, just 24% of Polish recipients received HSC from Polish donors, by 2019 the figure was as high as 67%, and reached 63% in 2020. The CBMDR is an example of proper strategy on registry development being implemented in Poland.

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.

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.

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.

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)

Hematological disorders are the third cause of hypereosinophilia, after allergic and parasitic disease. The objective of our study is to show the epidemiological, clinical, biological and therapeutic characteristics of hematological hypereosinophilia.This is a retrospective study over a 4-year period (March 2017-March 2021) concerning 14 patients with hematological hypereosinophilia.Fourteen patients were included (9 women and 5 men). The median age at diagnosis was 55 years. Hematological hypereosinophilia was mainly of clonal etiology. Clinical manifestations were either specific to hypereosinophilia, such as organ damage, or related to the etiology of hypereosinophilia, such as hepato-splenomegaly and lymphadenopathy. Moderate and severe forms were the most commonly reported. Several other quantitative and qualitative abnormalities of the blood picture were reported. Identification of the FIP1L1-PDGFRA fusion gene by molecular biology (RT-PCR) was positive in two patients. Imatinib was the main treatment for clonal forms.Hematological hypereosinophilia is a rare and complex pathology. Our study has confirmed this epidemiological, clinical, biological and therapeutic heterogeneity and has enabled us to realize the contribution of molecular biology in the diagnosis and the treatment of hypereosinophilia.Les affections hématologiques représentent la troisième cause des hyper éosinophilies. L’objectif de notre travail est d’étudier les caractéristiques épidémiologiques, étiologiques, cliniques, biologiques et thérapeutiques des hyperéosinophilies hématologiques.Il s’agit d’une étude rétrospective menée sur une période de 4 années (mars 2017-mars 2021). Cette étude a colligé 14 patients atteints d’hyperéosinophilie hématologique.Quatorze patients ont été inclus (9 femmes et 5 hommes). L’âge médian au moment du diagnostic était de 55 ans. L’hyperéosinophilie hématologique était principalement d’étiologie clonale. Les manifestations cliniques étaient soit spécifiques à l’hyperéosinophilie telles que les atteintes d’organes, soit liées à l’étiologie de l’hyperéosinophilie telles que l’hépato-splénomégalie et les adénopathies. Les formes modérées et sévères étaient les plus fréquemment rapportées. Plusieurs autres anomalies quantitatives et qualitatives de l’hémogramme ont été rapportées. L’identification du gène de fusion FIP1L1-PDGFRA par biologie moléculaire (RT-PCR) était positive chez deux patients. L’imatinib était le traitement de choix des formes clonales.L’hyperéosinophilie hématologique est une pathologie rare et complexe. Notre étude a permis de confirmer cette hétérogénéité épidémiologique, étiologique, clinique, biologique et thérapeutique et de montrer l’apport de la biologie moléculaire dans le diagnostic et le traitement de cette pathologie.

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.

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.

The aim of this study was to clarify the clinical and microbiological characteristics of Corynebacterium bacteremia in hematological patients. We retrospectively reviewed the medical records of patients with Corynebacterium bacteremia from April 2013 to June 2018. The causative Corynebacterium species were identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Drug susceptibility tests were performed using the broth microdilution method recommended by the Clinical and Laboratory Standards Institute. In total, 147 cases of Corynebacterium bacteremia were identified during the study period. Corynebacterium striatum was the most frequent pathogen. Catheter-related bloodstream infection was diagnosed in 19.7% of all patients, and moderate/severe oral or severe gastrointestinal mucosal impairment was detected in 19.7%. Polymicrobial infection was found in about 20% of cases, with Enterococcus faecium being the most frequent isolate. The overall 30-day mortality was 34.7% (51/147). Multivariate analysis showed that E. faecium co-infection (odds ratio (OR) 9.3; 95% confidence interval (CI) 2.1-40), systemic corticosteroids (OR 3.6; 95% CI 1.4-8.9), other immunosuppressive drugs (OR 0.32; 95% CI 0.13-0.76), and a Pitt bacteremia score ≥4 (OR 12; 95% CI 3.9-40) were significant risk factors for overall 30-day mortality. The drug susceptibility rates for beta-lactam antimicrobial agents were quite low. All isolates were susceptible to glycopeptides and linezolid. However, some C. striatum isolates were resistant to daptomycin. Corynebacterium bacteremia can occur in the presence of several types of mucosal impairment. Our drug susceptibility data indicate that Corynebacterium bacteremia in hematological patients could be treated by glycopeptides or linezolid.

Most eukaryotes harbor two distinct pre-mRNA splicing machineries: the major spliceosome, which removes >99% of introns, and the minor spliceosome, which removes rare, evolutionarily conserved introns. Although hypothesized to serve important regulatory functions, physiologic roles of the minor spliceosome are not well understood. For example, the minor spliceosome component ZRSR2 is subject to recurrent, leukemia-associated mutations, yet functional connections among minor introns, hematopoiesis and cancers are unclear. Here, we identify that impaired minor intron excision via ZRSR2 loss enhances hematopoietic stem cell self-renewal. CRISPR screens mimicking nonsense-mediated decay of minor intron-containing mRNA species converged on LZTR1, a regulator of RAS-related GTPases. LZTR1 minor intron retention was also discovered in the RASopathy Noonan syndrome, due to intronic mutations disrupting splicing and diverse solid tumors. These data uncover minor intron recognition as a regulator of hematopoiesis, noncoding mutations within minor introns as potential cancer drivers and links among ZRSR2 mutations, LZTR1 regulation and leukemias. Loss of function of the minor spliceosome component ZRSR2 enhances hematopoietic stem cell self-renewal through minor intron retention of its target LZTR1, which is a regulator of RAS-related GTPases. Minor intron retention of LZTR1 was also identified in Noonan syndrome and diverse solid tumor types.

Purpose This multi-institutional retrospective study sought to examine the hematologic effects of craniospinal irradiation (CSI) in pediatric patients with medulloblastoma using proton or photon therapy. Methods and Materials Clinical and treatment characteristics were recorded for 97 pediatric patients with medulloblastoma who received CSI without concurrent chemotherapy or with concurrent single-agent vincristine from 2000 to 2017. Groups of 60 and 37 patients underwent treatment with proton-based and photon-based therapy, respectively. Overall survival was determined by Kaplan-Meier curves with log-rank test. Comparisons of blood counts at each timepoint were conducted using multiple t tests with Bonferroni corrections. Univariate and multivariate analyses of time to grade ≥3 hematologic toxicity were performed with Cox regression analyses. Results Median age of patients receiving proton and photon CSI was 7.5 years (range, 3.5-22.7 years) and 9.9 years (range, 3.6-19.5 years), respectively. Most patients had a diagnosis of standard risk medulloblastoma, with 86.7% and 89.2% for the proton and photon cohorts, respectively. Median total dose to involved field or whole posterior fossa was 54.0 Gy/Gy relative biological effectiveness (RBE) and median CSI dose was 23.4 Gy/Gy(RBE) (range, 18-36 Gy/Gy[RBE]) for both cohorts. Counts were significantly higher in the proton cohort compared with the photon cohort in weeks 3 to 6 of radiation therapy (RT). Although white blood cell counts did not differ between the 2 cohorts, patients receiving proton RT had significantly higher lymphocyte counts throughout the RT course. Similar results were observed when excluding patients who received vertebral body sparing proton RT or limiting to those receiving 23.4 Gy. Only photon therapy was associated with decreased time to grade ≥3 hematologic toxicity on univariate and multivariable analyses. No difference in overall survival was observed, and lymphopenia did not predict survival. Conclusions Patients who receive CSI using proton therapy experience significantly decreased hematologic toxicity compared with those receiving photon therapy.

Purpose Integrating moderate hypofractionation to the macroscopic tumor with elective nodal irradiation while sparing the organs at risk (OAR) in chemoradiotherapy of locally advanced non-small-cell lung cancer. Methods From 2010–2018, treatment, patient and tumor characteristics of 138 patients from two radiation therapy centers were assessed. Chemoradiotherapy by intensity-modulated radiation therapy (IMRT) with a simultaneous integrated boost (SIB) to the primary tumor and macroscopic lymph node metastases was used. Results A total of 124 (90%) patients received concurrent chemotherapy. 106 (76%) patients had UICC (Union for International Cancer Control) stage ≥IIIB and 21 (15%) patients had an oligometastatic disease (UICC stage IV). Median SIB and elective total dose was 61.6 and 50.4 Gy in 28 fractions, respectively. Furthermore, 64 patients (46%) had an additional sequential boost to the primary tumor after the SIB-IMRT main series: median 6.6 Gy in median 3 fractions. The median cumulative mean lung dose was 15.6 Gy (range 6.2–29.5 Gy). Median follow-up and radiological follow-up for all patients was 18.0 months (range 0.6–86.9) and 16.0 months (range 0.2–86.9), respectively. Actuarial local control rates at 1, 2 and 3 years were 80.4, 68.4 and 57.8%. Median overall survival and progression-free survival was 30.0 months (95% confidence interval [CI] 23.5–36.4) and 12.1 months (95% CI 8.2–16.0), respectively. Treatment-related toxicity was moderate. Radiation-induced pneumonitis grade 2 and grade 3 occurred in 13 (9.8%) and 3 (2.3%) patients. Conclusions Chemoradiotherapy using SIB-IMRT showed promising local tumor control rates and acceptable toxicity in patients with locally advanced and in part oligometastatic lung cancer. The SIB concept, resulting in a relatively low mean lung dose, was associated with low numbers of clinically relevant pneumonitis. The overall survival appears promising in the presence of a majority of patients with UICC stage ≥IIIB disease.

Background Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is associated with a high fatality rate (34%), which is higher in the presence of co-morbidities. The aim of the current study was to assess the clinical course and the outcome in hematological or oncological malignancy cases, diagnosed with MERS-CoV. Methods This is a case series of hematological /oncological cases, diagnosed with MERS-CoV, in a tertiary care setting in 2015. The cases were identified based on the World Health Organization (WHO) MERS-CoV case definition. The demographic, clinical, and outcome data were retrieved from the patients’ medical charts and electronic health records. Results In total, nine hematological or oncological cases were identified, diagnosed with MERS-CoV. The baseline malignant condition was hematological malignancy in seven patients, as well as colon cancer and osteosarcoma in one patient each. Six (67%) patients were male. The median age was 65 years (range 16–80 years). Co-morbidities included chronic kidney disease (n = 3.33%), diabetes mellitus (n = 3.33%), and hypertension (n = 2.22%). The presenting symptoms were shortness of breath (n = 6.66%), fever (n = 5.55%), cough (n = 2.22%), and diarrhea (n = 2.22%). Chest x-rays indicated bilateral infiltrates in 6 patients (66%). The PCR (polymerase chain reaction) test was repeated in six patients to confirm the diagnosis. The mortality rate was 100%, and the median time to death was 26 days (range 15–77 days). Conclusion MERS-CoV infection in this small cohort of hematology or oncology patients has a 100% mortality rate, regardless of the status of the underlying disease. The confirmation of the diagnosis may require repeated testing. Additional studies are required to verify the findings and to elucidate the disease pathogenesis in cancer patients.

[Abstract] Objectives: To report a COVID-19 outbreak among workers and inpatients at a medical ward for especially vulnerable patients. Methods: Descriptive study of a nosocomial COVID-19 outbreak registered in March-April 2020 at medical ward of onco-hematological patients in an Spanish hospital. Confirmed cases were hospitalized patients, healthcare and non-healthcare workers who tested positive by PCR on a nasopharyngeal swab. Results: Twenty-two COVID-19 cases (12 workers and 10 inpatients) were laboratory-confirmed. Initial cases were a healthcare provider and a visitor who tested positive. The median patients age was 73 years (range 62-88). The main reason of admission was haematological in 8 patients and oncologic in 2. All patients followed an immunosuppressive treatment, 5/10 with high-flow oxygen nebulizations. Five patients presented a moderate/serious evolution, and 5 patients died. The mean workers age was 42.1±10.9. One healthworker required Intensive Care Unit admission, and all of them recovered completely. Conclusions: In the hospital setting, close patients surveillance for SARS-CoV-2 is essential, especially in immunosuppressed patients. Replacing nebulizations or high-flow oxygen therapies, when other equivalent options were available, to reduce dispersion, and controlling ventilation ducts, together with hygiene measures and an active follow-up on inpatients, visitors and workers appear to be important in preventing nosocomial outbreaks.

Background The number of young patients with hematological disease requiring total hip arthroplasty (THA) is expected to increase. We aimed to investigate the long-term THA outcomes in patients with osteonecrosis of the femoral head (ONFH) following allogeneic bone marrow transplantation (BMT) for hematological disease. Methods All patients who underwent THA for osteonecrosis after BMT from 1997 to 2012 were identified at 2 institutions. Using propensity scores, 75 THAs in 45 patients were matched for age, gender, body mass index, American Society of Anesthesiologists score, and year of surgery with 75 THAs in 58 patients with idiopathic ONFH without a history of hematological disease (1:1 ratio). The mean age at surgery was 36.7 years and 52% were men. Clinical and radiographic evaluations were performed and clinical scores were obtained at last follow-up. Kaplan-Meier analyses were used to compare survivorship. Results At a mean follow-up of 10.6 ± 3.5 years, clinical, radiographic, and survivorship outcomes, and the Harris hip scores were similar between both groups. The 13-year survivorship for all-cause revision was 93.4% for the BMT group and 95% for the control group (P = .928). No significant differences were observed between groups in the rates of reoperation (4% vs 5.3%, P = 1.000), 90-day readmission (all 5.3%), or overall mortality (4.4% vs 1.7%, P = .681). No hips had periprosthetic joint infection or septic loosening in either group. Osteolysis occurred in none of the BMT patients and in 2 hips (2.7%) of the control patients (P = .497). Conclusion This large cohort multicenter survey at 11-year follow-up shows that contemporary cementless THA in young hematological disease patients after allogeneic BMT is not associated with a higher risk for surgical complications, revision, reoperation, readmission, and mortality compared to a matched cohort of idiopathic ONFH.

Background and AimsIn the United Kingdom, patients on clozapine whose hematological parameters fall below certain thresholds are placed on the Central Non-Rechallenge Database (CNRD), meaning that they cannot be prescribed clozapine again except under exceptional circumstances. This practice was discontinued in the United States in 2015 by expanding the hematological monitoring guidelines, allowing more patients to receive clozapine. Our objective was to investigate the implications this policy change would have on clozapine utilization in the United Kingdom.MethodsThis was an observational, retrospective analysis of patients registered on the CNRD in a large mental health trust. The first objective was to compare the number of patients placed on the CNRD under the United Kingdom and the US Food and Drug Administration (FDA) criteria. The second objective was to explore the hematological and clinical outcomes of CNRD patients. The third objective was to investigate the hematological outcomes of patients rechallenged on clozapine after nonrechallengeable status.ResultsOne hundred and fifteen patients were placed on CNRD from 2002 to 2019, of whom 7 (6%) met the equivalent criteria for clozapine discontinuation under the FDA guidelines. Clinical outcomes, as measured by the Clinical Global Impression-Severity scale, were worse 3 months after clozapine cessation than on clozapine (t = −7.4862; P < .001). Sixty-two (54%) patients placed on CNRD were rechallenged. Fifty-nine of those (95%) were successfully rechallenged; 3 patients were placed back on CNRD, only one of which would have had to stop clozapine again under FDA criteria.ConclusionImplementation of the updated FDA’s monitoring criteria in the United Kingdom would significantly reduce clozapine discontinuation due to hematological reasons. The evidence suggests an urgent need for revising the UK clozapine monitoring guidelines to improve outcomes in treatment-resistant schizophrenia.

High-dose methotrexate (HD-MTX) at 3 g/m2 is one of the strategies for central nervous system (CNS) prophylaxis in the first-line treatment of aggressive lymphomas, especially in diffuse large B cell lymphoma patients with high-risk CNS-International Prognostic Index. The objective of our study was to retrospectively analyze the safety of 2 cycles of systemic HD-MTX administered as an ambulatory regimen. Between January 2013 and December 2016, 103 patients were carefully selected on 6 criteria, including age 34, performance status 0 or 1, normal renal and hepatic functions, good understanding of practical medical guidance, and no loss of weight. Strict procedures of HD-MTX infusion were observed including alkalinization, urine pH monitoring, and leucovorin rescue. Renal and hepatic functions were monitored at days 2 and 7. MTX clearance was not monitored. Toxicities and grades of toxicity were collected according to the NCI-CTCAE (version 4.0). Among the 103 selected patients, 92 (89%) patients successfully completed the planned 2 cycles of HD-MTX on an outpatient basis. Eleven patients completed only 1 cycle, 3 because of lymphoma progression and 8 because of toxicity including 3 grade II hepatotoxicity, 2 grade I/II renal toxicity, 1 grade III neutropenia, 1 active herpetic infection, and 1 grade III ileus reflex. Reported adverse events (AE) included 92 (84%) grade I/II and 18 (16%) grade III/IV. Grade III hepatotoxicity, mostly cytolysis, was the most frequent AE observed with 8 (8%) events. Grade III/IV hematologic toxicities concerned 9 patients with 8 grade III/IV neutropenia and 1 thrombocytopenia. Renal toxicity was rare, mild, and transient, observed with 4 (4%) grade I/II events. Ambulatory administration of HD-MTX at 3 g/m2 without MTX clearance monitoring is safe with strict medical guidance. It requires careful selection of patients before administration, and a renal and hepatic monitoring after the administration.

Objectives Coronavirus disease 19 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is associated with diverse clinical, including hematologic, abnormalities. We describe peripheral blood and bone marrow findings in deceased and living patients with COVID-19. Methods We examined bone marrows from 20 autopsies and 2 living patients with COVID-19 using H&E-stained slides and immunohistochemical stains. Clinical history and laboratory values were reviewed. HScore was calculated to estimate risk of hemophagocytic lymphohistocytosis (HLH). Results The deceased patients included 12 men and 8 women (aged 32 to >89 years; median, 63 years). Hematologic abnormalities included frequent neutrophilic leukocytosis, lymphopenia, anemia, and thrombocytopenia; one patient showed striking erythrocytosis. The bone marrows were all normocellular to hypercellular, most showing maturing trilineage hematopoiesis with myeloid left shift. In all 19 evaluable bone marrows, hemophagocytic histiocytes were identified. The HScore for secondary HLH ranged from 35 to 269 (median, 125; >169 in 5 patients). Coinfections were identified in 6 patients. In 2 living patients, bone marrow showed maturing trilineage hematopoiesis, including one showing few hemophagocytic histiocytes. Conclusions Peripheral blood from deceased patients with COVID-19 frequently showed neutrophilic leukocytosis, lymphopenia, and, rarely, secondary polycythemia; hemophagocytosis was common in their bone marrow. Consistent with other studies, we provide histopathologic evidence of secondary HLH development in patients with COVID-19.

The maximum tolerated dose of the panobinostat and carfilzomib combination in patients with relapsed/refractory multiple myeloma (RRMM) was not reached in our previous dose-escalation study. We report additional dose levels in the phase I/II, single-arm, multicenter, standard 3+3 dose-escalation expansion-cohort study (NCT01496118). Patients with RRMM were treated with panobinostat 30 mg, carfilzomib 20/56 mg/m2 (N = 3), or panobinostat 20 mg, carfilzomib 20/56 mg/m2 (N = 33). Treatment cycles lasted 28 days; panobinostat: days 1, 3, 5, 15, 17, 19; carfilzomib: days 1, 2, 8, 9, 15, 16. For dose level 6 (DL 6), median age was 63 years (range, 49-91 years), 60.6% were male, 42.4% were high risk. Patients received a median of two prior therapies (range 1-7); proteasome inhibitors (PI; 100%), immunomodulatory imide drugs (IMiD; 78.8%), and stem cell transplant (36.4%); 48.5%, 51.1% , and 24.2% were refractory to prior PI or prior IMiD treatment or both, respectively. Patients completed a median of seven (range 1-40) treatment cycles. Overall response rate (primary endpoint) of evaluable patients in the expansion cohort (N = 32): 84.4%; clinical benefit rate: 90.6%. With a median follow-up of 26.1 months (range, 0-72.5 months), median (95% CI) progression-free survival, time-to-progression and overall survival of patients was 10.3 (6.1, 13.9), 11.7 (5.6, 14.5), and 44.6 (20.8, N/A) months, respectively. Common adverse events (AEs) included thrombocytopenia (78.8%), nausea (63.6%), fatigue (63.6%), diarrhea (51.5%), and vomiting (51.5%). Seven patients had serious treatment-related AEs. There was one treatment-related death. In conclusion, panobinostat plus carfilzomib is an effective steroid-sparing regimen for RRMM. This article is protected by copyright. All rights reserved.

Background: We investigated the ocular manifestations in patients with Kabuki syndrome(KS).Methods: A retrospective chart review was performed in 10 patients with KS were referred to the Department...