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Hematologic abnormalities are common in HIV and involve all blood cell lineages. A study on cytopenias, as correlated with disease progression, can be valuable in resource-limited settings. This study aimed to determine the hematologic profile of HIV patients and its association with CD4 count and antiretroviral (ARV) treatment.This is a retrospective cohort study involving adult Filipino HIV patients with complete blood count (CBC) and CD4 count determinations prior to the initiation of ARV treatment and after ≥6 months of ARV treatment. Logistic regression was performed to determine the association between cytopenias and a CD4 count200 cells/µL.The study included 302 patients. Anemia was the most common cytopenia. Anemia and leukopenia were associated with an increased likelihood of having a CD4 count200 cells/µL in ARV-naïve patients. In ARV-treated patients, leukopenia was associated with an increased probability of having a CD4 count200 cells/µL. An increase in hemoglobin, white blood cell (WBC) and platelet counts was observed after ≥6 months of ARV treatment.Anemia and leukopenia can be used as markers of immune status in HIV-infected individuals and improvement in the CBC parameters can be used to assess response to ARV treatment. Routine monitoring of hematologic parameters is recommended.

Myelodysplastic syndromes (MDS) are a group of heterogeneous clonal hematopoietic stem cell disorders. The 2020 Surveillance, Epidemiology, and End Results data demonstrates the incidence rate of MDS increases with age especially in those greater than 70 years of age. Risk stratification that impact prognosis, survival, and rate of acute myeloid leukemia (AML) transformation in MDS is largely dependent on revised International Prognostic Scoring System along with molecular genetic testing as a supplement. Low risk MDS typically have a more indolent disease course in which treatment is only initiated to ameliorate symptoms of cytopenias. In many, anemia is the most common cytopenia requiring treatment and erythroid stimulating agents, are considered first line. In contrast, high risk MDS tend to behave more aggressively for which treatment should be initiated rapidly with Hypomethylating Agents (HMA) being in the frontline. In those with high risk MDS and eligible, evaluation for allogeneic stem cell transplant should be considered as this is the only potential curative option for MDS. With the use of molecular genetic testing, a personalized approach to therapy in MDS has ensued. As the treatment landscape in MDS continues to flourish with novel targeted agents, we ambitiously seek to improve survival rates especially among the relapsed/refractory and transplant ineligible.

Congenital mutations of the Wilms' tumor 1 (WT1) gene can lead to various abnormalities, including renal/gonadal developmental disorders and cardiac malformations. Although there have been many reports of somatic WT1 mutations in patients with acute myeloid leukemia and myelodysplastic syndrome, congenital WT1 mutations have not been reported in hematological disorders. We herein report a patient with early-onset clonal cytopenia of undetermined significance that was associated with a congenital mutation of WT1 and an acquired mutation of DNMT3A [encoding DNA (cytosine-5)-methyltransferase 3A].

Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease that commonly manifests as cutaneous rashes, renal disease, gastrointestinal dysfunction, and cytopenia. Hematological anomalies are frequently associated with drug-induced toxicity in SLE patients. Colony-stimulating factors have been used to treat drug-induced cytopenia in past case reports; however, evidence suggests that colony-stimulating factors can exacerbate autoimmune disorders, including SLE. This case report presents two patients with SLE exacerbations after colony-stimulating factor administration. The first case is a young male with SLE who developed pancytopenia with a white blood cell count (WBC) of 1 × 109 cells/L. The patient was administered filgrastim during his initial admission and presented to the hospital 2 days after discharge in cardiac arrest with a WBC of 66.7 × 109 cells/L. The second case is a 49-year-old female with SLE who was administered sargramostim in response to a WBC count of 9 × 109 cells/L. The patient experienced a drastic increase in WBC followed by a cardiac arrest. These cases highlight the need for more research regarding the safe use of colony-stimulating factors in SLE patients.

Clonal cytogenetic abnormalities (CCA) in donor-derived cells after stem cell transplant (SCT) are typically reported in donor-derived cell neoplasms, but CCA also may reflect a constitutional abnormality in the donor or may be present in a recipient without overt hematological malignancy. We reviewed 8515 tests on 2035 patients, who had allogenic sex mismatched SCT and underwent serial cytogenetic analysis between 2006 and 2020 in our institution. A constitutional CCA was observed in 3 patients: inv(10), t(1;5), and t(13;14). A somatic CCA without overt neoplasia was detected in 12 patients: del(7q) (n = 6), del(20q) (n = 3), der(11)t(11;11) (n = 1), t(1;9) (n = 1), dup(6p)(n = 1). In this group, four patients with cytopenia had del(7q), and an association between del(7q) and an adverse overall survival (OS) was observed [HR:5.99; 95%CI 1.23–29.92). Four patients had a donor-derived cell neoplasm: myelodysplastic syndrome (n = 3) and acute myeloid leukemia (n = 1), and all four neoplasms had loss of 7q. In our cohort, ∼1% of the patients (19/2,035) had CCA in donor-derived cells. Balanced constitutional CCA can pose a reproductive risk to donor. Loss of 7q is the most common somatic CCA, in donor-derived cells.

Follicular lymphoma, the most common indolent lymphoma, originates from germinal centre B-cells of the lymphoid follicle, and is characterized by t(14;18). Clinical manifestations include the presence of lymphadenopathy, sometimes accompanied by constitutional symptoms or cytopenia. Diagnosis is established through the identification of a B-cell proliferation of nodular pattern in the lymph node biopsy. Upon staging with PET-CT and bone marrow biopsy, a significant proportion of patients do not need immediate treatment. When therapy is indicated, commonly used regimens include anti-CD20 immunotherapy with or without chemotherapy. Although overall survival for most patients is prolonged, relapses are very frequent, and early relapse and transformation to an aggressive lymphoma portend a much worse prognosis. New therapies are under development, which will most likely change outcomes for FL patients in the near future.

Background Clonal hematopoiesis (CH) can be found in various myeloid neoplasms (MN), such as myelodysplastic syndromes (MDS), myelodysplastic syndromes/myeloproliferative neoplasms (MDS/MPN), also in pre-MDS conditions. Methods Cytogenetics is an independent prognostic factor in MDS, and fluorescence in-situ hybridization (FISH) can be used as an adjunct to karyotype analysis. In the past 5 years, only 35 of 100 newly diagnosed MDS and MDS/MPN patients were identified abnormalities, who underwent the FISH panel. In addition, we examined a cohort of 51 cytopenic patients suspected MDS or MDS/MPN with a 20-gene next generation sequencing (NGS), including 35 newly diagnosed MN patients and 16 clonal cytopenias of undetermined significance (CCUS) patients. Results Compared with the CCUS group, the MN group had higher male ratio (22/13 vs 10/6), cytogenetics abnormalities rate (41.4% vs 21.4%) and frequency of a series of mutations, such as ASXL1 (28.6% vs 25%), U2AF1 (25.7% vs 25%), RUNX1 (20% vs 0.0%); also, higher adverse mutations proportion (75% vs 85.2%), and double or multiple mutations (54.3% vs 43.75%). There were 7 MN patients and 4 CCUS patients who experienced cardio-cerebrovascular embolism events demonstrated a significant difference between the two groups (25% vs 20%). Ten of the 11 patients had somatic mutations, half had DNA methylation, while the other half had RNA splicing. Additionally, six patients had disease transformation, and four patients had mutated U2AF1, including two CCUS cases and two MDS-EB cases. Following up to January 2021, there was no significant difference in over survival between the CCUS and MN groups. Conclusion NGS facilitates the diagnosis of unexplained cytopenias. The monitoring and management of CCUS is necessary, also cardio-cerebrovascular embolism events in patients with CH need attention in the clinical practice.

Myelodysplastic syndromes (MDS) are clonal hematopoietic disorders with heterogeneous presentation, ranging from indolent disease courses to aggressive diseases similar to acute myeloid leukemia (AML). Approximately 90% of MDS patients harbor recurrent mutations , which - with the exception of mutated SF3B1 -have not (yet) been included into the diagnostic criteria or risk stratification for MDS. Accumulating evidence suggests their utility for diagnostic workup, treatment indication and prognosis. Subsequently, in patients with unexplained cytopenia or dysplasia identification of these mutations may lead to earlier diagnosis. The acquisition and expansion of additional driver mutations usually antecedes further disease progression to higher risk MDS or secondary AML and thus, can be clinically helpful to detect individuals that may benefit from aggressive treatment approaches. Here, we review our current understanding of somatic gene mutations, gene expression patterns and flow cytometry regarding their relevance for disease evolution from pre-neoplastic states to MDS and potentially AML.

Objective To develop and validate a prognostic model for LEF discontinuation with abnormal blood test results. Methods Data from the Clinical Practice Research Datalink Gold and Aurum were used for model development and external validation, respectively. Participants prescribed LEF between 1 January 2007 and 31 December 2019 were followed up from 6 months after the first general practitioner prescription to the earliest of date of outcome, death, 5 year follow-up or 31 December 2019. Candidate prognostic factors were ascertained using theory and data-driven approaches. Penalized Cox regression was performed to develop the risk equation, followed by internal validation using 500 bootstraps to correct for optimism. Multiple imputation was applied to handle missing data. Model performance was assessed in terms of calibration and discrimination. Results Data for 1487 and 2329 participants contributing 3140 and 5246 person-years follow-up were included in the development and validation cohorts, respectively. Thirteen candidate predictors were included in the model. Epilepsy and either cytopenia or elevated liver enzymes during the first 6 months of shared-care LEF prescription were strong predictors of drug discontinuation with a hazard ratio of 4.39 (95% CI 1.74, 11.06) and 3.06 (2.15, 4.35), respectively. The unadjusted and optimism-adjusted calibration slope in development data was 1.00 (95% CI 0.75, 1.25) and 0.72 (95% CI 0.47, 0.97), respectively. The calibration slope in validation data was 0.91 (95% CI 0.74, 1.07). The model showed prognostic separation with an optimism-adjusted Royston D statistic of 0.73 (95% CI 0.44, 1.02). Conclusion We have developed and externally validated an easy-to-use prognostic model that may be used to risk stratify monitoring for LEF toxicity and to make informed choices about risks when choosing treatments.

Ibrutinib is a targeted therapy drug that blocks the activity of Bruton’s tyrosine kinase, and it is an approved treatment for several mature B-cell malignancies including chronic lymphocytic leukaemia (CLL). Side effects include infections, cytopenia, nausea, and diarrhoea. In this report, we describe a case of hepatitis B reactivation in a female CLL patient undergoing treatment with ibrutinib. Diagnosis was confirmed with highly elevated hepatitis B virus DNA and a prior blood sample confirmed previous exposure. Ibrutinib was paused, and antiviral therapy was initiated with prompt clinical improvement. Ibrutinib was reinitiated shortly after clinical improvement. Thus, our case report demonstrates that systematic HBV screening is essential before starting treatment with ibrutinib. We suggest that antiviral prophylaxis is considered for patients at risk of reactivation, and ibrutinib may be continued following HBV reactivation with proper antiviral treatment.

Germline DDX41 variants in myeloid neoplasms (MNs) are not uncommon, and we explored the prevalence and characterized the clinical and pathologic features in a cohort of 3132 unrelated adult MN patients. By targeted next-generation sequencing, we identified 28 patients (20 men and 8 women) with pathogenic germline DDX41 variants who developed acute myeloid leukemia (AML), in which only 3 (11%) had a family history (FH) of MNs. A subacute clinical course of cytopenia (mean duration of 11.2 months, range 0-72 months) prior to the initial AML diagnosis was accompanied by a low blast count (median at 30%, range 20-70%) in hypocellular marrows (93% of all patients), in vast contrast to the typical proliferative subtypes of AML in the elderly. Most patients had a normal karyotype (75%) and acquired a second DDX41 variant (69%). A favorable overall survival (OS) was observed in comparison to that of common subtypes of AML with wild-type DDX41 in age-matched patients. Our study demonstrated that the frequent germline pathogenic DDX41 variants characterized a clinically distinct AML entity. Features characteristic of DDX41-mutated AML include male predominance, often lack of FH, indolent course, low proliferative potential, frequent somatic DDX41 variants, and a favorable OS.

A 71-year-old woman with a four-year history of chronic lymphocytic leukemia (CLL) received ibrutinib as initial treatment due to progressive anemia and thrombocytopenia. Eleven months after the start of the treatments, although her cytopenia had ameliorated, she developed classic Hodgkin lymphoma, a rare form of Richter's transformation. She was successfully treated with two courses of adriamycin, vinblastin, bleomycin and dacarbazine followed by radiotherapy. In general, several clinical, genetic and molecular factors are associated with Richter's transformation. In addition, our present case suggested that ibrutinib could be a potential risk factor for Richter's transformation in CLL patients.

Bone marrow (BM) lymphocyte subsets are evaluated by flow cytometry or immunohistochemistry for diagnostic purposes; however, CD4:CD8 T lymphocyte ratios are often erroneously interpreted using peripheral blood ranges. There are few and no recent studies describing the composition of lymphocytes within the marrow space, or normal reference ranges. Lymphocyte subsets in cytopenic patients and hospital autopsy BM specimens were evaluated to better characterize CD4:CD8 ratios. Ten patients with a history of cytopenia were identified from 2017 to 2021. Clinical history, cytogenetic testing, and results of a next generation sequencing panel were reviewed to rule out hematolymphoid disease. Thirty-five decedents who underwent a hospital autopsy from 2018 to 2019 were identified. History of hematolymphoid disease was ruled out by chart review. Immunohistochemical staining for CD3, CD20, CD4, and CD8 was evaluated with digital image analysis. Findings were compared to peripheral blood flow cytometry in a group of 20 living patients. BM CD4:CD8 ratios by image analysis were significantly lower than peripheral blood, mean in cytopenic patients 0.37:1 and mean in decedents 0.51:1 versus 2.6:1 (p = 0.99). Lymphoid aggregates were encountered with increasing frequency in older individuals. These findings aid in the evaluation of BM lymphocyte subsets and distribution both in living patients and autopsy evaluation. We also present a practical approach to image analysis.

The incidence and prognosis of clonal hematopoiesis in patients with isolated neutropenia among patients with idiopathic cytopenia of undetermined significance (ICUS), known as ICUS-N or chronic idiopathic neutropenia (CIN) patients, is poorly defined. The current study sought to investigate the frequency and clinical significance of mutations of genes implicated in myeloid malignancies using next-generation sequencing in patients with CIN (n = 185) with a long follow-up. We found that 21 (11.35%) of 185 patients carried a total of 25 somatic mutations in 6 genes with a median variant allele frequency of 12.75%. The most frequently mutated genes were DNMT3A and TET2 involving >80% of patients, followed by IDH1/2, SRSF2, and ZRSR2. The frequency of transformation to a myeloid malignancy was low in the total group of patients (5 of 185 patients [2.70%]). However, from the transformed patients, 4 belonged to the clonal group (4 of 21 [19.05%]) and 1 to the nonclonal group (1 of 164 [0.61%]), indicating that the presence of mutation(s) confers a relative risk for transformation of 31.24 (P = .0017). The variant allele frequency of the mutant clones in the transformed patients was >10% in all cases, and the genes most frequently associated with malignant transformation were SRSF2 and IDH1. No significant differences were identified between the clonal and nonclonal groups in the severity of neutropenia. Patients with clonal disease were older compared with nonclonal patients. These data contribute to the better understanding of the heterogeneous entities underlying ICUS and highlight the importance of mutation analysis for the diagnosis and prognosis of patients with unexplained neutropenias.

Pediatric HIV is a significant contributor to childhood morbidity and mortality. As HIV infects bone marrow CD34-positive progenitor cells, the hematological abnormalities are well-expected. The viral load is much higher in children predisposing them to opportunistic infections and hematopoietic malignancies. The present study aimed to determine the spectrum of hematological abnormalities that may yield clinically useful information in HIV-infected children. This was a retrospective study of 19 HIV-infected children who underwent bone marrow examination. Overall, 20 peripheral blood and bone marrow samples were analyzed for morphological changes in all hematopoietic lineages. Immunohistochemistry was performed on trephine biopsy sections for evaluation of B and T cells and cytomegalovirus inclusions. Anemia was the most common cytopenia (95%), followed by thrombocytopenia (45%) and leukopenia (40%). Myelodysplasia was noted in 70% of cases. Dysmegakaryopoiesis was predominant in 65% of cases, while dyserythropoiesis was noted in 25% of cases. Hemophagocytosis and reactive cellular changes were noted in 20% of cases each. Benign lymphoid aggregates and granulomatous inflammation were observed in 15% and 10% of cases, respectively. Significant myelofibrosis was found in 35% of cases. One case showed infiltration by Burkitt lymphoma. Parvoviral inclusions were identified in 1 case. An interstitial increase and aggregates of CD8 + T cells and reduced CD4 + T cells were noted. CD20 + B cells were normal to mildly increased in the bone marrow. Bone marrow examination provides clinically significant information in pediatric HIV revealing the underlying cause of hematopoietic abnormalities and allows the exclusion of major hematological neoplasms.

Background Secondary hemophagocytic lymphohistiocytosis (sHLH) is a rare and fatal disease characterized by uncontrolled immune cell activation that can lead to a cytokine storm. Unfortunately, this condition can occur even during pregnancy, threatening both maternal and fetal lives. Case presentation A 23-year-old nulliparous woman at 26 weeks of gestation presented with continuous fever, coughing, and sore throat. Upon arrival at our hospital, her temperature was >38°C and laboratory findings indicated cytopenia (neutrophil count, 779/μL; hemoglobin level, 10.2 g/dL; platelet count, 29,000/μL), elevated ferritin level (1,308 ng/mL), and elevated soluble interleukin-2 receptor level (11,200 U/mL). Computed tomography showed marked splenomegaly. Bone marrow examination revealed hemophagocytosis, and blood examination showed a plasma Epstein–Barr virus (EBV) DNA level of 8.9 × 105 copies/μg. The monoclonal proliferation of EBV-infected T cells was confirmed by Southern blotting, and the patient was diagnosed with chronic active EBV-associated sHLH and T-cell lymphoproliferative disease. Immediately after admission, the patient’s condition suddenly deteriorated. She developed shock and disseminated intravascular coagulation, requiring endotracheal intubation along with methylprednisolone pulse and etoposide therapy. Although the patient recovered, she delivered a stillborn baby. After delivery, she was treated with reduced-dose dexamethasone, etoposide, ifosfamide, and carboplatin (DeVIC) and steroid (dexamethasone), methotrexate, ifosfamide, L-asparaginase, and etoposide (SMILE) chemotherapies. Five months after diagnosis, she received human leukocyte antigen-haploidentical allogeneic bone marrow transplantation from her sister. She remains in remission for 5 months from the time of transplantation to the present. Conclusions sHLH, which may cause maternal and fetal death, should be carefully considered in critically ill pregnant women, particularly those presenting with continuous fever and cytopenia.

Objectives To examine flow cytometric (FCM) findings in clonal cytopenia of undetermined significance (CCUS) in relation to variant allele fraction (VAF) and mutation risk. Methods Nine FCM parameters, including 5 FCM metrics (Meyerson-Alayed scoring scheme [MASS] parameters) we previously used to identify myelodysplastic syndromes (MDS), were compared among 96 CCUS samples, 100 low-grade MDS samples and 100 samples from patients without somatic alterations (controls). Results FCM findings did not differ between CCUS samples with less than 20% VAF and controls. CCUS samples with more than 20% VAF (CCUS >20% VAF) demonstrated more than 1 abnormal FCM parameter at a frequency between MDS and controls. Abnormalities in CCUS with high-risk alterations (CCUS(hi)) were similar to MDS, with no statistical difference in the percentage of cases with more than 1 FCM abnormality or a positive MASS score. The positive predictive value (PPV) for clinically significant myeloid processes; MDS, CCUS(hi), and CCUS >20% VAF compared with other CCUS samples and controls was 94.8%, with 96.5% specificity and 61% sensitivity using a modified MASS score. A subset of MDS (43%) was distinguished from CCUS(hi) and CCUS >20% VAF using 3 parameters, with a 93.5% PPV and 83.3% specificity. Conclusions FCM abnormalities can distinguish high-risk CCUS based on VAF or alteration type from low-risk CCUS and MDS in many cases. The findings are of potential utility in the evaluation of patients with cytopenias.

Data are scarce regarding both the safety and immunogenicity of the BNT162b2 mRNA COVID-19 vaccine in patients undergoing immune cell therapy; thus, we prospectively evaluated these two domains in patients receiving this vaccine after allogeneic hematopoietic cell transplantation (HCT; n = 66) or after CD19-based chimeric antigen receptor T cell (CART) therapy (n = 14). Overall, the vaccine was well tolerated, with mild non-hematologic vaccine-reported adverse events in a minority of the patients. Twelve percent of the patients after the first dose and 10% of the patients after the second dose developed cytopenia, and there were three cases of graft-versus-host disease exacerbation after each dose. A single case of impending graft rejection was summarized as possibly related. Evaluation of immunogenicity showed that 57% of patients after CART infusion and 75% patients after allogeneic HCT had evidence of humoral and/or cellular response to the vaccine. The Cox regression model indicated that longer time from infusion of cells, female sex, and higher CD19+ cells were associated with a positive humoral response, whereas a higher CD4+/CD8+ ratio was correlated with a positive cellular response, as confirmed by the ELISpot test. We conclude that the BNT162b2 mRNA COVID-19 vaccine has impressive immunogenicity in patients after allogeneic HCT or CART. Adverse events were mostly mild and transient, but some significant hematologic events were observed; hence, patients should be closely monitored.

Due to an increased incidence of copper deficiency, we investigated adult patients who had low serum levels of copper with cytopenia at our hospital from March 2014 to March 2021.We retrospectively reviewed the clinical data of patients who had been diagnosed with cytopenia due to copper deficiency at the Aichi Medical University Hospital from March 2014 to March 2021.In the 15 patients with cytopenia secondary to low serum copper level, 11 had cytopenia of two to three lineages; three (27%) had pancytopenia, and eight (73%) had bicytopenia. Of the 15 patients, nine (60%) underwent bone marrow examinations; three (30%) showed typical morphologic features associated with copper deficiency, such as multiple clear cytoplasmic vacuoles in erythroblasts and myeloid cells, and three (30%) showed dysplastic features as observed in myelodysplastic syndrome. Among the 14 (93%) patients who were treated with copper supplements, had cessation of zinc supplements, or both, 11 (73%) and eight (53%) showed normal copper levels and hematological improvement, respectively.Copper deficiency is more common than expected and should be considered in patients with unexplained cytopenia.

Hemophagocytic lymphohistiocytosis (HHL), a severe hyperinflammatory syndrome caused by aberrant activation of macrophages and cytotoxic T cells, is clinically manifested as a febrile onset along with cytopenias, high ferritin serum level and splenomegaly. In adult patients, secondary causes of it should be looked for, such as autoimmune and infectious diseases and neoplasms. Prompt initiation of treatment is important due to the high mortality of this syndrome.A case of a 53-year-old patient diagnosed with HHL associated with T-cell lymphoma is presented as a sudden onset of several symptoms and signs of HHL, along with infectious complications.Results: Once the diagnosis of HHL was made, treatment with Etoposide and Dexamethasone was started, and with the diagnosis of T-cell lymphoma established, chemotherapy treatment with a CHOEP scheme was started, with a favorable initial evolution.As HHL is a rare entity associated with high mortality, initial suspicion must be high when facing an acute onset of fever, cytopenia and splenomegaly. Nonetheless, diagnosing HHL is challenging and often appear superimposed on multiple infectious diseases. The early initiation of treatmbent is important given the high mortality of this pathologyLa linfohistiocitosis hemofagocítica (LHH) es un síndrome hiperinflamatorio severo causado por activación aberrante de macrófagos y células T citotóxicas que se manifiesta clínicamente como un cuadro febril asociado a citopenias, hiperferritininemia y esplenomegalia. Ante su diagnóstico en adultos se deben buscar causas secundarias como neoplasias hematológicas. El inicio precoz del tratamiento es importante debido a su elevada mortalidad.Se presenta el caso de una paciente de 53 años de edad que se le realizó diagnóstico de LHH asociada a Linfoma de células T. La forma de presentación de dicho cuadro fue de manera abrupta con varios síntomas y signos de dicho síndrome, además de múltiples complicaciones infecciosas asociadas.Ante el diagnóstico inicial de LHH se inició tratamiento con etopósido y dexametasona, y al obtener el diagnóstico de Linfoma de células T, se instauró tratamiento quimioterápico con esquema de CHOEP, con evolución inicial favorable.La LHH es una entidad poco frecuente asociada a una elevada mortalidad, por lo que su índice de sospecha debe de ser elevado ante un cuadro clínico y analítico compatible. Sin embargo, su diagnóstico constituye un gran desafío clínico, pudiendo presentarse en algunas ocasiones superpuesto a cuadros infecciosos múltiples. El inicio precoz del tratamiento es importante debido a su alta mortalidad.

Immune-mediated adverse events (imAEs) are complications of therapy with immune checkpoint inhibitors, which arise as a result of autoimmune inflammation. The article summarizes systemic (fatigue, fever), cutaneous (rash, itching), gastrointestinal (diarrhea, colitis, hepatitis, pancreatic dysfunction), endocrinological (hypothyroidism, hypophysitis, adrenal insufficiency, diabetes mellitus), pulmonary (pneumonitis, pleuritis), rheumatological (arthralgia), neurological (headache, sensory and motor disorders), renal (acute interstitial nephritis, lupus-like nephritis, granulomatous nephritis, diffuse interstitial nephritis and minimal change disease), hematological (anemia, cytopenia), cardiovascular (myocarditis) and ocular (conjunctivitis, episcleritis, ceratitis, blepharitis and uveitis) imAE. Pathogenetic mechanisms and treatment approaches (in accordance with toxicity grade and clinical recommendations) are discussed. Early symptom recognition, patient education and timely intervention are crucial for imAE correction.

Hepatitis-associated aplastic anemia (HAA) is a form of acquired aplastic anemia (AA) in which bone marrow failure develops after an acute attack of hepatitis. Bone marrow failure leading to AA is generally severe in cases of HAA and fatal if left untreated. This retrospective multicenter study investigated clinical and laboratory characteristics, possible causes, treatment, and outcome of HAA in children. Twenty patients from 8 centers were included in the study. Aspartate aminotransferase and alanine aminotransferase were 10×ULN in 16 patients. Acute liver failure developed in 5 (29%) patients. Pancytopenia was simultaneously present in 6 of 20 (30%) patients. Eleven of the 20 patients (55%) were alive, in remission and transfusion free. Those who were alive either had undergone hematopoietic stem cell transplantation and/or immunosuppressive treatment, except 1 patient who had received no treatment. Patients with the diagnosis of acute hepatitis should be evaluated and followed up carefully for presence of cytopenia, so that definitive treatment of AA can be initiated in a timely and appropriate manner when needed. Copyright r 2021 Wolters Kluwer Health, Inc. 34669357

Objectives Intravascular large B-cell lymphoma (IVLBCL) is a rare subtype of non-Hodgkin lymphoma with uncommon clinical presentations and poor prognosis. The purpose of this study is to report the clinical features and outcome of IVLBCL in a single institution of Taiwan. Patient and methods Ten patients with IVLBCL diagnosed from June 2006 to January 2018 were retrospectively reviewed. Results The median age was 61 (range 39–88) years. The most common presentation was fever (90%), cytopenia (90%), and confusion (50%). For all patients, the median progression free survival (PFS) and overall survival (OS) were 12.6 (95% confidence interval [CI] 0.0–76.1) and 18.8 (95% CI 0–59.3) months, respectively. Six patients received rituximab combined chemotherapy, and the other one patient was treated with chemotherapy alone. Six of seven (85.7%) patients achieved complete response after chemotherapy. The median PFS and OS for six patients who completed treatment were not reached. Three-year PFS and OS rates were 80% and 75%, respectively. Conclusions Our study showed that patients might achieve durable remission after rituximab-based chemotherapy. The outcome of IVLBCL patients may further improve if early diagnosis and prompt treatment were made.

Mantle cell lymphoma (MCL) is a rare and clinically aggressive lymphoma subtype. Current approaches have greatly improved patients outcomes, but relapse is inevitable. In phase IIIII clinical trials, ibrutinib has shown significant activity in patients with relapsed or refractory (R/R) MCL.To assess efficacy and toxicity of ibrutinib monotherapy in patients with R/R MCL in routine practice outside of clinical trials.The study enrolled patients with confirmed R/R MCL who had received at least one line of previous chemotherapy. ECOG 24, cytopenia, infectious complications, hemorrhagic syndrome were not exclusion criteria. Patients received daily oral ibrutinib 560 mg until progression or unacceptable toxicity.From May 2015 to September 2020 ibrutinib therapy was started in 106 patients with R/R MCL in 16 regions of Russia. The median age was 66 years; ECOG2 18%, blastoid variant (or Ki6740% or WBC50109/l) 43%. The median number of previous treatment lines was 2 (111). The ORR was 78.4% (CRR 27.4%). The median PFS was 13.6 months and OS 23.2 months. In the blastoid group the median PFS was 4.4 months vs 36.5 months in the alternative group (p0.001), the median OS 9.0 vs 41.0 (p=0.001). The median OS of patients after progression on ibrutinib was 3.2 months. The common complications are hemorrhages (63%), diarrhea (62%), myalgia and muscle cramps (60%), infections (31%), skin and nail toxicity 15%, arrhythmia 8%. None of recipients had to completely discontinue ibrutinib therapy due to complications.Ibrutinib is effective and well tolerated in routine practice of R/R MCL treatment and our results are consistent with international clinical trials. The favorable toxicity profile and the high response rate made it possible to prescribe ibrutinib in severe somatic status, cytopenia, and even in the presence of infectious complications.Обоснование. Лимфома из клеток мантийной зоны (ЛКМЗ) редкая и агрессивная В-клеточная лимфома. Интенсификация химиотерапии значительно улучшила результаты лечения, но развитие рецидива неизбежно. В исследованиях IIIII фазы ибрутиниб продемонстрировал высокую эффективность у пациентов с рецидивом и резистентным (р/р) течением ЛКМЗ. Цель. Оценить эффективность и токсичность монотерапии ибрутинибом у пациентов с р/р ЛКМЗ в повседневной практике. Материалы и методы. В исследование включены пациенты с подтвержденным диагнозом р/р ЛКМЗ, получившие не менее одной линии химиотерапии. Тяжелый соматический статус, цитопения, инфекционные осложнения и геморрагический синдром не служили противопоказаниями для начала терапии. Ибрутиниб назначался в дозе 560 мг ежедневно до прогрессирования или развития неприемлемой токсичности. Результаты. С мая 2015 по сентябрь 2020 г. включены 106 пациентов в 16 регионах России. Медиана возраста 66 лет; ECOG2 18%; бластоидный вариант (или Ki6740%, или WBC50109/л) 43%. Медиана предшествующих линий терапии 2 (111). Общий ответ достигнут у 78,4% (полная ремиссия 27,4%). Медиана беспрогрессивной выживаемости (БПВ) 13,6 мес, общей выживаемости (ОВ) 23,2 мес. При бластоидном варианте медиана БПВ составила 4,4 мес против 36,5 мес в альтернативной группе (p0,001), медиана ОВ 9,0 мес против 41,0 мес (р=0,001). Медиана ОВ при развитии резистентности к ибрутинибу 3,2 мес. Наиболее частые осложнения: геморрагии (63%), диарея (62%), миалгии и мышечные судороги (60%), инфекции (31%), кожная токсичность 15%, аритмия 8%. Ни одному из пациентов полностью терапию ибрутинибом из-за токсичности не остановили. Заключение. Ибрутиниб эффективен и хорошо переносится в рутинной практике терапии р/р ЛКМЗ, а результаты согласуются с данными международных исследований. Благоприятный профиль токсичности и высокая частота ответов позволили назначать ибрутиниб при тяжелом соматическом статусе, цитопении или наличии инфекционных осложнений.

Introduction The diagnosis of myelodysplastic syndromes (MDS) and myelodysplastic/myeloproliferative neoplasms (MDS/MPN) is based on morphology and cytogenetics/FISH findings per 2017 WHO classification. With rare exceptions, somatic mutations have not been incorporated as the diagnostic criteria. Methods We analyzed the utility of mutational analysis with a targeted 54-gene or 40-gene next-generation sequencing (NGS) panel in the diagnosis of MDS and MDS/MPN. Results We retrospectively collected 92 patients who presented with unexplained cytopenia with or without cytosis, including 32 low-grade MDS (MDS-L), 18 high-grade MDS (MDS-H), 5 therapy-related MDS (MDS-TR), 19 MDS/MPN, and 18 negative cases. Of 92 patients, 197 somatic mutations involving 38 genes were detected and had variant allele frequency (VAF) ranging from 3% to 99%. The most common mutated genes were TET2, ASXL1, RUNX1, TP53, SRSF2, and SF3B1. MDS-L, MDS-H, MDS-TR, and MDS/MPN showed an average number of somatic mutations with a mean VAF of 1.9/33%, 2.6/30%, 2/36%, and 4/41%, respectively. SF3B1 mutations were exclusively observed in MDS-L and MDS/MPN. TP53 gene mutations were more frequently seen in MDS-H and MDS-TR. Among 34 patients with a diagnosis of MDS or MDS/MPN with normal cytogenetics, 31 patients (91%) had at least 1 mutation and 24 patients (71%) had ≥2 mutations with ≥10% VAF. Conclusion A myeloid mutational panel provides additional evidence of clonality besides cytogenetics/FISH studies in the diagnosis of cytopenia with or without cytosis. Two or more mutations with ≥10% VAF highly predicts MDS and MDS/MPN with a positive predictive value of 100%.

Background Unprovoked pulmonary embolism (uPE) is a severe and frequent condition. Identification of new risk factors is mandatory to identify patients that would benefit from a long-term treatment. Clonal hematopoiesis of indeterminate potential (CHIP) is defined by the acquisition of somatic mutations that drive clonal expansion in the absence of cytopenia. Its prevalence is estimated of 5% in the population above 65 years. Since inflammation and endothelial dysfunction may share a pathophysiological pathway(1), we hypothesized that CHIP, may be a risk factor for uPE.Methods We conducted a pilot retrospective observational study. Patients with iPE between 18 to 65 years old were included. PE was considered as unprovoked, when no transient nor persistant risk factor was present and when thrombophilia testing was negative. We excluded documented atherosclerosis, personal or familial history of VTE and presence of cytopenias. CHIP proportion in uPE patients were analyzed using next generation sequencing of the coding sequence of a custom panel composed by DNMT3A, ASXL1, SF3B1, TET2 and TP 53.Results Upon 61 patients with uPE consecutively included, a total of 19 somatic mutations were found in 12 patients (20%) IC95% [10 - 20]. 15 mutations were found in DNMT3A gene, 3 in ASXL1 and one in TET2. There was no diference in terms of age, PE location, DVT presence and risk stratification in CHIP carriers and non carriers.Conclusion We report for the first time, the presence of high rates of CHIP in patients presenting with uPE. Thus, CHIP may be a new risk factor for VTE. These results need to be confirmed in an ongoing prospective case-control study including more patients and using a more diverse gene panel to better determine CHIP incidence in uPE.

Background. The true causes of mortality and risk factors for pneumonia caused by COVID-19 require detailed analysis. Purpose: to clarify the risk factors for death in pneumonia caused by the SARS-CoV-2 virus. Materials and methods. A total of 196 patients with pneumonia of coronavirus etiology were examined. The observation group consisted of 68 patients with a lethal outcome, the comparison group consisted of 128 patients discharged with improvement. The assessment of the significance of risk factors for death was carried out by determining the magnitude of the relative risk and the etiological fraction. The results of the study were subjected to statistical processing with the calculation of the mean values, errors of the mean values, the criterion of reliability of the Student’s indicators (t). Results. The likelihood of death in patients with pneumonia caused by COVID-19 increases with increasing age of patients, living in the city, with pro-longed persistence of febrile syndrome, the need for re-hospitalization and transfer to the intensive care unit, and a large amount of damage. Respiratory failure of the III degree, renal failure, pleurisy, toxic liver damage, hematomas of various localization increase the risk of death. The course of COVID-19 infection is aggravated by chronic heart failure, coronary heart disease, diabetes mellitus, and chronic obstructive pulmonary disease. Laboratory predictors of an unfavorable outcome are cytopenia (lymphopenia, thrombocytopenia, anemia), a significant increase in ESR, CRP, D-dimer. Conclusion. Timely identification and consideration of risk factors for death will make it possible to adjust the volume of treatment measures in order to improve the prognosis for the life of patients with COVID-19-associated pneumonia. © 2021, Science and Innovation Center Publishing House. All rights reserved.

Autoimmune cytopenias (AICs) affect 5% to 9% of patients with chronic lymphocytic leukemia (CLL). Targeted drugs—ibrutinib, idelalisib, and venetoclax—have a prominent role in the treatment of CLL, but their impact on CLL-associated AICs is largely unknown. In this study, we evaluated the characteristics and outcome of preexisting AICs and described the incidence, quality, and management of treatment-emergent AICs during therapy with targeted drugs in patients with CLL. We collected data from 572 patients treated with ibrutinib (9% in combination with an anti-CD20 monoclonal antibody), 143 treated with idelalisib-rituximab, and 100 treated with venetoclax (12% in combination with an anti-CD20 monoclonal antibody). A history of preexisting AICs was reported in 104 (13%) of 815 patients. Interestingly, 80% of patients whose AICs had not resolved when treatment with a targeted drug was started experienced an improvement or a resolution during therapy. Treatment-emergent AICs occurred in 1% of patients during ibrutinib therapy, in 0.9% during idelalisib therapy, and in 7% during venetoclax therapy, with an estimated incidence rate of 5, 6, and 69 episodes per 1000 patients per year of exposure in the 3 treatment groups, respectively. The vast majority of patients who developed treatment-emergent AICs had unfavorable biological features such as an unmutated IGHV and a del(17p) and/or TP53 mutation. Notably, despite AICs, 83% of patients were able to continue the targeted drug, in some cases in combination with additional immunosuppressive agents. Overall, treatment with ibrutinib, idelalisib, or venetoclax seems to have a beneficial impact on CLL-associated AICs, inducing an improvement or even a resolution of preexisting AICs in most cases and eliciting treatment-emergent AICs in a negligible portion of patients.

Myelodysplastic Syndromes (MDS) are a group of heterogeneous hematologic disorders characterized by bone marrow involvement. Iron overload is the result of multiple transfusions and high levels of apoptosis. Based on a literature review, ferritin was identified as an important marker of iron accumulation in organs such as liver, heart and pancreas in patients with MDS. Some studies also demonstrated that iron overload caused cell cycle arrest causing apoptosis and progression to leukemia, high levels of reactive oxygen species and low levels of HIF-1a, causing apoptosis, being related to the presence of cytopenia in MDS.

Introduction Human immunodeficiency virus (HIV) infection is a state of profound immunodeficiency. Disorders of hematopoietic system are a common but often overlooked complication of HIV infection. This can manifest at any stage of the disease but more commonly in the advanced stage with low CD4 count. Anemia is the most common hematological abnormality in HIV patients and prevalence ranges from 1.3 to 95%. As HIV disease progresses, the prevalence and severity of anemia also increase. Hence, this study was undertaken to assess the hematological parameters of HIV-infected patients on highly active antiretroviral therapy (HAART) at different treatment durations with the hope to improve the HAART outcome in HIV patients and its correlation with CD4 count. Methods This prospective longitudinal study enrolled 134 HIV-infected patients admitted to or attending the OPD in the Department of Medicine or Antiretroviral Therapy (ART) Center (Center of Excellence), Regional Institute of Medical Sciences (RIMS), Imphal, Manipur, from 2018 to 2020. Complete hemogram, CD4 count, and other related-blood investigations were studied. Results The mean age of the study population was 39.9 ± 11.04 years. Of the 134 patients, 75 (56%) were males and 59 (44%) were females. Twelve (9%) patients had a history of injecting drug use (IDU). TLE (tenofovir, lamivudine, efavirenz) regimen was started on 112 (83.6%) patients and the majority of them (69/134 [51.5%]) had a CD4 count of 200 to 499 cells/mm3, which increased significantly 6 months after HAART to 99 to 1,149 cells/mm3, with a mean of 445 ± 217 cells/mm3. There were significant improvements in hemoglobin (Hb) levels, total leukocyte count (TLC), absolute neutrophil count (ANC), and absolute lymphocyte count (ALC) after HAART indicating a positive correlation with CD4 count (p < 0.05). Thrombocytopenia was observed higher after HAART when compared to baseline. There was a positive correlation between platelet count and CD4 count. However, the mean corpuscular volume (MCV) and erythrocyte sedimentation rate (ESR) had a negative correlation with CD4 count. Conclusion The study inferred a strong positive correlation between CD4 and Hb levels, TLC, ANC, ALC, and platelet count after HAART with improvement in these values as CD4 count increases. Specific treatment intervention based on the changes in the immunohematological profile trends can help prevent most of the adverse effects on HIV patients in our community.

This study investigated the frequency of and predictive factors for autoimmune lymphoproliferative syndrome (ALPS) in children with lymphoma, chronic immune cytopenia, and nonmalignant organomegaly. Thirty-four children with suspected ALPS (n=13, lymphoma; n=12, immune cytopenia; n=9, nonmalignant organomegaly) were included. Double-negative T-cells, lymphocyte apoptosis, and genetic findings were analyzed. Patients were stratified into two groups as proven/probable ALPS and clinically suspected patients according to the ALPS diagnostic criteria. Of the 34 patients, 18 (53%) were diagnosed with proven/probable ALPS. One patient had a mutation (c.652-2AC) in theBu çalışmanın amacı malign olmayan organomegali, kronik immün sitopeni ve lenfomalı çocuklarda otoimmün lenfoproliferatif sendrom (OILS) sıklığını ve belirleyici faktörlerini araştırmaktır. Bu çalışmaya OILS şüpheli 34 hasta dahil edildi (13 hasta lenfoma, 5 hasta otoimmün hemolitik anemi, 7 hasta kronik immün trombositopenik purpura ve 9 hasta malign olmayan organomegali). Çift negatif T-hücreler, lenfosit apoptozis ve genetik bulgular analiz edildi. Hastalar OILS tanı kriterlerine göre kesin ve yüksek olasılıklı OILS’li hastalar ve klinik şüpheli OILS’li hastalar olarak iki gruba ayrıldı. Çalışmaya dahil edilen 34 hastanın, 18’i (%53) kesin ve yüksek olasılıklı OILS’di. Malign olmayan organomegalisi olan bir çocukta FAS geninde mutasyon (c.652-2AC) saptandı. Klinik şüpheli hasta 16 (%47) idi. OILS için belirleyici faktörler; lenfomalı hastalarda anemi ve trombositopeni, kronik immün sitopenili hastalarda splenomegali ve lenfadenopati; malign olmayan organomegalisi olan hastalarda genç yaş idi. OILS belirli risk gruplarında nadir olmayabilir. Çalışmamız, ilk tanıda sitopenisi olan lenfomalı çocuklarda, immün sitopenisi olan nonmalign organomegalili çocuklarda ve izlem sırasında organomegalisi gelişen kronik immün trombositopenik purpura ve otoimmün hemolitik anemili çocuklarda OILS taramasının yararlı olabileceğine işaret etmektedir.

We present a case of a healthy 62-year-old woman who developed recurrent seizures preceded by subacute cognitive slowing, ataxia, night sweats, and weight loss. She was found to have cytopenias, multifocal T2/FLAIR hyperintensities on magnetic resonance imaging (MRI), and magnetic susceptibility artifact lesions on susceptibility weighted imaging (SWI). Her symptoms, imaging and laboratory abnormalities all improved with high-doses of steroids and intravenous immunoglobulin (IVIG). But recurred several weeks after completing treatment. Despite extensive work-up, she required multiple hospitalizations and repeat diagnostic studies to arrive at a diagnosis. With an expert discussant in hematology and oncology, we review the differential diagnosis and stepwise approach of unexplained neuro-inflammatory syndromes with cytopenias and systemic symptoms. Our case highlights how time, empiric treatment response, and repeated diagnostic studies refine differential diagnoses and subsequent evaluation. After revealing the diagnosis, we discuss the heterogenous clinical manifestations of this disease process.

The heterogeneous nature of myelodysplastic syndrome (MDS) brings a very variable prognosis of patients with the need for individualized treatment. The prognosis and treatment depend on the conventional determination of IPSS (International Prognostic Scoring System) and its revised form IPSS-R, which divides patients into lower and higher risk groups. Treatment of patients with lower risk of MDS include the improvement of cytopenia, especially anemia. The goal of treatment in patients with higher risk of MDS is delaying disease progression and improve patient survival. The only curative method for therapy of MDS is allogeneic hematopoietic stem cell transplantation (HSCT), howewer it is rarely applicable due to the age and comorbidities of patients.

Chronic lymphocytic leukaemia/small lymphocytic lymphoma is a common subtype of non-Hodgkin lymphoma that is often diagnosed after finding an incidental lymphocytosis on a routine blood count. Key diagnostic tests are peripheral blood morphology and immunophenotyping. At all stages of disease, patients are vulnerable to infections and other malignancies. Treatment is only indicated in those who develop significant disease-related constitutional symptoms, and/or bulky lymphadenopathy, massive splenomegaly, or cytopenia. An increasing number of prognostic biomarkers are now available to assess likely disease outcome and response to different types of treatment. Use of newer agents such as Bruton's tyrosine kinase inhibitors and B cell lymphoma 2 inhibitors have started to replace more traditional chemo-immunotherapy and have increased overall life expectancy.

Background The objective of this study was to describe the most common medical complications in simultaneous pancreas-kidney recipients in our center. Methods Retrospective and descriptive study of complications observed in a series of 73 simultaneous pancreas-kidney transplant recipients, which included 54 men and 19 women with an average age of 40.6 years, between February 2009 and April 2019. The study assessed the incidence of cytopenia, viral infections, tumors, and graft rejection. Frequency tables were created for each complication in the analysis. Results Cytopenia was the most common complication, either by itself or associated with a different complication, and it was found in 23.3% of all patients. The most common infection was cytomegalovirus, which was in 55.6% of all 9 patients who presented infections in spite of universal prophylaxis with valganciclovir, followed by herpes virus (11.1%), papillomavirus (11.1%), and polyoma BK virus (22.2%). Regarding tumors, the number of patients who presented this complication was low; 2 gynecologic tumors were detected (cervical intracellular neoplasia and one ovarian tumor), and 1 case of skin tumor was also observed. There were 3 cases of acute rejection, which represents 4.1% of all patients. Rejection was cellular and steroid-sensitive except for 1 case that was humoral, with good response to treatment. Conclusions In spite of the doses of immunosuppressive drugs received by these patients, the incidence of infections was low, and cytomegalovirus was the most common infection. As a consequence of the drugs administered, virtually all patients developed cytopenia. The number of tumors observed in this series was low in spite of the immunosuppressive treatment.

Shambel Araya,1,2 Moges Wordofa,1 Mintesnot Aragaw Mamo,2,3 Yakob Gebregziabher Tsegay,2– 4 Abebe Hordofa,2,5 Abebe Edao Negesso,1 Tewodros Fasil,1 Betelhem Berhanu,1 Hermela Begashaw,1 Asegdew Atlaw,2 Tirhas Niguse,1 Mahlet Cheru,1 Zemenu Tamir1 1Department of Medical Laboratory Sciences, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia; 2Department of Medical Laboratory, Millennium COVID-19 Treatment and Care Centre, St. Paul Millennium Medical College, Addis Ababa, Ethiopia; 3Department of Medical Biotechnology, Institute of Biotechnology, University of Gondar, Gondar, Ethiopia; 4Research and Development Center, College of Health Sciences, Defense University, Addis Ababa, Ethiopia; 5Department of Medical Laboratory, Legehare General Hospital, Addis Ababa, EthiopiaCorrespondence: Moges Wordofa Email heranmakmow@gmail.comBackground: Coronavirus disease 2019 (COVID-19) is a systemic infection with cardiovascular, pulmonary, gastrointestinal, neurological, and hematological manifestations. Abnormal hematological findings are thought to have a role in early risk stratification and prognostication of COVID-19 patients. However, the data on hematological abnormalities associated with the disease among Ethiopian COVID-19 patients are limited.Objective: To determine the magnitude of hematological abnormalities among COVID-19 patients admitted at Millennium COVID-19 referral treatment center, Addis Ababa, Ethiopia.Methods: A prospective cross-sectional study was conducted among COVID-19 patients admitted to Millennium COVID-19 referral treatment center from May to July, 2020. A total of 334 COVID-19 patients were included using convenience sampling. Socio-demographic data and disease severity status of admitted patients were recorded. Three milliliters of venous blood was collected and analyzed by Beckman Coulter DXH-600 automated analyzer to determine complete blood count (CBC). The data were entered and analyzed using SPSS version 23 software. Association of age, sex, and disease severity with hematological abnormalities was analyzed using binary logistic regression. An odds ratio and 95% confidence interval were used to measure the strength of association. P-value < 0.05 was considered as statistically significant.Results: Of 334 admitted COVID-19 patients, the majority were males (62.3%) and 69.8% had moderate disease conditions. The overall magnitude of any cytopenia and pancytopenia was 41% and 1.8%, respectively. The magnitude of anemia, thrombocytopenia, and leukopenia was 24.9%, 21.6%, and 5.4%, respectively. Lymphopenia (72.2%) was the most common hematological abnormality. COVID-19 patients with severe and critical disease were more likely to develop anemia, leukocytosis, neutrophilia, and combined neutrophilia-lymphopenia than those with moderate disease condition, with a significant association.Conclusion: Lymphopenia was the most common hematological abnormality observed among COVID-19 patients. Hematological abnormalities such as anemia, leukocytosis, neutrophilia, and combined neutrophilia-lymphopenia were significantly associated with disease severity. Monitoring and evaluation of hematological parameters could provide prognostic insight into the management and risk stratification of COVID-19 patients. However, further studies are required to fully understand the utility of hematological parameters for the prognosis of COVID-19 disease.Keywords: hematological parameters, COVID-19, disease severity

DDX41 mutations are associated with hematologic malignancies including myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), but the incidence in idiopathic cytopenia of undetermined significance (ICUS) is unknown. We investigated the incidence, genetic characteristics, and clinical features of DDX41 mutations in Korean patients with ICUS, MDS, or AML. We performed targeted deep sequencing of 61 genes including DDX41 in 457 patients with ICUS (n=75), MDS (n=210), or AML (n=172). Germline DDX41 mutations with causality were identified in 28 (6.1%) patients, of whom 27 (96.4%) had somatic mutations in the other position of DDX41. Germline origins of the DDX41 mutations were confirmed in all of the 11 patients in whom germline-based testing was performed. Of the germline DDX41 mutations, p.V152G (n=10) was most common, followed by p.Y259C (n=8), p.A500fs (n=6), and p.E7* (n=3). Compared with non-mutated patients, patients with a DDX41 mutation were more frequently male, older, had a normal karyotype, low leukocyte count, and hypocellular marrow at diagnosis. Three of the four ICUS patients with germline DDX41 mutations progressed to MDS. The incidence of DDX41 mutations in Korean patients was high and there was a distinct mutation pattern, in that p.V152G was a unique germline variant. ICUS harboring germline DDX41 mutations may be regarded as a hereditary myeloid neoplasm. Germline DDX41 mutations are not uncommon and should be explored when treating patients with myeloid malignancies.

Hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammation syndrome. In adults, secondary HLH is mostly observed. HLH is often triggered by infections, malignancies or autoimmune disorders. However, HLH cases in association with immunotherapies have been described recently. HLH in critically ill patients is often difficult to differentiate from sepsis. Both conditions can also be present at the same time. Early diagnosis and timely initiation of an adequate immunosuppressive therapy are essential for the further course and the prognosis of HLH. Therefore, HLH should represent a differential diagnosis in critically ill patients with persistent fever and additional symptoms (e.g. enlarged spleen, neurologic symptoms) or laboratory parameters (e.g. hyperferritinemia, cytopenia, increased transaminases) compatible with HLH. The diagnosis of HLH is made using the HLH-2004 criteria. The probability of the presence of HLH can be calculated using the HScore. High-dose corticosteroids represent the cornerstone of HLH treatment. Etoposide, immunoglobulins, anakinra or other drugs are added depending on the trigger. The course of HLH is influenced by the time of treatment initiation, the underlying trigger and the response to treatment. Generally, the prognosis of critically ill HLH patients is poor.Bei der hämophagozytischen Lymphohistiozytose (HLH) handelt es sich um ein Hyperinflammationssyndrom bedingt durch aberrant aktivierte Makrophagen und T‑Zellen. Beim Erwachsenen ist in erster Linie die erworbene Form anzutreffen. Häufige Auslöser sind Infektionen, Malignome und Autoimmunerkrankungen. Zuletzt wurden zudem zunehmend Fälle berichtet, in denen das Auftreten im Zusammenhang mit stattgehabten Immuntherapien zu sehen war. Auf der Intensivstation ist die HLH aufgrund des ähnlichen klinischen Erscheinungsbilds oft schwer von der Sepsis abzugrenzen. Zum Teil liegen beide zeitgleich vor. Die frühzeitige Diagnosestellung und Einleitung einer adäquaten immunsuppressiven Therapie ist für den weiteren Verlauf und die Prognose der HLH essenziell. Deshalb muss bei kritisch kranken Patienten mit persistierendem Fieber und entsprechenden Symptomen (z. B. Splenomegalie, neurologische Auffälligkeiten) oder Laborveränderungen (z. B. erhöhter Ferritinwert, Zytopenie von 2 oder 3 Zellreihen, erhöhte Transaminasen) das Vorliegen einer HLH in Betracht gezogen werden. Die Diagnose wird mithilfe der HLH-2004-Kriterien gestellt. Mit dem HScore kann die Wahrscheinlichkeit des Vorliegens einer HLH berechnet werden. Hochdosierte Kortikosteroide stellen den Grundpfeiler der HLH-Therapie dar. Je nach Auslöser werden Etoposid, Immunglobuline, Anakinra oder weitere Medikamente ergänzt. Der Verlauf hängt neben einem frühzeitigen Behandlungsbeginn vom Auslöser sowie dem Ansprechen auf die Therapie ab. Insgesamt ist die Prognose der HLH trotz maximaler intensivmedizinischer Behandlung ungünstig und sie ist mit einer hohen Letalität assoziiert.

Suspicion of myelodysplastic syndromes (MDS) is the most common reason for bone marrow aspirate in elderly patients. This study aimed to prospectively validate the accuracy for flow cytometric analysis of peripheral blood neutrophil myeloperoxidase expression in ruling out MDS. We enrolled 62 consecutive patients who were referred for suspected MDS, based on medical history and peripheral blood cytopenia. The accuracy of intra-individual robust coefficient of variation (RCV) for peripheral blood neutrophil myeloperoxidase expression was assessed with a prespecified 30% threshold. Cytomorphological evaluation of bone marrow aspirate performed by experienced hematopathologists confirmed MDS in 23 patients (prevalence, 37%), unconfirmed MDS in 32 patients (52%, including 3 patients with idiopathic cytopenia of undetermined significance (ICUS)), and was uninterpretable in 7 patients (11%). The median intra-individual RCV values for neutrophil myeloperoxidase expression in peripheral blood were 37.4% (range, 30.7-54.1), 29.2% (range, 28.1-32.1), and 29.1% (range, 24.7-37.8) for patients with confirmed suspicion of MDS, ICUS, and unconfirmed suspicion of MDS, respectively (P

The virus SARS-CoV-2 commonly causes self-resolving, flu-like illnesses in the majority of patients, but a critical illness can be seen in 5% of cases - especially in the elderly population or in patients with multiple comorbidities. When COVID-19 is severe, it can cause pneumonia and hypoxemic respiratory failure, and can progress to viremia involving multiple organ systems. It causes significant cytopenia, mainly severe lymphopenia, and excessive exhaustion of CD8+ T cells, resulting in an immunocompromised state and cytokine storm. Furthermore, COVID-19 can commonly be complicated with acute thrombotic events, including venous thromboembolism, acute stroke, acute myocardial infarction, clotting of hemodialysis and extracorporeal membrane oxygenation (ECMO) catheters, and acute limb ischemia. This makes SARS-COV-2 a unique virus with an undiscovered pathophysiology. Therefore, patients with COVID-19 need close monitoring of their symptoms and laboratory parameters, and early hospitalization and treatment in severe cases. Early identification of severe cases and the abovementioned complications of COVID-19 could decrease the morbidity and mortality caused by the disease. In the study, we summarize what is currently known about the hematological manifestations and complications of COVID-19.

Thrombocytopenia is a frequent hematological complication of human immunodeficiency virus infection which can occur at any stage of HIV infection. The various cytopenias correlate directly with the degree of immunosuppression. However, isolated thrombocytopenia, may be the initial presentation of HIV infection. Incidence of thrombocytopenia is around 10% - 40% and in some patient only thrombocytopenia may be the first sign of HIV infection or AIDS. Since few studies are available from Asian countries we decide to study thrombocytopenia in HIV infection or AIDS from India.The study was conducted at a teaching hospital in India after obtaining ethical permission from the institute. Subjects were recruited after taking written informed consent. Two hundred subjects of both sex and in the age group 18-60 years were recruited for study. Blood samples were collected and analysed on same day within two hours. Platelet count of < 1.5 lakh/mm was defined as thrombocytopenia. Data analysis was carried out using Statistical Package for Social Science (SPSS) version 16.0. p value < 0.05 considered as significant and p value > 0.05 non-significant. The mean platelet count was 2.06935lakh/ mmand highest and lowest platelet count were 4.1lakh/mm and 0.63lakh/mmrespectively. Out of two hundred, 8.5% subjects had thrombocytopenia. Females had a slightly higher prevalence as compared to males but it was not statistically significant (p=0.22). Likewise more of younger age group patients had thrombocytopenia. No significant relation was found between platelet count and ART status (p=0.773). Thrombocytopenia is a common finding in HIV infection. Peripheral destruction of platelets and ineffective platelet production leads to thrombocytopenia among HIV patients. ART improves platelet count and must be started as soon as possible.

Biruk Bayleyegn,1 Berhanu Woldu,1 Aregawi Yalew,1 Desie Kasew,2 Fikir Asrie1 1Department of Hematology and Immunohematology, College of Medicine and Health Science, University of Gondar, Gondar, Ethiopia; 2Department of Medical Microbiology, College of Medicine and Health Science, University of Gondar, Gondar, EthiopiaCorrespondence: Biruk Bayleyegn Email birukbayle@gmail.comBackground: Human immunodeficiency virus (HIV) and intestinal parasites co-infections are the most common causes of clinical illness and death, especially for children living in resource constrained setting. Therefore, the aim of this study was to determine the prevalence and associated factors of intestinal parasites among highly active anti-retroviral therapy (HAART) initiated children.Methods: Cross-sectional study was conducted among 255 HAART initiated HIV-infected children at the University of Gondar Comprehensive Specialized Hospital from January to April 2020. Socio-demographic characteristics were collected using a structured questionnaire via a face-to-face interview. Clinical data of the children were collected by reviewing the medical records. Venous blood was collected for complete blood counts, viral load determination, and blood film examination. Flotation concentration technique was done in addition to direct wet mount for parasitological examination. Bi-variable and multi-variable logistic regression analysis were used to check the presence of significant association, and P-value< 0.05 was considered as statistically significant.Results: The overall prevalence of intestinal parasite infection (IPI) among the study participants was 22.4% (95% CI=17– 28%). The presence of opportunistic infection (AOR=2.09 95% CI=1.81– 5.43), no eating under-cooked animal products (AOR=0.38 95% CI=0.16– 0.94), male sex (AOR=0.45 95% CI=0.22– 0.90), viral load rate > 1,000 copies/mL (AOR=1.80 95% CI=1.67– 4.19), and cytopenia (AOR=2.71 95% CI=1.59– 12.25) showed significant association with the prevalence of IPI.Conclusion: Entamoeba histolytica and Ascaris lumbricoides were the most prevalent intestinal parasites among HAART initiated children. Among HAART initiated children, IPI were associated with gender, cytopenia, viral load, undercooked animal products, and the presence of opportunistic infections. Therefore, health education, prompt treatment, and regular deworming should be implemented to alleviate the burden of intestinal parasites in HIV-infected children.Keywords: intestinal parasite, HIV, children, Ethiopia

Background: Dengue is a severe and notifiable infection in Sri Lanka and other tropical countries.There are other febrile illnesses,which have the same symptoms as dengue. Identifying early changingmarkers in blood and their changing patterns in dengue and other febrile illnesses will help to differentiatedengue patients from other febrile illnesses.It is important for the early recovery and management of the dengue patients. Methods: Dengue suspected 288 patients were selected from adult medical wards inTeaching hospital-Peradeniya, after initial screening process. Out of whole population, 56% were RTPCRpositive for dengue and RT-PCR negative population (44%) was named as other febrile illnesses.Results of variations in liver enzymes, full blood count (FBC), demographic and hospitalization detailsin both groups were obtained from hospital records. Results: Male predominance and highly affectedyoung population were detected in both groups. Number of days from onset of fever to admission tothe hospital is lower and hospitalization period is higher in dengue than other febrile illnesses. Onadmission, higher level of aspartate transaminase, significant lymphopenia and higher mean cell volume(MCV) were noticed in dengue patients. On discharge, lower total white blood cell count, lower absolutelymphocyte count, lower platelet count and increased levels of transaminases were detected in denguecompared with other febrile illnesses. Conclusion: From dengue suspected admissions, 44% was due toother febrile illnesses which was very difficult to distinguish by symptoms of dengue. Young patients withmale predominance is common in dengue as well as in other febrile illnesses. Recovery of cytopenia inFBC and normalization of liver transaminases were lower in dengue. Bangladesh Journal of Medical Science Vol.20(1) 2021 p.101-106

Background/aim Recent evidence suggests that Vitamin D deficiency may be associated with varying degrees of peripheral blood cytopenia(s). However, the effect of Vitamin D on hematopoiesis is largely unknown. According to predefined inclusion criteria, here we analyzed the correlation between serum Vitamin D level and hematological parameters. Materials and methods In the present cohort study, a total of 12.709 patients were screened. In the first data set, all patients were included. However, in the second one, only patients (9.936) with no complete blood count (CBC) abnormality and any nutritional deficiency (Iron, Vitamin B12 and Folic acid) were evaluated. According to the level of Vitamin D levels, patients were divided into the four groups. Vitamin D level was 10 ng/mL in group 1, 10–20 ng/mL in group 2, 20–30 ng/mL in group 3, and above of 30 ng/mL in group 4. Hematological parameters were analyzed and compared with Vitamin D levels. Hb level and RBC, WBC, ANC, ALC counts were excepted as major hematological parameters. Results Median age of the 12709 subjects was 41 years and 61.9% was female. We have not observed statistically significant difference between datasets regarding both demographic parameters and median Vitamin D levels.Posthoc analysis revealed a positive trend regarding major hematological parameters through group 2 (10–20 ng/ml) when compared to other Vitamin D groups except for platelet counts (All P values were

ObjectiveTo evaluate the prevalence of hyposmia and dysgeusia in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and their temporal relationship with the onset of other symptoms.MethodsWe performed a retrospective analysis of patients admitted during the month of March 2020 to the nonintensive COVID unit of Udine University Hospital on the basis of a positive swab test and/or of clinical-radiologic signs of SARS-CoV-2 infection. Patients were interviewed with a standardized questionnaire. Clinical and laboratory data were collected. Data were analyzed with descriptive statistics, and results expressed as point estimates and 95% confidence intervals (CIs).ResultsOf 141 patients admitted, 93 were interviewed. Hyposmia and dysgeusia were present in 58 cases (62.4%). In 22.4% of them, olfactory and gustatory impairment clearly preceded systemic symptoms. The presence of active smoking was very limited in both groups: 8.6% in hyposmic vs 2.9% in normosmic patients (odds ratio 3.2; 95% CI 0.3–28.6). Moreover, total leukocytes and neutrophils count were respectively 23% (effect estimate 1.23; 95% CI 1.06–1.42) and 29% (effect estimate 1.29; 95% CI 1.07–1.54) lower in the hyposmic cohort. No difference was found for other inflammatory biomarkers.ConclusionsHyposmia and dysgeusia are common in SARS-CoV-2 infection and can precede systemic symptoms. They should be actively searched and prompt close monitoring and isolation until infection is confirmed or disproven. The lower number of total leukocytes and neutrophils in hyposmic patients might indicate an early-phase virus-induced cytopenia.