Increasing insight in the value of repetitive COVID-19 vaccination in patients with haematological malignancies in the Omicron era.

The study by Kevlicius et al. from Lithuania gives further confirmation of the efficacy of booster mRNA COVID-19 vaccination for patients with haemato-oncological malignancies in the Omicron era. The risk of COVID-19 and mortality was considerably reduced when patients received the booster vaccination. The threshold of the humoral response to vaccination that was protective for haemato-oncological patients was defined. In particular, ruxolitinib and anti-CD20 treatments limited the humoral response to the third booster vaccination. These data may influence the clinical management of haemato-oncological patients in future waves of the COVID-19 pandemic, regarding for example the selection of patients for passive immunization against SARS-CoV-2. Commentary on: Kevlicius et al. Immunogenicity and clinical effectiveness of mRNA vaccine booster against SARS-CoV-2 Omicron in patients with haematological malignancies: A national prospective cohort study. Br J Haematol 2024;204:497-506.

The (reverse) paradox of lupus anticoagulant: A case report.

INTRODUCTION: Systemic Lupus Erythematosus (SLE) is often associated with antiphospholipid syndrome (APS), which manifests as recurrent thrombotic events or obstetric complications in presence of antiphospholipid antibodies. Hereby we present a case of a child who presented with low grade fever, superficial thrombophlebitis with mucosal bleeding and was diagnosed as Lupus Anticoagulant Hypoprothrombonemia Syndrome (LAHS). CASE: A 7-year-old girl was hositalized with complaints of fever and spontaneous bleeding from gums and epistaxis. On examination, she had multiple small tender nodular lesions with greenish hue of overlying skin suggesting superficial thrombophlebitis and mild non-tender hepatosplenomegaly. Her coagulogram revealed normal platelet counts and deranged PT and APTT. ESR and CRP were raised. Serology for viral infections, blood and urine cultures were negative. Patient had persistent coagulopathy, mucosal bleeding and low-grade fever despite supportive treatment. She was tested for anti-nuclear antibodies (ANA) in view of suspicion of autoimmune process. ANA was positive in high titer with speckled pattern on indirect immunofluorescence. Mixing studies showed correction of PT and non-correction of APTT. PT based factors were normal except for prothrombin (FII) which was low and remained low despite dilution. APTT based factors (FVIII and FIX) were low but corrected on dilution. This was suggestive of prothrombin deficiency and a presence of a nonspecific inhibitor of APTT pathway (likely lupus anticoagulant). Presence of antiprothrombin antibodies established the diagnosis of LAHS. ENA profile was positive for SmD1, Ro60 and Ku. Complement levels were low. Direct Coomb's test was positive but there was no evidence of hemolysis. Lupus anticoagulant by DRVVT and anti-cardiolipin antibodies by ELISA were positive. Patient was diagnosed as Systemic Lupus Erythematosus with Lupus Anticoagulant Hypoprothrombinemia Syndrome. She was treated with IV methylprednisolone. Patient showed significant improvement in form of resolution of fever, mucosal bleeding, correction of deranged INR and reversal of hypocomplementemia. She was discharged on hydroxychloroquine, mycophenolate mofetil and tapering doses of prednisolone. On follow up, child was doing well and her prothrombin time and complement levels had normalized. Low dose aspirin was aspirin was added for thromboprophylaxis.

Exposure-efficacy and exposure-safety analyses of ropeginterferon alfa-2b treatment in patients with polycythaemia vera.

AIMS: To investigate the exposure-response (E-R) relationship, including exposure-efficacy and exposure-safety, of ropeginterferon alfa-2b treatment in patients with polycythaemia vera (PV). METHODS: Based on the results of the phase II trial A20-202 regarding ropeginterferon alfa-2b in patients with PV, E-R analyses were performed to evaluate the efficacy and safety of the given dosing regimen. The E-R analyses were based on logistic and linear regression and the relationship between exposure to ropeginterferon alfa-2b and key efficacy and safety variables. The key efficacy variables included complete haematologic response (CHR) and reduction of the driver mutation JAK2V617F. The safety variable was treatment-related adverse events (TRAEs). RESULTS: A clear relationship between the exposure to ropeginterferon alfa-2b and CHR was observed, with an increase in drug exposure resulting in an increased probability of achieving CHR. Similar CHR probabilities were observed in the third and fourth quantiles of the average concentration at Week 24. The results from the exposure-JAK2V617F model indicated that the JAK2V617F allele burden decreased with increasing exposure to ropeginterferon alfa-2b and baseline body surface area. Exposure-safety analysis revealed a risk of AEs associated with transaminase abnormalities, which were not associated with clinical significance. CONCLUSIONS: Our analyses have shown that patients with PV treated with ropeginterferon alfa-2b had an increased probability of achieving CHR and a molecular response with acceptable safety risks at the 250-350-500 µg titration dosing regimen. This study has provided the relevant data for the application of a biologics licence of ropeginterferon alfa-2b for PV treatment in China.

Evaluation of interleukin-8 levels in the diagnosis of invasive pulmonary aspergillosis in patients with haematological malignancies.

This study aimed to determine the level of interleukin (IL)-8 in diagnosing of invasive pulmonary aspergillosis (IPA). We conducted this study with 50 controls and 25 IPA patients with haematological malignancies. Demographic data, haematological diagnoses, chemotherapy regimen, galactomannan level, fungal culture, and computed tomography findings of the patients were evaluated prospectively. IL-8 levels were studied with the ELISA method. The mean age of patients in the case group was 60.84 ± 15.38 years, while that of the controls was 58.38 ± 16.64 years. Of the patients, 2/25 were classified as having 'proven', 13/25 as 'probable', and 10/25 as 'possible' invasive aspergillosis (IA). Serum IL-8 levels were found to be significantly higher in the case group compared to the controls. There was a negative correlation between serum IL-8 levels and neutrophil counts and a positive correlation with the duration of neutropenia. A significant cutoff value for serum IL-8 parameter in detecting IPA disease was obtained as ≥274 ng/l; sensitivity was 72%; specificity was 64%; PPV was 50%; and NPV was 82%. In the subgroup analysis, there was no significant difference in serum IL-8 levels between the case group and the patients in the neutropenic control group, while a significant difference was found in with the patients in the non-neutropenic control group. Serum IL-8 levels in neutropenic patients who develop IPA are not adequate in terms of both the diagnosis of the disease and predicting mortality. New, easily applicable methods with high sensitivity and specificity in diagnosing IPA are still needed.

Although a significant cutoff value for serum interleukin (IL)-8 was found in the diagnosis of IPA, there was no statistical difference in serum IL-8 when subgroup analysis was performed with neutropenic control patients. Therefore, serum IL-8 is not a successful marker in diagnosing neutropenic patients with IPA.

Navigating the clinical landscape: Update on the diagnostic and prognostic biomarkers in multiple myeloma.

Multiple myeloma, a complex hematologic malignancy, has devastating consequences for patients, including dramatic bone loss, severe bone pain, and pathological fractures that markedly decrease the quality of life and impact the survival of affected patients. This necessitates a refined understanding of biomarkers for accurate diagnosis and prognosis of such severe malignancy. Therefore, this article comprehensively covers current research, elucidating the diverse spectrum of biomarkers employed in clinical settings. From traditional serum markers to advanced molecular profiling techniques, the review provides a thorough examination of their utility and limitations. Through this scoping review, emphasis is placed on the evolving landscape of personalized medicine, where biomarkers play a pivotal role in tailoring therapeutic strategies. The integration of genomic, proteomic, next generation sequencing and flow cytometric data further enriches the discussion, unravelling the molecular intricacies underlying disease progression. The updated criteria allow for the treatment of people who clearly would benefit from therapy and might live longer if treated before significant organ damage occurs. Navigating through the evolving diagnostic and prognostic paradigms in multiple myeloma, this article equips clinicians and researchers with crucial insights for optimizing patient care and advancing future therapeutic approaches.

Health professionals' perceptions of prehabilitation before haematopoietic cell transplantation to optimise candidacy in older adults.

PURPOSE: Haematologic malignancies for the most part are diseases of the elderly. Haematopoietic stem cell transplantation (HSCT) remains the only potentially curative strategy for many patients but carries substantial morbidity and mortality risks, particularly in frail or co-morbid patients. Pre-transplant optimisation of key targets through prehabilitation may have significant clinical impact. METHODS: We utilised qualitative methodology (semi-structured interviews) to gain insights and understanding of the perceptions of medical, nursing and allied health professionals towards prehabilitation before haematopoietic cell transplantation to optimise candidacy in older adults. Thematic analysis was performed using a qualitative descriptive approach completed in duplicate by two researchers. RESULTS: Between August and October 2023, eleven health professionals participated from four large cancer centres across the island of Ireland (n = 3 consultant haematologists, n = 7 specialist haematology nurses and n = 1 senior haematology physiotherapist). Four major themes were identified. The themes comprehensive biopsychosocial care and increasing demand for transplant in older patients highlight the unique challenges impacting older adults who receive HSCT. The multimodality pathways of care theme highlights the heterogeneity of treatment pathways across different clinical sites and disease types. This has implications for the prehabilitation: logistics and benefits theme, which indicated strong support for prehabilitation but emphasised that implementation must consider national reach and context. CONCLUSIONS: There is broad national multidisciplinary interest in the development of prehabilitation programmes for patients being considered for transplant. Our results will inform the development of services in this area in consideration of national reach, malignancy-specific pathways and the unique factors associated with older age.

Quality outcomes for end-of-life care among people with haematological malignancies at a New Zealand cancer centre.

BACKGROUND: Little is known about the end-of-life (EOL) experience and specialist palliative care use patterns of patients with haematological malignancies (HMs) in New Zealand. AIMS: This retrospective analysis sought to examine the quality of EOL care received by people with HMs under the care of Auckland District Health Board Cancer Centre's haematology service and compare it to international data where available. METHODS: One hundred consecutive adult patients with HMs who died on or before 31 December 2019 were identified. We collected information on EOL care quality indicators, including anticancer treatment use and acute healthcare utilisation in the last 30 days of life, place of death and rate and timing of specialist palliative care input. RESULTS: During the final 14 and 30 days of life, 15% and 27% of the patients received anticancer therapy respectively. Within 30 days of death, 22% had multiple hospitalisations and 25% had an intensive care unit admission. Death occurred in an acute setting for 42% of the patients. Prior contact with hospital and/or community (hospice) specialist palliative care service was noted in 80% of the patients, and 67% had a history of hospice enrolment. Among them, 15% and 28% started their enrolment in their last 3 and 7 days of life respectively. CONCLUSIONS: The findings highlight the intensity of acute healthcare utilisation at the EOL and high rates of death in the acute setting in this population. The rate of specialist palliative care access was relatively high when compared with international experiences, with relatively fewer late referrals.

Changes in respiratory infection trends during the COVID-19 pandemic in patients with haematologic malignancy.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has changed respiratory infection patterns globally. However, its impact on community-acquired pneumonia (CAP) in high-risk patients with haematological malignancies (HM) is uncertain. We aimed to examine how community-acquired pneumonia aetiology in patients with haematological malignancies changed during the COVID-19 pandemic. METHODS: This was a retrospective study that included 524 patients with haematological malignancies hospitalised with community-acquired pneumonia between March 2018 and February 2022. Patients who underwent bronchoscopy within 24 h of admission to identify community-acquired pneumonia aetiology were included. Data on patient characteristics, laboratory findings, and results of bronchioalveolar lavage fluid cultures and polymerase chain reaction tests were analysed and compared to identify changes and in-hospital mortality risk factors. RESULTS: Patients were divided into the 'pre-COVID-19 era' (44.5%) and 'COVID-19 era' (55.5%) groups. The incidence of viral community-acquired pneumonia significantly decreased in the COVID-19 era, particularly for influenza A, parainfluenza, adenovirus, and rhinovirus (pre-COVID-19 era vs. COVID-19 era: 3.0% vs. 0.3%, P = 0.036; 6.5% vs. 0.7%, P = 0.001; 5.6% vs. 1.4%, P = 0.015; and 9.5% vs. 1.7%, P < 0.001, respectively), whereas that of bacterial, fungal, and unknown community-acquired pneumonia aetiologies remain unchanged. Higher Sequential Organ Failure Assessment scores and lower platelet counts correlated with in-hospital mortality after adjusting for potential confounding factors. CONCLUSIONS: In the COVID-19 era, the incidence of community-acquired pneumonia with viral aetiologies markedly decreased among patients with haematological malignancies, with no changes in the incidence of bacterial and fungal pneumonia. Further studies are required to evaluate the impact of COVID-19 on the prognosis of patients with haematological malignancies and community-acquired pneumonia.

Efficacy of Normalising Serum Zinc Level for Patients with Olfactory Dysfunction and Zinc Deficiency.

INTRODUCTION: Zinc deficiency may worsen the severity of olfactory dysfunction; however, the relationship between serum zinc levels and therapeutic effects on olfactory dysfunction remains uncertain. This study investigated the relationship between normalising serum zinc levels and the therapeutic effects on olfactory dysfunction. METHODS: Forty-two patients diagnosed with post-infectious, post-traumatic, and idiopathic olfactory dysfunction, with serum zinc levels <70 µg/dL, were included in the study. All patients were treated with mecobalamin, tokishakuyakusan, and polaprezinc. The patients were divided into 2 groups: the zinc-normalised (≥70 µg/dL) and zinc-deficient (<70 µg/dL) groups, based on their post-treatment serum zinc levels. Olfactory test results were compared in each of the 2 groups. RESULTS: The patients were treated for a median of 133 days. The zinc-normalised group had significantly better results in all olfactory tests (detection/recognition thresholds of the T&T olfactometer, odour identification test (Open Essence), Visual Analogue Scale for olfactory dysfunction, and self-administered odour questionnaire). In contrast, only the self-administered odour questionnaire showed a significant improvement in the zinc-deficient group, with no significant differences observed in the other olfactory tests. When comparing the changes in the olfactory test scores between the 2 groups, significant differences were observed in the detection/recognition thresholds of the T&T olfactometer test and Open Essence results. CONCLUSION: These findings suggest that patients with olfactory dysfunction may have difficulty improving their olfactory function if they also have zinc deficiency. Furthermore, normalisation of zinc deficiency may contribute to the improvement of olfactory dysfunction with general treatment.

The effects of spiritual wellbeing on life satisfaction in hematologic cancer patients aged 65 and older in Turkey: mediating role of hope.

BACKGROUND: The mediating role of hope in the effects of spiritual wellbeing on life satisfaction in elderly haematologic cancer patients in Turkey was investigated in the present study. METHODS: The study was conducted in a descriptive, cross-sectional and correlational design. The study was conducted with 150 patients aged 65 and older who were diagnosed with haematologic cancer and who were referred to a university hospital haematology clinic and outpatient clinic. Research data were collected with Descriptive Information Form, Dispositional Hope Scale (DHS), Spiritual Well-being Scale (FACIT-Sp-12) and Satisfaction with Life Scale (SWLS). RESULTS: FACIT-Sp-12 score was 37.25 ± 7.29; DHS score was 40.42 ± 8.29, SWLS score was 16.24 ± 8.79. FACIT-Sp-12 (ß = 0.668) and DHS (ß = 0.226) were found to affect SWLS positively. In terms of the effect of FACIT-Sp-12 on SWLS, DHS has a mediating role and makes the positive effect of FACIT-Sp-12 on SWLS stronger (ß = 0.771). CONCLUSIONS: Spiritual wellbeing levels of the participants in our study were found to be high, while their levels of satisfaction with life and hope were found to be moderate. It was also concluded that spiritual wellbeing had a direct effect on satisfaction with life and an indirect effect through the mediating role of hope.

Prolonged haematologic toxicity in CAR-T-cell therapy: A review.

Chimeric antigen receptor-T-cell (CAR-T-cell) therapy is a novel immunotherapy with encouraging results for treatment of relapsed/refractory haematologic malignancies. With increasing use, our understanding of immune-mediated side effects such as cytokine release syndrome and neurotoxicity has improved; nevertheless, prolonged haematologic toxicity (PHT), with a high incidence rate, remains underrecognized. Owing to heterogeneity in populations, the CAR-T cells used and diseases treated as well as differences in the definition of PHT, its rate, risk factors and management vary across studies. In this review, we provide a narrative of PHT occurring in patients following CAR-T-cell therapy; evidence of PHT treatment strategies is also presented, with the aim of contributing to systematic understanding of PHT.

Protein biomarkers for response to XPO1 inhibition in haematologic malignancies.

XPO1 (Exportin-1) is the nuclear export protein responsible for the normal shuttling of several proteins and RNA species between the nucleocytoplasmic compartment of eukaryotic cells. XPO1 recognizes the nuclear export signal (NES) of its cargo proteins to facilitate its export. Alterations of nuclear export have been shown to play a role in oncogenesis in several types of solid tumour and haematologic cancers. Over more than a decade, there has been substantial progress in targeting nuclear export in cancer using selective XPO1 inhibitors. This has resulted in recent approval for the first-in-class drug selinexor for use in relapsed, refractory multiple myeloma and diffuse large B-cell lymphoma (DLBCL). Despite these successes, not all patients respond effectively to XPO1 inhibition and there has been lack of biomarkers for response to XPO1 inhibitors in the clinic. Using haematologic malignancy cell lines and samples from patients with myelodysplastic neoplasms treated with selinexor, we have identified XPO1, NF-κB(p65), MCL-1 and p53 protein levels as protein markers of response to XPO1 inhibitor therapy. These markers could lead to the identification of response upon XPO1 inhibition for more accurate decision-making in the personalized treatment of cancer patients undergoing treatment with selinexor.

Outcome of early treatment of SARS-CoV-2 infection in patients with haematological disorders.

Outcome of early treatment of COVID-19 with antivirals or anti-spike monoclonal antibodies (MABs) in patients with haematological malignancies (HM) is unknown. A retrospective study of HM patients treated for mild/moderate COVID-19 between March 2021 and July 2022 was performed. The main composite end-point was treatment failure (severe COVID-19 or COVID-19-related death). We included 328 consecutive patients who received MABs (n = 120, 37%; sotrovimab, n = 73) or antivirals (n = 208, 63%; nirmatrelvir/ritonavir, n = 116) over a median of two days after symptoms started; 111 (33.8%) had non-Hodgkin lymphoma (NHL); 89 (27%) were transplant/CAR-T (chimaeric antigen receptor T-cell therapy) recipients. Most infections (n = 309, 94%) occurred during the Omicron period. Failure developed in 31 patients (9.5%). Its independent predictors were older age, fewer vaccine doses, and treatment with MABs. Rate of failure was lower in the Omicron versus the pre-Omicron period (7.8% versus 36.8%, p < 0.001). During the Omicron period, predictors of failure were age, fewer vaccine doses and diagnosis of acute myeloid leukaemia/myelodysplastic syndrome (AML/MDS). Independent predictors of longer viral shedding were age, comorbidities, hospital admission at diagnosis, NHL/CLL, treatment with MABs. COVID-19-associated mortality was 3.4% (n = 11). The mortality in those who developed severe COVID-19 after early treatment was 26% in the Omicron period. Patients with HM had a significant risk of failure of early treatment, even during the Omicron period, with high mortality rate.

Antibody status following booster vaccination against SARS-CoV-2 virus in patients with haematologic malignancies.

Antibody titres in 462 patients with haematological malignancies after the second (D2) and third (D3) SARS-CoV-2 vaccine were compared with those of healthy controls (HCs). Significant decay of antibody titre was observed pre D3, but titre surged post D3. The number of seronegative patients decreased from 79 (17.1%) to 44 (9.5%) from post D2 to post D3, and patients with adequate antibody titre increased from 204 (44.2%) to 358 (77.5%). Of the patients who received B-cell-targeted therapy, 80% were seronegative and 71% remained seronegative after D3. CD19+, CD4+, CD8+ cell counts, and immunoglobulin G (IgG) levels were identified as independent predictors for adequate serologic response.

Molecular epidemiology and disease severity of influenza virus infection in patients with haematological disorders.

Influenza virus infection is a common cause of self-limiting respiratory tract infection (RTI), however immunocompromised patients are at an increased risk for a severe course of disease or fatal outcome. We therefore aimed to gain a better understanding of the molecular epidemiology of influenza viruses from patients with haematological disorders and their impact on the clinical course of disease. Molecular analysis using polymerase chain reaction (PCR) of nasopharyngeal swabs was performed for influenza virus in haematological patients at the Heidelberg University Hospital. Clinical data was evaluated to identify associated risk factors. For phylogenetic analysis, the hemagglutinin (HA) gene was sequenced. Out of 159 influenza positive patients, 117 patients developed upper RTI (influenza A: n = 73; influenza B: n = 44). Lower RTI was observed in n = 42 patients (26%), n = 22/42 patients developed severe disease and n = 16/159 (10.1%) patients died. Risk factors for lower RTI were nosocomial infection (p = 0.02), viral shedding for ≥14 days (p = 0.018), IgG levels <6 g/dL (p = 0.046), bacterial/fungal co-infections (p < 0.001). Risk factors for fatal outcome were age ≥65 years (p = 0.032), bacterial/fungal (p≤0.001) co-infections and high viral load (p = 0.026). Sequencing of the HA gene (n = 115) revealed subtype A(H3N2) (n = 46), A(H1N1)pdm09 (n = 24), B/Victoria (n = 34), B/Yamagata (n = 11). There was no correlation between influenza (sub)type and lower RTI. Influenza infection in haematological patients is associated with significant morbidity and mortality, the risk for aggravating co-infections, prolonged viral shedding and nosocomial transmission emphasizing the need for infection control.

Bispecific anti-CD3×anti-CD155 antibody mediates T-cell immunotherapy in human haematologic malignancies.

T cells are important components in the cell-mediated antitumour response. In recent years, bispecific antibodies (Bi-Abs) have become promising treatments because of their ability to recruit T cells that kill tumours. Here, we demonstrate that CD155 is expressed in a wide range of human haematologic tumours and report on the ability of the bispecific antibody anti-CD3 x anti-CD155 (CD155Bi-Ab) to activate T cells targeting malignant haematologic cells. The specific cytolytic effect of T cells armed with CD155Bi-Ab was evaluated by quantitative luciferase assay, and the results showed that the cytolytic effect of these cells was accompanied by an increase in the level of the cell-killing mediator perforin. Moreover, compared with their unarmed T-cell counterparts, CD155Bi-Ab-armed T cells induced significant cytotoxicity in CD155-positive haematologic tumour cells, as indicated by lactate dehydrogenase assays, and these results were accompanied by increased granzyme B secretion. Furthermore, CD155Bi-Ab-armed T cells produced more T-cell-derived cytokines, including TNF-α, IFN-γ, and IL-2. In conclusion, CD155Bi-Ab enhances the ability of T cells to kill haematologic tumour cells, and therefore, CD155 may serve as a novel target for immunotherapy against haematologic malignancies.

The role of bone marrow microenvironment on CAR-T efficacy in haematologic malignancies.

In recent years, chimeric antigen receptor-T (CAR-T) cell therapy has emerged as a novel immunotherapy method. It has shown significant therapeutic efficacy in the treatment of haematological B cell malignancies. In particular, the CAR-T therapy targeting CD19 has yielded unprecedented efficacy for acute B-lymphocytic leukaemia (B-ALL) and non-Hodgkin's lymphoma (NHL). In haematologic malignancies, tumour stem cells are more prone to stay in the regulatory bone marrow (BM) microenvironment (called niches), which provides a protective environment against immune attack. However, how the BM microenvironment affects the anti-tumour efficacy of CAR-T cells and its underlying mechanism is worthy of attention. In this review, we discuss the role of the BM microenvironment on the efficacy of CAR-T in haematological malignancies and propose corresponding strategies to enhance the anti-tumour activity of CAR-T therapy.

Relapses are common in severe hematologic systemic lupus erythematosus and may be prevented by early institution of immunosuppressive agents: Α real-life single-center study.

BACKGROUND: Hematologic manifestations are common in systemic lupus erythematosus (SLE), either at initial presentation or during the course of the disease, but data regarding their natural history are scarce. OBJECTIVE: To describe the characteristics, treatments, and outcomes of severe hematological manifestations in a large cohort of lupus patients. METHODS: Retrospective cohort study of patients in the "Attikon" lupus cohort who had a history of a severe hematologic manifestation, defined as autoimmune hemolytic anemia (AIHA) with hemoglobin < 8 g/dL, thrombocytopenia with platelet count < 30,000/mm3, Evans syndrome with hemoglobin < 8 g/dL, and/or platelet count < 30,000/mm3, neutropenia with < 500 neutrophils/mm3, thrombotic microangiopathy (TMA)/thrombotic thrombocytopenic purpura (TTP)-like syndrome, or macrophage activation syndrome (MAS). Demographic and clinical characteristics, treatments, and outcomes were recorded. RESULTS: From over 300 patients with hematologic manifestations, 41 qualified as severe (70.7% women, mean [SD] age at SLE diagnosis 42.6 [18.0] years). Hematologic manifestations preceded SLE diagnosis in 13 patients (31.7%), was concomitant to SLE diagnosis in 16 patients (39%), and occurred during the course of the disease in 12 (29.3%) patients, with a mean (SD) disease duration of 8.7 (5.5) years. Thrombocytopenia was the most common severe hematological manifestation (56.1%), followed by AIHA (17.1%) and TTP-like syndrome (12.2%). For initial treatment, all patients were treated with glucocorticoids (GC), while rituximab and cyclophosphamide were the most frequently used immunosuppressive agents. Following initial treatment, relapse occurred in 22 patients (53.7%). Compared to patients that did not relapse, those that relapsed had less often received concomitant immunosuppressive agents following treatment of initial episode (n = 17/23, 73.9% vs 5/17, 29.4%, p = 0.005). CONCLUSION: Severe hematologic disease in SLE has a high risk of relapse, which may be mitigated by the early institution of GC-sparing agents.

Monocytosis in primary care and risk of haematological malignancies.

Monocytosis (≥0.5 × 109 /L in peripheral blood) is the hallmark of chronic myelomonocytic leukaemia (CMML) but may be present in a spectrum of diseases including other haematological malignancies. In the primary care sector, monocytosis is a relatively common finding, but its predictive value for haematological malignancy is unknown. We included 663 184 adult primary care patients from the greater Copenhagen area with one or more differential cell counts registered between 2000 and 2016 and followed them in the extensive nationwide Danish health data registers for 3 years after blood sampling. We used logistic regression to model the risk of haematological malignancy and death following monocytosis. Monocytosis was associated with an increased risk of all types of haematological malignancy with the greatest relative risk increase observed in CMML with an OR of 105.22 (95% confidence interval: 38.27-289.30). Sustained monocytosis (at least two requisitions in 3 months) further increased CMML risk, although the diagnosis was still very rare, that is, observed in only 0.1% of these individuals. Outside the haematological setting, the absolute risk of haematological malignancy associated with monocytosis is low and haematological malignancy should mainly be suspected when monocytosis is sustained or the clinical presentation raises suspicion of malignancy.

Risk factors for nosocomial rectal colonisation with carbapenem-resistant Gram-negative bacilli in children with haematological malignancies: a case-control study.

BACKGROUND: Rectal colonisation with carbapenem-resistant Gram-negative bacilli (CR-GNB) may cause CR-GNB infection in children with haematological malignancies (HMs) haematological. To date, information on its epidemiology is limited. This study aimed to assess the the risk factors for rectal colonisation with CR-GNB in children with HMs. METHODS: A case-control study in a tertiary children's hospital in Hangzhou City, was conducted between July 2019, and September 2021. Based on the hospitalisation date, children in the CR-GNB colonisation group and control groups were matched at a ratio of 1:2. Conditional logistic regression models were used to compute the adjusted odds ratios (aORs) and 95% confidence intervals (CIs) of the risk factors for CR-GNB rectal colonisation in children with HMs. RESULTS: A total of 85 non-duplicated CR-GNB isolates were collected from rectal swab samples of 69 children with HMs. The 30-day mortality rates were 5.8% in the CR-GNB colonisation group and 0% in the control group (P = 0.020).colonisation In the conditional logistic regression model, the aORs were 6.84 (95% CI 1.86-25.20) for acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL), 4.16 (95% CI 1.17-14.84) for prior concomitant infections within the last 1 month, 2.33 (95% CI 1.16-4.69) for prior carbapenems usage within the last 1 month and 7.46 (95% CI 1.81-30.67) for prior hematopoietic stem-cell transplantation (HSCT). CONCLUSION: AML/ALL, prior concomitant infections within the last 1 month, prior carbapenems usage within the last 1 month, and prior HSCT are associated with an increased risk of rectal colonisation with CR-GNB in children with HMs.