Search

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Summary: Background: Autoimmune diseases are known to be associated with an increased risk of cancer. Whether maternal immune dysregulation can have an impact on the development of haematological malignancies in offspring remains uncertain. Therefore, we explored the association between offspring risk of haematological malignancies and maternal autoimmune disease using a real-world nationwide population-based study. Methods: In this case–control study, we identified 2172 children with haematological malignancies between 2004 and 2019 from Taiwan's National Health Insurance program and compared them with population-based controls without haematologic malignancies, who were matched with each individual at a ratio of 1:4. The medical information of the autoimmune mothers were obtained from the Taiwan Maternal and Child Health Database. Conditional logistic regression was used to estimate the odds ratio for haematologic malignancy in offspring. Furthermore, subgroup and stratified analyses were conducted. Findings: Among the rheumatologic diseases in our study, Crohn's disease was the most common disease both in the haematological malignancy group (1.1%) and the control group (0.9%). In multivariable analysis, the odds ratio for haematological malignancy in offspring with maternal autoimmune diseases was 1.2 (95% confidence interval [CI] 0.91–1.58). The overall risk of haematologic malignancy was not significantly higher when adjusted for specific risk factors, including neonatal age, maternal age, family income, urbanization, maternal occupation, birth weight, or maternal comorbidity, except for prematurity. When comparing different autoimmune diseases among haematological malignancies and the control group, maternal psoriatic arthritis/psoriasis had the highest adjusted overall risk for haematological malignancies (adjusted OR 2.11, CI 0.89–5), followed by ankylosing spondylitis (adjusted OR 1.45, CI 0.7–3), autoimmune thyroiditis (OR 1.26, CI 0.57–2.81), systemic lupus erythematosus (OR 1.21, CI 0.48–3.02), Crohn's disease (OR 1.19, CI 0.75–1.9), and Sjogren's syndrome (OR 1.18, CI 0.65–2.15), but no significance was reached in these analyses. Multivariable analysis of risk factors associated with haematological malignancy subtypes was done. It showed no associations between maternal autoimmune disease and childhood haematological malignancies. Interpretation: We found no significant relationship between maternal autoimmune disease and childhood haematological malignancies. The influence of maternal immune dysregulation on the next generation with respect to haematological malignancies development may be limited. Funding: There was no funding source for this study.

Abstract 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

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the clinical features of splenomegaly, mainly focussing on cytopenia, in patients with systemic lupus erythematosus (SLE). Cytopenia was commonly observed in 111 SLE patients with splenomegaly (n = 79, 71.2%). During the follow‐up period, two patients developed haematologic malignancy after the diagnosis of SLE and splenomegaly, but no patients experienced severe complications (e.g. splenic rupture) related to splenomegaly. [ABSTRACT FROM AUTHOR]

BackgroundDetection of galactomannan (GM) from bronchoalveolar lavage fluid (BALF) or serum is broadly used for diagnosis of invasive aspergillosis (IA), although the sensitivity of GM from serum is lower in non-neutropenic patients. We evaluated the Aspergillus galactomannan Lateral Flow assay (LFA) with digital readout from serum in a mixed cohort of patients.MethodsWe performed a retrospective two-centre study evaluating the LFA from serum of patients with clinical suspicion of IA obtained between 2015 and 2021 at the University of California San Diego and the Medical University of Graz. The sensitivity and specificity was calculated for proven/probable aspergillosis versus no aspergillosis. Correlation with same-sample GM was calculated using Spearman correlation analysis and kappa statistics.ResultsIn total, 122 serum samples from 122 patients were analysed, including proven IA (n = 1), probable IA or coronavirus-associated pulmonary aspergillosis (CAPA) (n = 27), and no IA/CAPA/non-classifiable (n = 94). At a 0.5 ODI cut-off, the sensitivity and specificity of the LFA was 78.6% and 80.5%. Spearman correlation analysis showed a strong correlation between serum LFA ODI and serum GM ODI (ρ 0.459, p

Ribavirin use for respiratory syncytial virus (RSV) infection in patients with haematologic malignancies (HM) and haematopoietic stem cell transplant (HSCT) recipients remains controversial. To summarize the current evidence of ribavirin treatment in association with mortality and progression to lower respiratory tract infection (LRTI) among patients with HM/HSCT with RSV infection. MEDLINE, Embase, and the Institute for Scientific Information Web of Science. Randomized controlled trials and observational studies investigating the effects of ribavirin, compared with treatment without ribavirin, for RSV infection. Patients with HM/HSCT. Ribavirin versus no ribavirin. The risk of bias in non-randomized studies of exposure (ROBIN-E). The random-effects model was used to calculate the pooled OR (pOR) with 95% CI for the pooled effect estimates of ribavirin benefits. Grading of recommendation assessment, development, and evaluation was used to evaluate the certainty of evidence. One randomized controlled trial and 14 observational studies were included, representing 1125 patients with HM/HSCT. Ribavirin use was not associated with lower all-cause or RSV-associated mortality with pORs [95% CI] of 0.81 [0.40, 1.66], I2 = 55% (low certainty of evidence) and 0.48 [0.11, 2.15], I2 = 64% (very low certainty of evidence), respectively. In subgroup analyses, ribavirin use was associated with lower mortality in patients with HM/HSCT with LRTI with pOR [95% CI] of 0.19 [0.07, 0.51], I2 = 0% (moderate certainty of evidence). In subgroup analyses among studies providing adjusted OR, ribavirin use was associated with lower all-cause mortality with pOR of 0.41 [0.23, 0.74], I2 = 0% (moderate certainty of evidence). In addition, aerosolized ribavirin was associated with lower progression to LRTI with pOR [95% CI] of 0.27 [0.09, 0.80], I2 = 71% (low certainty of evidence). Ribavirin may be a reasonable option to treat RSV in patients with HM/HSCT in the absence of other effective antiviral agents. [ABSTRACT FROM AUTHOR]

Patients diagnosed with haematologic malignancies (HMs) have a higher risk of developing subsequent solid tumours, such as melanoma. Patients with HM were mostly excluded from clinical trials but potentially derive less benefit from immune checkpoint inhibitors (ICIs) due to disease- or treatment-related T- or B-cell dysfunction. All advanced melanoma patients treated with anti-PD-1-based treatment or targeted therapy between 2015 and 2021 were included from the prospective nationwide Dutch Melanoma Treatment Registry. Progression-free survival (PFS) and melanoma-specific survival (MSS) were analysed for patients with HM (HM+) and without HM (HM−). A cox model was used to account for confounders associated with PFS and MSS. In total, 4638 advanced melanoma patients received first-line anti-PD-1 monotherapy (n = 1763), ipilimumab-nivolumab (n = 800), or BRAF(/MEK) inhibitors (n = 2075). Concurrent HMs were present for 46 anti-PD1-treated patients, 11 ipilimumab-nivolumab-treated patients and 43 BRAF(/MEK)-inhibitor-treated patients. In anti-PD-1-treated patients, the median PFS was 2.8 months for HM+ and 9.9 months for HM− (p = 0.01). MSS was 41.2 months for HM+ and 58.1 months for HM− (p = 0.00086). In multivariable analysis, the presence of an HM was significantly associated with higher risk of melanoma progression (HR adj 1.62; 95% confidence interval [95% CI] 1.15–2.29; p = 0.006) and melanoma-related death (HR adj 1.74; 95% CI 1.09–2.78; p = 0.020). Median PFS and MSS for first-line BRAF(/MEK-) inhibitor-treated HM+ and HM− patients were not significantly different. Patients with HM and advanced melanoma show significantly worse melanoma-related outcomes when treated with ICI, but not targeted therapy, compared to patients without HM. Clinicians should be aware of potentially altered effectiveness of ICI in patients with active HM. • Largest cohort of metastatic melanoma (MM) and haematologic malignancy (HM) patients. • Immunotherapy-treated MM patients with a concurrent HM had significantly worse PFS. • PFS was not worse for patients with HM treated with targeted therapy. [ABSTRACT FROM AUTHOR]

Summary: 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. [ABSTRACT FROM AUTHOR]

Summary: 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. [ABSTRACT FROM AUTHOR]

Background: Organising pneumonia (OP) is reported in patients with haematologic malignancy suspected of having invasive mould disease, yet little is known about this relationship. Objective: To investigate molecular evidence of invasive mould pneumonia in paraffin‐embedded lung tissues from histologically diagnosed OP patients with suspected invasive mould pneumonia. Patients/Methods: Patients with haematologic malignancy suspected to have invasive pulmonary mould disease who underwent lung biopsy at a tertiary hospital, Seoul, South Korea, between 2008 and 2020, were retrospectively reviewed. To find molecular evidence of fungal infection, PCR assay was used to detect Aspergillus‐ and Mucorales‐specific DNA within OP lung tissue sections. Results: Forty‐seven patients with suspected invasive mould pneumonia underwent lung biopsy and 15 (32%) were histologically diagnosed as OP without any evidence of fungal hyphae. Of these 15 patients, 3 (20%) received allogenic haematopoietic stem cell transplantation prior to developing OP. Before biopsy, 2 and 13 patients had probably and possible invasive mould disease, respectively. The median antifungal treatment length was 81 [8–114] days, and the median steroid treatment dosage was 0.35 mg/kg/day for 36 days (methylprednisolone equivalent doses), respectively. After biopsy, three patients with possible invasive mould infection revealed probable invasive pulmonary aspergillosis. From the 15 paraffin‐embedded lung tissues, 6 (40%) exhibited positive PCR assay results for detecting Aspergillus‐ and Mucorales‐specific DNA. Conclusions: More than one third of OP cases in patients with suspected invasive mould pneumonia exhibited molecular evidence of invasive mould infection by fungus‐specific PCR in lung tissues, likely associated with concurrent or prior fungal infection. [ABSTRACT FROM AUTHOR]

Summary: Outpatient palliative‐care facilitates timely supportive‐care access; however, there is a paucity of studies on the timing of referral in the outpatient setting for patients with haematologic malignancy. We examined the trend in timing of outpatient palliative‐care referrals over a 10‐year period in patients with haematologic malignancies at our comprehensive cancer centre. We included consecutive patients with a diagnosis of haematologic malignancy who were seen at our outpatient palliative‐care clinic between 1 January 2010 and 31 December 2019. We collected data on patient characteristics, symptom burden and supportive‐care interventions at outpatient palliative‐care consultation. The primary outcome was time from outpatient palliative‐care consultation to death or last follow‐up. In all, 384 patients were referred by leukaemia (n = 143), lymphoma (n = 213), and stem cell transplant (n = 28) services. The median time from outpatient palliative‐care referral to death was 3.4 years (IQR 2.4–5.3) with a significant increase in both the number of referrals per year (p = 0.047) and the timing of referral between 2010 and 2019 (p = 0.001). Patients with haematologic malignancies were referred in a timely fashion to our outpatient palliative‐care clinic, with earlier and greater numbers of referrals over time. [ABSTRACT FROM AUTHOR]

Summary: T cells play crucial roles in the antitumour immune response. However, their dysfunction leads to inefficient tumour eradication. New members of the B7 family have moved to the fore of cancer research because of their involvement in T cell-mediated immune escape and tumorigenesis. Recently, bispecific antibodies (Bi-Abs) have become attractive because of their ability to activate T cells to target tumours. In this study, we examined the expression of new B7 family members B7-H4, B7-H5, B7-H6, and B7-H7 in human haematological tumour cells. Furthermore, we explored whether B7-H6 is an efficient target for T cell-induced cytotoxicity in haematologic malignant cells. We determined the capability of T cells armed with the bispecific antibody anti-CD3 × anti-B7-H6 (B7-H6Bi-Ab) to target haematological tumours in K562, Thp-1, Daudi, Jurkat, and U266 cells. Compared with their T cell counterparts, B7-H6Bi-Ab-armed T cells demonstrated significant cytotoxicity induction in B7-H6+ haematological tumour cells, according to quantitative luciferase and lactate dehydrogenase assays, and their activity was accompanied by increased levels of the secreted killing mediators granzyme B and perforin. Moreover, B7-H6Bi-Ab-armed T cells produced more T cell-derived cytokines: TNF-α, IFN-γ, and IL-2. In addition, compared to the control T cells, a higher level of the activation marker CD69 was detected on the B7-H6Bi-Ab-armed T cells. Taken together, these data suggest that the antitumour effect of B7-H6Bi-Ab-armed T cells may be a promising immunotherapy for use in future haematologic treatments. [ABSTRACT FROM AUTHOR]

What is known and objectives: Augmented renal clearance (ARC) is characterized by enhanced renal clearance, which leads to insufficient vancomycin exposure and treatment failure. In haematologic malignancy patients, determination of optimal vancomycin dosage is essential because of high stake of life‐threatening bacterial infection and increased clearance. The aim of this study was to describe vancomycin pharmacokinetic parameters in haematologic malignancy with augmented renal clearance children and define the appropriate dosing regimen to achieve an AUC0‐24h/MIC ≥400. Methods: Hematologic malignancy with ARC children was enrolled in this retrospective study. The vancomycin PPK model was established by non‐linear mixed‐effects modelling programme. Goodness‐of‐fit (GOF) plots, non‐parametric bootstrap, normalized prediction distribution error (NPDE) and visual predictive checks (VPCs) were carried out for internal evaluation of the final model. Monte Carlo simulation method was used to stimulate the optimal dosage regimens. Results: Fifty‐three patients with 106 samples were included. A one‐compartment model with first‐order elimination was developed, and the final model was as follows: CL (L/h) = 6.32×（WT/70）0.75 × e0.0467; V(L) = 39.6×(WT/70), where WT denotes weight (kg). The internal validation of the model showed a good prediction performance. Monte Carlo simulation results showed that when MIC was 0.5 mg/L or 1 mg/L, the recommended doses to achieve a target of AUC0‐24h/MIC ≥400 were 25 to 40 and 50 to 75 mg/kg/d, respectively. With decreasing weight, the recommended dosage to achieve an AUC0‐24h/MIC ≥400 increased. What is new and conclusion: A one‐compartment vancomycin PPK model was established in haematologic malignancy with augmented renal clearance children with weight with allometric scaling as a significant covariate. When MIC was 1 mg/L, current recommended paediatric dosages were insufficient in haematologic malignancy with augmented renal clearance children and should be increased. [ABSTRACT FROM AUTHOR]

Objective: Bone marrow aspiration and lumbar puncture play essential roles in the diagnosis and treatment of haematological disorders. These repeated invasive procedures lead to considerable pain and stress in children, which is emotionally stressful for their parents. This study aimed to compare the effectiveness and outcomes of two combinations of midazolam-ketamine (MK) and propofol-sufentanil (PS) in painful procedures of children with haematologic malignancy. Methods: In this prospective, randomised, double-blind clinical trial, we enrolled 80 eligible patients with haematologic malignancy aged 2-14 years. We randomly allocated them to the MK and PS groups. We recorded and compared the level of sedation, pain severity, hemodynamic indices, the onset of effect, duration of recovery and complications during and after procedure in the two groups. We analysed the data using the SPSS software. We used Mann-Whitney U, independent t-test, chi-square and Fisher's exact tests to compare continuous and categorical variables. Results: From initially enrolled patients, 68 patients completed the study (38 in PS and 30 in MK group). The levels of sedation and the mean score of pain intensity were significantly lower in the MK group than those in the PS group (p<0.05). Movements and the needs to repeat the dose were significantly lower in the MK group than those in the PS group (p<0.05). Conclusion: During bone marrow aspiration and lumbar puncture procedures in children with haematologic malignancy, the findings of this trial suggest that MK combination therapy provides better sedation and analgesia than PS. [ABSTRACT FROM AUTHOR]

Background: Anthracycline-treated childhood cancer survivors are at higher risk of cardiotoxicity, especially with cumulative doses received above 250 mg/m2. Dexrazoxane is the only option recommended for cardiotoxicity prevention in high-risk patients supported by randomised trials but its cost-effectiveness in paediatric cancer patients has not been established. Methods: A cost-effectiveness model applicable to different national healthcare system perspectives, which simulates 10,000 patients with either sarcoma or haematologic malignancies, based upon baseline characteristics including gender, age at diagnosis, cumulative anthracycline dose and exposure to chest irradiation. Risk equations for developing congestive heart failure and death from recurrence of the original cancer, secondary malignant neoplasms, cardiac death, pulmonary death, and death from other causes were derived from published literature. These are applied to the individual simulated patients and time until development of these events was determined. The treatment effect of dexrazoxane on the risk of CHF or death was based upon a meta-analysis of randomised and non-randomised dexrazoxane studies in each tumour type. The model includes country specific data for drug and administration costs, all aspects of heart failure diagnosis and management, and death due to different causes for each of the five countries considered; France, Germany, the UK, Italy, and Spain. Results: Dexrazoxane treatment resulted in a mean QALY benefit across the five countries ranging from 0.530 to 0.683 per dexrazoxane-treated patient. Dexrazoxane was cost-effective for paediatric patients receiving anthracycline treatment for sarcoma and for haematologic malignancies, irrespective of the cumulative anthracycline dose received. The Incremental Cost Effectiveness Ratio (ICER) was favourable in all countries irrespective of anthracycline dose for both sarcoma and haematological malignancies (range: dominant to €2196). Individual ICER varied considerably according to country with dominance demonstrated for dexrazoxane in Spain and Italy and ratios approximately double the European average in the UK and Germany. Conclusions: Dexrazoxane is a highly cost-effective therapy for the prevention of anthracycline cardiotoxicity in paediatric patients with sarcoma or haematological malignancies in Europe, irrespective of the healthcare system in which they receive treatment. These benefits persist when patients who receive doses of anthracycline > 250 mg/m2 are included in the model. [ABSTRACT FROM AUTHOR]

Summary: Background: Posaconazole is used to prevent invasive fungal infections (IFIs) in patients with haematologic malignancy. In this study, we compared plasma posaconazole concentrations (PPCs) and the incidence of breakthrough IFIs between patients with haematologic malignancy receiving posaconazole oral suspension vs tablet. Methods: We retrospectively collected data on adult patients with haematologic malignancies who received posaconazole prophylaxis during chemotherapy from April 2014 through May 2018. A total of 242 cases with PPCs, 88 in the oral suspension group and 154 in the tablet group, were included in this study. Results: Patients receiving tablets achieved a significantly higher mean PPC than did those on oral suspension (1.631 ± 0.878 μg/mL in the tablet group vs. 0.879 ± 0.585 μg/mL in the oral suspension group). One hundred and thirty‐seven of 154 patients (89.0%) receiving tablets had PPCs of 0.7 μg/mL or more, while only 41 of 88 patients (46.6%) receiving oral suspension attained an optimal level (P <.001). The incidence of breakthrough IFIs was significantly higher in the oral suspension group compared with in the tablet group (14.8% of oral suspension vs. 4.5% of tablet; P =.005). In the analysis including patients receiving posaconazole tablets, hypoalbuminemia (< 3.5 g/dL) was found to be a risk factor associated with suboptimal levels (odds ratio: 8.872; 95% confidence interval: 3.011 ‐ 26.141; P <.001). Conclusions: Suboptimal PPCs in the tablet group were less common than those in the oral suspension group. Therapeutic drug monitoring may be still necessary even in patients receiving posaconazole tablets, especially in those with hypoalbuminemia. [ABSTRACT FROM AUTHOR]

Background: Patients with haematologic malignancies receiving chemotherapy have a high risk of developing febrile neutropenia and bloodstream infections. The benefit of adjunctive gentamicin treatment for enterococcal bloodstream infections is debated. In this study, we compare the treatment outcome of a cell wall-active antibiotic with and without gentamicin for enterococcal bacteraemia in patients with neutropenia. Methods: The observational study was performed from 1999 through 2016. Patients with bacteraemia due to non-high level gentamicin-resistant enterococci were included. Analyses were performed in two data sets of episodes with enterococcal bacteraemia. One data set consisting of all included episodes (full cohort, n = 154) and one with propensity score-matched episodes (n = 96). The primary endpoint was death within 30 days, and the secondary outcomes were defervescence and persistence of enterococcal bloodstream infection after initiation of anti-enterococcal therapy. Results: Episodes with gentamicin treatment (n = 82, full cohort; n = 48, propensity score-matched cohort) were comparable with episodes without gentamicin treatment (n = 72, full cohort; n = 48, propensity score-matched cohort) with regard to patient- and disease-related characteristics. Enterococcus faecium (40.9%) was the most frequently isolated organism. In the propensity score-matched cohort, there was no difference in 30-days mortality (14.6% in episodes with gentamicin versus 16.7% in episodes without gentamicin, p = 1), median time to defervescence (1 versus 2 days, p =.37) or persistence of enterococcal bloodstream infection for ≥72 h (9.4% versus 7.5%, p = 1). Conclusions: In our study with neutropenic patients, treatment with a cell wall-active antibiotic without adjunctive gentamicin for episodes with enterococcal bloodstream infection was as effective as combination therapy with gentamicin. [ABSTRACT FROM AUTHOR]

Summary Background Allogeneic haematopoietic cell transplantation (HCT) is often associated with poor oral intake due to painful mucositis and gastrointestinal sequalae that occur following a preparative regimen of intensive chemotherapy and/or total body radiation. Although attractive to assume that optimal nutrition improves HCT outcomes, there are limited data to support this. It is also unclear whether artificial nutrition support should be provided as enteral tube feeding or parenteral nutrition (PN). Methods We analysed day-100 non-relapse mortality (NRM), incidence of acute graft-versus-host disease (GvHD), acute gastrointestinal GvHD, 5-year survival and GvHD-free/relapse-free survival (GRFS) according to both route and adequacy of nutritional intake prior to neutrophil engraftment, together with other known prognostic factors, in a retrospective cohort of 484 patients who underwent allogeneic HCT for haematologic malignancy between 2000 and 2014. Results Multivariate analyses showed increased NRM with inadequate nutrition (hazard ratio (HR) 4.1; 95% confidence interval (CI) 2.2–7.2) and adequate PN (HR 2.9; 95% CI 1.6–5.4) compared to adequate enteral nutrition (EN) both P <.001. There were increased incidences of gastrointestinal GvHD of any stage and all GvHD ≥ grade 2 in patients who received PN (odds ratio (OR) 2.0; 95% CI 1.2–3.3; P =.006, and OR 1.8; 95% CI 1.1–3.0; P =.018, respectively), compared to adequate EN. Patients who received adequate PN and inadequate nutrition also had reduced probabilities of survival and GRFS at 5 years. Conclusion Adequate EN during the early transplantation course is associated with reduced NRM, improved survival and GRFS at 5 years. Furthermore, adequate EN is associated with lower incidence of overall and gut acute GvHD than PN, perhaps because of its ability to maintain mucosal integrity, modulate the immune response to intensive chemo/radiotherapy and support the gastrointestinal tract environment, including gut microflora. [ABSTRACT FROM AUTHOR]

Summary: Objectives: Bronchoalveolar lavage galactomannan (BAL‐GM) is a mycological criterion for diagnosis of probable invasive aspergillosis (IA) per European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORT‐MSG) consensus criteria, but its real‐world positive predictive value (PPV) has not been well‐studied. Our aim was to estimate the PPV of BAL‐GM in a contemporary cohort of patients with positive BAL‐GM. Methods: We identified consecutive patients with ≥1 positive BAL‐GM value (index ≥ 0.5) at Brigham and Women's Hospital from 11/2009 to 3/2016. We classified patients as having no, possible, probable, or proven IA, excluding BAL‐GM as mycological criterion. Results: We studied 134 patients: 54% had hematologic malignancy (HM), and 10% were solid organ transplant (SOT) recipients. A total of 42% of positive (≥0.5) BAL‐GM results were falsely positive (PPV 58%). The number of probable IA cases was increased by 23% using positive BAL‐GM as mycologic criterion alone. PPV was higher in patients with HM or SOT (P < 0.001) and with use of higher thresholds for positivity (BAL‐GM ≥ 1 vs 1‐0.8 vs 0.8‐0.5: P = 0.002). Conclusions: 42% of positive BAL‐GM values were falsely positive. We propose a critical reassessment of BAL‐GM cutoff values in different patient populations. Accurate noninvasive tests for diagnosis of IA are urgently needed. [ABSTRACT FROM AUTHOR]

Objectives We sought to determine the frequency at which patients with elevated voriconazole (VRC) levels but no clinically evident central nervous system (CNS) toxicity subsequently develop CNS toxicity. Methods We retrospectively reviewed the records of adult patients with haematolologic malignancy who had a VRC serum level >5.5 μg/mL at MD Anderson Cancer Center (January 2010 to December 2015). Patients with any documented CNS toxicity at the time the VRC level was obtained or patients whose VRC was discontinued as a response to high VRC level were excluded. Neurologic status was assessed using standard grading scales. Demographic and clinical characteristics, including potentially interacting medications, were correlated with the development of toxicity. Results We identified 320 such patients (mean age, 57 ± 15 years; 202 male (63%)). Subsequent CNS toxicity was documented in only 16 patients (5%). The most common CNS toxicities were visual disturbances (9/16, 56%), depressed consciousness (5/16, 31%) and cognitive disturbance (4/16, 19%). Patients with CNS toxicity tended to be older than those without (64 ± 8 vs 57 ± 15 y, p 0.08). The use of one or more neurotoxic drugs was common in patients with subsequent CNS toxicity (14/16, 88%). Reduction of VRC dose associated with the high VRC level did not correlate with less subsequent CNS toxicity. Conclusions Development of subsequent CNS toxicity is uncommon in haematolologic malignancy patients with elevated VRC levels who had no evidence of toxicity at the time the level was obtained. Automatic reduction of VRC dose out of concern for impending CNS toxicity might not be warranted. [ABSTRACT FROM AUTHOR]

Introduction: Due to increasing intensity and complexity of therapies and longer survivorship, many patients with haematologic malignancy (HM) are at risk of invasive fungal disease (IFD). Mortality from IFD is high and treatment of an episode of IFD results in an excess length of hospital stay and costs and delays delivery of curative therapy of the underlying haematologic condition. Therefore, prevention and early recognition and treatment of IFD are crucial. Areas covered: Risk factors particular to certain HMs and haematopoietic stem cell transplantation, as well as those risk factors universal to all HM groups are examined. Expert commentary: Risk stratification identifies those patients who would benefit most from mould active versus yeast active prophylaxis and those who can be safely managed with monitoring and clinically driven interventions for IFD. This approach aids in antifungal stewardship. [ABSTRACT FROM AUTHOR]

Acute lymphoblastic leukaemia (ALL) presenting as peripheral blood hypereosinophilia is very rare and the incidence is <1%. The characteristic feature of patients with ALL and hypereosinophilia is the absence of blasts in peripheral blood, and this might lead to misdiagnosis of ALL. It is important for clinicians and pathologists to be aware of this uncommon initial presentation of ALL to avoid delay in diagnosis. We report a 37‑year‑old man who presented with fever and respiratory symptoms and was found to have hypereosinophilia in peripheral blood. His bone marrow and lymph node biopsies were diagnostic of ALL. [ABSTRACT FROM AUTHOR]

In tumour lysis syndrome ( TLS), metabolic alterations caused by the destruction of malignant cells manifest as laboratory abnormalities with (clinical TLS) or without (laboratory TLS) organ dysfunction. This prospective multicentre cohort study included 153 consecutive patients with malignancies at high risk for TLS (median age 54 years (interquartile range, 38-66). Underlying malignancies were acute leukaemia (58%), aggressive non-Hodgkin lymphoma (29.5%), and Burkitt leukaemia/lymphoma (12.5%). Laboratory TLS developed in 17 (11.1%) patients and clinical TLS with acute kidney injury ( AKI) in 30 (19.6%) patients. After adjustment for confounders, admission phosphates level (odds ratio [ OR] per mmol/l, 5.3; 95% confidence interval [95% CI], 1.5-18.3), lactic dehydrogenase ( OR per x normal, 1.1; 95% CI, 1.005-1.25), and disseminated intravascular coagulation ( OR, 4.1; 95% CI, 1.4-12.3) were associated with clinical TLS; and TLS was associated with day-90 mortality ( OR, 2.45; 95% CI, 1.09-5.50; P = 0.03). In this study, TLS occurred in 30.7% of high-risk patients. One third of all patients experienced AKI, for which TLS was an independent risk factor. TLS was associated with increased mortality, indicating a need for interventional studies aimed at decreasing early TLS-related deaths in this setting. [ABSTRACT FROM AUTHOR]

Aim: H1N1 influenza virus infections in immunosuppressive patients cause complications. Clinical and laboratory findings of H1N1 positive haematology patients were evaluated in this study. Materials and methods: The "H1N1 Swine Influenza Suspicious Case Notification Form and Inpatient Follow-up Form" was prepared for 15 patients with suspected H1N1 infection between October 2009 and May 2010. H1N1 was detected by real-time RT-PCR assay. For all cases medical records were reviewed for clinical, demographic, and haematologic information. Results: H1N1 positivity was confirmed using real-time RT-PCR in 9 out of 15 patients (11 men, 4 women). One of the 9 patients had been followed up due to aplastic anaemia, 1 due to Evans syndrome, and the remaining 7 due to haematologic malignancy. Among the 9 patients diagnosed with H1N1, 3 had previously undergone autologous haemopoietic stem cell transplantation (HSCT). H1N1 was detected in HSCT recipients in the early post-transplant period (range 7-21 days). The most prominent symptoms were as follows: high fever, cough, vomiting, nausea, and diarrhoea, in descending order. Oseltamivir was given to all patients. Eight patients responded to the treatment and recovered clinically. One patient (57-year-old female with multiple myeloma), required intensive care and she died due to severe sepsis and pneumonia. Conclusion: Our data show that subjective findings like headache and fatigue often seen in influenza infections were not the dominant clinical presentation in these patients. These infections should be considered in patients with haematological malignancy, and appropriate treatment and prophylaxis should be started early. [ABSTRACT FROM AUTHOR]

Background: The risks of haematologic malignancies in female patients with systemic lupus erythematosus (SLE) have been observed to be higher in young age groups than in old age groups. However, the age-risk relationship between haematologic malignancies and SLE is poorly defined. Design and methods: A retrospective cohort study was conducted nationwide with newly diagnosed SLE female patients during the period of 1997 to 2001 using the database acquired from the Taiwan National Health Research Institute. Each patient in the study was randomly frequency matched with five SLE-free people based on age. The subsequent developments of haematologic malignancies were observed until the date haematologic cancer was diagnosed or December 2008. The age-adjusted standardized incidence ratios (SIRs), the incidence per 1000 person-years, the follow-up duration to the diagnosis of haematologic malignancies and the cumulative hazard rates of haematologic malignancies between SLE and controls were analysed. Results: A total of 35 lymphoid and 14 myeloid malignancies were observed among 9349 female SLE patients. Further, significantly higher incidences of both lymphoid and myeloid malignancies were found in SLE patients (SIR: 3.30, 95% confidence interval (CI) = 2.20–4.93 and SIR: 2.86, 95% CI = 1.49–5.09). Also, two peaks of risk ratios for lymphoid malignancies were found in patients aged 21–30 years and 41–50 years. It was observed that the follow-up duration for haematologic malignancies was significantly shorter in SLE patients than in controls (73.21 vs. 105.25 months, respectively). In addition, higher cumulative hazard rates in both lymphoid and myeloid malignancies were found in SLE patients (p < 0.0001). Conclusion: Female SLE patients have a higher incidence of haematologic malignancy in different age groups, and with shorter incubating time than SLE-free people. [ABSTRACT FROM AUTHOR]

Combination treatment of paediatric invasive fungal infections (IFIs) has rarely been reported. A total of 17 children with 19 IFI episodes were enrolled in the study. The median age of the patients was 5.3 (range 0.5-17) years. IFI was classified as proven in 4, probable in 12 and possible in 3 episodes. These patients received empiric antifungal treatment, which consisted of liposomal amphotericin B (LAmB) monotherapy for a median duration of 12 days (range 3-69 days). All patients were refractory to LAmB; therefore, caspofungin was added to the therapy in 11 patients. In the remaining six patients, LAmB was ceased and a combination of caspofungin and voriconazole was started. Among the patients who received caspofungin + LAmB, four did not show favourable response and the combination was switched to caspofungin + voriconazole. The median (range) and total duration of the therapy were 7 (3-14) days and 91 patient days for LAmB + caspofungin combination and 49 (7-126) days and 516 patient days for caspofungin + voriconazole combination. We found a favourable response rate of 68.4% in 16 proven or probable IFI episodes. Twelve-week survival rate of these patients was 75%. No serious side effect was observed among the patients. Our data suggest that combination antifungal therapy is safe and effective in children with haematological malignancies. [ABSTRACT FROM AUTHOR]

Xanthogranuloma (XG) is rarely observed in adults and has been reported to be associated with chronic myelogenous leukaemia (CML) and/or neurofibromatosis type 1 (NF1). A 68-year-old woman with adult T-cell leukaemia/lymphoma (ATLL) gradually developed disseminated XGs over the 3 years since disease onset. Histopathological examination of a skin biopsy revealed the presence of histiocytes in the dermis with a few Touton giant cells admixed with lymphoid cells. The lesions of XGs persisted despite chemotherapy with prednisolone and chlorambucil for her ATLL. This is the first report of disseminated XGs associated with ATLL. The association of disseminated XGs with haematologic malignancies was reviewed and the possible pathogenesis of this association will be discussed. [ABSTRACT FROM AUTHOR]