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Myelofibrosis (MF) is the most symptomatic form of myeloproliferative neoplasm and carries the worst outcome. Allogeneic hematopoietic stem cell transplantation is the only therapy with potential for cure at present, but is limited by significant mortality and morbidity. JAK inhibition is the mainstay of treatment for intermediate- and high-risk MF. Ruxolitinib is the most widely used JAK1/2 inhibitor and provides durable effects in controlling symptom burden and spleen volumes. Nevertheless, ruxolitinib may not adequately address the underlying disease biology. Its effects on mutant allele burden, bone marrow fibrosis, and the prevention of leukemic transformation are minimal. Multiple small molecules are being tested in multiple phase 2 and 3 studies as either monotherapy or in combination with JAK2 inhibitors. In this review, the role of LSD1/KDM1A inhibition as a potential disease-modification strategy in patients with myelofibrosis is described and discussed.

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Aggressive medical care can increase suffering and the health-care burden on patients with advanced haematological malignancies. Our palliative care team has been pioneering an integrated palliative care (IPC) programme for patients with advanced haematological malignancies in Hong Kong since 2018. The aim of the study was to evaluate the effect of IPC on the administration of chemotherapy or other treatments within the 14 days before death; multiple (more than one) emergency department visits within the 90 days before death; multiple (more than one) unplanned hospitalisations within the 90 days before death; and intensive care unit admission within the 90 days before death. We retrospectively reviewed the outcomes of patients with advanced haematological malignancies who received IPC during the period of Jan 1, 2017, to Dec 31, 2020. Patients who died on the day of referral to palliative care or younger than 18 years were excluded. Our IPC programme comprised: early palliative care referral and advance care planning discussions; baseline and regular assessment of patient's physical and psychospiritual distress and family concerns; consensus for symptom management and supportive services; and regular meetings with haematologists to review and modify care plans for their patients and community providers. Patients matched by disease status and patient characteristics but who did not receive IPC were selected as control in a 1:2 ratio. Descriptive statistics were used to illustrate general patient characteristics, stratified by matching group. Multivariate analyses were used to assess the effect of IPC on the outcomes of interest. The effect of duration of IPC on patient outcomes was also investigated. Ethical approval for this study was issued by the Institutional Review Board of the University of Hong Kong and Hospital Authority Hong Kong West Cluster (reference UW 18–282). 317 patients with advanced haematological malignancies (of whom 105 received IPC) were included for analysis. The primary diagnosis was lymphoma (134 [42%] of 317 patients), leukaemia (106 [33%]), myelodysplastic syndrome (46 [15%]), and myeloma (31 [10%]). The use of IPC was associated with less multiple emergency department visits (odds ratio 0·19 [95% CI 0·16–0·23]; p=0·019], reduced multiple unplanned hospitalisations (0·24 [0·19–0·31]; p=0·0021), and lower risk of intensive care unit admission (0·12 [0·08–0·18]; p=0·0032) within the 90 days before death, and decreased need of chemotherapy or other treatments within the 14 days before death (0·34 [0·25–0·46]; p=0·0012). Receiving IPC for more than 90 days was associated with 2% fewer multiple emergency department visits, 12% less multiple unplanned hospitalisations, 3% less intensive care unit admissions, and 11% less need of chemotherapy or other treatments in the defined near-death intervals. This study was limited by its retrospective design and the scarcity of details on the frequency and intensity of the palliative care service. Despite these limitations, we found that the use of IPC service was associated with reduced need for acute and aggressive medical services in patients with advanced haematological malignancies. None.

Background The epidemiology and treatment of acute promyelocytic leukaemia (APL) are changing. We have incorporated oral arsenic trioxide (oral-ATO) into induction/maintenance. Methods Newly-diagnosed APL from 1991 to 2021 divided into three 10-year periods were studied to define its epidemiology and how oral-ATO impacted on its outcome. Primary endpoints included APL incidence, early deaths (ED, first 30 days), and overall survival (OS). Secondary endpoints included post-30-day OS, relapse-free survival (RFS), and incidence of second cancers. Results APL occurred in 374 males and 387 females at a median age of 44 (1–97) years. Annual incidences increased progressively, averaging 0.32 per 100,000 people. All-trans retinoic acid (ATRA)-based and oral-ATO-based regimens were used in 469 and 282 patients. There were 144 EDs, occurring almost exclusively in ATRA-based inductions (N = 139), being more with males, age > 50 years, leucocyte > 10 × 10 9 /L, diagnosis during 1991–2009 and fewer with oral-ATO-based regimens. After a median of 75 (interquartile range: 14–161) months, 5-year and 10-year OS were 68.1% and 63.3%, inferior with males, age > 50 years, leucocyte > 10 × 10 9 /L, high-risk Sanz score and superior with oral-ATO-based regimens. Factoring out EDs, 5-year and 10-year post-30-day OS were 84.0% and 78.1%, inferior with males and superior with oral-ATO-based regimens. In 607 CR1 patients, the 5-year RFS was 83.8%, superior with diagnosis in 2010–2021 and oral-ATO-based regimens. Second cancers developed in 21 patients, unrelated to oral-ATO-based regimens. Conclusions There was an increasing incidence of APL, and all survivals were superior with the use of oral-ATO-based regimens. This study formed part of the Acute Promyelocytic Leukaemia Asian Consortium Project (ClinicalTrials.gov identifier: NCT04251754).

Acute promyelocytic leukaemia (APL) results from the reciprocal chromosomal translocation t(15;17)(q24;21) (PML–RARA gene fusion). We have formulated an oral, economical, and outpatient-based preparation of arsenic trioxide and shown that it is efficacious for newly diagnosed and relapsed APL. In this study, we aimed to define the epidemiological landscape of APL in Hong Kong and to assess the effect of oral arsenic trioxide therapy on patient outcomes. This retrospective analysis of patients diagnosed with APL in Hong Kong between Jan 1, 1991, and March 31, 2021 (data censored on Nov 30, 2021) had incidence of APL, early death (within 30 days of hospitalisation), and overall survival as primary outcomes, and incidence of other primary cancers as a secondary outcome. Oral all-trans retinoic acid (ATRA) plus chemotherapy or oral arsenic trioxide were used. ATRA plus chemotherapy comprised induction with ATRA (45 mg/m2 per day, divided in two doses, for 42 days) and daunorubicin (50 mg/m2 per day intravenously for 3 days); consolidation with two cycles of daunorubicin (for 2 days) and cytarabine (100 mg/m2 per day intravenously for 5 days); and 24 months of maintenance therapy with ATRA (for 15 days every 3 months), 6-mercaptopurine (90 mg/m2 per day), and methotrexate (15 mg/m2 per week). The arsenic trioxide approach comprised two dosing schedules: for patients diagnosed between Jan 1, 2013, and Dec 31, 2017, arsenic trioxide was included in induction and maintenance only; induction was with arsenic trioxide (0·15 mg/day for 42 days), ATRA, oral ascorbic acid (1000 mg/day for 42 days), and daunorubicin; consolidation was with two cycles of daunorubicin and cytarabine; and 24 months of maintenance with arsenic trioxide, ATRA, and ascorbic acid (all for 14 days every 2 months). For patients diagnosed between Jan 1, 2018, and March 31, 2022, arsenic trioxide was included in induction, consolidation, and maintenance, substantially reducing exposure to chemotherapy; induction was with arsenic trioxide (0·15 mg/kg per day for 42 days), ATRA and ascorbic acid (for 42 days), and daunorubicin (given only to patients presenting with a leucocyte count of 10 × 109 cells/L); consolidation was with two cycles of arsenic trioxide, ATRA, and ascorbic acid (all for 14 days every 28 days); and 24 months of maintenance therapy with arsenic trioxide, ATRA, and ascorbic acid. Multivariate cox regression analysis was used to find prognostic indicators for overall survival. This ongoing study was approved by the University of Hong Kong's Institutional Review Board and is registered with ClinicalTrials.gov, NCT04251754. 751 patients (387 [51%] women and 364 [49%] men) were identified (median age 44 years [IQR 31–57]), for an annual incidence of 0·32 per 100 000 people. 469 (62%) patients received ATRA plus chemotherapy and 282 (38%) patients received oral arsenic trioxide. After a median follow-up of 75 months (IQR 14–161), 271 (36%) patients had died, with early death constituting 144 (53%) cases, all occurring in patients in the ATRA plus chemotherapy cohort. 5-year overall survival in the full cohort was 68% and 10-year overall survival was 63%. On multivariate analysis, being male (p=0·019), older than 50 years (p<0·0001), having a leucocyte count of >10 × 109cells/L at presentation (p<0·0001), and having ATRA plus chemotherapy regimens (p<0·0001) were all associated with worse overall survival. In the oral arsenic trioxide cohort, 5-year overall survival was 92% and 10-year overall survival was 85%. In the ATRA plus chemotherapy cohort, 5-year overall survival was 55% and 10-year overall survival was 51%. Second cancers developed in 21 patients (eight never exposed to oral arsenic trioxide; 13 with previous exposure to oral arsenic trioxide during induction, maintenance, or relapse). The incidence of second cancers in patients exposed to oral arsenic trioxide did not differ from that in patients never exposed to oral arsenic trioxide (incidence rate ratio 2·14 [95% CI 0·89–5·17], p=0·099). Oral arsenic trioxide plus ATRA was associated with fewer early deaths and better long-term survival than ATRA plus chemotherapy, with shorter hospital stays and outpatient treatment as distinct health-care advantages. Health and Medical Research Fund of the Hong Kong Special Administrative Region, China (code 08191946).

Appreciation of the properties of arsenic trioxide (ATO) has redefined the treatment landscape for acute promyelocytic leukaemia (APL) and offers promise as a treatment for numerous other diseases. The benefits of ATO in patients with APL is related to its ability to counteract the effects of PML::RARA, an oncoprotein that is invariably detected in the blood or bone marrow of affected individuals. The PML::RARA oncoprotein is degraded specifically by binding to ATO. Thus ATO, in combination with all-trans retinoic acid, has become the curative treatment for ATO. The multiple mechanisms of action of ATO has also paved the way for application in various condition encompassing autoimmune or inflammatory disorders, solid organ tumours, lymphomas and other subtypes of AML. The development of oral formulation of ATO (oral ATO) has reduced costs of treatment and improved treatment convenience allowing widespread applicability. In this review, we discuss the mechanisms of action of ATO, the development of oral ATO, and the applications of oral ATO in APL and other diseases.

Background Effective clinician-patient communication is essential for delivering quality end-of-life care. However, there are no validated measures to assess the quality of end-of-life communication for Chinese patients. Methods This study aims to cross-culturally adapt and validate the patient-reported Quality of Communication Questionnaire (QOC) for Chinese speaking patients. The QOC was translated and adapted using a standardized methodology consisting of forward translations, backward translations, expert panel review, and testing with patients. We conducted a cross-sectional study to perform principal component, content validity, internal consistency, convergent and discriminant validity analyses of the 16-item Chinese QOC (C-QOC). Subjects were Chinese-speaking advanced cancer ( n  = 82) and advanced chronic kidney disease ( n  = 68) patients attending outpatient clinics in five hospitals or receiving home-based palliative care in Hong Kong. Results The content validity of the C-QOC was established by an expert panel. The C-QOC has a 3-component structure (general communication skills, communication about illness trajectory, and end-of-life care planning subscales) and demonstrated good internal consistency (Cronbach’s α = 0.88; subscales 0.84–0.90). Convergent validity was supported by positive association between C-QOC score and overall clinician communication quality ( r  = 0.47, p  < 0.001) and clinician comfort in discussing dying ( r  = 0.63, p  < 0.001). Discriminant validity was demonstrated by the stronger association between overall clinician communication quality and general communication skills, compared to the other two subscales. Conclusions The C-QOC is a valid, reliable, and culturally relevant instrument for evaluating the quality of clinician end-of-life care communication by Chinese patients with advanced cancer and chronic kidney disease.

South Asians bear a greater burden of cardiovascular disease (CVD) compared to other ethnic groups and hypertension is a major modifiable risk factor. The purpose of this study was to examine rates and predictors of uncontrolled blood pressure among an immigrant Punjabi Sikh community in Vancouver. We recruited 350 adults (40% women; mean age 67.3 ± 11.9 years) across 5 Sikh temples and measured blood pressure, heart rate, height, weight, waist circumference, socio-demographic background, and health history. 42% of participants had uncontrolled blood pressure of which one-third reported no previous history of hypertension. Based on modified cut-offs for South Asians, the mean waist circumferences across groups were well above target and 50% classified as obese. A higher percentage in the uncontrolled group (vs. controlled group) were of an older age, had a diabetes history and reported a physically active lifestyle. Findings suggest more efforts are needed to reduce the rates of uncontrolled blood pressure in this community. Interventions such as blood pressure drives, community-based outreach programs, and physical activity and dietary interventions should be explored to lower this CVD risk factor in this community.

IntroductionNeutropenic fever (NF) has a crude mortality rate of 3–18%. International guidelines recommend that all patients with NF receive ultrabroad-spectrum antibiotics (UBSAs) within 1 hour of emergency department (ED) registration. However, over 70% patients presenting to hospital with suspected NF (sNF) cannot access absolute neutrophil count (ANC) result within 1 hour, do not have NF and do not require UBSAs. In ED and hospitalised patients with sNF, we hypothesise that the ASTERIC protocol effectively and safely reduces the use of UBSAs compared with standard care alone.Methods and analysisThis pragmatic, parallel, multicentre, type 1, hybrid effectiveness-implementation, stepped-wedge, before-and-after, cluster randomised controlled trial aims to evaluate whether antibiotic prescribing can be safely reduced through implementing a multifaceted antibiotic stewardship intervention (ASTERIC) in adult patients with sNF presenting to EDs. The sNF was defined as a fever with a single oral temperature of ≥38.3°C (101°F) within 24 hours before ED registration or a temperature of ≥38.0°C (100.4°F) sustained over a 1-hour period, following last chemotherapy or targeted therapy within 6 weeks for any solid tumour, or in any period following therapies against leucaemia, lymphoma, myelodysplastic syndrome, aplastic anaemia, multiple myeloma or recipient of HSCT. The study will involve eight hospitals in Hong Kong with variable baseline practice. We will include 704 adult patients (352 patients in pre-implementation and post-implementation periods, respectively) with sNF (tympanic temperature ≥38.3°C) and 48 staff participants (6 staff participants in each hospital). Healthcare professionals will receive a multifaceted stewardship intervention consisting of risk assessment tools, fast-track ANCs, a decision tool for patient management and antibiotic use, supported by an educational package and staff interaction programmes (ASTERIC protocol). Patients’ blood ANC, and cancer therapy and chronic illness therapy scores will be measured. The RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) and Proctor conceptual frameworks will be followed for evaluation of implementation. The main outcome measures are the mean total dose of UBSAs prescribed in 7 days and serious adverse events at 30 days. Data analysis will incorporate intention-to-treat, per-protocol and as-treated analyses for service outcomes (effectiveness, safety, quality of life assessments and cost-effectiveness) and mixed methods for implementation outcomes, informed by the Theoretical Domains Framework. We expect that the study results will inform health policy with improvement in hospital services in treating stable sNF, evidenced by improved safe antibiotic stewardship, early antibiotic de-escalation and reduced costs and length of stay.Ethics and disseminationThe institutional review boards of all study sites approved this study. This study will establish the ASTERIC protocol safely improves antibiotic stewardship and clinical management in adult patients with sNF. We will disseminate the findings through peer-reviewed publications, conference presentations and educational activities. All patients with sNF will be influenced by the new protocol which is agreed at hospital level. Randomisation is at hospital level, not patient level. Patient consent is sought for follow-up and data access, not for treatment. Staff consent is sought for interviewing.Trial registration numberNCT06794320.

A personalized prognostic model that takes into account the unique molecular features of primary myelodysplastic neoplasm (MDS) in Asia patients is lacking. Diagnostic clinicopathologic features, cytogenetic changes, and gene mutations of ethnic Asian patients with primary MDS were analyzed. Variables were evaluated for associations with overall survival (OS), leukemia-free survival (LFS), and time to progression to secondary AML (TTP-sAML). Prognostic scores were built as a weighted sum of prognostic variables for each patient. The cohort comprised 1225 patients, with at least one gene mutation identified in 1177 patients (96%). Genomic factors associated with inferior outcomes included monosomy 7, del(5q), and GNAS and TP53 mutations for OS; trisomy 19, del(5q), monosomy 7, and GNAS , PTPN11 and TP53 mutations for LFS; and i(17q), del(5q), and NPM1 , NRAS , GNAS , IDH2 , SF3B1 and RUNX1 mutations for TTP-sAML. The Asian Prognostic Scoring System (APSS) was determined, stratifying patients into six prognostic risk categories. The APSS, compared with the International Prognostic Scoring System molecular (IPSS-M), showed superior concordance indices (C-indices) for OS (0.73 versus 0.57), LFS (0.72 versus 0.59), and TTP-sAML (0.75 versus 0.65) for this Asian cohort. In conclusion, the APSS enhanced prognostication of primary MDS in Asia.