Simultaneous merkel cell carcinoma and acute myeloid leukaemia: A diagnostic challenge.

Merkel cell carcinoma is a very aggressive primary skin tumour with a high risk of local recurrences and lymphatic and distant metastases. The frequent association between this carcinoma and other skin tumour and lymphoid malignancies, its similar cellular morphology with leukocytes, and limited infiltration in bone marrow constituted a challenging diagnosis. We report an unusual case of an 82-year-old male who simultaneously presented Merkel cell carcinoma and acute myeloid lymphoma. The diagnosis was established through flow cytometry, immunohistochemical studies and next generation sequencing (NGS) analysis. Flow cytometry allowed for the differentiation of the two cell populations in bone marrow aspirate, which was crucial to the diagnosis of Merkel cell carcinoma and acute myeloid leukaemia (AML), after confirmed by immunohistochemistry. AML could be classified based on NGS results. Following diagnosis, the patient received palliative care and died 50 days later. immunophenotypic analysis by flow cytometry and Immunohistochemical study was crucial to establish the diagnosis of simultaneous affection of Merkel cell carcinoma and hematologic disorder.

Minor histocompatibility antigens to predict, monitor or manipulate GvL and GvHD after allogeneic hematopoietic cell transplantation.

Allogeneic hematopoietic cell transplantation (alloHCT) provides a potential curative treatment for haematological malignancies. The therapeutic Graft-versus-Leukaemia (GvL) effect is induced by donor T cells attacking patient hematopoietic (malignant) cells. However, if healthy non-hematopoietic tissues are targeted, Graft-versus-Disease (GvHD) may develop. After HLA-matched alloHCT, GvL and GvHD are induced by donor T cells recognizing polymorphic peptides presented by HLA on patient cells, so-called minor histocompatibility antigens (MiHAs). The balance between GvL and GvHD depends on the tissue distribution of MiHAs and T-cell frequencies targeting these MiHAs. T cells against broadly expressed MiHAs induce GvL and GvHD, whereas those targeting MiHAs with hematopoietic-restricted expression induce GvL without GvHD. Recently, the MiHA repertoire identified in natural immune responses after alloHCT was expanded to 159 total HLA-I-restricted MiHAs, including 14 hematopoietic-restricted MiHAs. This review explores their potential relevance to predict, monitor, and manipulate GvL and GvHD for improving clinical outcome after HLA-matched alloHCT.

Prenatal origin of NUTM1 gene rearrangement in infant B-cell precursor acute lymphoblastic leukaemia.

Rearrangement of NUTM1 gene (NUTM1r) is one of the most frequent aberrations occurring in infants (younger than 1 year at diagnosis) with B-cell precursor Acute Lymphoblastic Leukaemia (BCP-ALL). In this study we had the unique opportunity to analyze the umbilical cord blood (UCB) sample from one infant patient with NUTM1r BCP-ALL. Herein we reported for the first time that NUTM1r infant ALL arise prenatally, as both the patient-specific CUX1::NUTM1 fusion gene, as well as two IG/TR leukaemic markers were already present and detectable in the patient's UCB at birth. Our results clearly demonstrate the prenatal origin of NUTM1r infant BCP-ALL.

Neurological manifestations in dogs with acute leukemia.

Canine acute leukemia is a rare hematopoietic neoplasm. Neurological abnormalities have been frequently reported in dogs with acute leukemia (AL). However, the description of the presentation and findings are limited. This study aimed to describe the clinical findings in dogs with acute leukemia presenting with neurological signs as their primary complaint. The database of a private referral hospital was searched for cases that presented to the neurological department with neurological deficits and were subsequently diagnosed with acute leukemia. Six cases were included; all had neurological clinical signs and an abnormal neurological examination. All cases had a focal neuroanatomical localisation on neurological examination (brain n = 4; spinal = 2). Out of the four dogs with a complete magnetic resonance imaging (MRI) study, there was an ill-defined infiltrative pattern with abnormal signal intensity in the central nervous system (CNS) in three dogs and the loss of grey and white matter differentiation in the brain (n = 2) and/or spinal cord (n = 2). Other MRI findings included abnormal meningeal enhancement (n = 3), changes affecting spinal nerves and epaxial muscles (n = 2), and lymphadenopathy in the field of view (n = 2). The bone marrow assessment on MRI showed evidence of signal change (n = 3), characterized by a loss of normal fat opacity and an abnormal degree of contrast enhancement. The cerebrospinal fluid (CSF) analysis of the four dogs showed an increased protein level with non-specific pleocytosis and without evidence of malignant cells. Treatment with cytotoxic medication was implemented in two dogs. The dogs diagnosed with acute leukemia had focal neuroanatomical localisation, an infiltrative CNS pattern, and bone marrow remodulation on MRI with an increase in CSF protein and negative cytology analysis.

Extramedullary Paravertebral Mass: An Unusual Presentation of Hairy Cell Leukaemia.

Background: Hairy cell leukaemia (HCL) is an uncommon, indolent, B-cell, lymphoproliferative disorder typically involving peripheral blood, spleen and bone marrow. It is commonly presenting with pancytopenia, monocytopenia and massive splenomegaly, while accounting for 2% of lymphoid leukaemias. Cases of extranodal lesions caused by HCL are rare, although these have been reported. Here, we report a case of HCL presenting as a paravertebral mass without systemic involvement. Case description: A 58-year-old man was admitted to our hospital due to progressive difficulty walking for a month, without any other symptoms. Blood examination noted mild anaemia with Hb=12.6 g/dl and mild thrombocytopenia of 140,000/µl. Magnetic resonance imaging (MRI) and computed tomography (CT) imaging demonstrated a T6 posterior paravertebral mass lesion, extending into the spinal canal with metastatic bone lesions along the thoracic and lumbar spine. Further imaging study with CT indicated mild splenomegaly (13.4 cm) and an enlarged abdominal lymph node (3.5 cm) near celiac trifurcation. Conclusion: A core-needle biopsy from the paravertebral mass was performed. Results showed small-sized cells with round or oval nuclei, and pale cytoplasm with immunophenotype: B-cell origination with CD20+, Cyclin D1+, DBA.44+, Annexin+ and BRAF+, indicative of HCL. LEARNING POINTS: Hairy cell leukaemia (HCL) is relatively uncommon, accounting for 2% of all leukaemia cases.Extramedullary and skeletal involvement in HCL is rare and shares morphological characteristics with other peripheral small B-cell lymphoma neoplasms.Spine biopsy is essential for diagnosis in these cases, since it is always helpful to narrow the differential diagnosis.Correct diagnosis is essential for treatment of HCL and leads most patients to clinical remission and sometimes long-term cures.

Measurable residual disease (MRD)-testing in haematological cancers: A giant leap forward or sideways?

Measurable residual disease (MRD)-testing is used in many haematological cancers to estimate relapse risk and to direct therapy. Sometimes MRD-test results are used for regulatory approval. However, some people including regulators wrongfully believe results of MRD-testing are highly accurate and of proven efficacy in directing therapy. We review MRD-testing technologies and evaluate the accuracy of MRD-testing for predicting relapse and the strength of evidence supporting efficacy of MRD-guided therapy. We show that at the individual level MRD-test results are often an inaccurate relapse predictor. Also, no convincing data indicate that increasing therapy-intensity based on a positive MRD-test reduces relapse risk or improves survival. We caution against adjusting therapy-intensity based solely on results of MRD-testing.

Targeting the redox vulnerability of acute myeloid leukaemia cells with a combination of auranofin and vitamin C.

Acute myeloid leukaemia (AML) is a heterogeneous disease characterized by complex molecular and cytogenetic abnormalities. Pro-oxidant cellular redox status is a common hallmark of AML cells, providing a rationale for redox-based anticancer strategy. We previously discovered that auranofin (AUF), initially used for the treatment of rheumatoid arthritis and repositioned for its anticancer activity, can synergize with a pharmacological concentration of vitamin C (VC) against breast cancer cell line models. In this study, we observed that this drug combination synergistically and efficiently killed cells of leukaemic cell lines established from different myeloid subtypes. In addition to an induced elevation of reactive oxygen species and ATP depletion, a rapid dephosphorylation of 4E-BP1 and p70S6K, together with a strong inhibition of protein synthesis were early events in response to AUF/VC treatment, suggesting their implication in AUF/VC-induced cytotoxicity. Importantly, a study on 22 primary AML specimens from various AML subtypes showed that AUF/VC combinations at pharmacologically achievable concentrations were effective to eradicate primary leukaemic CD34+ cells from the majority of these samples, while being less toxic to normal cord blood CD34+ cells. Our findings indicate that targeting the redox vulnerability of AML with AUF/VC combinations could present a potential anti-AML therapeutic approach.

Molecular and cellular mechanisms of chemoresistance in paediatric pre-B cell acute lymphoblastic leukaemia.

Paediatric patients with relapsed B cell acute lymphoblastic leukaemia (B-ALL) have poor prognosis, as relapse-causing clones are often refractory to common chemotherapeutics. While the molecular mechanisms leading to chemoresistance are varied, significant evidence suggests interactions between B-ALL blasts and cells within the bone marrow microenvironment modulate chemotherapy sensitivity. Importantly, bone marrow mesenchymal stem cells (BM-MSCs) and BM adipocytes are known to support B-ALL cells through multiple distinct molecular mechanisms. This review discusses the contribution of integrin-mediated B-ALL/BM-MSC signalling and asparagine supplementation in B-ALL chemoresistance. In addition, the role of adipocytes in sequestering anthracyclines and generating a BM niche favourable for B-ALL survival is explored. Furthermore, this review discusses the role of BM-MSCs and adipocytes in promoting a quiescent and chemoresistant B-ALL phenotype. Novel treatments which target these mechanisms are discussed herein, and are needed to improve dismal outcomes in patients with relapsed/refractory disease.

Mutational cooperativity of RUNX1::RUNX1T1 isoform 9a and oncogenic NRAS in zebrafish myeloid leukaemia.

RUNX1::RUNX1T1 (R::RT1) Acute Myeloid Leukaemia (AML) remains a clinical challenge, and further research is required to model and understand leukaemogenesis. Previous zebrafish R::RT1 models were hampered by embryonic lethality and low penetrance of the malignant phenotype. Here, we overcome this by developing an adult zebrafish model in which the human R::RT1 isoform 9a is co-expressed with the frequently co-occurring oncogenic NRASG12D mutation in haematopoietic stem and progenitor cells (HSPCs), using the Runx1+23 enhancer. Approximately 50% of F0 9a+NRASG12D transgenic zebrafish developed signs of haematological disease between 5 and 14 months, with 27% exhibiting AML-like pathology: myeloid precursor expansion, erythrocyte reduction, kidney marrow hypercellularity and the presence of blasts. Moreover, only 9a+NRASG12D transplant recipients developed leukaemia with high rates of mortality within 40 days, inferring the presence of leukaemia stem cells. These leukaemic features were rare or not observed in animals expressing either the NRAS or 9a oncogenes alone, suggesting 9a and NRAS cooperation drives leukaemogenesis. This novel adult AML zebrafish model provides a powerful new tool for investigating the basis of R::RT1 - NRAS cooperativity with the potential to uncover new therapeutic targets.

Effects of different conditioning regimens on HLA-mismatched microtransplantation and changes in fine immune indices in acute myeloid leukaemia.

The aim of this study was to observe the effects of different conditioning regimens on fine immune indices after microtransplantation (MST) in patients with acute myeloid leukaemia (AML). This article discusses the possible immune mechanism of microtransplantation and describes a more optimized conditioning regimen. A total of 55 AML patients who received MST treatment at the Second Hospital of Lanzhou University from August 2015 to October 2023 were included in this study, and 13 AML patients who did not receive MST but directly received the maintenance therapy were included as the control group (C). The MST patients were divided into a conditioning regimen with venetoclax group (A) and a conditioning regimen without venetoclax group (B). The fine immune indices were detected by flow cytometry and cytometric bead array analysis. Changes in the immune indices before and after treatment were observed, and the progression-free survival (PFS) and overall survival (OS) of patients in the MST group were analysed. Compared with those in Group B, patients in Group A had better PFS and OS. The proportion of Treg cells and the expression level of IL-2 were increased, while TNF-α and IFN-α were decreased after MST (P < 0.05). In Group B, total T cells, CD4+T cells and CD4+/CD8+T cells decreased; NK cells and total B cells increased; and IL-17A first increased and then decreased during the MST (P < 0.05). There were significant differences in total B cells, IL-4 and IFN-γ between Group A and Group B during MST. Moreover, there were significant differences in total T cells, CD4+T cells, Treg cells, IL-17A, IFN-γ and IL-2 between the patients in the MST group and those in the control group (P < 0.05). The MST conditioning regimen containing venetoclax significantly changed the fine immune indices and showed improved efficacy, which is worthy of further study and clinical application.

Construction and validation of a SASP-related prognostic signature in patients with acute myeloid leukaemia.

Acute myeloid leukaemia (AML) is a common and highly aggressive haematological malignancy in adults. Senescence-associated secretory phenotype (SASP) plays important roles in tumorigenesis and progression of tumour. However, the prognostic value of SASP in patients with AML has not been clarified. The present study aims to explore the prognostic value of SASP and develop a prognostic risk signature for AML. The RNA-sequencing data was collected from the TCGA, GTEx and TARGET databases. Subsequently, differentially expressed gene analysis, univariate Cox regression and LASSO regression were applied to identified prognostic SASP-related genes and construct a prognostic risk-scoring model. The risk score of each patient were calculated and patients were divided into high- or low-risk groups by the median risk score. This novel prognostic signature included 11 genes: G6PD, CDK4, RPS6KA1, UBC, H2BC12, KIR2DL4, HSF1, IFIT3, PIM1, RUNX3 and TRIM21. The patients with AML in the high-risk group had shorter OS, demonstrating that the risk score acted as a prognostic predictor, which was validated in the TAGET-AML dataset. Univariate and multivariate analysis revealed the risk score was an independent prognostic factor in patients with AML. Furthermore, the present study revealed that the risk score was associated with immune landscape, immune checkpoint gene expression and chemotherapeutic efficacy. In the present study, we constructed and validated a unique SASP-related prognostic model to assess therapeutic effect and prognosis in patients with AML, which might contribute to understanding the role of SASP in AML and guiding the treatment for AML.

A systematic review of health state utility values for older people with acute myeloid leukaemia.

PURPOSE: Older people with acute myeloid leukaemia (AML) have a poor prognosis, reduced health-related quality of life (HRQoL) and require substantial healthcare resources. The objectives of this systematic review were to determine what health state utility values (HSUVs) are reported in the literature that can be used in economic evaluations of interventions for older people with AML, identify research gaps, and discuss directions for future research. METHODS: The following databases were searched for studies published from inception until Feb 2023: PubMed, EMBASE, CINAHL, PsycINFO, Cochrane, and EconLit. Studies were included if they reported on HSUVs of people with AML >60 years, or HRQoL data that could be mapped to HSUVs using currently published algorithms. RESULTS: Of 532 studies identified, 7 met inclusion (4 full studies and 3 conference abstracts). Twenty-eight potentially eligible studies were excluded as they did not report HRQoL measures in sufficient detail to be mapped to utility values. Included studies reported on health states of newly diagnosed disease (n=4 studies), intensive therapy (n=1 study), controlled remission (n=3 studies), and relapsed or refractory disease (n=2 studies). No studies reported on low intensity therapy or supportive care health states. Utility values were largely reported via the EuroQol and ranged from 0.535 (intensive therapy) to 0.834 (controlled remission). CONCLUSION: There are gaps in knowledge on HSUVs for older people with AML, particularly for certain treatment-related health states. Future articles should publish comprehensive HRQoL outcomes to enable use in economic evaluation.

Leukaemic Optic Neuropathy in a Patient with Treated Acute Lymphoblastic Leukaemia: Optical Coherence Tomography as an Aid to Diagnosis.

Leukaemic optic neuropathy is an uncommon cause of visual loss which represents a neuro-oncological emergency with the potential of irreversible blindness if untreated. It can be difficult to diagnose, often presenting with normal neuroradiological and cerebrospinal fluid findings. We present the case of a 26-year-old woman with T-cell acute lymphoblastic leukaemia with optic neuropathy secondary to leukaemic infiltration, who demonstrated features on optical coherence tomography that aided the diagnosis of this condition. This included the presence of numerous, small, hyperreflective opacities erupting from the optic nerve head, which improved following treatment with radiotherapy and chemotherapy, and later recurred when the condition relapsed. This finding may help clinicians differentiate between other causes of optic neuropathy as well as assessing response to treatment and monitoring for recurrence.

Decoction of Yougui Wan combined with Wuzi Yanzong Wan ameliorates thin endometrium in a mouse model.

BACKGROUND: This study aimed to determine the effect and mechanism of the Decoction of Yougui Wan combined with Wuzi Yanzong Wan (DYWWYW), a traditional Chinese herbal formula, in a mouse model with thin endometrium induced by 95% ethanol. METHODS: Thin endometrium mice were treated with progynova (0.002 mg) as well as a low and high dose of DYWWYW (0.05 and 0.5 mL DYWWYW, respectively, diluted in 2 mL normal saline). Western blotting and qRT-PCR analyses were performed to determine the protein and mRNA expression levels, respectively, of integrin αγß3 and leukaemia inhibitor factor (LIF) in uterus tissues. Serum oestradiol and progesterone concentrations were determined via ELISA. The remaining thin endometrium mice were mated with male mice, and the number of embryos implanted in the different groups was calculated. RESULTS: A high dose of DYWWYW effectively ameliorated the injury of endometrium caused by 95% ethanol. The levels of oestradiol, progesterone, αγß3 and LIF in thin endometrium mice treated with a high dose of DYWWYW were also significantly elevated. Additionally, a high dose of DYWWYW remarkably increased the number of embryo implantations in mice with thin endometrium. CONCLUSION: DYWWYW has improvement effects on thin endometrium by elevating the levels of endogenous oestradiol, progesterone, αγß3, and LIF in a mouse model.

During the reproductive cycle, endometrium thickness of more than 7 mm is considered as a cut-off value for successful embryo implantation. Currently, although therapies for the improvement of endometrium thickness such as sildenafil, endometrial scraping, granulocyte colony-stimulating factor and low dose of aspirin have been tried, the effects on patients are not consistent. Consequently, it is necessary to seek novel therapies to increase endometrium thickness effectively. A 95% ethanol-induced thin endometrium female ICR mouse model was established in this study. High dose of Decoction of Yougui Wan combined with Wuzi Yanzong Wan (DYWWYW) effectively ameliorated the injury of endometrium and remarkably increased the number of embryo implantations in thin endometrium mice. Additionally, the levels of some key indicators including oestradiol, progesterone, αγß3, and LIF were also increased in thin endometrium mice treated with high dose of DYWWYW. Therefore, DYWWYW was feasible in increasing endometrium thickness in a mouse model.

Intestinal mucositis, systemic inflammation and bloodstream infections following high-dose methotrexate treatment in childhood acute lymphoblastic leukaemia: Comparison between the NOPHO ALL 2008 protocol and the ALLTogether1 protocol.

Severe intestinal mucositis (IM) increases the risk of bloodstream infections (BSI) and inflammatory toxicity during acute lymphoblastic leukaemia (ALL) induction treatment. However, the implications of IM in subsequent ALL therapy phases after achieving remission remain unknown. This study investigated the relationship between IM (measured by plasma citrulline and the chemokine CCL20) and the development of BSI and systemic inflammation (reflected by C-reactive protein, CRP) in children with ALL during high-dose methotrexate (HDMTX) treatment, an important part of ALL consolidation therapy. The study compared patients treated according to the NOPHO ALL 2008 protocol (n = 52) and the ALLTogether1 protocol (n = 42), both with identical HDMTX procedures but different scheduling. One week post-HDMTX, citrulline dropped to median levels of 14.5 and 16.9 µM for patients treated according to the NOPHO ALL 2008 and ALLTogether1 protocols, respectively (p = 0.11). In a protocol and neutrophil count-adjusted analysis, hypocitrullinaemia (<10 µmol/L) was associated with increased odds of BSI within 3 weeks from HDMTX (OR = 26.2, p = 0.0074). Patients treated according to the NOPHO ALL 2008 protocol exhibited increased mucosal- and systemic inflammation post-HDMTX compared to patients treated according to ALLTogether1, with increased CCL20 (14.6 vs. 3.7 pg/mL, p < 0.0001) and CRP levels (10.0 vs. 1.0 mg/L, p < 0.0001). Both citrulline and CCL20 correlated with CRP for these patients (rs = -0.44, p = 0.0016 and rs = 0.35, p = 0.016, respectively). These results suggest that hypocitrullinaemia following HDMTX increases the risk of BSI, confirming previous observations from more intensive treatments. Moreover, these data indicate that the patients' vulnerability to mucositis and inflammatory toxicity after chemotherapy varies with treatment protocol.

Real-world comparative effectiveness of venetoclax-obinutuzumab versus Bruton tyrosine kinase inhibitors for frontline chronic lymphocytic leukaemia.

Real-world evidence comparing clinical outcomes between venetoclax and Bruton tyrosine kinase inhibitors (BTKis) in patients with frontline (1 L) chronic lymphocytic leukaemia (CLL) is lacking. We compared treatment effectiveness of 1 L venetoclax plus obinutuzumab (VenO) versus BTKi-based regimens. This retrospective observational study using Optum Clinformatics Data Mart® included adult patients with CLL (≥2 outpatient or ≥1 inpatient claim) who received VenO or BTKi-based regimens in 1 L (1/2019-9/2022). Baseline characteristics were balanced using stabilised inverse probability weighting. Outcomes included duration of therapy (DoT), persistence, time to next treatment or death (TTNT-D), and time off-treatment. Among 1506 eligible patients (VenO: 203; BTKi: 1303), the median follow-up duration was 12.6 (VenO) and 16.2 months (BTKi). Median DoT for VenO was 12.3 months; persistence remained higher in VenO versus BTKi through expected 1 L fixed treatment duration. Median TTNT-D was not reached for VenO; however, more VenO- versus BTKi-treated patients had not switched therapies/experienced death through Month 12 (87.1% vs. 75.3%). Among patients that discontinued, median time to discontinuation was 11.7 vs. 5.9 months for VenO versus BTKi and median time off-treatment was 11.3 vs. 4.3 months. In this real-world study, VenO was associated with better effectiveness outcomes than BTKi-based regimens in 1 L CLL.

Down syndrome-associated leukaemias: current evidence and challenges.

Children with Down syndrome (DS) are at increased risk of developing haematological malignancies, in particular acute megakaryoblastic leukaemia and acute lymphoblastic leukaemia. The microenvironment established by abnormal haematopoiesis driven by trisomy 21 is compounded by additional genetic and epigenetic changes that can drive leukaemogenesis in patients with DS. GATA-binding protein 1 (GATA1) somatic mutations are implicated in the development of transient abnormal myelopoiesis and the progression to myeloid leukaemia of DS (ML-DS) and provide a model of the multi-step process of leukaemogenesis in DS. This review summarises key genetic drivers for the development of leukaemia in patients with DS, the biology and treatment of ML-DS and DS-associated acute lymphoblastic leukaemia, late effects of treatments for DS-leukaemias and the focus for future targeted therapy.

Treatment with low-dose tyrosine kinase inhibitors due to significant haematologic toxicity in patients with CML with prolonged treatment failure prevents haematologic progression.

BACKGROUND: A lower dosage of tyrosine kinase inhibitors (TKIs) in patients with chronic myeloid leukaemia (CML) has shown efficacy in managing short-term toxicity and maintaining a deep molecular response in patients who fail to achieve treatment-free remission. METHOD: From over 700 patients with CML who were treated at two centres over the last three decades, this retrospective study identified eight patients characterised by long-term treatment failure and simultaneous prolonged significant haematologic toxicity that prevented the use of the standard tyrosine kinase inhibitor dosage. RESULTS: Patients had a high or intermediate ELTS risk score, and most had significant comorbidities. Two patients were treated previously with busulfan, and four were aged over 70, which might explain the reduced pool of normal haematopoietic stem cells. However, concomitant myelodysplastic syndrome or the presence of clonal haematopoiesis of indeterminate potential was not demonstrated. Despite prolonged treatment failure, the survival of these patients (who were ineligible for stem cell transplantation) ranged from 45-396 months. Neither mutations in the ABL kinase domain nor additional cytogenetic abnormalities developed during the treatment of these patients, prompting speculation about the low selective pressure of low-dose tyrosine kinase inhibitors and/or the absence of mutations at diagnosis. CONCLUSION: It is important not to stop treatment with tyrosine kinase inhibitors at a low personalised dosage in CML patients with prolonged significant haematologic toxicity despite long-term treatment failure.

CREST-UK: Real-world effectiveness, safety and outpatient delivery of CPX-351 for first-line treatment of newly diagnosed therapy-related AML and AML with myelodysplasia-related changes in the UK.

Favourable outcomes with CPX-351 versus conventional 7 + 3 were demonstrated in the pivotal phase III trial in adults aged 60-75 years with newly diagnosed, highrisk/secondary acute myeloid leukaemia (AML). As a complement to the clinical trial and to address important data gaps, the CPX-351 Real-World Effectiveness and SafeTy (CREST-UK; NCT05169307) study evaluated the use of CPX-351 in routine clinical practice in the UK, in 147 patients with newly diagnosed therapy-related AML or AML with myelodysplasia-related changes. Best response of complete remission or complete remission with incomplete platelet or neutrophil recovery was achieved by 53% of evaluable patients. Kaplan-Meier median overall survival (OS) was 12.8 months (95% confidence interval 9.2-15.3). Fifty (34%) patients proceeded to haematopoietic cell transplantation (HCT); median OS landmarked from the HCT date was not reached. There were no new safety concerns with CPX-351 identified in CREST-UK. Patients treated with CPX-351 in the outpatient setting spent an average of 24.4, 16.7, 28.2, and 27.7 fewer days on the ward compared with inpatients during first induction, second induction, first consolidation, and second consolidation, respectively. The results from CREST-UK provide valuable insights into the effectiveness, safety, and outpatient delivery of CPX-351 in routine clinical practice in the UK.