RESUMO
Leukemia is a prevalent pediatric cancer with significant challenges, particularly in relapsed or refractory cases. Chimeric antigen receptor T-cell (CAR-T) therapy has emerged as a personalized cancer treatment, modifying patients' T cells to target and destroy resistant cancer cells. This study reviews the current therapeutic options of CAR-T therapy for leukemia, addressing the primary obstacles such as antigen escape and T-cell exhaustion. We explore dual-targeting strategies and their potential to improve treatment outcomes by preventing the loss of target antigens. Additionally, we examine the mechanisms of T-cell exhaustion and strategies to enhance CAR-T persistence and effectiveness. Despite remarkable clinical successes, CAR-T therapy poses risks such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Our findings highlight the need for ongoing research to optimize CAR-T applications, reduce toxicities, and extend this innovative therapy to a broader range of hematologic malignancies. This comprehensive review aims to provide valuable insights for improving leukemia treatment and advancing the field of cancer immunotherapy.
Assuntos
Imunoterapia Adotiva , Leucemia , Linfócitos T , Humanos , Imunoterapia Adotiva/métodos , Leucemia/terapia , Leucemia/imunologia , Linfócitos T/imunologia , Receptores de Antígenos Quiméricos/imunologia , Antígenos de Neoplasias/imunologia , Animais , Exaustão das Células TRESUMO
Autologous stem cell transplantation (ASCT) emerges as a therapeutic strategy following remission in adult acute leukemia (AL). It offers advantages over allogeneic hematopoietic stem cell transplantation (allo-HSCT), including independence from donor availability, absence of graft-versus-host disease (GVHD), and a reduced risk of transplant-related mortality. Furthermore, when juxtaposed with the extended regimens of consolidation chemotherapy, ASCT stands out by markedly abbreviating treatment duration, alleviating the economic strain on patients, and enhancing their overall quality of life. Despite these benefits, the adoption of ASCT among adult AL patients in China remains disproportionately low. To enhance clinical physicians' understanding of the role and position of ASCT in AL management and to improve the clinical efficacy of ASCT, it is urgent to establish a consensus among experts on ASCT for adult acute leukemia in our nation.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Transplante Autólogo , Adulto , Humanos , Doença Aguda , China , Consenso , Doença Enxerto-Hospedeiro/prevenção & controle , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia/terapiaAssuntos
Hematopoese , Leucemia , Humanos , Hematopoese/efeitos dos fármacos , Animais , Leucemia/imunologia , Leucemia/tratamento farmacológico , Leucemia/patologia , Leucemia/terapia , Receptores de Antígenos de Linfócitos T/imunologia , Receptores de Antígenos de Linfócitos T/metabolismo , Receptores de Antígenos de Linfócitos T/genética , CamundongosRESUMO
Hematologic cancers, notably leukemias and lymphomas, pose significant challenges to healthcare systems globally, due to rising incidence rates and increasing costs. This study aimed to estimate the phase and lifetime health system total costs (not net costs) of care for patients diagnosed with leukemia and lymphoma in Ontario, Canada. We conducted a population-based study of patients diagnosed between 2005 and 2019, using data from the Ontario Cancer Registry linked with health administrative databases. Costs were estimated using a phase-based approach and stratified by care phase and cancer subtype. Acute lymphocytic leukemia (ALL) patients had the highest mean monthly initial (CAD 19,519) and terminal (CAD 41,901) costs among all cancer subtypes, while acute myeloid leukemia (AML) patients had the highest mean monthly cost (CAD 7185) during the continuing phase. Overall lifetime costs were highest for ALL patients (CAD 778,795), followed by AML patients (CAD 478,516). Comparatively, patients diagnosed with Hodgkin lymphoma (CAD 268,184) and non-Hodgkin lymphoma (CAD 321,834) had lower lifetime costs. Major cost drivers included inpatient care, emergency department visits, same-day surgeries, ambulatory services, and specialized cancer drugs. Since 2005, the cost structure has evolved with rising proportions of interventional drug costs. Additionally, costs were higher among males and younger age groups. Understanding these costs can help guide initiatives to control healthcare spending and improve cancer care quality.
Assuntos
Custos de Cuidados de Saúde , Linfoma , Humanos , Masculino , Feminino , Custos de Cuidados de Saúde/estatística & dados numéricos , Linfoma/economia , Linfoma/terapia , Pessoa de Meia-Idade , Adulto , Idoso , Leucemia/economia , Leucemia/terapia , Ontário , Adulto Jovem , Adolescente , Idoso de 80 Anos ou maisRESUMO
Acute leukemia is a rapidly progressive cancer of the blood and bone marrow that requires a high degree of complex, specialized, resource-intensive clinical and supportive care. The aging Canadian population has introduced an unprecedented demand on the health care system for a variety of illnesses, including acute leukemia. The purpose of this work was to develop organizational requirements for service providers delivering care for patients aged 18 years and older with acute leukemia within a single-payer health care system in Ontario. This initiative was intended to support streamlining high-quality health care across Ontario. We worked collaboratively with an expert panel to conduct a review of the literature to synthesize the organizational requirements for delivering acute leukemia care. A total of 229 requirements were developed. The requirements were categorized into themes including (1) facility requirements, including infrastructure, data management, safety, policies and procedures; (2) availability of clinical services and service complexity; (3) personnel, including roles, responsibilities, and ongoing education; (4) patient care; (5) quality management; (6) clinical research; and (7) laboratory services. These requirements will act as a framework for the provision of service, complexity of care, safety, accessibility, and quality care across all levels from the patient, organization, and system perspectives. This framework will help support person-centred care, emphasizing providing care close to home, while optimizing the use of specialized resources. Moving forward, Ontario Health (Cancer Care Ontario) will continue to work with acute leukemia service providers in the province to determine compliance and focus improvement efforts in priority areas.
Assuntos
Atenção à Saúde , Leucemia , Qualidade da Assistência à Saúde , Humanos , Ontário , Atenção à Saúde/normas , Leucemia/terapia , Doença AgudaRESUMO
BACKGROUND Allogeneic hematopoietic stem cell transplantation (allo-HSCT) using umbilical cord blood is a valuable therapy option for patients with acute leukemia (AL). Acute graft-versus-host disease (aGVHD) remains the most frequently encountered complication. This study investigated risk factors for aGVHD and assessed whether post-transplant serum ferritin (SF) within 2 weeks is a potential biomarker for aGVHD in pediatric patients with AL undergoing umbilical cord blood transplantation (UCBT). MATERIAL AND METHODS We conducted a retrospective cohort study of 71 patients with AL who underwent UCBT at the Children's Hospital of Soochow University between 2017 and 2022. We evaluated several factors related to aGVHD. Univariate and multivariate analyses were performed using the proportional subdistribution hazard regression model of Fine and Gray. Analyses of overall survival (OS) were performed using the Kaplan-Meier method, and differences were compared using log-rank tests. RESULTS Of the 71 patients, 23 (32.4%) experienced grade II-IV aGVHD, of whom 18 (25.4%) developed grade III-IV aGVHD. Patients with grade II-IV and III-IV aGVHD had worse 5-year OS (69.4±10%, p=0.01; and 60.6±11.6, P=0.007, respectively). Conditioning intensity was a risk factor for grade III-IV aGVHD (HR: 0.34, 95% CI: 0.13-0.89, P=0.027). An SF level >1650 ng/mL within 2 weeks post-transplant was associated with an increased risk of severe aGVHD (HR: 3.61, 95% CI: 1.09-11.97, P=0.036). CONCLUSIONS Post-transplant SF within 2 weeks was a potential biomarker for developing severe aGVHD. Higher levels of post-transplant SF are associated with a higher incidence of grade II-IV aGVHD and grade III-IV aGVHD.
Assuntos
Biomarcadores , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Ferritinas , Doença Enxerto-Hospedeiro , Humanos , Doença Enxerto-Hospedeiro/sangue , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/diagnóstico , Masculino , Feminino , Ferritinas/sangue , Criança , Estudos Retrospectivos , Pré-Escolar , Biomarcadores/sangue , Adolescente , Lactente , Doença Aguda , Leucemia/sangue , Leucemia/terapia , Fatores de Risco , Leucemia Mieloide Aguda/sangue , Leucemia Mieloide Aguda/terapiaRESUMO
KMT2A (alias: mixed-lineage leukemia [MLL]) gene mapping on chromosome 11q23 encodes the lysine-specific histone N-methyltransferase 2A and promotes transcription by inducing an open chromatin conformation. Numerous genomic breakpoints within the KMT2A gene have been reported in young children and adults with hematologic disorders and are present in up to 10% of acute leukemias. These rearrangements describe distinct features and worse prognosis depending on the fusion partner, characterized by chemotherapy resistance and high rates of relapse, with a progression-free survival of 30-40% and overall survival below 25%. Less intensive regimens are used in pediatric patients, while new combination therapies and targeted immunotherapeutic agents are being explored in adults. Beneficial therapeutic effects, and even cure, can be reached with hematopoietic stem cell transplantation, mainly in young children with dismal molecular lesions; however, delayed related toxicities represent a concern. Herein, we summarize the translocation partner genes and partial tandem duplications of the KMT2A gene, their molecular impact, clinical aspects, and novel targeted therapies.
Assuntos
Rearranjo Gênico , Histona-Lisina N-Metiltransferase , Leucemia , Proteína de Leucina Linfoide-Mieloide , Humanos , Proteína de Leucina Linfoide-Mieloide/genética , Histona-Lisina N-Metiltransferase/genética , Leucemia/genética , Leucemia/terapia , Transplante de Células-Tronco Hematopoéticas , Translocação GenéticaRESUMO
HLA class II antigen presentation is modulated by the activity of the peptide editor HLA-DM and its antagonist HLA-DO, with their interplay controlling the peptide repertoires presented by normal and malignant cells. The role of these molecules in allogeneic hematopoietic cell transplantation (alloHCT) is poorly investigated. Balanced expression of HLA-DM and HLA-DO can influence the presentation of leukemia-associated antigens and peptides targeted by alloreactive T cells, therefore affecting both anti-leukemia immunity and the potential onset of Graft versus Host Disease. We leveraged on a large collection of bulk and single cell RNA sequencing data, available at different repositories, to comprehensively review the level and distribution of HLA-DM and HLA-DO in different cell types and tissues of the human body. The resulting expression atlas will help future investigations aiming to dissect the dual role of HLA class II peptide editing in alloHCT, and their potential impact on its clinical outcome.
Assuntos
Antígenos HLA-D , Leucemia , Humanos , Leucemia/terapia , Leucemia/imunologia , Leucemia/genética , Antígenos HLA-D/genética , Antígenos HLA-D/imunologia , Transplante de Células-Tronco Hematopoéticas , Apresentação de Antígeno , Peptídeos/imunologia , Peptídeos/genética , AloenxertosRESUMO
Objective: To analyze the causes and demographic characteristics of pre-engraftment mortality in patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) and investigate the risk factors and measures for preventing pre-engraftment mortality. Methods: A retrospective case analysis, involving a total of 7 427 patients who underwent allo-HSCT at Peking University People's Hospital between January 2016 and July 2023, was conducted. Results: Among the 7 427 patients who underwent allo-HSCT, 56 cases (0.75% ) experienced pre-engraftment mortality. The median time to death for these 56 patients was +7 (-3 to +38) days after stem cell infusion. The median times to death for patients with acute leukemia (AL), severe aplastic anemia (SAA), and myelodysplastic syndrome (MDS) were +11 (-1 to +38), +3 (-1 to +34), and +16 (-1 to +38) days, respectively (P=0.013). The main causes of pre-engraftment mortality were infection (39.3% ), cardiac toxicity (28.6% ), and intracranial hemorrhage (26.8% ). Infection was the most common cause of pre-engraftment mortality in patients with AL and MDS (55.0% and 60.0% ), whereas cardiac toxicity was predominantly observed in patients with SAA (71.4% ), with no cases in patients with AL and only one case in patients with MDS. Among patients who died from intracranial hemorrhage, 53.3% had severe infections. The median times to death for infection, cardiac toxicity, and intracranial hemorrhage was +11 (-1 to +38), +2.5 (-1 to +17), and +8 (-3 to +37) days, respectively (P<0.001) . Conclusions: Infection is the primary cause of pre-engraftment mortality in allo-HSCT, and severe cardiac toxicity leading to pre-engraftment mortality should be closely monitored in patients with SAA.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Transplante Homólogo , Humanos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Estudos Retrospectivos , Fatores de Risco , Síndromes Mielodisplásicas/terapia , Anemia Aplástica/terapia , Doença Enxerto-Hospedeiro/etiologia , Masculino , Feminino , Pessoa de Meia-Idade , Leucemia/terapia , Leucemia/mortalidade , AdultoRESUMO
Chimeric antigen receptor T (CAR T) cell therapy has been proven to be successful against a variety of leukemias and lymphomas. This paper undertakes an analytical and numerical study of a mathematical model describing the competition of CAR T, leukemia, tumor, and B cells. Considering its significance in sustaining anti-CD19 CAR T-cell stimulation, a B-cell source term is integrated into the model. Through stability and bifurcation analyses, the potential for tumor eradication, contingent on the continuous influx of B cells, has been revealed, showing a transcritical bifurcation at a critical B-cell input. Additionally, an almost heteroclinic cycle between equilibrium points is identified, providing a theoretical basis for understanding disease relapse. Analyzing the oscillatory behavior of the system, the time-dependent dynamics of CAR T cells and leukemic cells can be approximated, shedding light on the impact of initial tumor burden on therapeutic outcomes. In conclusion, the study provides insights into CAR T-cell therapy dynamics for acute lymphoblastic leukemias, offering a theoretical foundation for clinical observations and suggesting avenues for future immunotherapy modeling research.
Assuntos
Linfócitos B , Imunoterapia Adotiva , Humanos , Linfócitos B/imunologia , Imunoterapia Adotiva/métodos , Leucemia/terapia , Leucemia/imunologia , Receptores de Antígenos Quiméricos/imunologia , Modelos Biológicos , Linfócitos T/imunologiaRESUMO
Acute leukaemia is a group of aggressive malignancies with a high mortality rate. The reduction in functional immune cells due to the disease itself and radiotherapy/chemotherapy makes the patients susceptible to co-infections, of which pulmonary infection is a major cause of death. Early accurate diagnosis and appropriate treatment may prevent the spread of infection in patients with acute leukaemia complicated with pulmonary infection, thus reduce serious complications such as sepsis, respiratory failure and multi-organ failure. However, there are still clinical difficulties in the diagnosis and treatment of pulmonary infections in acute leukemia patients. Therefore, the current research advances in the diagnosis and treatment of bacterial, fungal and viral infections in the lungs of patients with acute leukemia were briefly summarized in this review.
Assuntos
Leucemia , Humanos , Leucemia/complicações , Leucemia/terapia , Doença Aguda , Infecções RespiratóriasRESUMO
Over the past 30 years the incorporation of monoclonal antibody (mAb) treatments into the management of hematologic malignancies has led to significant improvements in patient outcomes. The key limitation of mAb treatments is the necessity for target antigen presentation on major histocompatibility complex (MHC) and costimulatory molecules to elicit a cytotoxic immune response. With the advent of bispecific antibodies (BsAbs), these limitations can be overcome through direct stimulation of cytotoxic T cells, thus limiting tumor cell evasion. BsAbs are rapidly being incorporated into treatment regimens for hematologic malignancies, and there are now seven FDA-approved treatments in this class, six of which have been approved in the past year. In this review we describe the function, complications, and clinical trial data available for CD3 BsAbs in the treatment of lymphoma, myeloma, and leukemia.
Assuntos
Anticorpos Biespecíficos , Complexo CD3 , Neoplasias Hematológicas , Humanos , Anticorpos Biespecíficos/uso terapêutico , Anticorpos Biespecíficos/farmacologia , Anticorpos Biespecíficos/imunologia , Complexo CD3/imunologia , Complexo CD3/antagonistas & inibidores , Neoplasias Hematológicas/imunologia , Neoplasias Hematológicas/tratamento farmacológico , Neoplasias Hematológicas/terapia , Ensaios Clínicos como Assunto , Antineoplásicos Imunológicos/uso terapêutico , Antineoplásicos Imunológicos/farmacologia , Mieloma Múltiplo/imunologia , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/terapia , Linfoma/imunologia , Linfoma/tratamento farmacológico , Linfoma/terapia , Animais , Leucemia/imunologia , Leucemia/tratamento farmacológico , Leucemia/terapiaRESUMO
Though sterile diet, post-transplantation surgery is a clinical strategy for patient care to prevent the infiltration of gut pathogens, less is known about its effects on the gut microbiome. Here, the gut microbiome dynamics of leukemia patients following a 120-day "sterile-normal" diet strategy posthematopoietic cell transplantation are examined. In contrast to the traditional idea, a sterile diet leads to the lowest gut microbiota diversity (p < 0.05) and short-chain fatty acids, promoted the proliferation of potential pathogens such as Streptococcus (up by 16.93%) and Lactobacillus (up by 40.30%), and 43.32% reduction in nodes and an 85.33% reduction in edges within the microbial interaction's network. Interestingly, a normal diet allows the gut microbiome recovery and significantly promotes the abundance of beneficial bacteria. These results indicate that a sterile diet leads to a collapse of the patient's gut microbiome and promoted the proliferation of potential pathogens. This assay is a starting point for a more sophisticated assessment of the effects of a sterile diet. The work also suggests a basic principle for the re-establishment of microbial equilibrium that supplementation of microbial taxa may be the key to the restoration of the degraded ecosystem.
Assuntos
Dieta , Microbioma Gastrointestinal , Transplante de Células-Tronco Hematopoéticas , Microbioma Gastrointestinal/fisiologia , Humanos , Transplante de Células-Tronco Hematopoéticas/métodos , Dieta/métodos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Leucemia/terapia , Leucemia/microbiologiaRESUMO
INTRODUCTION: Skeletal muscle function is an important prognostically relevant indicator in patients with acute leukemia (AL), but skeletal dysfunction during chemotherapy is not well understood. This study aimed to investigate the factors that influence changes in skeletal muscle function from before the start of chemotherapy to before allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: This was a retrospective cohort study that included 90 patients with AL who underwent chemotherapy before transplantation to perform allo-HSCT (men, 67.3%; median age, 53 years). The outcome measure was defined as changes in skeletal muscle function from before chemotherapy to before allo-HSCT, and was assessed by measuring the psoas muscle index (PMI) as skeletal muscle quantity and computed tomography values (CTV) as skeletal muscle quality using a computed tomography scanner. We examined the differences in PMI and CTV before chemotherapy and allo-HSCT, and the factors associated with changes in PMI. RESULT: The mean PMI for before chemotherapy and allo-HSCT were 4.6 ± 1.4 cm2/m2 and 4.0 ± 1.3 cm2/m2 and significant differences were observed (p < 0.001). However, the mean CTV before chemotherapy and allo-HSCT were 47.3 ± 4.5 HU and 47.4 ± 5.0 HU, respectively, and no significant differences were found (p = 0.798). In stepwise multiple regression analysis, age and sex were identified as factors related to changes in PMI (age, p = 0.019; sex, p = 0.001). CONCLUSION: We found that skeletal muscle quantity decreased during chemotherapy in patients with AL and was influenced by male sex and older age. TRIAL REGISTRATION NUMBER: TRIAL REGISTRATION NUMBER: 34-096(11,243). Date of registration: September 11, 2023.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Músculo Esquelético , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Estudos Retrospectivos , Adulto , Transplante de Células-Tronco Hematopoéticas/métodos , Músculo Esquelético/fisiopatologia , Idoso , Tomografia Computadorizada por Raios X/métodos , Estudos de Coortes , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/terapia , Músculos Psoas , Adulto Jovem , Leucemia/terapia , Leucemia/tratamento farmacológico , Transplante Homólogo/métodos , Doença Aguda , Antineoplásicos/efeitos adversos , Antineoplásicos/administração & dosagemRESUMO
Schizophrenia (SCZ) and schizoaffective disorder (SHZ) are psychiatric disorders commonly identified in individuals in their late adolescence or early adulthood. Comorbidities are common, though a concurrent diagnosis of leukemia, one of the most frequently occurring cancers of adolescence, has not yet been described in such cases. This case study outlines the clinical presentation, course, and treatment response of two 17-year-old male adolescents whose psychotic disorders complicated their leukemia treatment. The first patient was diagnosed with leukemia and subsequently with SCZ while undergoing leukemia treatment. The second patient was diagnosed with SHZ prior to the onset of leukemia. The case study will follow the methodology of Robert E. Stake (Abma & Stake, 2014), as the two cases share a leukemia diagnosis and the reported mental health impact connected with cancer-directed treatment. Early identification and treatment are critical for both psychotic disorders and cancers, often impacting the long-term prognosis. However, when co-occurring, their interplay can present unique challenges to care.
Assuntos
Transtornos Psicóticos , Humanos , Masculino , Transtornos Psicóticos/psicologia , Adolescente , Esquizofrenia/complicações , Leucemia/psicologia , Leucemia/complicações , Leucemia/terapiaRESUMO
Bloodstream infections (BSI) are one of the leading causes of morbidity and mortality in children and young adults receiving chemotherapy for malignancy or undergoing hematopoietic stem cell transplantation (HSCT). Antibiotic prophylaxis is commonly used to decrease the risk of BSI; however, antibiotics carry an inherent risk of complications. The aim of this manuscript is to review levofloxacin prophylaxis in pediatric oncology patients and HSCT recipients. We reviewed published literature on levofloxacin prophylaxis to prevent BSI in pediatric oncology patients and HSCT recipients. Nine manuscripts were identified. The use of levofloxacin is indicated in neutropenic children and young adults receiving intensive chemotherapy for leukemia or undergoing HSCT. These results support the efficacy of levofloxacin in pediatric patients with leukemia receiving intensive chemotherapy and should be considered in pediatric patients undergoing HSCT prior to engraftment.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Levofloxacino , Humanos , Levofloxacino/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Criança , Adolescente , Masculino , Pré-Escolar , Feminino , Antibioticoprofilaxia/métodos , Neoplasias , Leucemia/terapia , Antibacterianos/uso terapêutico , Adulto , Adulto JovemRESUMO
In Italy, 1400 children and 800 adolescents are diagnosed with cancer every year. About 80% of them can be cured but are at high risk of experiencing severe side effects, many of which respond to rehabilitation treatment. Due to the paucity of literature on this topic, the Italian Association of Pediatric Hematology and Oncology organized a Consensus Conference on the role of rehabilitation of motor impairments in children/adolescents affected by leukemia, central nervous system tumors, and bone cancer to state recommendations to improve clinical practice. This paper includes the consensus on the rehabilitation of children and adolescents with these cancers.
Assuntos
Neoplasias Ósseas , Neoplasias do Sistema Nervoso Central , Leucemia , Humanos , Adolescente , Criança , Itália , Neoplasias do Sistema Nervoso Central/reabilitação , Neoplasias Ósseas/reabilitação , Leucemia/reabilitação , Leucemia/terapia , Feminino , Masculino , Pré-EscolarRESUMO
BACKGROUND: Bleeding is a primary outcome for many transfusion-related trials in acute leukaemia (AL) patients, typically graded using the World Health Organisation (WHO) bleeding scale (clinically significant bleed (CSB) is ≥grade 2). This composite outcome fails to differentiate minor bleeds that may not be significant, poorly represents the total burden of bleeding and lacks input from healthcare providers (HCPs) and patients. As part of a multi-step project to create a better bleeding tool for trials, our objective was to identify HCPs' perspectives on the components of CSB in AL patients. STUDY DESIGN AND METHODS: Using qualitative description, we interviewed 19 physicians and nurses who care for AL patients undergoing induction chemotherapy. Participants were recruited from professional organisations, networks and social media. An inductive approach to conventional content analysis was used. RESULTS: HCPs identified features of CSB as the anatomical site of bleeding, amount of bleeding, need for intervention and changes in vital signs. Using these characteristics, bleeding events were categorised into three groups: clinically significant, could evolve into a CSB and not clinically significant. HCPs considered the patient's condition, bleeding history and clinical intuitions when deciding whether a bleed could escalate into serious bleeding. DISCUSSION: Using data from HCPs, we categorised bleeds as clinically significant, could evolve into a CSB, and not significant. A study of patients' perspectives on the importance of different kinds of bleeding is the next step to creating a bleeding definition that is informed by evidence, clinicians and patients.