Best Practice & Research Clinical Haematology最新文献

Mature B-cell lymphoma in children, adolescents and young adults comprises three major histological subtypes including in order of frequency Burkitt, germinal center diffuse large B-cell lymphoma and primary mediastinal B-cell lymphoma. The cure rate of the first two with aggressive short chemotherapy based on clinical grouping is ∼90% in resource rich countries. Recent data has shown that incorporation of immune therapy has enhanced event free survival in advanced patients. Future studies will address the possibility of reducing the burden of chemotherapy by substitution of immune based therapies.

Clinical trials form the cornerstone of the science-based approach to improving patient outcomes. A trial needs to be designed and performed carefully to provide valid evidence to inform medical science and to protect the safety and well-being of its participants. The development of a clinical trial involving blood and marrow transplant (BMT) requires special considerations, including the rare disease populations involved and transplant-specific outcomes of interest that necessitate appropriate analysis techniques to evaluate.

This article reviews key considerations and best practices for the design and conduct of a clinical trial in BMT, including the selection of patient population, treatment groups, objectives and endpoints, targeted sample size, statistical analysis strategy, provisions for monitoring patient safety and trial progress, and dissemination of trial results. The practical application of these principles is demonstrated using BMT CTN 1301, a recently completed clinical trial evaluating regimens for chronic graft-versus-host disease prevention in transplant patients.

The preferred approach to compare two treatments is a randomized controlled trial (RCT). Indeed, randomization ensures that the groups compared are similar. Well-designed and well-conducted RCTs thus allow to draw causal conclusions on the relative efficacy and safety of treatments compared. However, it is not always possible to conduct RCTs for all clinical questions of interest, and observational data may also be used to infer on the relative effectiveness of treatments. In this review, we present different approaches that allow statistically valid comparisons of the effectiveness of treatments using observational data under some assumptions. Those are based on regression modelling or the propensity score. We also present the principles of target trial emulation.

Financial toxicity (FT) is a term used to describe the objective financial burden of cancer care including the associated coping behaviors used by patients and their caregivers. FT has been shown to result in both direct financial burdens and in clinically relevant outcomes, such as non-adherence with care, diminished quality of life, and even decreased overall survival. Much of the data has been described in solid tumors, with limited investigations in the malignant hematology population. Patients with hematologic malignancies undergoing hematopoietic stem cell transplantation (HSCT) face a unique financial burden driven by lengthy hospitalizations and acute and chronic morbidity that have downstream implications on their income and costs. In this review, we discuss the prevalence of FT in patients with leukemia who are eligible for HSCT. We review the impact of FT on financial and clinical outcomes and the role of various interventions that have been studied within this population.

Missing data are frequently encountered across studies in clinical haematology. Failure to handle these missing values in an appropriate manner can complicate the interpretation of a study's findings, as estimates presented may be biased and/or imprecise. In the present work, we first provide an overview of current methods for handling missing covariate data, along with their advantages and disadvantages. Furthermore, a systematic review is presented, exploring both contemporary reporting of missing values in major haematological journals, and the methods used for handling them. A principal finding was that the method of handling missing data was explicitly specified in a minority of articles (in 76 out of 195 articles reporting missing values, 39%). Among these, complete case analysis and the missing indicator method were the most common approaches to dealing with missing values, with more complex methods such as multiple imputation being extremely rare (in 7 out of 195 articles). An example analysis (with associated code) is also provided using hematopoietic stem cell transplantation data, illustrating the different approaches to handling missing values. We conclude with various recommendations regarding the reporting and handling of missing values for future studies in clinical haematology.

Despite the rapidly evolving treatment landscape for acute myeloid leukemia (AML), allogeneic hematopoietic cell transplantation (allo-HCT) remains an important and potentially curative treatment option for many high-risk AML patients. Cardiovascular disease is an important competing risk throughout allo-HCT and a key driver of morbidity and mortality long after treatment. Cardio-oncology is a new discipline in cardiology which provides multidisciplinary care and expertise to complex cancer patients with the aims of optimizing cardiovascular health plus monitoring and treating potential cardiotoxicity related to cancer treatments. As allogeneic HCT techniques get more sophisticated there will be an increase in transplant eligible older patients with a rise in comorbidities including established cardiovascular disease highlighting the need for close collaboration with cardio-oncology specialists from the time of diagnosis through late survivorship.

Apheresis is an automated process to separate the whole blood of a patient or a donor, collect or remove specific blood components, and return the remaining back to the individual. Apheresis is an integral part of blood and marrow transplantation and has been increasingly utilized in novel cellular therapies for a variety of blood disorders. This review uses clinical cases to highlight the multiple roles of apheresis in the care of adult leukaemia patients, including therapeutic leukapheresis in hyperleukocytosis, mobilized peripheral blood hematopoietic progenitor cell collection in donors, mononucleated cell collection in preparation of donor lymphocyte infusion or chimeric antigen receptor T cells manufacture, and extracorporeal photopheresis in the treatment of graft versus host diseases.

The most common indication for allogeneic hematopoietic cell transplant (alloHCT) is maintenance of remission after initial treatment for patients with acute myeloid leukemia (AML). Loss of remission, relapse, remains however the most frequent cause of alloHCT failure. There is strong evidence that detectable persistent disease burden (“measurable residual disease”, MRD) in patients with AML in remission prior to alloHCT is associated with increased risk of post-transplant relapse. MRD status as a summative assessment of response to pre-transplant therapy may allow superior patient-personalized risk stratification compared with models solely incorporating pre-treatment variables. An optimal methodology for AML MRD detection has not yet been established, but molecular methods such as DNA-sequencing may have additional prognostic utility compared to current approaches. There is growing evidence that intervention on AML MRD positivity may improve post-transplant outcomes. New initiatives will generate actionable data on the clinical utility of AML MRD testing for patients undergoing alloHCT.