Best Practice & Research Clinical Haematology最新文献

Allogeneic haematopoietic stem cell transplantation (HSCT) remains the only potential cure for intermediate to high-risk acute myeloid leukaemia (AML). The therapeutic effect of HSCT is largely dependent on the powerful donor-derived immune response against recipient leukaemia cells, known as graft-versus-leukaemia effect (GvL). However, the donor-derived immune system can also cause acute or chronic damage to normal recipient organs and tissues, in a process known as graft-versus-host disease (GvHD). GvHD is a leading cause of non-relapse mortality in HSCT recipients. There are many similarities and cross talk between the immune pathways of GvL and GvHD. Studies have demonstrated that both processes require the presence of mismatched alloantigens between the donor and recipient, and activation of immune responses centered around donor T-cells, which can be further modulated by various recipient or donor factors. Dissecting GvL from GvHD to achieve more effective GvHD prevention and enhanced GvL has been the holy grail of HSCT research. In this review, we focused on the key factors that contribute to the immune responses of GvL and GvHD, the effect on GvL with different GvHD prophylactic strategies, and the potential impact of various AML relapse prevention therapy or treatments on GvHD.

The treatment of malignant and nonmalignant hematologic disorders continues to benefit from significant scientific advancement and progress in the use of hematopoietic cell transplantation and cellular therapies. However, barriers associated with receiving these lifesaving treatments and care remain, which necessitate innovative approaches to overcome, so all persons in need can receive these therapies. This article reviews barriers to receiving hematopoietic cell transplantation and cellular therapies, and highlights novel approaches taken by the National Marrow Donor Program in reducing barriers for all patients in need.

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.