Best Practice & Research. Clinical Haematology

According to the 2022 World Health Organization (WHO) Classification (5th edition), the term myelodysplastic neoplasms (abbreviated MDS) has been introduced to replace myelodysplastic syndromes. MDS are a group of clonal hematopoietic stem cell diseases characterized by cytopenia(s), dysplasia in one or more of lineages, ineffective hematopoiesis, and an increased risk of progression to bone marrow failure or to acute myeloid leukemia (AML). Current NCCN guidelines and recent review articles have provided in depth discussion on the clinical diagnosis and management of MDS...

The goal of a disease classification system is (or should be) to provide a tool for researchers and clinicians to study and treat the disease. The last decade has seen a markedly improved understanding of the pathophysiology of acute myeloid leukemia (AML), the development of new methods to measure the disease, and approval by the Food and Drug Administration (FDA) of at least ten new therapies targeted to its treatment. In response, in 2022 one updated and one new AML classification system were published. In the same year, the European LeukemiaNet updated their recommendations about how to incorporate the advances in diagnosis and treatment into the risk stratification of AML and its treatment...

Hodgkin lymphoma (HL) is a highly curable B-cell malignancy of germinal center origin. Biologically it is a hematologic malignancy that is highly dependent on the immune microenvironment and utilizes immune escape through upregulation of the programmed-death ligands on the neoplastic cells. Despite being highly curable, consensus is lacking nationally and internationally about the optimal approach to management, particularly in limited-stage disease. The addition of brentuximab vedotin and checkpoint inhibitors for the management of HL has led to a rapidly changing treatment landscape...

No abstract text is available yet for this article.

Donor lymphocyte infusion (DLI) is an important treatment modality in the management of relapsed hematological malignancies after allogeneic hematopoietic cell transplantation (allo-HCT). Donor T lymphocytes can be used in a therapeutic, pre-emptive or prophylactic manner in an attempt to stimulate a graft versus leukemia (GVL) effect and eradicate residual disease or even prevent relapse in a high-risk setting. DLIs are not without complications, however, graft versus host disease (GVHD) in particular. Data to date is limited to retrospective and small prospective studies...

Blood-related diseases are complex diseases with diverse origins, treatments and prognosis. In haematology studies, investigators are interested in multiple outcomes and multiple prognostic variables that may change value over the course of follow-up. These time-dependent variables can be of different nature. Time-dependent events such as treatment with haematopoeitic stem cell transplant (HCT) and acute or chronic graft-versus-host disease (GVHD) typically interact with outcomes respectively after diagnosis or HCT...

While the mainstay of treatment for high-risk or relapsed, refractory leukemia has historically revolved around allogeneic hematopoietic stem cell transplant (allo-HSCT), targeted immunotherapies have emerged as a promising therapeutic option, especially given the poor prognosis of patients who relapse after allo-HSCT. Novel cellular immunotherapies that harness the cytotoxic abilities of the immune system in a targeted manner (often called "adoptive" cell therapy), have changed the way we treat r/r hematologic malignancies and continue to change the treatment landscape given the rapid evolution of these powerful, yet sophisticated precision therapies that often offer a less toxic alternative to conventional salvage therapies...

One of the consistent features in development of hematopoietic stem cell transplant (HCT) for Acute Lymphoblastic Leukemia (ALL) is the rapidity with which discoveries in the laboratory are translated into innovations in clinical care. Just a few years after murine studies demonstrated that rescue from radiation induced marrow failure is mediated by cellular not humoral factors, E. Donnall Thomas reported on the transfer of bone marrow cells into irradiated leukemia patients. This was followed quickly by the first descriptions of Graft versus Leukemia (GvL) effect and Graft versus Host Disease (GvHD)...

No abstract text is available yet for this article.

Observational studies and clinical trials in hematology aim to examine treatments for blood disorders. The outcomes being studied must address the goals of the study and provide meaningful information about treatment course, disease progression, describe patients' survival experience and quality of life. Endpoints are the specific measures of these outcomes, and much consideration should be given to their selection. In this review, we describe the outcomes and endpoints frequently used in studying hematologic diseases and provide general guidelines for their statistical analysis...

It is common to study time-to-event data in cancer research such as hematopoietic cell transplantation (HCT) for leukemia. The extensive work has been done for the univariate survival outcome, that is, one event type. However, in practice a subject is often exposed to multiple types of outcomes. In this article, we review various types of right-censored data with multiple outcome types including competing risks data, recurrent event data, and composite endpoints. We also provide hematopoietic cell transplantation data examples...

Allogeneic hematopoietic stem cell transplantation (HSCT) is commonly utilized in the management of leukemia across multiple subtypes. Graft versus leukemia (GVL) is a critical component of successful transplantation and involves donor cells eradicating residual leukemia within the recipient. Graft versus host disease (GVHD) by contrast is a common complication of the transplantation process in which donor cells identify the recipient's various organ systems as foreign, thereby leading to a multitude of organ toxicities that can be described as autoimmune in nature...

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...

In many haematological diseases, the survival probability is the key outcome. However, when the population of patients is rather old and the follow-up long, a significant proportion of deaths cannot be attributed to the studied disease. This lessens the importance of common survival analysis measures like overall survival and shows the need for other outcome measures requiring more complex methodology. When disease-specific information is of interest but the cause of death is not available in the data, relative survival methodology becomes crucial...

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...

Research is based on trying to find answers to specific questions or to test hypotheses. Studies are thus undertaken to generate data which, with appropriate statistical methods, will help to determine the validity of the science under investigation. The aim of this paper is not to provide answers on which statistical methods to use, but will concentrate on suggesting the best ways of presenting the results of appropriately analysed data. And presentation is the key, because however well conducted and analysed a study may be, incorrect or inappropriate presentation of the findings will severely hamper its publication potential...

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...

Allogeneic hematopoietic stem cell transplantation mortality has declined over the years, though prevention and management of treatment-related toxicities and post-transplant complications remains challenging. Applications of pharmacogenomic testing can potentially mitigate adverse drug outcomes due to interindividual variability in drug metabolism and response. This review summarizes clinical pharmacogenomic applications relevant to hematopoietic stem cell transplantation, including antifungals, immunosuppressants, and supportive care management, as well as emerging pharmacogenomic evidence with conditioning regimens...

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...

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...