Best Practice & Research Clinical Haematology最新文献

Acute GVHD occurs in nearly 50% of patients receiving hematopoietic cell transplantation (HCT), and is the major driver of mortality. However, progress in the development of new acute GVHD therapeutics has been slow, in part due to heterogeneity in acute GVHD data collection and interpretation among centers. Herein, we first describe the methods used by the Mount Sinai Acute GVHD International Consortium (MAGIC) to standardize acute GVHD data collection and curation. We then review the utility of serum biomarkers, specifically the MAGIC Algorithm Probability (MAP) that combines two GI biomarkers (ST2 and REG3α) that has been shown to be more accurate than changes in clinical symptom severity after GVHD treatment. We then present preliminary data on the feasibility of a surrogate clinical trial endpoint that combines clinical response and MAP two weeks after treatment. This novel endpoint is an earlier and potentially better predictor of non-relapse mortality than the current gold standard of clinical response four weeks after treatment.

The treatment of acute lymphoblastic leukemia (ALL) has changed significantly over the last decade. With the approval of novel antibody based therapies in the relapsed/refractory setting, many of these agents are starting to be used in the upfront setting in clinical trials for older patients. These results have been impressive, and further trials are underway. Other targeted therapies (i.e. BCL inhibitors) are being explored. This article will discuss the incorporation of novel agents to “replace” chemotherapy in induction.

Despite cure rates approaching 100% for some subsets of patients, survivors of childhood acute lymphoblastic leukemia (ALL) report a multitude of short- and long-term side effects. Indeed, the long-term complications of pediatric ALL treatment regimens can be associated with significant morbidity and mortality. Identifying mitigation strategies and developing more effective, less toxic therapies is a central goal of current research.

Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative approach for patients with acute myeloid leukemia (AML), relapse is a common occurrence. Several strategies, such as choice of conditioning regimen, donor lymphocyte infusions, pharmacologic agents, and cellular therapy approaches, are currently being developed to improve transplantation outcomes. This review outlines some important interventions and considerations to lower the burden of post-transplantation relapse in AML.

The safe diminution of leukemic cell numbers to a level such that the patient will not succumb to their disease has been an achievable, yet often elusive goal in AML. Disease heterogeneity based both on biological features as well as on patient characteristics such as age, exposure to prior to anti-cancer chemotherapy and co-morbidities play a role in an allowing the physician to predict which patient has a greater or lesser chance to be cured after a diagnosis of acute myeloid leukemia. Cure rates range from 95% in younger patients with non-high-risk acute promyelocytic leukemia to essentially zero in older adults with intrinsically resistant biologies such as complex karyotype and/or TP53 mutations. One unifying feature of all AMLs, however, is the notion that whatever initial therapy is used, while possible to eradicate all morphological evidence of disease in a sizeable fraction of patients, an initial cycle (or two) is not sufficient to yield a low enough disease burden to prevent eventual relapse. Thus, the application of additional chemotherapy after the initial complete remission is received (post-remission therapy generally or consolidation therapy if a myelointense approach is used) is absolutely required for the patient to have a reasonable chance at cure. The widely accepted principle of the need to provide post-remission therapy leads to multiple controversies pertaining to the appropriate intensity, drug choice, and duration of exposure to consolidation chemotherapy, which can range from repetitive cycles of non-intensive therapy, up to and including a myeloblative allogeneic stem cell transplant. In this review, both the principles and the individual strategies that can be used once remission is achieved, will be examined.

The advances and progress in the understanding and management of acute leukemia and myelodysplasia continue to occur at an exponential rate. While this has led to more therapy options, clinicians and researchers are now facing more challenges in terms of clinical decision-making and more unanswered questions. This paper has outlined some conundrums in acute leukemia and myelodysplasia, and the efforts that are underway to address these.

Evaluating response to treatment in MDS represents a major challenge due to its associated complexity and heterogeneity. Although response criteria have been proposed by the IWG and revised on several occasions, these criteria have limitations. This review has outlined some refinements that can be used to improve response assessment and to ensure the identification of clinically meaningful endpoints.

Antiphospholipid syndrome and the coagulopathy of COVID-19 share many pathophysiologic features, including endotheliopathy, hypercoagulability, and activation of platelets, complement pathways, and neutrophil extracellular traps, all acting in concert via a model of immunothrombosis. Antiphospholipid antibody production in COVID-19 is common, with 50% of COVID-19 patients being positive for lupus anticoagulant in some studies, and with non-Sapporo criteria antiphospholipid antibodies being prevalent as well. The biological significance of antiphospholipid antibodies in COVID-19 is uncertain, as such antibodies are usually transient, and studies examining clinical outcomes in COVID-19 patients with and without antiphospholipid antibodies have yielded conflicting results. In this review, we explore the biology of antiphospholipid antibodies in COVID-19 and other infections and discuss mechanisms of thrombogenesis in antiphospholipid syndrome and parallels with COVID-19 coagulopathy. In addition, we review the existing literature on safety of COVID-19 vaccination in patients with antiphospholipid antibodies and antiphospholipid syndrome.