Best practice & research. Clinical haematology
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GATA2 gene encodes a zinc finger transcription factor crucial for normal hematopoiesis. Its haploinsufficiency, caused by a great variety of heterozygous loss-of-function mutations, underlies one of the most common causes of inherited bone marrow failure, recognized as GATA2 deficiency. ⋯ The only curative treatment is allogenic hematopoietic stem cell transplantation (HSCT), that can restore the function of both hematopoietic and immune system and prevent lung deterioration. Currently, there are no consensus guidelines about the management of patients affected by GATA2 deficiency, especially with regard to the optimal time to proceed to HSCT.
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Best Pract Res Clin Haematol · Mar 2020
ReviewThe changing role of high dose melphalan with stem cell rescue in the treatment of newly diagnosed multiple myeloma in the era of modern therapies-back to the future!
State of the art treatment for myeloma involves using 3-drug combinations incorporating immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs). Clinical trials for 4-drug combinations incorporating monoclonal antibodies added to IMiD and PI based backbones are underway. Recent retrospective analyses show that patients who attain MRD negativity have similar long term outcomes regardless of early or delayed high dose melphalan with autologous stem cell support (HDM-ASCT). ⋯ Short of data from future prospective clinical trials addressing the question of the role of HDM-ASCT in MRD negative patients, varying expert opinions inherently arise. In this paper, we present the historical context of HDM-ASCT and data supporting 3-drug combinations. We then propose that a viable option for patients who reach MRD negativity is to transition to maintenance therapy directly without early HDM-ASCT, and reserving stem cell harvest to cases where HDM-ASCT is a possibility at relapse.
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Best Pract Res Clin Haematol · Mar 2020
ReviewMaintenance therapy and need for cessation studies in multiple myeloma: Focus on the future.
With ten years of follow-up since the advent of the modern paradigm of combination induction therapy, consolidative autologous stem-cell transplant, and lenalidomide maintenance, median survival for multiple myeloma has increased to almost 50% at 10 years. Given this outlook, the overarching goal of maintenance therapy is to spare patients from the toxicities of aggressive or otherwise intrusive therapies while ideally extending survival or, at the least, extending progression-free survival or time until next treatment. ⋯ The historical context and evidence for choice of agent, duration of treatment, and current strategies and ongoing trials will be discussed - as well as a focus on unmet needs. The case for studies investigating cessation of therapy and risk and response-adapted approaches will be underscored given that the current paradigm likely results in overtreatment for some patients.
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Best Pract Res Clin Haematol · Jun 2019
ReviewVenetoclax-based therapies for acute myeloid leukemia.
The prognosis of adult acute myeloid leukemia (AML) remains poor, with the long-term survival rate less than 50%. However, the current paradigms of treatment are changing through a better understanding of the disease genetics and pathophysiology. Since 2017, eight new drugs have been approved by the U. ⋯ Preclinical data demonstrated the anti-leukemic efficacy of venetoclax in AML and its synergy when combined with hypomethylating agents or chemotherapy agents. Clinical trials have demonstrated the clinical benefit of venetoclax-based therapies in newly diagnosed AML, leading to the recent FDA approval of venetoclax in combination with hypomethylating agents or low-dose cytarabine for older adults with newly diagnosed AML. Herein, we focus on the role of single-agent BCL-2 inhibition in AML and review the clinical studies of venetoclax-based combination regimens and the evolving mechanisms of resistance.
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Myelodysplastic syndromes and acute myeloid leukemia are sporadic for the majority of cases affecting the elderly population. Inherited cases, however, do occur. ⋯ The recognition of these germline syndromes is essential in the management and follow-up of patients. Herein, we review the conditions associated with hereditary myeloid leukemia with a special clinical focus on management and monitoring.