228 research outputs found
MRD in AML: The Role of New Techniques
No full textIn the context of precision medicine, assessment of minimal residual disease (MRD) has been used in acute myeloid leukemia (AML) to direct individual treatment programs, including allogeneic stem cell transplantation in patients at high-risk of relapse. One of the limits of this approach has been in the past the paucity of AML markers suitable for MRD assessment. Recently, the number of biomarkers has increased, due to the identification of highly specific leukemia-associated immunophenotypes by multicolor flow-cytometry, and of rare mutated gene sequences by digital droplet PCR, or next-generation sequencing (NGS). In addition, NGS allowed unraveling of clonal heterogeneity, present in AML at initial diagnosis or developing during treatment, which influences reliability of specific biomarkers, that may be unstable during the disease course. The technological advances have increased the application of MRD-based strategies to a significantly higher number of AML patients, and the information deriving from MRD assessment has been used to design individual post-remission protocols and pre-emptive treatments in patients with sub-clinical relapse. This led to the definition of MRD-negative complete remission as outcome definition in the recently published European Leukemianet MRD guidelines. In this review, we summarized the principles of modern technologies and their clinical applications for MRD detection in AML patients, according to the specific leukemic markers
An evaluation of enasidenib for the treatment of acute myeloid leukemia
No full textIntroduction: Despite recent progress, the prognosis of acute myeloid leukemia remains poor, mainly in older and in relapsed/refractory patients. Recently, a large number of novel agents have been developed thanks to a better understanding of its pathogenesis. Among these, the potent inhibitor of the isocitrate dehydrogenase-2 (IDH2) mutant protein, enasidenib (formerly AG-221), has demonstrated promising antileukemic activity by targeting IDH2 mutations. Area covered: This review describes the mechanisms of action, the pharmacodynamic and pharmacokinetic properties, the safety, and efficacy of enasidenib. Phase I/II/III clinical trials are also reported and discussed. Expert opinion: Enasidenib is a novel agent able to differentiate leukemic blasts in functional, maturating cells. This drug is characterized by oral bioavailability and good tolerability. As a monotherapy, it demonstrates clinical and laboratorial improvement, in 19.6% and 38.8% of cases respectively. Differentiation syndrome is the most relevant, potentially life-threatening side effect, which physicians must be aware of. The authors believe that the way forwards now is to explore the role of enasidenib as a chemoresistance revertant when associated with chemotherapy, as a 'bridge to transplant' or when associated other novel agents if we wish to maximize its use
THERAPY-RELATED MYELOID NEOPLASMS: CONSIDERATIONS FOR PATIENTS’ CLINICAL EVALUATION.
No full textTherapy-related myeloid neoplasms (t-MNs) encompass a specific sub-group of myeloid malignancies arising after exposure to radio/cytotoxic agents for the treatment of unrelated diseases. Such malignancies present unique features, including advanced age, high comorbidities burden, and unfavorable genetic profiles. All these features justify the need for a specific diagnostic work-up and dedicated treatment algorithms. However, as new classification systems recognize the unique clinical characteristics exhibited by t-MN patients, how to assess fitness status in this clinical setting is largely unexplored. Optimizing fitness assessment would be crucial in the management of t-MN patients, considering that factors usually contributing to a worse or better outcome (like age, comorbidities, and treatment history) are patient-specific.In the absence of specific tools for fitness assessment in this peculiar category of AML, the aim of this review is to describe all those factors related to patient, treatment, and disease that allow planning treatments with an optimal risk/benefit ratio
Fitness in acute myeloid leukemia, state of the art and future directions
No full textAcute Myeloid Leukemia (AML) is a complex disease whose
outcome can be variably influenced by several clinical and
biological factors. Although there is still no consensus on how to
integrate these elements to best guide treatment choice,
multiparametric models, commonly called fitness scores, have
been developed to evaluate each patient’s ability to tolerate
therapies. These models consider various risk factors, including
disease biology, comorbidities, physical and cognitive function.
To date, several scoring systems can be used to categorize
patients on their fitness for intensive or non-intensive therapies.
However, existing tools mainly focus on identifying patients
suitable for conventional intensive chemotherapy and fail to
address the complexities of less-fit patients who might benefit
from innovative intensive, less-intensive, and even maintenance
strategies. As treatment landscapes are in constant
evolution, identifying intermediate level of fitness through
recalibration of existing scores or development of new ones
should be prioritized. Considering all the above, this review
aims to report on the state of the art of fitness assessment in
AML and discuss possible future directions on this topic
Evaluation of the prognostic relevance of L-selectin and ICAM1 expression in myelodysplastic syndromes
No full textAn aberrant pattern of expression of L-selectin and intercellular adhesion molecule 1 (ICAM1) may characterise CD34+ blast cells in myelodysplastic syndromes (MDS) and secondary acute myeloid leukaemia (sAML)
Optimal post-remission therapy for flow-cytometry minimal residual disease positive adult patients with acute myeloid leukemia
No full textMinimal residual disease detection in pediatric acute myeloid leukemia: does flow cytometry score a point over molecular biology?
No full textSevere autoimmune hemolitic anemia in a patient with chronic lymphocytic leukemia responsive to fludarabine-based treatment.
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