123 research outputs found
Is There a Better Therapeutic Time Window from Diagnosis to Treatment for Elderly Acute Myeloid Leukemia Patients Receiving Hypomethylating Agents?
No full textTHERAPY-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
Time for Dynamic Assessment of Fitness in Acute Myeloid Leukemia
No full textInformed treatment decision-making in acute myeloid leukemia (AML) requires a comprehensive evaluation of all clinical and biological features that may affect the outcome with any given type or intensity of therapy [...
Real-world treatments and clinical outcomes in unfit AML patients receiving first-line treatment or best supportive care in Italy (CURRENT study)
No full textReal-world data on treatment patterns and outcomes of patients with acute myeloid leukemia unfit for intensive chemotherapy are lacking before the advent of precision medicine in this setting.Herein, we present the Italian sub-analysis of the CURRENT study in AML patients unfit for first line intensive chemotherapy, evaluating patients’ outcomes between 2015 and 2018.Among 74 evaluable patients, 62 received systemic treatments (most used therapy was hypomethylating agents), while 12 best supportive care.Key results include both efficacy and safety data, as well as HCRU and treatment patterns. In first-line therapy cohort median OS was 13.4 months vs. 2.7 months for BSC
Comparative analysis of azacitidine and intensive chemotherapy as front-line treatment of elderly patients with acute myeloid leukemia
No full textThe present observational study aimed to compare the efficacy of azacitidine (AZA) and intensive chemotherapy (IC) in elderly patients with untreated acute myeloid leukemia (AML), diagnosed according to WHO criteria. In the two groups, we evaluated complete remission (CR), overall survival (OS), and disease-free survival (DFS). The AZA group included 89 patients; median age was 73 years (range 61–80) and median white blood cell count (WBCc) 2.5 × 109/L (range 0.27–83), 45% of the patients had BM blasts ≥ 30%, and 44 (49%) had a secondary AML (sAML). Karyotype was evaluable in 69 patients: 51 (74%) had intermediate-risk abnormalities and 18 (26%) an unfavorable risk karyotype. IC group consisted of 110 patients who received an induction course with mitoxantrone, cytarabine, and etoposide, followed by two consolidation cycles including idarubicin, cytarabine, and etoposide. Median age was 67 years (range 61–78) and median WBCc 8.0 × 109/L (range 0.69–258); 44 (40%) had a sAML. Karyotype was evaluable in 88 patients, 71 (81%) had intermediate risk, and 17 (19%) unfavorable risk karyotype. To minimize the effects of treatment selection bias, adjustments were made using the propensity-score matching method, which yielded 74 patient pairs. CR rate was significantly higher in IC vs AZA group (73 vs 25%, respectively) (p < 0.0001), but the 3-year OS rates and median OS were not significantly different (21.6 vs 11% and 15.8 vs 13 months, respectively). Our analysis suggests similar outcomes with AZA compared to IC. Controlled, randomized clinical trials are warranted to confirm this conclusion
From Biology to Clinical Practice: Iron Chelation Therapy With Deferasirox
No full textIron chelation therapy (ICT) has become a mainstay in heavily transfused hematological patients, with the aim to reduce iron overload (IOL) and prevent organ damage. This therapeutic approach is already widely used in thalassemic patients and in low-risk Myelodysplastic Syndrome (MDS) patients. More recently, ICT has been proposed for high-risk MDS, especially when an allogeneic bone marrow transplantation has been planned. Furthermore, other hematological and hereditary disorders, characterized by considerable transfusion support to manage anemia, could benefit from this therapy. Meanwhile, data accumulated on how iron toxicity could exacerbate anemia and other clinical comorbidities due to oxidative stress radical oxygen species (ROS) mediated by free iron species. Taking all into consideration, together with the availability of approved oral iron chelators, we envision a larger use of ICT in the near future. The aim of this review is to better identify those non-thalassemic patients who can benefit from ICT and give practical tips for management of this therapeutic strategy
Current strategies for detection and approach to measurable residual disease in Acute Myeloid Leukemia
No full textBaseline cytogenetic/genetic features have been widely recognized to play a critical prognostic role in acute myeloid leukemia (AML) and have proven useful in designing riskadapted treatment strategies. Nevertheless, to improve further the outcome of AML patients we are still in need of accurate methods to explore the quality of response and to adequately discriminate patients who are likely to relapse over time from those who are in deep and stable remission. In this view, is it well established that measurement of leukemic cells surviving chemotherapy (called measurable residual disease, MRD) during the course of treatment may be a reliable biomarker in predicting relapse. Detection of MRD relies on highly sensitive techniques, such as quantitative polymerase chain reaction and multiparametric flow cytometry, which, due to their levels of specificity and sensitivity, are increasingly included in the decision-making process of AML treatment. In the present manuscript, we will review the current techniques of MRD investigation and their clinical contribution to AML management
Deferasirox in the treatment of iron overload during myeloproliferative neoplasms in fibrotic phase: does ferritin decrement matter?
No full textFew data are available on the treatment with DFX in patients with
transfusion dependent Ph-Myeloproliferative Neoplasms in fibrotic phase.
Here we report 48MPNpatients and iron overload treated with DFX.
Starting DFX dose was 20 mg/Kg in 23 patients, 15 mg/Kg in 20
patientsand 10 mg/Kg in 5 patients. After a median treatment of 27.6
months, 5 patients achieved ferritin< 500 ng/ml, 11 < 1000 ng/ml and 3 a
reduction> 50\% of basal ferritin with a global response rate of 41\%.
As to hematological improvement, 9/47 patients (19.1\%) showed a
persistent rise of Hb> 1.5 g/dl, with disappearance of transfusion
requirement in 6 cases. The median OS from DFX initiation in patients
with chelation response was 61.0 months compared to 15.8 months in
patients without chelation efficacy. Treatment with DFX is feasible and
effective in MPN with iron overload and a hematological improvement can
occur in a sizeable rate of patients
Azacytidine for the treatment of retrospective analysis from the Gruppo Laziale for the study of Ph-negative MPN
No full textTo highlight the role of azacytidine (AZA) in patients with myeloproliferative neoplasms developing blast phase (MPN-BP), we evaluated retrospectively 19 patients [M/F 15/4, median age 71.3 years, interquartile range (IQR) 64.5-77.7] reported in the database of our cooperative group. Median time from diagnosis to BP evolution was 52.7 months (IQR 11.2-181.8). All patients were treated with AZA at the standard dosage of 75 mg/m(2). Two patients died early after 5-AZA initiation from pulmonary fungal infection and respiratory failure respectively, 4 patients had a disease progression, 4 patients a stable disease, 3 patients had an hematological improvement, 1 patient a partial response and 5 pts (26.3%) a complete response (CR) after 4, 4, 4, 5, and 12 months. The median cumulative survival from BP evolution was 9.9 months (95%CI 6.6-13.1): the comparison with an historical cohort of 72 patients with MPN-BP treated with approaches other than AZA (median cumulative survival 3.1 months, 95%CI 1.1-5.0) showed a significant advantage for patients treated with AZA (p = 0.02). Our data confirm the relative efficacy and safety of AZA in this group of patients with otherwise dismal prognosis, underlining the possible achievement of long-lasting responses in a sizeable portion of them. (C) 2015 Elsevier Ltd. All rights reserved
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