&lt;p&gt;Efficacy and toxicity of cladribine for the treatment of refractory acute myeloid leukemia: a meta-analysis&lt;/p&gt;

Zhou, An-Qi; Han, Qi; Song, Haoming; Zi, Jian; Ma, Jinlong; Ge, Zheng

doi:10.2147/dddt.s207425

Cited by 16 publications

(13 citation statements)

References 25 publications

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“…The unaffordable prices of traditionally developed compounds combined with an unmet clinical need to improve OS in AML have encouraged the exploration of repurposing as a feasible strategy [ 42 ]. Several examples of drug repurposing in AML have been identified in the literature [ 43 , 44 ]; most often, these arise serendipitously through observed side effects, as evidenced by thalidomide [ 20 ]. More recently, compounds have been identified through the application of high-throughput screening (HTS) [ 45 ].…”

Section: Discussionmentioning

confidence: 99%

Multiplex Screening for Interacting Compounds in Paediatric Acute Myeloid Leukaemia

Cairns

Lappin

Mutch

et al. 2021

IJMS

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Paediatric acute myeloid leukaemia (AML) is a heterogeneous disease characterised by the malignant transformation of myeloid precursor cells with impaired differentiation. Standard therapy for paediatric AML has remained largely unchanged for over four decades and, combined with inadequate understanding of the biology of paediatric AML, has limited the progress of targeted therapies in this cohort. In recent years, the search for novel targets for the treatment of paediatric AML has accelerated in parallel with advanced genomic technologies which explore the mutational and transcriptional landscape of this disease. Exploiting the large combinatorial space of existing drugs provides an untapped resource for the identification of potential combination therapies for the treatment of paediatric AML. We have previously designed a multiplex screening strategy known as Multiplex Screening for Interacting Compounds in AML (MuSICAL); using an algorithm designed in-house, we screened all pairings of 384 FDA-approved compounds in less than 4000 wells by pooling drugs into 10 compounds per well. This approach maximised the probability of identifying new compound combinations with therapeutic potential while minimising cost, replication and redundancy. This screening strategy identified the triple combination of glimepiride, a sulfonylurea; pancuronium dibromide, a neuromuscular blocking agent; and vinblastine sulfate, a vinca alkaloid, as a potential therapy for paediatric AML. We envision that this approach can be used for a variety of disease-relevant screens allowing the efficient repurposing of drugs that can be rapidly moved into the clinic.

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Section: Discussionmentioning

confidence: 99%

Multiplex Screening for Interacting Compounds in Paediatric Acute Myeloid Leukaemia

Cairns

Lappin

Mutch

et al. 2021

IJMS

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“…It was reported that pretreatment with cladribine increased the rate of Ara-CTP accumulation in leukemic blasts by 50-65% in in vitro and in vivo pharmacological studies [21]. A recent meta-analysis reported that the CR rate of cladribine used in refractory AML patients was 42.2% (95% CI: 31.0-54.3%), and the ED rate was 6.8% (95% CI: 4.3-10.6%) [22]. To date, there have been reviews report on cladribine-containing regimens used for induction therapy of newly diagnosed AML patients, but these studies only listed the results of clinical trials without statistical analysis and no comparison between different regimens was conducted [3,21].…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of cladribine addition to induction treatment of newly diagnosed acute myeloid leukemia: a systematic review and meta-analysis

Pan

2021

Hematology

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Objectives: Compared with the 3 + 7 regimen, the cladribine-containing regimen has led to improvements in the rate of complete remission (CR) in the treatment of newly diagnosed acute myeloid leukemia (AML) patients. We conducted a systematic review and metaanalysis to investigate the overall efficacy and safety of cladribine-containing regimens in the induction treatment of newly diagnosed AML patients. Methods: Eligible studies were identified from the PubMed, EMBASE, and Cochrane Library databases. Efficacy was assessed by CR rate, disease-free survival (DFS), and overall survival (OS). Safety was evaluated based on the early death (ED) rate, days for neutrophils<0.5 × 10 9 /L, days for platelets<50 × 10 9 /L, and duration of hospital stay after treatment. Results: A total of 14 clinical trials were included in this meta-analysis, enrolling a total of 1058 newly diagnosed AML patients. The pooled estimate with a 95% confidence interval (CI) for CR was 64% (95% CI: 58-70%). Compared with the control group, the CR rate of the cladribinecontaining regimen was higher (OR was 1.92 (95% CI: 1.55-2.38)). The combined ED rate was estimated to be 10% (95% CI: 5-14%). Compared with the control group, the ED rate of the cladribine-containing regimen was not increased (OR was 1.09 (95% CI: 0.78-1.53)). Conclusion:This meta-analysis suggests that cladribine-containing regimens are likely to be effective and safe for induction treatment of newly diagnosed AML patients. However, large sample size and prospective controlled studies are needed to confirm our findings.

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“…In the new therapeutic setting, it is used in combination with cytarabine, idarubicin, or both [ 30 ]. Cladribine resulted in being an effective anti-AML therapying in a meta-analysis of 10 clinical trials [ 31 ]. It improves clinical outcomes with no adverse effects when added to standard therapy [ 32 ].…”

Section: Drug Repurposing In Amlmentioning

confidence: 99%

Has Drug Repurposing Fulfilled Its Promise in Acute Myeloid Leukaemia?

Valli¹,

Gruszka-Westwood²,

Alcalay³

2020

JCM

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Drug repurposing is a method of drug discovery that consists of finding a new therapeutic context for an old drug. Compound identification arises from screening of large libraries of active compounds, through interrogating databases of cell line gene expression response upon treatment or by merging several types of information concerning disease–drug relationships. Although, there is a general consensus on the potential and advantages of this drug discovery modality, at the practical level to-date no non-anti-cancer repurposed compounds have been introduced into standard acute myeloid leukaemia (AML) management, albeit that preclinical validation yielded several candidates. The review presents the state-of-the-art drug repurposing approach in AML and poses the question of what has to be done in order to take a full advantage of it, both at the stage of screening design and later when progressing from the preclinical to the clinical phases of drug development. We argue that improvements are needed to model and read-out systems as well as to screening technologies, but also to more funding and trust in drug repurposing strategies.

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<p>Efficacy and toxicity of cladribine for the treatment of refractory acute myeloid leukemia: a meta-analysis</p>

Cited by 16 publications

References 25 publications

Multiplex Screening for Interacting Compounds in Paediatric Acute Myeloid Leukaemia

Multiplex Screening for Interacting Compounds in Paediatric Acute Myeloid Leukaemia

Efficacy and safety of cladribine addition to induction treatment of newly diagnosed acute myeloid leukemia: a systematic review and meta-analysis

Has Drug Repurposing Fulfilled Its Promise in Acute Myeloid Leukaemia?

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