The role of cladribine in acute myeloid leukemia: an old drug up to new tricks

Molica, Matteo; Breccia, Massimo; Capria, Saveria; Trisolini, Silvia Maria; Foà, Roberto; Jabbour, Elias; Kadia, Tapan M.

doi:10.1080/10428194.2019.1672060

Cited by 10 publications

(11 citation statements)

References 62 publications

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“…Lysosomes hold a potential for cancer therapy, and with newer classes of anti-cancer agents that utilize lysosomes, cancer therapeutic approaches could be tailored to become more tumor-specific with less off-target toxicities [ 201 ]. Cytarabine is one of the few recognized therapies for AML in younger people when combined with anthracyclines or stem cell transplantation, but it is ineffective in older patients [ 202 , 203 ]. Therefore, targeted treatments, which are less stringent in general therapy, may be very successful as monotherapy.…”

Section: Discussionmentioning

confidence: 99%

RETRACTED: Lysosomes in Stem Cell Quiescence: A Potential Therapeutic Target in Acute Myeloid Leukemia

Jain

Bose

Arya

et al. 2022

Cancers

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Lysosomes are cellular organelles that regulate essential biological processes such as cellular homeostasis, development, and aging. They are primarily connected to the degradation/recycling of cellular macromolecules and participate in cellular trafficking, nutritional signaling, energy metabolism, and immune regulation. Therefore, lysosomes connect cellular metabolism and signaling pathways. Lysosome’s involvement in the critical biological processes has rekindled clinical interest towards this organelle for treating various diseases, including cancer. Recent research advancements have demonstrated that lysosomes also regulate the maintenance and hemostasis of hematopoietic stem cells (HSCs), which play a critical role in the progression of acute myeloid leukemia (AML) and other types of cancer. Lysosomes regulate both HSCs’ metabolic networks and identity transition. AML is a lethal type of blood cancer with a poor prognosis that is particularly associated with aging. Although the genetic landscape of AML has been extensively described, only a few targeted therapies have been produced, warranting the need for further research. This review summarizes the functions and importance of targeting lysosomes in AML, while highlighting the significance of lysosomes in HSCs maintenance.

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Section: Discussionmentioning

confidence: 99%

RETRACTED: Lysosomes in Stem Cell Quiescence: A Potential Therapeutic Target in Acute Myeloid Leukemia

Jain

Bose

Arya

et al. 2022

Cancers

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“…Cladribine induces a decline in methylated cytosines in CpG sequences by decreasing C‐5 MTase activity, which is different from the mechanism of decitabine 12 . Moreover, it synergizes with cytarabine and may increase the synthesis of the triphosphate of cytarabine, an active antileukemic metabolite of cytarabine 13 …”

Section: Introductionmentioning

confidence: 95%

Cladribine‐ and decitabine‐containing conditioning regimen has a low post‐transplant relapse rate in patients with relapsed or refractory acute myeloid leukemia and high‐risk myelodysplastic syndrome

Tong

Jin

et al. 2023

Intl Journal of Cancer

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To reduce the risk of relapse after allogeneic hematopoietic stem cell transplantation (allo‐HSCT), there have been continuing efforts to optimize the conditioning regimens. Our study aimed to analyze the risk factors associated with the relapse of relapsed/refractory (R/R), high‐risk acute myeloid leukemia (AML) and high‐risk myelodysplastic syndrome (MDS) post‐transplant and the efficacy of a new conditioning regimen involving decitabine and cladribine. Clinical data of 125 patients with R/R AML, high‐risk AML and high‐risk MDS who underwent allo‐HSCT were collected. In addition, 35 patients with R/R AML, high‐risk AML and high‐risk MDS received treatment with a new conditioning regimen including decitabine and cladribine. Cox regression analysis was used to identify risk factors associated with OS, RFS and relapse. Among 125 patients who underwent allo‐HSCT, CR before allo‐HSCT and matched sibling donors were independent protective factors for OS. DNMT3A abnormality was an independent risk factor for both relapse and RFS. Among 35 patients who received a new conditioning regimen containing decitabine and cladribine, only six patients relapsed and 1‐year cumulative incidence of relapse was 11.7%. Moreover, this new regimen showed efficient MRD clearance early after allo‐HSCT. The combined decitabine‐ and cladribine‐based conditioning regimen showed a low relapse rate and a high survival without an increased incidence of GVHD or adverse effects and thus has potential for use in allo‐HSCT for R/R AML, high‐risk AML and high‐risk MDS.

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“…• Fludarabine, high dose cytarabine, and idarubicin (FLAG-ida) has been shown to be an effective regimen 102 ○ Superior rates of remission and reduced risk of relapse compared with a 10 day cytarabine plus daunorubicin regimen were shown, but also with increased toxicity and thus no improvement in overall survival • Other intensive cytotoxic regimens incorporating clofarabine have been investigated [103][104][105] • Cladribine, another nucleoside analog, has also been investigated in combination with daunorubicin and cytarabine (eg, the "DAC regimen"), with response rates of up to 70% in de novo acute myeloid leukemia (AML) and 40-50% in relapsed/refractory AML 83 blasts to linger in an immature state. 8 The addition of the isocitrate dehydrogenase inhibitors blocks this process and allows for resumption of more normal differentiation, sometimes leading to the complication of "differentiation syndrome," in which the rapid maturation of many immature white blood cells leads to dyspnea, fever, pulmonary infiltrates, and hypoxia.…”

Section: Conventional Chemotherapymentioning

confidence: 99%

Advances in acute myeloid leukemia

Newell

Cook

2021

BMJ

255

174

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Acute myeloid leukemia (AML) is an uncommon but potentially catastrophic diagnosis with historically high mortality rates. The standard of care treatment remained unchanged for decades; however, recent discoveries of molecular drivers of leukemogenesis and disease progression have led to novel therapies for AML. Ongoing research and clinical trials are actively seeking to personalize therapy by identifying molecular targets, discovering patient specific and disease specific risk factors, and identifying effective combinations of modalities and drugs. This review focuses on important updates in diagnostic and disease classifications that reflect new understanding of the biology of AML, its mutational heterogeneity, some important genetic and environmental risk factors, and new treatment options including cytotoxic chemotherapy, novel targeted agents, and cellular therapies.

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The role of cladribine in acute myeloid leukemia: an old drug up to new tricks

Cited by 10 publications

References 62 publications

RETRACTED: Lysosomes in Stem Cell Quiescence: A Potential Therapeutic Target in Acute Myeloid Leukemia

RETRACTED: Lysosomes in Stem Cell Quiescence: A Potential Therapeutic Target in Acute Myeloid Leukemia

Cladribine‐ and decitabine‐containing conditioning regimen has a low post‐transplant relapse rate in patients with relapsed or refractory acute myeloid leukemia and high‐risk myelodysplastic syndrome

Advances in acute myeloid leukemia

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