Long-term results of all-trans retinoic acid and arsenic trioxide in non-high-risk acute promyelocytic leukemia: update of the APL0406 Italian-German randomized trial

Cicconi, Laura; Platzbecker, Uwe; Avvisati, Giuseppe; Paoloni, Francesca; Thiede, Christian; Vignetti, Marco; Fazi, Paola; Ferrara, Felicetto; Divona, Mariadomenica; Albano, Francesco; Efficace, Fabio; Sborgia, Marco; Bona, Eros Di; Breccia, Massimo; Borlenghi, Erika; Cairoli, Roberto; Rambaldi, Alessandro; Melillo, Lorella; Nasa, Giorgio La; Fiedler, Walter; Brossart, Peter; Hertenstein, Bernd; Salih, Helmut R.; Annibali, Ombretta; Wattad, Mohammed; Lübbert, Michael; Brandts, Christian; Hänel, Mathias; Röllig, Christoph; Schmitz, Norbert; Link, Hartmut; Frairia, Chiara; Fozza, Claudio; D’Arco, Alfonso Maria; Renzo, Nicola Di; Cortelezzi, Agostino; Fanfani, Francesco; Döhner, Konstanze; Ganser, Arnold; Döhner, Hartmut; Amadori, Sergio; Mandelli, Franco; Voso, Maria Teresa; Ehninger, Gerhard; Schlenk, Richard F.; Lo‐Coco, Francesco

doi:10.1038/s41375-019-0589-3

Cited by 57 publications

(61 citation statements)

References 11 publications

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“…Dexamethasone treatment (10 mg every 12 h for at least 3 days) was used at the first suspicion of DS. The excellent outcomes of the chemo-free regimen were also emphasized by the recent update [40] of this pivotal study, showing an increased advantage over time of the ATRA/ATO combination in terms of EFS (96.6% at 72 months vs. 77.4% in the ATRA/chemotherapy group), and a significantly reduced cumulative incidence of relapse (1.7 vs. 15.5%, respectively). The long-lasting advantage of the chemo-free regimen, concentrating the treatment in about 7 months, doubted the role of maintenance, especially pointing out the 2% increased prevalence of secondary leukemias in the ATRA/chemotherapy arm.…”

Section: Clinical Use Of Arsenic In Apl: the Long Journey To A Chemotmentioning

confidence: 77%

When Poisons Cure: The Case of Arsenic in Acute Promyelocytic Leukemia

Gurnari¹,

Bellis²,

Divona³

et al. 2019

Chemotherapy

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Arsenic has been known for centuries for its double-edged potential: a poison and at the same time a therapeutic agent. The name "arsenikon," meaning "potent," speaks itself for the pharmaceutical properties of this compound, questioned and analyzed for at least 2000 years. In the last decades, acute promyelocytic leukemia (APL) has evolved from a highly fatal to a curable disease, due to the use of all-transretinoic acid and, more recently, arsenic trioxide combinations. The success of these entirely chemo-free regimens increased the awareness of APL and reduced the prevalence of early deaths, which was an impending issue in this disease. Further improvements are expected with the next use of oral arsenic formulations, which will allow a complete outpatient approach, at least in the post-induction settings, further improving patients' quality of life. The wide use of standardized approaches in APL will also help unravel long-standing open questions, including the pathogenesis, prevention, and treatment of the differentiation syndrome and of short-term organ toxicities. In the long term, the study of survivorship issues, such as fertility and organ-related and psychological damages, in the increasing number of survivors will help further improve their life after APL.

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Section: Clinical Use Of Arsenic In Apl: the Long Journey To A Chemotmentioning

confidence: 77%

When Poisons Cure: The Case of Arsenic in Acute Promyelocytic Leukemia

Gurnari¹,

Bellis²,

Divona³

et al. 2019

Chemotherapy

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“…Arsenic trioxide (ATO) in association with ATRA is the standard combination therapeutic approach for low and intermediate-risk acute promyelocytic leukemia (APL) patients ( 141 ). It has been reported that ATO is able to inactivate TP53 functions via the 26S proteasome pathway ( 142 ).…”

Section: Other Therapeutic Perspectivesmentioning

confidence: 99%

TP53 Mutations in Acute Myeloid Leukemia: Still a Daunting Challenge?

et al. 2021

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TP53 is a key tumor suppressor gene with protean functions associated with preservation of genomic balance, including regulation of cellular senescence, apoptotic pathways, metabolism functions, and DNA repair. The vast majority of de novo acute myeloid leukemia (AML) present unaltered TP53 alleles. However, TP53 mutations are frequently detected in AML related to an increased genomic instability, such as therapy‐related (t-AML) or AML with myelodysplasia-related changes. Of note, TP53 mutations are associated with complex cytogenetic abnormalities, advanced age, chemoresistance, and poor outcomes. Recent breakthroughs in AML research and the development of targeted drugs directed at specific mutations have led to an explosion of novel treatments with different mechanisms. However, optimal treatment strategy for patients harboring TP53 mutations remains a critical area of unmet need. In this review, we focus on the incidence and clinical significance of TP53 mutations in de novo and t-AML. The influence of these alterations on response and clinical outcomes as well as the current and future therapeutic perspectives for this hardly treatable setting are discussed.

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“…Post-induction, there were five deaths while in remission in the ATRA + chemotherapy group, of which two had therapy-related myeloid neoplasm, while two died while in remission in the ATO + ATRA group of which one had colon carcinoma. Additionally, there were four deaths due to relapse in the ATRA + chemotherapy group (19,33).…”

Section: Apl0406 (Clinicaltrialsgov Identifier: Nct00482833)mentioning

confidence: 99%

Evolving Chemotherapy Free Regimens for Acute Promyelocytic Leukemia

Kulkarni

2021

Front. Oncol.

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With the treatment advances over the last three decades, acute promyelocytic leukemia (APL) has evolved from being the most malignant form of acute leukemia to a leukemia with excellent long term survival rates. In the present review, we have summarized data leading to the development of the currently used treatment regimens for APL, which incorporate either none or minimal chemotherapeutic drugs. We have discussed the historical aspects of APL treatment along with the challenges associated with chemotherapy-based approaches and our experience with the use of single agent arsenic trioxide (ATO) which was one of the first successful, non-chemotherapy approaches used for APL. Subsequently, we have reviewed the data from major clinical trials in low-intermediate risk APL and high risk APL which guide the current clinical practice in APL management. With accumulating data on oral ATO, we postulate that the treatment for low-intermediate risk APL will be a completely oral ATO + ATRA regimen in the future. While for high-risk APL, we believe that minimal anthracycline use with ATO + ATRA might become the standard of care soon. A number of promising non-chemotherapy drugs with pre-clinical data would merit clinical testing in the high risk and relapsed setting, with potential to translate to a complete oral chemotherapy free combination regimen in combination with ATO and ATRA.

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Long-term results of all-trans retinoic acid and arsenic trioxide in non-high-risk acute promyelocytic leukemia: update of the APL0406 Italian-German randomized trial

Cited by 57 publications

References 11 publications

When Poisons Cure: The Case of Arsenic in Acute Promyelocytic Leukemia

When Poisons Cure: The Case of Arsenic in Acute Promyelocytic Leukemia

TP53 Mutations in Acute Myeloid Leukemia: Still a Daunting Challenge?

Evolving Chemotherapy Free Regimens for Acute Promyelocytic Leukemia

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