Real world data with concurrent retinoic acid and arsenic trioxide for the treatment of acute promyelocytic leukemia

Kulkarni, Uday; Selvarajan, Sushil; Lionel, Sharon; Prakash, Mithun Abraham; Palani, Hamenth Kumar; Balasundaram, Nithya; Venkataraman, Arvind; Korula, Anu; Devasia, Anup J.; Na, Fouzia; Janet, Nancy Beryl; Nair, Sukesh C.; Abraham, Aby; Mani, Thenmozhi; Lakshmanan, Jeyaseelan; Arunachalam, Arun Kumar; Balasubramanian, Poonkuzhali; George, Biju

doi:10.1038/s41408-022-00619-3

Cited by 9 publications

(14 citation statements)

References 14 publications

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“…However, the results of the SD rats fed with NaAsO 2 showed that the decrease in TG content might indicate arsenic damage to SD rats' liver, resulting in insufficient synthesis or secretion of very low-density lipoprotein (VLDL), and reduced TG transport from inside to outside the liver cells, which might cause imbalance in synthesis, degradation, and secretion of liver lipid metabolism, causing abnormal deposition of lipids in liver cells. Arsenic trioxide had a significant effect on the treatment of acute promyelocytic leukemia [ 33 ]; interestingly, triglyceride levels were increased during treatment [ 34 ], so the specific mechanisms of arsenic and triglyceride needed to be further studied.…”

Section: Discussionmentioning

confidence: 99%

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The Molecular Mechanism of Hepatic Lipid Metabolism Disorder Caused by NaAsO2 through Regulating the ERK/PPAR Signaling Pathway

Zhang

et al. 2022

Oxidative Medicine and Cellular Longevity

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Chronic arsenic exposure is a risk factor for human fatty liver disease, and the ERK signaling pathway plays an important role in the regulation of liver lipid metabolism. However, whether ERK plays a role in the progression of arsenic-induced liver lipid metabolism disorder and the specific mechanism remain unclear. Here, by constructing a rat model of liver lipid metabolism disorder induced by chronic arsenic exposure, we demonstrated that ERK might regulate arsenic-induced liver lipid metabolism disorders through the PPAR signaling pathway. Arsenic could upregulate the expression of PPARγ and CD36 in the rat liver, decrease the expression of PPARα and CPT-1 in the rat liver, increase the organ coefficient of the rat liver, decrease the content of TG in rat serum, and promote fat deposition in the rat liver. In the arsenic-induced rat model of hepatic lipid metabolism disorder, we found that the expression of p-ERK was increased. In order to further explore whether the ERK signaling pathway was involved in arsenic-induced liver lipid metabolism disorder, we exposed L-02 cells to different arsenic concentrations, and the results showed that arsenic significantly increased the expression of P-ERK in L-02 cells in a dose-dependent manner. We further treated L-02 cells with ERK inhibitors and found that the expression of TG, PPARα, and CPT-1 in L-02 cells increased, while the expression of P-ERK, PPARγ, and CD36 decreased. In conclusion, ERK may be involved in arsenic-induced liver lipid metabolism disorder by regulating the PPAR signaling pathway. These findings are expected to provide a new targeting strategy for arsenic-induced liver lipid metabolism disorder.

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Section: Discussionmentioning

confidence: 99%

“…Oxidative Medicine and Cellular Longevity promyelocytic leukemia [33]; interestingly, triglyceride levels were increased during treatment [34], so the specific mechanisms of arsenic and triglyceride needed to be further studied. Meanwhile, NaAsO 2 exposure significantly reduced TG content and fat particles in L-02 cells.…”

Section: Discussionmentioning

confidence: 99%

The Molecular Mechanism of Hepatic Lipid Metabolism Disorder Caused by NaAsO2 through Regulating the ERK/PPAR Signaling Pathway

Zhang

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…Overall, 43% of patients were high risk in our study. This is similar to other real‐world data published from India 9–11 . In all, 82% of patients had bleeding manifestations at presentation in our study, including 24 (11.7%) who presented with a major bleed and 17 (8.3%) who presented with an intracerebral bleed.…”

Section: Discussionsupporting

confidence: 91%

“…Further, a high percentage of patients had evidence of fungal infection (13.6%), which is similar to our previously published data. 19 Kulkarni et al 10 also reported a 55% incidence of documented infection during APL induction, including eight patients with fungal infection. Infection was also the most common cause of death in patients who did not die within the first 7 days of therapy.…”

Section: Variablementioning

confidence: 97%

Long‐term real‐world outcomes of patients with acute promyelocytic leukaemia treated with arsenic trioxide and all‐trans retinoic acid without chemotherapy—a retrospective, single‐centre study

et al. 2022

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Summary Arsenic trioxide (ATO) and all‐trans retinoic acid (ATRA) form the backbone of the treatment of acute promyelocytic leukaemia (APL), with the addition of chemotherapy for high‐risk patients. We describe our experience of treating patients with APL of all risk classes with ATO and ATRA without chemotherapeutic agents. Patients received induction with ATO and ATRA followed by three cycles of consolidation with ATO and ATRA (each 1 month apart) after achieving morphological remission. Patients with intermediate‐ and high‐risk disease received a further 2 years of maintenance with ATRA, 6‐mercaptopurine and methotrexate. A total of 206 patients were included in the study. The majority of the patients were intermediate risk (51.9%), followed by high risk (43.2%). Differentiation syndrome was seen in 41 patients (19.9%). Overall, 25 patients (12.1%) died within 7 days of initiating therapy. Seven patients relapsed during follow‐up. The mean (SD) estimated 5‐year event‐free survival (EFS) and overall survival (OS) in the entire cohort was 79% [5.8%] and 80% [5.8%] respectively. After excluding patients who died within 7 days of therapy initiation, the mean (SD) estimated 5‐year EFS and OS was 90% [5.8%] and 93% [3.9%] respectively. Our study shows that treatment of all risk classes of APL with ATO and ATRA without chemotherapy is associated with excellent long‐term outcomes in the real‐world setting.

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“…Compared to a standard ATRA and idarubicin regimen, ATRA/ATO resulted in higher EFS and reduced relapse rate at 4 years with no-difference in OS and quality of life (52). Long-term follow-up studies demonstrated the durability of the response and good short-and long-term tolerability without significant adverse effects (53)(54)(55).…”

Section: Adult Data On Chemotherapy-free Treatment For Aplmentioning

confidence: 99%

Chemotherapy-free treatment for acute promyelocytic leukemia: the pediatric view of a revolutionary tale

et al. 2023

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The addition of all-trans retinoic acid (ATRA) to the standard anthracycline-base chemotherapy has revolutionized the treatment of acute promyelocytic leukemia (APL) over the last decades, becoming a model for precision medicine. The protocols based on the combination of ATRA and chemotherapy allowed obtaining excellent response rates both for children and adults. However, the persistence of anthracycline chemotherapy as a backbone was a matter of concern for both acute and long-term complications. Efforts in reducing anthracycline cumulative dose or even eliminating anthracycline have been pursued in more recent pediatric protocols thanks to the introduction of arsenic trioxide (ATO). The impressive results of the ATRA/ATO combinations led to the introduction of protocols completely chemotherapy-free for standard-risk adult patients as the standard of care, whereas pediatric chemo-free protocols are still currently under evaluation. In this Review, we will critically retrace the history of this unique revolution in precision medicine, discussing the peculiar advantages for pediatric patients with APL.

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Real world data with concurrent retinoic acid and arsenic trioxide for the treatment of acute promyelocytic leukemia

Cited by 9 publications

References 14 publications

The Molecular Mechanism of Hepatic Lipid Metabolism Disorder Caused by NaAsO2 through Regulating the ERK/PPAR Signaling Pathway

The Molecular Mechanism of Hepatic Lipid Metabolism Disorder Caused by NaAsO2 through Regulating the ERK/PPAR Signaling Pathway

Long‐term real‐world outcomes of patients with acute promyelocytic leukaemia treated with arsenic trioxide and all‐trans retinoic acid without chemotherapy—a retrospective, single‐centre study

Chemotherapy-free treatment for acute promyelocytic leukemia: the pediatric view of a revolutionary tale

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