Azacitidine-induced pneumonitis and literature review

Abstract

We present a case of azacitidine-induced pneumonitis which is a rare adverse drug reaction and reported in less than 0.1% of cases. Common side effects of azacitidine are weakness, nausea, vomiting, constipation, injection site reactions, insomnia, among others. Our patient received azacitidine to treat her acute myeloid leukaemia and began to develop shortness of breath which progressed to dyspnoea at rest after completing a 7-day course of azacitidine and venetoclax. Initial chest X-ray revealed severe airspace disease for which the patient began receiving broad spectrum antibiotics, antifungals and antivirals therapy. Although infectious workup revealed invasive aspergillosis she did not clinically and radiologically improve despite being on isavuconazole until high-dose glucocorticoids were initiated. This case illustrates the importance of recognising and understanding the potential side effects of azacitidine and other chemotherapy agents as some adverse drug reactions can be life-threatening.

Azacitidine-Induced Pneumonitis in a Patient With Acute Myeloid Leukemia and Hyperleukocytosis

“…It is described as interstitial pneumonitis, and clinical manifestations include fever, dyspnea, cough, and hypoxemia. The most common radiologic findings are interstitial or ground-glass opacities, with some cases also reporting consolidation and airway opacities [6][7][8][9]. Bronchoscopy with bronchoalveolar lavage (BAL) can aid in excluding alternative diagnosis, and biopsy may show patterns characteristic of drug-related toxicity, such as organizing pneumonia [10].…”

Hypermethylation of the Promoter of miR-338-5p Mediates Aberrant Expression of ETS-1 and Is Correlated With Disease Severity Of Astrocytoma Patients

“…While using Decitabine, this study also used inhibitors of other mechanisms. Azacitidine (5-Azacytidine, 5-AzaC, Ladakamycin, AZA, 5-Aza, CC-486) is a nucleoside analog of cytidine, which inhibits DNA methylation by binding to DNA methyltransferase in competition with cytidine (75)(76)(77)(78). Our results show that Azacitidine can also down-regulate the promoter methylation rate of miR-338-5p, but the activity of Decitabine is better than that of Azacitidine (that is, the inhibitory activity of Decitabine is higher than that of Azacitidine at the same concentration).…”

Azacitidine induced lung injury: report and contemporary discussion on diagnosis and management

“…Azacitidine hypomethylates the replicating DNA and inhibits its function through the dephosphorylation of azacitidine to 5-aza-2' V-deoxycytidine diphosphate by ribonucleotide reductase (6). The 5-aza-2' Vdeoxycytidine diphosphate then is phosphorylated into triphosphate, which binds stoichiometrically to DNA methyltransferase and inhibits it irreversibly which hypomethylates the DNA regulatory sequences and increase gene transcription restoring the normal function of tumor suppressor genes and cell maturation (3,6,10,(26)(27)(28).…”

“…genes, which, in turn, drives the neoplastic transformation to AML (3,(6)(7)(8)(9). MDS and AML tend to occur more often in people over the age of 60 years, with a male predominance (10,11). Since most patients are of older age, the chances of having more comorbidities and being unfit increase, which, in turn, limits the ability to use curative therapies, such as stem cell transplant (1).…”

“…By blocking DNA methyltransferase, 5azacytidine prevents the methylation of newly produced DNA (DNMT), restoring normal function to genes involved in differentiation and proliferation (12)(13)(14)(15)(16). Since then, azacytidinebased combinations have also been tested and developed in MDS, although with limited success, and in AML, where it led to a number of subsequent US-FDA approvals in patients ineligible for highintensity therapy (10,(17)(18)(19)(20)(21)(22)(23)(24).…”