Azacitidine-induced massive pericardial effusion in a child with myelodysplastic syndrome

Abstract

Introduction Pericardial effusions are rare yet potentially fatal conditions in children. Azacitidine is a DNA-hypomethylating agent used in the treatment of myelodysplastic syndrome. Although seldomly described in adults, no cases of azacitidine-induced pericardial effusion have been reported in children. Case report A 7-year-old boy with myelodysplastic syndrome presented with a large pericardial effusion with risk for cardiac tamponade after his first azacitidine cycle. Management & outcome The patient was admitted to a pediatric ICU, antibiotic and steroid therapy were initiated. Pericardiocentesis was done due to hemodynamic instability. Serum and pericardial fluid complementary evaluation excluded infectious and malignant causes. The pericardial effusion did not reappear and additional pleural and ascitic slight effusions responded well to diuretics. Follow-up azacitidine cycles were administered by tapering daily dosages and using adjunctive steroid therapy, with no additional adverse events. Discussion We report the first pediatric case of large pericardial effusion secondary to azacitidine therapy in a child with MDS. This adverse reaction has not been described in pediatric patients, in which this therapeutic option has been increasingly used. We seek to raise awareness on the potential life-threatening cardiotoxicity of azacitidine in pediatric patients.

Pericardial Effusion: A Novel Presentation of Aplastic Anemia

“…The patient in our case eventually progressed to MDS and was treated with decitabine and venetoclax. While decitabine is a hypomethylating agent similar to azacitidine, it has never been reported in association to pericardial effusion, whereas azacitidine has in some case reports [3,4]. The fact that his aplastic anemia evolved into MDS in a relatively short period of time (18 months) further supports the theory that his pericardial effusion was immune-mediated and strongly linked to evolving MDS in the background of SAA.…”

“…Aplastic anemia may coexist with or evolve into another hematologic disorder, particularly paroxysmal nocturnal hemoglobinuria, MDS, or acute myeloid leukemia. Interestingly, few cases of pericardial effusion have been reported in association with MDS [1][2][3][4], as well as case reports describing viral [18] or autoimmune [19,20] pericardial effusions in the setting of allogeneic hematopoietic cell transplant for MDS as well. An autoimmune mechanism has been proposed to explain an intrinsic link between pericardial effusion and MDS [1,2].…”

“…Several reports describe abnormal T-cell responses to antigen presentation, as well as abnormal B/T-cell communication in MDS, which may lead to maladaptive immune responses [1]. Further literature illustrates that therapy with alemtuzumab, azacitidine, cyclophosphamide, or fludarabine in the treatment of MDS has been associated with pericardial effusion [3,4,14].…”

“…Pericardial effusion present with myeloproliferative disorders and other malignancies is most often due to the direct extension of neoplasm into the pericardium. However, with myelodysplastic syndrome (MDS), pericardial effusion appears to be immune-mediated [1,2] or treatment-related [3,4]. Additionally, patients with MDS are immunocompromised due to bone marrow suppression, which can lead to infectious pericardial effusions [5].…”