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Hemophagocytic lymphohistiocytosis as an unexpected complication of Venetoclax+Azacitidine in Acute Myeloid Leukemia


Hematology & Transfusion International Journal
Ovilla-Martinez Roberto,1 Perez-Lozano Uendy,2 Cota-Rangel Xochitl,Baez-Islas Pamela1

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Abstract

1.1.Background: Venetoclax is a drug that targets BCL-2 protein in cancer cells, first approved for chronic lymphocytic leukemia, this drug has showed efficacy also in acute myeloid leukemia in non-intense chemotherapy candidates in combination with hypomethylating agents as azacitidine and decitabine. This scheme has shown efficiency in acute myeloid leukemia reporting overall response rate (CR) in 61% in untreated elderly patients combined with azacitidine or decitabine.Febrile neutropenia was reported in 30%, thrombocytopenia in 47%, and serious infections in 33%. Hemophagocytic lymphohistiocytosis (HLH) is an uncommon hematologic disorder caused by a proinflammatory state manifested by cytopenias and elevation of acute phase reactants; it is a severe complication of some diseases and to our knowledge it has never been reported secondary to venetoclax plus azacitidine. Early treatment is fundamental for success in HLH.

1.2.Case Series: Three cases of HLH secondary to venetoclax plus azacitidine have appeared in our medical group in patients treated for acute myeloid leukemia. One elderly woman and elderly men with previously untreated acute myeloid leukemia presented HLH with laboratory and bone marrow findings, both responded to dexamethasone plus ruxolitinib. The third case was documented in a male diagnosed with blast phase chronic myeloid leukemia who also responded to dexamethasone plus ruxolitinib. No patient died from HLH.

Conclusion:Here we report three cases of patients with HLH after the treatment with azacitidine plus venetoclax. We suspect that the great effect of venetoclax in synergy with azacitidine can liberate enough proinflammatory cytokines in the medullar niche to induce HLH. Early recognition is vital for soon treatment and successful management of this potential complication

Keywords

hemophagocytic lymphohistiocytosis, acute myeloid leukemia, 5-azacitidine, venetoclax, ruxolitinib

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