Acute myeloid leukemia (AML) is associated with dismal outcomes, especially in older patients. The use of intensive chemotherapy currently represents the most common option for young/adult AML patients. Nevertheless, older patients are frequently ineligible for it or have a disease that is refractory to standard chemotherapy. As an alternative, azacitidine or decitabine monotherapy has been used, but hypomethylating agents have been associated with a low chance of survival. Since the results of Viale-A got published in August 2020, we have been living a new era in Hematology due to the possibility of treating elderly patients with AML suffering from comorbidities. The most frequent adverse events of the azacitidine-venetoclax combination were thrombocytopenia, neutropenia, and febrile neutropenia in 45%, 42%, and 42% of the cases, respectively. But now, in real clinical practice outside of a clinical trial, we have detected a few cases with rebound thrombocytosis during initial cycles of treatment.

Describe an AML patient who presented thrombosis of the arm due to very high thrombocytosis of 1,550 x 109/L during the first cycle of azacitidine-venetoclax treatment.

Our patient presented translocation involving the long arm of chromosome 3 at 3q26 in which myeloid disorders had already been identified as 3q21q26 syndrome. Very recently, Othman et al. reported the incidence of rebound thrombocytosis without clinical manifestation during azacitidine-venetoclax combination for AML treatment. No case presented had such high platelet count and thrombosis as presented herein. Othman et al. suggested rebound thrombocytosis would be due to the capability of blasts to hide thrombopoietin (TPO) via increased expression of TPO receptor MPL, but the mechanism underlying the thrombocytosis remains unclear.

The 3q21q26 syndrome is rare but occurs in a high-risk myelodysplastic syndrome (MDS) or the setting of AML and is commonly associated with thrombocytosis. These chromosomal abnormalities result in aberrant expression of the protooncogene ecotropic virus integration site – 1 (EVI1) located at 3q26.2, and through mechanisms not completely understood, myeloid and erythroid differentiation are profoundly suppressed while the megakaryocytic lineage shows marked hyperplasia. This case illustrates the importance of critical surveillance of platelet count during the initial cycle of venetoclax plus azacytidine.