Rebound Thrombocytosis after Induction Chemotherapy is a Strong Biomarker for Favorable Outcome in AML Patients

Abstract

Whereas the molecular events underlying acute myeloid leukemia (AML) are increasingly identified, dynamics of hematologic recovery following induction chemotherapy remain mysterious. Platelet recovery may vary between incomplete and excess recovery among patients achieving remission. We analyzed platelet recovery after the first induction cycle in 291 consecutive AML patients. We defined excess platelet rebound (EPR) as platelet increase above 500 G/L. We observed EPR in 120 (41.2%) patients. EPR+ patients had lower platelets at diagnosis, higher marrow infiltration, more frequently NPM1 mutations, and were associated with ELN favorable risk. Absence of EPR correlated with complex karyotypes, ELN intermediate-I and adverse risk, and therapy-related AML. Overall survival was better in EPR+ patients than EPR- (median 125 vs 41 months; p = 0.04), as was disease-free survival. By multivariate analysis, EPR+ was an independent parameter associated with favorable survival. Plasma thrombopoietin (TPO) levels at diagnosis indicated EPR+ (p < 0.0001), while GATA-1, GATA-2, and MPL mRNA expression did not differ between EPR+ and EPR- patients. Finally, transcription factors blocking early megakaryopoiesis were upregulated in EPR- patients, while NFE2 involved in late megakaryocyte differentiation was increased in EPR+ patients. Our work identifies mechanisms involved in platelet recovery after induction chemotherapy.

Dynamic trajectory of platelet counts after the first cycle of induction chemotherapy in AML patients

“…Currently, the selection of appropriate therapeutic methods for AML mainly depends on the age of the patient and risk stratification, including cytogenetic and molecular features [ 4 ]. Nevertheless, the data collected after the initiation of AML treatment can potentially be as useful as the pretreatment characteristics [ 5 ]. Therefore, post-treatment data may be used in developing treatment decision-making strategies [ 6 ].…”

Rebound thrombocytosis is associated with response in AML patients treated with venetoclax and hypomethylating agents

“…Rebound thrombocytosis has been described in patients with AML treated with intensive induction chemotherapy and is correlated with favorable outcomes. 1 Larger studies will be needed to determine if rebound thrombocytosis is also correlated with durability of response and survival.…”

“…Hyperuricemia and abnormal ambulatory blood pressure monitoring (ABPM) represent two established modifiable risk factors associated with development of CKD. We performed a cross-sectional study of this cohort at baseline and identified that hyperuricemia and abnormal ABPM were associated with lower eGFR at baseline 1. This prospective study evaluated the annual change in estimated GFR (eGFR) among patients with and without hyperuricemia, nocturnal hypertension, and abnormal nocturnal dipping.…”

Screening for an underlying myeloproliferative neoplasm in patients with thrombocytosis post-induction chemotherapy for acute myeloid leukemia

“…Rebound thrombocytosis after induction chemotherapy occurs in up to 40% of patients with acute myeloid leukemia (AML) and may be associated with a favourable outcome [1] . Despite being a recognised cause of secondary thrombocytosis, this rebound phenomenon remains a trigger for the investigation of the myeloproliferative neoplasm (MPN)-associated, driver mutations of JAK2 V617F, CALR exon 9 and MPL exon 10 to determine whether the AML had transformed from an underlying MPN in whom the clinical management remains challenging [2] .…”