Comparison of Cytoreductive Therapies for Hyperleukocytosis and Leukostasis in Acute Myeloid Leukemia: A Perspective on the Updated American Society for Apheresis Guidelines
Authors: Avetian George , Ho Thuy , Bouligny Ian M. , Lee Hyun , Maher Keri 
Published: December 2024

Background: Hyperleukocytosis is a laboratory condition defined as white blood cell (WBC) count greater than 100x109/L that affects up to 20% of patients with acute myeloid leukemia (AML) at time of diagnosis. Patients who exhibit signs or symptoms attributable to tissue hypoxia, most commonly respiratory and neurologic, with this elevated WBC count are classified with the clinical diagnosis of leukostasis. Mainstay of treatment for both diagnoses is cytoreduction with therapies including hydroxyurea, leukapheresis, and chemotherapy. Recent guidelines by the American Society for Apheresis (ASFA) classified apheresis as a Category III recommendation (role not established) for only hyperleukocytosis, adding further confusion to the treatment strategies for these two separate conditions.

Methods: Retrospective analysis of 42 patients at Massey Comprehensive Cancer Center between 2014 and 2024 who received either hydroxyurea alone (n=19) or both hydroxyurea and leukapheresis (n=23) for hyperleukocytosis at time of AML diagnosis was performed. No patients received leukapheresis without other cytoreductive therapy. Baseline characteristics including age, Charlson Comorbidity Index (CCI), genetic risk stratification by ELN 2022, rates of FLT3-ITD mutations and KMT2A/MLL rearrangements, and initial WBC count were collected. Comparisons of complete remission rates (CR/CRi), 30- and 60-day mortality, median overall survival (OS), and rates of tumor lysis syndrome (TLS) and disseminated intravascular coagulation (DIC) were analyzed following propensity score matching (PSM) to account for differing initial WBC counts between the treatment groups. Rates of diagnosis of hyperleukocytosis versus leukostasis were also analyzed for each treatment group. Fisher's exact test, Mann-Whitney U test, and the Kaplan-Meier method were used for our analyses.

Results: PSM was used to match initial WBC counts between the hydroxyurea and combined cohorts (157.8 v. 170.5, p=0.379). Baseline characteristics for median age (65y v. 60y, p=0.276), CCI (5 v. 4, p=0.503), and ELN adverse risk rate (31.4% v. 26.1%, p=0.742) did not differ between these cohorts. Presence of FLT3-ITD mutations and KMT2A rearrangements were not different between the groups. No difference was exhibited between the hydroxyurea and combined cohorts with respect to rate of CR/CRi (36.5% v. 43.5%, p=0.758), 30- (10.5% v. 17.4%, p=0.673) and 60-day mortality (10.5% v. 34.8%, p=0.083), OS (7.77m v. 8.07m, p=0.607), and rates of TLS (0% v. 0%, p=1.000) and DIC (10.5% v. 8.7%, p=1.000). All patients who received the combined cytoreductive treatment were diagnosed or had a high suspicion for leukostasis by the hematologist, whereas none of the patients treated with hydroxyurea alone received the diagnosis (p&lt;0.001).

Conclusion: When accounting for differing WBC counts at time of diagnosis, cytoreduction with hydroxyurea alone produced similar outcomes compared to treatment with combination hydroxyurea and leukapheresis when analyzing for rate of CR/CRi, 30- and 60-day mortality, and median OS, and rates of TLS and DIC. Disease risk, and genetic aberrations commonly associated with hyperleukocytosis did not vary between the respective groups. Of note, all patients with the clinical diagnosis of leukostasis received leukapheresis, whereas none of the patients diagnosed with hyperleukocytosis only received leukapheresis. Despite this, there were no detectable differences between patient outcomes including early mortality, overall survival, and common complications. This lends further real-world support to the new ASFA guidelines for lack of strong evidence of benefit for this procedure.