Treatment of Hyperleukocytosis with Continuous Low Dose Cytarabine: A Single Institution Experience
Authors: Fraebel Johnathan , Diamond Akiva , Abuasab Tareq 
Published: December 2024

Background: Hyperleukocytosis, defined as a white blood cell count (WBC) greater than or equal to 50,000 or 100,000 cells/µL in patients with acute myeloid leukemia (AML), is associated with poor outcomes. There is an increased risk of early mortality often in excess of 20% at 4 weeks due to complications including leukostasis, tumor lysis syndrome (TLS), and disseminated intravascular coagulation (DIC) (Bewersdorf et al., 2020, Stahl et al., 2020). Hyperleukocytosis is an emergency that requires prompt treatment with cytoreductive therapy, including hydroxyurea, high dose cytarabine, and leukapheresis.

In this retrospective study, we describe the characteristics and outcomes of AML patients treated with continuous cytarabine infusion at initial presentation for hyperleukocytosis.

Methods: The electronic medical record was queried for all patients aged ≥18 years with a diagnosis of AML (newly diagnosed or relapsed refractory) who presented to Baylor St. Luke's Medical Center, Houston, TX, between June 2020 and June 2024. From an initial cohort of 110 patients with AML, we manually reviewed patient records to identify those who presented with hyperleukocytosis (WBC &gt;50K) and received continuous cytarabine for cytoreduction, not as part of the 7+3 chemotherapy regimen, prior to AML induction chemotherapy (7+3 chemotherapy for fit patients and a hypomethylating agent with venetoclax combination for unfit patients). Our analytic cohort consisted of 13 patients.

Results: A total of 13 patients with AML were analyzed, with a median age of 63 years (range: 27-82) and a female predominance (62%). Four patients (31%) were Black, and one (8%) was Hispanic. Eleven patients (85%) had newly diagnosed AML, and two patients (15%) had relapsed/refractory disease. One patient (8%) had secondary AML, and one patient (8%) had AML with myelodysplastic-related changes. Six patients (46%) and seven patients (54%) had intermediate and adverse risk by the ELN 2022 criteria, respectively. Five patients (38%) had FLT3 mutations (ITD or TKD), and 3 patients (23%) had TP53 mutations.

The median WBC at diagnosis was 79.9k (range: 50-277k). Seven patients (54%) had WBC counts of 50-99k, and six patients (46%) had WBC counts of 100k or more. All three patients with WBC &gt;150k and 50% of patients with WBC &gt;100k had FLT3-ITD mutations. Sixty-two percent of patients presented with clinical leukostasis, and 46% presented with DIC at diagnosis. Among patients with leukostasis, 23% had central nervous system involvement, 31% had renal involvement, and 38% had pulmonary involvement.

Ten patients (77%) were treated with hydroxyurea for cytoreduction prior to continuous cytarabine. The median dose of continuous cytarabine was 100 mg/m²/Day (range: 20-200 mg/m²), with a median therapy duration of five days (range: 3-7 days). TLS following therapy was seen in only two patients (15%), who were treated conservatively. The four-week and eight-week mortality rates were both 8% (1/13 patients). Among the 12 patients available for response assessment, 58% attained a complete response (CR), all of which were minimal residual disease (MRD) positive. With a median follow-up duration of 9.3 months, the median overall survival was 17.2 months.

Conclusions: Hyperleukocytosis is historically associated with poor four- and eight-week mortality. Our study demonstrates that cytoreduction with cytarabine 100mg/ m²/day by continuous infusion is feasible, safe, and associated with better-than-expected early mortality and low risk of TLS. The safety and efficacy of cytoreduction with continuous low dose cytarabine warrants prospective evaluation.