Introduction:

Hyperleukocytosis is traditionally defined as White Blood Count (WBC) greater than 100000/microliter. It is seen in Acute Leukemia (AL) and Chronic Leukemia (CL). However, the complications of leukocytosis with leukostasis, Diffuse Intravascular Coagulation (DIC) and tumor lysis (TLS) are usually hallmarks of AL particularly Acute Myeloid Leukemia (AML). There is no standard for management and controversy exists regarding the use of leukapheresis (Stahl M et al Leukaemia 2020) versus initiation of chemotherapy (Zhao J et al. Leuk Lymphoma 2021). Venetoclax is a bcl2 inhibitor that is being used in the management of AL. Here we report our experience using novel combination targeted therapy with Venetoclax for cytoreduction.

Methods:

This is a retrospective analysis of AL patients seen in a public tertiary care hospital in the emirates of Abu Dhabi in United Arab Emirates. The study period is between January 2023 to June 2024. Data was abstracted from the electronic medical records including patient demographics, diagnosis, laboratory values and treatment.

Results:

During the study period sixty-five patients presented with clinical features suggestive of AL. Fourteen (21 %) patients had hyperleukocytosis. The median age of the patients was 30 years (range 19 to 60 years). The median WBC was 134000/microliter (range 104-432,000/microliter).

Diagnostic work up included bone marrow biopsy with flow cytometry, karyotype analysis, Fluorescence in situ hybridization (FISH) and molecular studies (30 gene panel and FLT3 PCR).

The median period of reporting of the bone marrow result was 3 days (range 0-7 days).

Cytoreductive therapy was given with Dexamethasone 20 -40 mg intravenously daily with Hydroxyurea 2000 mg orally daily and Venetoclax orally (escalating from 100 mg day 1, 200 mg day 2 and 400 mg day 3 and onwards) while awaiting diagnosis.

There was a 50 % reduction of WBC by day 3 in most patients (64%). A WBC of less than 50000/microliter was achieved by day 4 in 57% of the cohort.

There was biochemical evidence of tumor lysis. This was managed medically by hydration, prevention of hyperuricemia and correction of electrolytes. Dialysis and critical care were not required.

Six patients refused further therapy and were lost to follow-up. Three patients died during induction period. Two patients went for allogeneic hematopoietic stem cell transplant, two patients had relapsed and refractory disease while one patient is in sustained remission post consolidation chemotherapy.

Conclusion:

The current experience using dexamethasone, Hydroxyurea and Venetoclax gives an alternate (leukapheresis and Cyclophosphamide/Cytarabine) and safe option for cytoreduction prior to exact diagnosis and initiation of therapy.

Disclosures

McCarthy:BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Off Label Disclosure:

Venetoclax as cytoreductive therapy in Acute Leukemia prior to Definitive therapy

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2024
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