Hyperleukocytosis Caused By Neulasta Complicated By Leukostasis Versus Asymptomatic Uncomplicated Hyperleukocytosis In AML. Two Cases and When To Leukapherese

Hyperleukocytosis may be complicated by intravascular leukostasis. 5-13% of adults diagnosed with acute myeloid leukemia (AML) present with hyperleukocytosis (Porcu P, Cripe LD et al Hyperleukocytic leukemias and leukostasis: Leukemia Lymphoma. 2000; 39:1–18). Leukapheresis is performed to treat complications of hyperleukocytosis in AML. No cell count cutoffs exist to prevent leukostasis with timely leukapheresis.

Neupogen (filgrastim) and Neulasta (pegfilgrastim) are used to reduce the duration of neutropenia in selected patients. Pegfilgrastim has reduced renal clearance, is more potent, and possesses a much longer half-life in vivo compared to filgrastim. Predicting leukocytic response to initial growth factor exposure is difficult. Asymptomatic hyperleukocytic responses may result. Symptomatic hyperleukocytosis with sequelae of leukostasis is rarely encountered with the use of growth factors (JCO, Antonio C. Wolff, Volume 24, Number 15 May 20 2006). We could find only one case report where leukapheresis was used to treat growth factor induced leukostasis (From FDA reports: Neulasta and Leukapheresis, eHealthMe August 7 2013). There are no guidelines to treat cell count cutoffs for leukapheresis in symptomatic patients with hyperleukocytosis resulting from growth factors. Shown below is data taken from FDA reports: eHealthMe 2013).

Summarizing data in tables above

Growth factor induced leukocytosis is directly proportional to age (Table 1).

Females are more susceptible to leukocytic response than males (Table 2).

Leukostasis is rare with growth factors, Neulasta > Neupogen (Table 3, 4).

Case #1 is that of an asymptomatic 69 year old male with AML, hyperleukocytosis, and white blood cell (WBC) counts of 270,000 with 98% circulating blasts. Cell counts trended down with Hydroxyurea. Case #2 is an elderly octogenarian male patient with MDS (IPSS 1) renal insufficiency (creatinine clearance = 31.9), a small serum IgA lambda M Spike, grade 3/4 neutropenia, and pancytopenia given 6 mg subcutaneous Neulasta. Within 7 hours, the patient became symptomatic (chest pain, dizziness, and headache). On presentation to the hospital the next day, WBC count was up to 130,000, complicated by intraocular flame hemorrhage, documented troponin elevation, and an EKG that confirmed a non ST elevation myocardial infarction (NSTEMI). Cell counts trended down to 50,000 range in approximately 3 days without treatment for hyperleukocytosis.

Neulasta should be used very cautiously in elderly patients, especially those with renal insufficiency. Patients who have symptomatic hyperleukocytosis should be seriously considered for interventions such as leukapheresis to prevent life threatening complications, regardless of the cause, growth factor or acute leukemia. Evidence-based guidelines for prevention of leukostasis are desperately needed.

No relevant conflicts of interest to declare.