CHAPTER 13: Leukemia

Leukostasis is a major cause of early mortality in patients with acute leukemias. Signs of leukostasis include altered sensorium, ischemic heart signs, respiratory distress, and priapism and are a function of the size, number, and type of leukemic cells.¹ Of these, immediate reduction of the number of leukemic cells can restore organ function and allow for subsequent anti-leukemia therapy.

A 64-year-old man in acute respiratory distress is found to have a white blood cell (WBC) count of 153 × 10⁹/L with 71% blasts. Labs reveal an elevated troponin level, and chest radiography demonstrates scattered bilateral opacifications. Peripheral smear review shows large immature cells with Auer rods. Peripheral blood flow cytometry was requested. Rapid leukocyte reduction was achieved with oral hydroxyurea.

Both pharmacological and mechanical methods of cytoreduction have been deployed in treating patients with hyperleukocytosis and signs of leukostasis.

Pharmacological cytoreduction

Diagnosis confirmed:

• Induction chemotherapy in suitable patients

Diagnosis confirmation pending:

• Hydroxyurea is effective in myeloid hyperleukocytosis; patients should be capable of enteral intake

• Systemic steroids can be effective against malignant lymphoid hyperleukocytosis and can be given orally or parenterally

• Vincristine is effective against malignant lymphoid cells and is given intravenously

• Cytarabine is effective in both myeloid and lymphoid hyperleukocytosis

• Anthracyclines are used in protocols in acute promyelocytic leukemia (APL)

Mechanical cytoreduction

• Leukapheresis is effective in both myeloid and lymphoid hyperleukocytosis²

• Leukapheresis is contraindicated in APL due to risks of disseminated intravascular coagulation (DIC)²

Hyperleukocytosis is arbitrarily defined as circulating WBC or blast count >100 × 10⁹/L. Leukostasis is a complication of hyperleukocytosis and results in end-organ ischemia and/or hemorrhage. Myeloid cells are larger and more rigid than lymphoid cells and produce cytokines, resulting in inflammatory endothelial changes; therefore, myeloid leukemias result in leukostasis at lower counts than their lymphoid counterparts.

Pros and cons of different leukoreduction methods:

Pharmacological methods

• Pros: No invasive procedures required, rapid administration, safer method in APL

• Cons: Off-target toxicities of pharmacological agents and higher rates of post-therapy respiratory distress in monocytic leukemias

Mechanical methods

• Pros: Rapid cytoreduction and possible role in asymptomatic hyperleukocytosis (prophylactic)³

• Cons: Requires central catheter placement and invasive procedures, requires special equipment and technical expertise, may trigger bleeding complications in APL, and does not obviate the need for chemotherapy

• Aggressive supportive care is equally important in the acute management of hyperleukocytosis and leukostasis and improves early mortality outcomes

• It is common practice to administer cytoreduction methods with cross-reactivity against both myeloid and lymphoid cells empirically until the diagnosis is established

• The number of treatment occurrences depends on the patient’s response; repeated treatment is often warranted

• Continue to monitor for signs of tumor lysis syndrome while treating hyperleukocytosis

1. Röllig C, Ehninger G. How I treat hyperleukocytosis in acute myeloid leukemia. Blood 2015;125(21):3246-52.

2. Schwartz J, ...