Treatment

Treatment (1 of 13)

The presented with blurry vision. Why is that a concern?

It may be caused by a cataract, which is readily treatable

The patient may have CNS involvement with CML

The patient may have leukostasis

Correct. Leukostasis is characterized by an extremely elevated blast cell count and symptoms of decreased tissue perfusion.

It is an indication of severe anemia

This sounds like hyperviscosity syndrome

Leukostasis occurs in patients with leukemia and very high white cell counts (it is also called symptomatic hyperleukocytosis). While it is a pathological diagnosis (presence of white cell plugs in the microvasculature) it may be inferred clinically when a patient with leukemia and hyperleukocytosis presents with clinical evidence of decreased tissue perfusion such as respiratory or neurological distress. The prevalence of leukostasis varies between different kinds of leukemia. Which one of the following types of leukemia has the lowest risk?

Acute myelogenous leukemia (AML)

Hyperleukocytosis is present in 10 to 20 percent of patients with newly diagnosed AML. In AML, it usually associates with myelomonocytic or monocytic leukemia or the microgranular variant of acute promyelocytic leukemia (APL). Compared to lymphoid blasts, myeloid blasts are larger, less deformable, and their cytokine products are more prone to activate inflammation and endothelial cell adhesion molecule expression. Thus, in AML patients, leukostasis can occur when WBC >100 × 109 /L while in ALL, it is rarer and may not occur until WBC >400 × 109/L.

Acute lymphoblastic leukemia (ALL)

Hyperleukocytosis is present in 10 to 30 percent of patients with newly diagnosed ALL. In ALL, it associates with male gender, T cell phenotype, infants, and patients ages 10-20 years.

Chronic lymphocytic leukemia (CLL)

Hyperleukocytosis is rare in patients with CLL.

Chronic myelogenous leukemia (CML)

May occur with CML when the WBC count exceeds 100 × 109 /L.

Let’s return to the case and consider other findings the patient might have related to leukostasis. The central nervous system and lungs are the common sites for symptomatic vascular obstruction, but other organs may be involved including the heart and kidney.

What are some neurological findings?

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Headache, confusion,
lethargy, dizziness, ataxia, papilledema, retinal
hemorrhage and intracranial hemorrhage

What are some respiratory findings?

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Tachypnea, dyspnea,
hypoxia, pulmonary infiltrates and respiratory failure; bilateral interstitial or alveolar infiltrates on imaging

What are some cardiac findings?

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Arrhythmia, myocardial infarction

What are some renal findings?

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Renal failure

Leukostasis is a medical emergency. If unrecognized, the 1-week mortality can be as high as 40%. What are the general modes of treatment?

Anti-inflammatory agents

Cytoreduction with hydroxyurea

Cytoreduction with leukapheresis

Therapeutic leukocytapheresis is a grade-2B indication for leukemia with a white blood cell (WBC) count of >100 x 109/L with leukostasis as per the American Society of Apheresis. Leukocytapheresis leads to rapid cytoreduction

Radiation therapy

Cytoreduction with induction chemotherapy

Definitive treatment of hyperleukocytosis involves induction chemotherapy with aggressive supportive care. CML with hyperleukocytosis is usually managed with chemotherapy. The usual chemotherapeutic agents used are imatinib, dasatinib, and nilotinib.

Does this patient have an increased risk for tumor lysis syndrome?

Yes

Patients with hyperleukocytosis may also present with tumor lysis syndrome (TLS) and disseminated intravascular coagulopathy (DIC). Supportive management includes allopurinol and hydration.

A high leukocyte count predisposes the patient to both leukostasis and tumor lysis syndrome (TLS).

How would you determine whether this patient has tumor lysis syndrome?

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Measure serum LDH, electrolyte panel (including phosphate, potassium, and calcium), renal function, and uric acid.

This patient had a low hemoglobin. Would you recommend red cell transfusion when he first presented?

Yes

Red cell transfusions will further increase viscosity, so it is preferable to wait until the white cell count is lowered.

The patient had blurry vision but denied other symptoms of leukostasis. His tumor lysis and DIC labs were negative.

Course in hospital:

The patient was admitted to the hospital to the malignant hematology service for a total of 6 days.
During day 1 of hospitalization, the patient received hydroxyurea 2g q8h until his counts decreased to less than 100 x 10⁹/L (total of 5 days); his blurry vision resolved on day 2.
WBC trend
- day 2 108 x 10⁹/L
- day 3 140 x 10⁹/L
- day 4 96 x 10⁹/L
- day 5. 61 x 10⁹/L
He was started on dasatinib on the second day of hospitalization
He was started on allopurinol and received IVF 100cc/hour for TLS prophylaxis

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