Discussion
Ocular complications may manifest as a symptom of severe, untreated leukemia. Although the pathophysiology behind ocular manifestations of CML is not well understood, it is most likely multifactorial. These mechanisms likely include infiltration by neoplastic cells leading to reduced blood flow, vascular stagnation, ischemia, and anemia1,3. There may also be thrombosis due to toxic products released by leukemic cells, and increased amounts of angiogenic factors that lead to elevated levels of vascular endothelial growth factor, fibroblast growth factor 2, and matrix metalloproteinases3. Severe, symptomatic leukocytosis is associated with an extremely high mortality rate that can lead to both respiratory failure and permanent neurological complications. When signs of organ failure begin to present, the death rate at one week approaches 90 percent4. Thus, prompt cytoreduction is necessary to improve clinical outcomes.
Although the mainstay of treatment for leukemic retinopathy remains induction chemotherapy at the underlying disorder, leukapheresis has become more common as an adjunctive or initial treatment. Prompt, effective reduction of the high white cell count can cause rapid improvement of visual symptoms. Leukapheresis aids in prompt reversal of microvascular sludging and should be considered for rapid cytoreduction during the initial stages, since drugs such as hydroxyurea or BCR-ABL tyrosine kinase inhibitors take a longer time to demonstrate their cytoreductive effects5,6. The process of leukapheresis involves removing whole blood from a patient through a central venous catheter, separating leukocytes out through an apparatus, and then transfusing the cytoreduced blood back to the patient. It is an efficacious procedure to rapidly reduce leukocytosis without necessitating donor transfusions or additional medications.
However, leukapheresis remains controversial as it has variable results in overall mortality benefits and has not been well-studied in different types of leukemia. Larger prospective studies have not shown consistent benefits or decreases in early morality rates and have only been studied in acute myeloid leukemia (AML) cases5,7,8. One study showed that although patients had a significant reduction in leukocytosis after therapeutic leukapheresis, they also displayed a higher death rate within the first 24 hours and an overall higher early death rate compared to patients with chemotherapy alone9. However, this study only looked at patients with AML rather than CML, although acute blast phase CML is treated similarly. In the 2021 review article by Yassin, et al, ophthalmologic manifestations from CML could only be found in the literature as case reports or case series2. Of the 38 CML cases reviewed, only two were treated with emergent leukapheresis; both cases showed little change in outcome2,10,11. This differs from our case in that significant improvement in vision was seen in two days. Leukapheresis for acute, symptomatic hyperleukocytosis currently is a grade 2B recommendation based on the American Society of Apheresis (ASFA), with most of its studies derived from AML cases as leukemic complications are more often seen in AML rather than CML12. Grade 2B recommendation is defined as a weak recommendation with moderate-quality evidence as per the ASFA. This likely stems from the variable outcomes seen in the reported AML cases that have been treated with leukapheresis, the paucity in literature of leukemic complications of CML treated with leukapheresis, and no improvement in outcome or even an association with early mortality in APL cases12. Lastly, its generalizability is limited in its accessibility as leukapheresis is an invasive procedure that requires a large bore central venous catheter and is only offered in select medical centers. Despite these limitations, given the few amount of other initial existing treatments to rapidly reduce leukocytosis, it may be a beneficial therapy to treat acute, severe consequences of extreme leukocytosis. In our patient, early initiation of leukapheresis, along with hydroxyurea therapy, resulted in reversal of leukemia-associated retinal changes.
Although leukapheresis in current studies have not been proven to have overall mortality benefits, our case shows that there may be a role for this procedure in reducing permanent vascular damage. Our patient successfully had reversal of his acute vision loss and was able to initiate chemotherapy shortly after his initial presentation. Further studies are needed to demonstrate the benefits of symptom relief of severe leukocytosis in conjunction with chemotherapy and hydroxyurea.