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.