Case Report
A 69-years-old male patient was diagnosed with chronic phase CML,
intermediate Sokal and Hasford scores. He had past medical history of
hypertension, stroke, iliac artery bypass, syphilis, age-related macular
degeneration, syphilitic left eye papillitis (diagnosed 2 years before
the CML and treated accordingly with benzathine penicillin), chronic
gastritis with angiectasia and prostate benign hyperplasia.
The patient started a first line treatment with Imatinib, which was
stopped 14 months later for non-optimal response (he only achieved a
morphological response, as shown in the graphic 1) and progressive
visual impairment that begun 3 months after starting the drug. The
Ophthalmologist reported the already known non-exudative macular
degeneration and papillitis of the left eye, however also found macular
edema bilaterally and right eye papillitis. An angiography, thoracic
radiography, lumbar puncture, tuberculin test, syphilis, brucella,
borrelia and HIV assays were requested, as well as a study for vitamin
deficit and a search for auto-imunne diseases. A cerebral CT scan showed
no recent abnormality. No organic cause was found for these
ophthalmologic disturbs apart from toxicity of imatinib. Oral
prednisolone was prescribed (20 mg daily for two weeks, then increased
to 60 mg for the papillitis, followed by progressive reduction
afterwards) with regression of the edema and the papillitis and minor
improvement of the visual deficit.
A second line therapy with Dasatinib 140 mg daily was then prescribed.
The patient had a significant reduction of the BCR-ABL transcript but it
still remained positive (a morphologic response was obtained once
again). The patient complained about the worsening of the visual acuity
4 months after starting the drug. The eye exam allowed the
identification of macular edema, the reason for being prescribed
prednisolone 20 mg daily for long time, with progressive dose reduction.
In the Optical Coherence Tomography (OCT) image there was evidence of
reduction of the thickness of both retina (left and right) to 172 ug in
the right eye and 183 ug in the left eye. The patient was submitted to
phacoemulsification therapy for cataracts in the right eye. Another OCT
image was repeated 20 months later showing a continuous progressive
reduction of the thickness of both retina, to 162 ug in the right eye
and 158 ug in the left eye, in the absence of the external retina and
with diffuse atrophy of RPE (retinal pigment epithelium). Dasatinib was
stopped three times for anemia (identified to be caused by duodenal
angiectasy), with blood transfusions, injectable and oral iron required
for long term. The patient also developed a pneumonia with pleural
effusion, which was assumed as a typical effect of Dasatinib (stopped 44
months after the first prescription).
Bosutinib 500 mg daily was started as third line therapy. The patient’s
performance status worsened progressively (with asthenia, dyspnea, worse
motor coordination, hyperuricemia, bone pain) mainly between the second
and third lines of therapy for the CML). The patient only achieved a
complete morphologic response but with the lowest level of the BCR-ABL
transcript (ratio BCR-ABL1/ABL1 0,4251 IS). There were also relevant
toxicities: two pneumonias (the drug was stopped in both infectious
events), grade 2 diarrhea (the drug was stopped for one week, being
re-started in reduced dose, progressively mounted until full dose) and
worsening of the ocular toxicity. The patient reported worsening of the
visual deficit one month after starting the drug, with progressive
retinal atrophy (in probable relation with the TKI). Oral prednisolone
was re-started (50 mg daily for 2 weeks, with progressive decreasing
dose) with no improvement. One month later the retinal atrophy was worse
and a macular edema was found (once again assumed to be caused by the
TKI). In the OCT image (3 years later) there was an accelerated
reduction of the thickness of all layers of both retina, and diffuse
absence of the external retina. This TKI was stopped after 16 months of
treatment, for the ophthalmologic toxicity in the absence of CML
response.
It is important to remember that a major molecular response (MMR) was
never achieved with any of the TKIs prescribed, however his symptoms
improved and a hematologic response (HR) was obtained, ensuring
patient’s autonomy. Considering the general state of this patient, the
toxicity reported and the absence of optimal response to TKIs, it was
decided to prescribe hydroxyurea as a fourth and palliative therapy.
There was a stabilization of the hematologic values and the patient’s
quality of life. The regular control of the BCR-ABL1 transcripts level
was stopped for the absence of benefit.