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.