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Success of imatinib in man with CML-CP wanting to have children
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A 40-year-old man who was training for a marathon developed a non-productive cough that did not respond to antibiotics and antitussives. His cough progressively worsened, and he developed some upper-left quadrant pain and discomfort, which he attributed to a possible rib sprain from the frequent coughs.
He then developed blurry vision in his right eye, for which he was seen by his ophthalmologist. Findings demonstrated a retinal hemorrhage. The patient presented to the ED for investigation of abnormal results from blood work.
The complete blood count showed a significant leukocytosis, with a white blood cell count of 301,000 cells/mcL, hemoglobin of 11 g/dL and a platelet count of 207,000 cells/mcL. The differential revealed 33% neutrophils, 10% bands, 3% lymphocytes, 3% monocytes, 2% eosinophils, 5% basophils, 23% metamyelocytes, 13% myelocytes, 3% blasts, and 5% promyelocytes.
The bone marrow biopsy was 95% cellular with 2% blasts. Karyotyping demonstrated the (9;22) translocation. Fluorescent in situ hybridization analysis was 97.5% positive for the fusion of BCR and ABL1 genes. Abdominal ultrasound revealed splenomegaly, with a 24 cm spleen. Therefore, the patient was diagnosed with chronic myelogenous leukemia, chronic phase (CML-CP).
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He was initially started on hydroxyurea therapy to lower the white blood cell count, especially given the complication of retinal hemorrhage. He experienced a rapid improvement in his white count and resolution of the visual symptoms. The next step was a discussion with the patient and his fiancée regarding long-term therapy with a tyrosine kinase inhibitor.
Imatinib success
In 1993, the International Randomized Study of Interferon (IRIS) and STI571 trial studied imatinib (Gleevec, Novartis; 400 mg daily) vs. interferon-alpha and cytarabine in newly diagnosed patients with CML-CP. The results showed superiority of imatinib in achieving complete hematologic responses, major and complete cytogenetic responses and major molecular responses.
Recent studies support the use of nilotinib (Tasigna, Novartis) or dasatinib (Sprycel, Bristol-Myers Squibb) as initial therapy. A phase 3, randomized, open-label study (ENESTnd trial) compared two doses of nilotinib (300 mg and 400 mg twice daily) to imatinib (400 mg). Nilotinib showed an improvement in the rates of major molecular response and complete cytogenetic response at 12 months compared with imatinib. Dasatinib (100 mg daily) was studied against imatinib (400 mg daily) in newly diagnosed CML-CP patients in a phase 3, randomized trial as well, and the results showed higher rates of complete cytogenetic responses and major molecular response at 12 months. Both drugs were well-tolerated.
Potential adverse effects
The difficulty in choosing a long-term TKI involved the patient’s recent engagement and desire to have children in the future. Imatinib has been shown to have negative side effects, including case reports of gynecomastia and oligospermia, in patients taking 600 mg to 800 mg imatinib. However, there have also been reports of successful pregnancy outcomes. One study from 2006 investigated 10 women and eight men, who conceived while on TKI therapy. The men were aged 26 to 38 years, and one male patient conceived twice. They took dosages of imatinib from 400 mg to 1,000 mg for a median of 18 months at the time of conception (range, 1-39 months). Eight healthy babies were delivered, with one requiring a successful surgery for gut malrotation. There was one spontaneous abortion, which could not be attributed to any other medical cause.
Another report in 2007 reported on five healthy babies born from four men on imatinib therapy. The patients’ ages ranged from 41 to 46 years and dosages were 400 mg to 800 mg. The pregnancies were uneventful.
Based on this data, the patient was started on imatinib 400 mg daily. He was advised that despite these previously reported successful pregnancies, imatinib may have harmful effects. The patient reached a complete hematologic response in 3 months and a complete cytogenetic response on his 6-month bone marrow examination. Long-term follow-up is needed and eagerly anticipated for all of the TKI therapy options.
Sheetal Shrimanker, MD, is chief fellow in the division of hematology and oncology at University of Medicine and Dentistry, New Jersey. She reports no relevant financial disclosures.
For more information:
- Ault P. J Clin Oncol. 2006;24:1204-1208.
- Gambacorti-Passerini C. Lancet. 2003;363:1954-1956.
- Kantarjian H. N Engl J Med. 2010;362:2260-2270.
- O’Brien SG. N Engl J Med. 2003;348:994-1004.
- Ramasamy K. Br J Haematol. 2007;137:374-375.
- Saglio G. N Engl J Med. 2010;362:2251-2259.
- Seshadri T. N Eng J Med. 2006;351:2134-2135.