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Year : 2021  |  Volume : 14  |  Issue : 3  |  Page : 187-189  

Chronic myelogenous leukemia in a child following treatment for bilateral retinoblastoma

1 Department of Ophthalmology, Ministry of Health, Al-Nahdha Hospital, Muscat, Sultanate of Oman
2 Department of Pediatric Ophthalmology, Sultan Qaboos University Hospital, Muscat, Sultanate of Oman
3 Department of Child Health, Sultan Qaboos University Hospital, Muscat, Sultanate of Oman
4 Department of Ocular Oncology, Sankara Nethralaya Hospital, Chennai, Tamil Nadu, India

Date of Submission05-Apr-2021
Date of Decision01-Aug-2021
Date of Acceptance12-Aug-2021
Date of Web Publication20-Oct-2021

Correspondence Address:
Dr. Sana Al-Zuhaibi
Department of Pediatric Ophthalmology, Sultan Qaboos University Hospital, P.O.Box 38, P.C. 123 Al-Khod, Muscat
Sultanate of Oman
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ojo.ojo_107_21

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A 3-year-old child was incidentally found to have chronic myelogenous leukemia (CML) during an admission for a routine ophthalmic examination under anesthesia. The child had received systemic chemotherapy and focal treatment for Groups C and D retinoblastoma in the right and left eye, respectively, when she was 7 months old. CML was treated with dasatinib, and the child attained a major molecular response. The child is now 3 years after treatment of CML, and the retinoblastoma remains inactive. CML following treatment of retinoblastoma is a rare occurrence. Long term and close monitoring of retinoblastoma patients who received systemic chemotherapy using serial blood tests is essential.

Keywords: Chemotherapy, chronic myelogenous leukemia, retinoblastoma

How to cite this article:
Al-Mahrouqi HH, Ganesh A, Al-Rawas A, Khetan V, Al-Zuhaibi S. Chronic myelogenous leukemia in a child following treatment for bilateral retinoblastoma. Oman J Ophthalmol 2021;14:187-9

How to cite this URL:
Al-Mahrouqi HH, Ganesh A, Al-Rawas A, Khetan V, Al-Zuhaibi S. Chronic myelogenous leukemia in a child following treatment for bilateral retinoblastoma. Oman J Ophthalmol [serial online] 2021 [cited 2023 Feb 2];14:187-9. Available from: https://www.ojoonline.org/text.asp?2021/14/3/187/328596

   Introduction Top

Retinoblastoma is the most common intraocular malignancy in children. It is estimated to affect one in 17,000 live births.[1]

Retinoblastoma is caused by mutations in the tumor suppressor gene, retinoblastoma gene 1 (RB1).[2] Germline mutations are heritable, give rise to bilateral multifocal disease, and an increased risk of second primary nonocular tumors. Bone, soft tissue, and skin cancers are the most common. Leukemias are rare, and when they occur, are usually acute (rather than chronic) leukemias related to prior radiation or chemotherapy.[3] It is thought that the RB1 gene does not contribute to leukemogenesis.[4]

We hereby present a rare case of chronic myelogenous leukemia (CML) diagnosed in a patient treated for bilateral retinoblastoma and the treatment outcome.

   Case Report Top

A 3-year-old girl was diagnosed with Groups C and D retinoblastoma (International Classification of Retinoblastoma) in the right and left eye, respectively, in 2014, when she was 7 months old [Figure 1] and [Figure 2]. She was the first child born to consanguineous parents. There was no family history of retinoblastoma. Molecular genetic testing for the RB1 was positive for a heterozygous variant designated c19dupC and predicted to result in premature protein termination (p.Arg7Profs*24).[5] Chemoreduction protocol[6] using carboplatin, vincristine, and etoposide was initiated [[Table 1] for cumulative dosage]. Chemotherapy resulted in full regression of the tumor in the right eye and partial regression in the left eye. Multiple sessions of focal therapy failed to result in complete regression of the tumor in the left eye. Intra-arterial chemotherapy was attempted but was abandoned due to failed cannulation of the ophthalmic artery. The left eye was eventually enucleated in 2015. Histopathological evaluation revealed choroidal invasion of <3 mm. There was no optic nerve invasion.
Figure 1: Fundus photograph of the right eye showing Group C retinoblastoma

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Figure 2: Fundus photograph of the left eye showing Group D retinoblastoma

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Table 1: Chemotherapy received by the child from November 2014 to April 2015

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In 2018, 3 years following the last cycle of chemotherapy, during a routine admission for ophthalmic examination under anesthesia (EUA), the peripheral blood showed a white blood cell count of 107 × 109/L. Subsequent bone marrow biopsy showed a hypercellular marrow with no blast cells. The genetic test was positive for the BCR/ABL p210 translocation. A diagnosis of CML was made. The EUA did not reveal any re-activation of the retinoblastoma tumors. Treatment was initiated with imatinib, but it was changed to dasatinib due to an inadequate response, resulting in a major molecular response. Three years after the diagnosis of CML, the patient remains in complete hematologic and cytogenetic remission, and the retinoblastoma continues to be inactive.

   Discussion Top

This report presents a rare occurrence of CML in a 3-year-old child treated for bilateral retinoblastoma.

Patients with bilateral retinoblastoma have a germline mutation of the RB1 gene and so are at high lifetime risk of developing second primary nonocular tumors after the initial diagnosis of retinoblastoma. More than 50% of the second nonocular primary tumors are bone or soft tissue tumors.[3] Acute hematological malignancies occur rarely, and the risk is known to be magnified by exposure to radiation and chemotherapy.[3],[7]

Leukemias in children are mostly acute and lymphoid in origin. CML accounts for only 1.5% of all leukemias.[8] Genetic susceptibility of the retinoblastoma patients to second primary nonocular tumors may play a major role in their occurrence, but the RB1 gene is thought to have no role in converting a hematopoietic cell into a malignant one. Marees et al.[9] reviewed the records of 668 retinoblastoma survivors diagnosed between 1945 and 2005 in the Dutch registry for second primary nonocular tumors with a median follow-up period of 21.9 years. The authors found only two cases of leukemia, and these two were in the nonhereditary retinoblastoma group. This supports the notion that leukemia might not be a second primary tumor related to genetic susceptibility alone but rather a condition occurring due to an interplay of various factors including the presence of the RB1 gene defect, chemoradiotherapy, and age at administration. Etoposide, in particular, is known to predispose to leukemia, usually of an acute type with short latency, and is dose dependent.[7] Most patients in the cohort reported by Gombos et al. were administered high-dose adjuvant chemotherapy.[7]

There is only one reported case in the literature of CML in a patient with bilateral retinoblastoma.[10] The patient developed CML over 20 years following treatment and responded well to dasatinib. The authors speculate that the CML was related to external beam radiotherapy. Our patient developed CML 2 years after the completion of chemotherapy and did not receive any radiotherapy. Treatment with dasatinib achieved a complete molecular therapeutic response. However, we cannot rule out the possibility that CML may well have resulted from a de novo mutation in the bone marrow.

   Conclusion Top

We have reported CML in a child with bilateral retinoblastoma treated with chemoreduction. Further research is warranted to ascertain whether treated retinoblastoma patients are at increased risk for CML compared to the general population. Given the risk of leukemia related to chemotherapy, long term, and close monitoring of retinoblastoma patients who have received systemic chemotherapy with serial blood tests are mandatory.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.


We would like to thank the staff at the Pediatric Ophthalmology Unit at Sultan Qaboos University Hospital.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

   References Top

Kivelä T. The epidemiological challenge of the most frequent eye cancer: Retinoblastoma, an issue of birth and death. Br J Ophthalmol 2009;93:1129-31.  Back to cited text no. 1
Friend SH, Bernards R, Rogelj S, Weinberg RA, Rapaport JM, Albert DM, et al. A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma. Nature 1986;323:643-6.  Back to cited text no. 2
Woo KI, Harbour JW. Review of 676 second primary tumors in patients with retinoblastoma: Association between age at onset and tumor type. Arch Ophthalmol 2010;128:865-70.  Back to cited text no. 3
Phillips RA, Gill RM, Zacksenhaus E, Bremner R, Jiang Z, Sopta M, Gallie BL, Hamel PA. Why don't germline mutations in RB1 predispose to leukemia? Curr Top Microbiol Immunol. 1992;182:485-91. doi: 10.1007/978-3-642-77633-5_61. PMID: 1490389.  Back to cited text no. 4
Richter S, Vandezande K, Chen N, Zhang K, Sutherland J, Anderson J, et al. Sensitive and efficient detection of RB1 gene mutations enhances care for families with retinoblastoma. Am J Hum Genet 2003;72:253-69.  Back to cited text no. 5
Shields CL, Fulco EM, Arias JD, Alarcon C, Pellegrini M, Rishi P, et al. Retinoblastoma frontiers with intravenous, intra-arterial, periocular, and intravitreal chemotherapy. Eye (Lond) 2013;27:253-64.  Back to cited text no. 6
Gombos DS, Hungerford J, Abramson DH, Kingston J, Chantada G, Dunkel IJ, et al. Secondary acute myelogenous leukemia in patients with retinoblastoma: Is chemotherapy a factor? Ophthalmology 2007;114:1378-83.  Back to cited text no. 7
Coebergh JW, Reedijk AM, de Vries E, Martos C, Jakab Z, Steliarova-Foucher E, et al. Leukaemia incidence and survival in children and adolescents in Europe during 1978-1997. Report from the automated childhood cancer information system project. Eur J Cancer 2006;42:2019-36.  Back to cited text no. 8
Marees T, Moll AC, Imhof SM, de Boer MR, Ringens PJ, van Leeuwen FE. Risk of second malignancies in survivors of retinoblastoma: More than 40 years of follow-up. J Natl Cancer Inst 2008;100:1771-9.  Back to cited text no. 9
Kamitori T, Umeda K, Tasaka K, Ogata H, Mikami T, Kato I, et al. Chronic myeloid leukemia following treatment for bilateral retinoblastoma. Pediatr Blood Cancer 2018;65:e27107.  Back to cited text no. 10


  [Figure 1], [Figure 2]

  [Table 1]


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