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Second primary malignancies in retinoblastoma patients treated with intra-arterial chemotherapy: the first 10 years
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  • Published on:
    AML and metastatic risk after ophthalmic artery chemosurgery for retinoblastoma
    • GUILLERMO L CHANTADA, Pediatric Oncologist Hospital JP Garrahan, Buenos Aires, Argentina and Hospital Sant Joan de Deu, Barcelona, Spain
    • Other Contributors:
      • PAULA S. SCHAIQUEVICH, PhD, Pharmacist

    We would like to add some data to this interesting discussion about the impact of ophthalmic artery chemosurgery or intra-arterial chemotherapy (OAC) in the occurrence of secondary malignancies in children with retinoblastoma with germline mutations of the Rb1 gene.
    The discussion about the incidence of secondary leukemia is an important one. Secondary leukemias usually present early in the patient follow-up, usually around 2-3 years. Systemic chemotherapy has been implicated in their occurrence since, they were not identified as a common secondary malignancy in patients with retinoblastoma not receiving chemotherapy1. Their occurrence is low1, but as the case Dr Meadows and Lahey report are usually refractory to treatment and usually fatal. In our series of patients treated with systemic chemoreduction for conservative therapy from Argentina, secondary AML was the most common fatal secondary malignancy with a total of 2 out of 129 cases. We had a third case in a child receiving chemotherapy for extraocular disease, similarly to Dr Meadows and Lahey’s case2. In our current, yet unpublished results with ophthalmic artery chemosurgery, we had no case of secondary AML , in 71 consecutive cases with bilateral retinoblastoma treated with OAC with a median follow-up of 42 months. Secondary AML has been widely reported as a complication of systemic chemotherapy in pediatric oncology patients 3 including those receiving epipodophillotoxins 4and also alkylating agents5. Cum...

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    Conflict of Interest:
    None declared.
  • Published on:
    Response to AML after OAC
    • David H. Abramson, Ocular Oncologist Memorial Sloan Kettering Cancer Center, New York, NY USA
    • Other Contributors:
      • Larissa A. Habib, Ophthalmologist
      • Jasmine H. Francis, Ocular Oncologist
      • Armida WM Fabius, PhD
      • Ira J. Dunkel, Oncologist
      • Y. Pierre Gobin, Interventional Radiologist

    Dear Sir,

    We are writing this letter in response to a “letter to the editor” from Drs. Leahey and Meadows about our recently published paper “Second primary malignancies in retinoblastoma patients treated with intra-arterial chemotherapy: the first 10 years”.1 There are a number of incorrect statements in their letter and we hope this letter will clarify those errors made by them.

    1) Drs. Leahey and Meadows state that…”the author’s report is profoundly misleading with regard to the risk of SPMs following OAC”. To prove that they then state that the median follow-up range is 2.5 years with a maximum follow-up of 12 years. How is that “profoundly misleading”? In the same paragraph they then state that patients failing OAC required radiation therapy and suggest that all of these second neoplasms are a consequence of radiation. That is not true. In our paper (page 273, Table 3) we documented that not one of the children who developed a second tumor had received radiation. How could radiation be the cause of a second tumor if the patients never received radiation? Dr. Leahey and Meadows also wrote that…”patients failing OAC require radiation”. That’s not true. On page 272 we stated that…”patients who received external beam radiation prior to presentation at our clinic were excluded from analysis”. None of the patients in this series received radiation after OAC and no patient in our center has received radiation in the past 10 years. We do not dispute that radia...

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    Conflict of Interest:
    None declared.
  • Published on:
    Acute Myeloid Leukemia following OAC
    • Ann Leahey, MD, Pediatric Oncologist Children's Hospital of Philadelphia
    • Other Contributors:
      • Anna Meadows, MD, Pediatric Oncologist

    Having read the article of secondary primary malignancies (SPM) in patients treated with ophthalmic artery chemosurgery (OAC) (1), we wish to update Dr. Habib’s report. A patient with unilateral Group D heritable retinoblastoma (RB) treated by their team with 5 OAC treatments in 2012 through 2013 developed acute myeloid leukemia (AML) on 4/26/2017 and died 3 months later.
    Following an intraocular recurrence after OAC and subsequent enucleation the patient’s care was transferred to our institution. Despite adjuvant chemotherapy he developed widespread bone and marrow metastases 8 months after enucleation. He then underwent intensive chemotherapy and an autologous stem cell transplant. Twenty eight months later he developed AML with a fms-like tyrosine kinase 3 (FLT3) mutation. Melphalan administered during all OAC treatments and the drugs administered following that failure must be implicated in this outcome (2). By failing to eradicate retinoblastoma, metastatic disease ensued requiring further treatment and subsequently, AML.
    The author’s report is profoundly misleading with regard to the risk of SPMs following OAC. Although the maximum period of follow-up is 12 years, the median is 2.5 years. Patients failing OAC required radiation therapy and are known to be 3 times more likely to develop additional cancers (3). We await that follow-up.
    The goal of RB care is cure. This patient’s course illustrates the danger of failing to prevent metastatic disease wi...

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    Conflict of Interest:
    None declared.