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 Table of Contents  
Year : 2016  |  Volume : 5  |  Issue : 3  |  Page : 246-249

Acute myeloid leukemia following radioiodine therapy: Case report and brief literature review

Department of Hematology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India

Date of Web Publication9-May-2016

Correspondence Address:
Ruchi Gupta
Department of Hematology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, C Block, Rai Bareily Road, Lucknow - 226 014, Uttar Pradesh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2278-0513.182065

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Radioiodine (RI) has been widely used in treatment of hyperthyroidism and thyroid cancer. The development of acute or chronic leukemia is a very rare complication of RI therapy. Here, we report two cases of acute myeloid leukemia occurring after the completion of RI therapy for follicular thyroid carcinoma along with a brief review of literature.

Keywords: Acute leukemia, radioiodine, review

How to cite this article:
Gupta R, Aggarwal G, Rahman K, Singh MK, Nityanand S. Acute myeloid leukemia following radioiodine therapy: Case report and brief literature review. Clin Cancer Investig J 2016;5:246-9

How to cite this URL:
Gupta R, Aggarwal G, Rahman K, Singh MK, Nityanand S. Acute myeloid leukemia following radioiodine therapy: Case report and brief literature review. Clin Cancer Investig J [serial online] 2016 [cited 2020 Apr 10];5:246-9. Available from:

  Introduction Top

Radioiodine (131 I) (RI) has been used in the treatment of thyroid cancer to eliminate residual thyroid tissue after thyroidectomy and to treat metastatic disease. Leukemia is an uncommon complication following exposure to ionizing radiation, and there are very few case reports documenting the occurrence of acute myeloid leukemia (AML), subsequent to RI therapy.[1],[2],[3],[4],[5],[6],[7],[8],[9] We hereby document two patients of follicular thyroid carcinoma (FTC) who developed AML after 3 years and 1 year completion of RI therapy.

  Case Reports Top

Case 1

A 56-year-old female presented with complaints of fatigue, loss of weight, and pallor to the hematology outpatient department (OPD) in 2011. She had undergone total thyroidectomy in 2004 for FTC. She had received 3 cycles of low-dose RI therapy (100 mCi) for 3 years. Simultaneously, she was administered high-dose RI (125 mCi) twice, during management. The cumulative dose received during the treatment period, until 2008, was 550 mCi. Her current hematological investigations in 2011 revealed pancytopenia and a bone marrow aspiration was performed. Bone marrow was found to be hypocellular [Figure 1], inset] with reduced normal hematopoiesis along with proliferation of approximately 60% blasts [Figure 1]. Immunophenotyping using flow cytometry showed these blasts to be positive for CD13, CD33, CD34, CD117, and human leukocyte antigens-DR, thus confirming a diagnosis of AML. Conventional cytogenetics showed a normal karyotype (46, XX). She was treated with standard doses of cytarabine and daunorubicin, using 3 + 7 induction protocol and was in morphological remission postinduction. Thereafter, the patient lost to follow-up.
Figure 1: Leishman-stained bone marrow aspirate smears showing proliferation of large blasts with opened up chromatin and scant to moderate amount of cytoplasm. The inset shows a hypocellular marrow particle

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Case 2

A 58-year-old male presented with weakness, petechial rashes to the hematology OPD in 2011. He had history of FTC with scalp metastases 8 years back. After thyroidectomy, he received low-dose RI therapy with I 131 and remnant ablation high-dose RI (6 monthly) till December 2008, followed by low-dose therapy till October 2010. The total amount of RI received was 1050 mCi. A complete blood count presently showed bicytopenia with hemoglobin of 4.8g/dl, platelet count (16,000/cumm), total leukocyte count of 6800/cumm with 25% circulating blasts. Bone marrow aspiration showed hypercellular marrow with marked erythroid hyperplasia. There was reversal of myeloid to erythroid ratio, with megaloblastic erythroid maturation and features of dyserythropoiesis [Figure 2]. There were approximately 40% blasts among the nonerythroid cell population. Flow cytometry showed positivity for CD13, CD34, CD33, CD117, CD2, and CD71 in the blasts, thus confirming a diagnosis of AML, morphologically consistent with FAB AML-M6. The patient was lost to follow-up.
Figure 2: Leishman-stained bone marrow smears showing erythroid hyperplasia with dyserythropoiesis, and distinct population of blasts with opened up chromatin and 2–3 prominent nucleoli

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  Discussion Top

Leukemia as a second malignancy after treatment of thyroid cancer is rare and was first reported in 1955.[1] Majority of the cases of leukemia documented in literature are of acute leukemia, both myeloid and lymphoid,[1],[2],[3],[4],[5],[6],[7],[8],[9],[10],[11],[12],[13],[14],[15],[16] followed by chronic myeloid leukemia [17],[18],[19],[20],[21] and rarely chronic lymphocytic leukemia. The overall incidence of acute leukemia following RI therapy, however, is low as documented by Menzel et al.[22] and Chow.[23] Chow in his cohort of 1348 patients did not observe any case of acute leukemia after a mean dose of 3.4 GBq (91.8 mCi) in papillary thyroid carcinoma and 4.14 GBq (111.89 mCi) in FTC. Similarly, de Vathaire et al.[24] in their study followed 1497 patients receiving an average of 7.2 GBq (194.59 mCi) of RI but found no instances of leukemia. A brief summary of the cases of acute leukemia developing in patients treated with 131 I for thyroid disorders has been tabulated in [Table 1]. In a recent study by Schroeder et al.,[15] they found 39 patients within a cohort of 3845 patients obtained from Dusseldorf Myelodysplastic Syndromes Registry in Germany, over approximately 30 years, who had developed myeloid neoplasm following RI therapy. These 39 patients comprised 18 patients of AML and 21 patients of myelodysplastic syndrome. The median time interval of progression to hematological abnormality was about 6.6 years (6–440 months). They also observed chromosomal aberrations in 68% of their cases. In our patients, the latency period was 3 years and 1 year, respectively, and conventional cytogenetics showed normal karyotype.
Table 1: Brief review of patients with acute leukemia following radioiodine therapy

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It has been observed that leukemias following RI therapy usually occur after cumulative doses higher than 800 mCi [6],[8] although there have been cases of acute leukemia developing after dosage of 150 mCi [9] and as low as 22.1 mCi.[11] This suggests that other factors may be interplaying in leukemogenesis. The exact etiopathogenesis of leukemias induced by RI therapy is not well-understood although its clastogenic effects and induction of chromosomal aberration, specifically of chromosome 17, are well documented in literature.[25],[26] It is believed that 131 I at any dose could cause sublethal damage to the bone marrow, and individual susceptibility plays an important role in patients developing leukemia after 131 I treatment. Thus, it is recommended that the bone marrow should not receive a total dose which exceeding 1000 mCi, and there should be an interval of at least 1 year between the doses.[7]

  Conclusion Top

Though the use of 131 I appears to be increasing even for nonmalignant thyroid diseases and its benefits in the treatment of hyperthyroidism and thyroid cancer are proven, these patients require a regular follow-up even after completion of therapy. Although the development of the secondary malignancies can be due to aging or other causes rather than exposure to 131 I treatment, there is sufficient cumulative evidence suggesting the role of RI therapy in leukemogenesis. Thus, a strict hematological follow-up is warranted in such patients, for early detection of myelodysplastic syndromes, leukemias, or other hematological disorders.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Blom PS, Querido A, Leeksma CH. Acute leukaemia following x-ray and radioiodine treatment of thyroid carcinoma. Br J Radiol 1955;28:165-6.  Back to cited text no. 1
McCormack KR, Sheline GE. Leukemia after radioiodine therapy for hyperthyroidism. Calif Med 1963;98:207-9.  Back to cited text no. 2
Brincker H, Hansen HS, Andersen AP. Induction of leukemia by 131-I treatment of thyroid carcinoma. Br J Cancer 1973;28:232-7.  Back to cited text no. 3
Advani SH, Hege UP. Leukemia after 131I treatment of thyroid cancer – Comments on the article 'Second cancer following chemotherapy and radiotherapy – An epidemiological perspective' by J. Kaldor. Acta Oncol 1992;31:65.  Back to cited text no. 4
Hall P, Boice JD Jr., Berg G, Bjelkengren G, Ericsson UB, Hallquist A, et al. Leukaemia incidence after iodine-131 exposure. Lancet 1992;340:1-4.  Back to cited text no. 5
Richards EM, Marcus RE. Acute promyelocytic leukaemia following radioiodine therapy. Clin Lab Haematol 1993;15:55-8.  Back to cited text no. 6
Bitton R, Sachmechi I, Benegalrao Y, Schneider BS. Leukemia after a small dose of radioiodine for metastatic thyroid cancer. J Clin Endocrinol Metab 1993;77:1423-6.  Back to cited text no. 7
Laurenti L, Salutari P, Sica S, Piccirillo N, Zini G, Zollino M, et al. Acute myeloid leukemia after iodine-131 treatment for thyroid disorders. Ann Hematol 1998;76:271-2.  Back to cited text no. 8
Roldán Schilling V, Fernández Abellán P, Domínguez Escribano JR, Rivas González C, Mut Barberá E, Calatayud Cendra R. Acute leukemias after treatment with radioiodine for thyroid cancer. Haematologica 1998;83:767-8.  Back to cited text no. 9
Piccirillo N, Sorà F, Laurenti L, Sica S, Chiusolo P, Leone G. Ph+acute lymphoblastic leukemia after iodine-131 treatment for thyroid cancer. Haematologica 1999;84:1050-1.  Back to cited text no. 10
Kolade VO, Bosinski TJ, Ruffy EL. Acute promyelocytic leukemia after iodine-131 therapy for Graves' disease. Pharmacotherapy 2005;25:1017-20.  Back to cited text no. 11
Grudeva-Popova J, Yaneva M, Zisov K, Ananoshtev N. Therapy-related acute promyelocytic leukemia after treatment with radioiodine for thyroid cancer: Case report with literature review. J BUON 2007;12:129-32.  Back to cited text no. 12
Focosi D, Galimberti S, Petrini M. Acute myeloid leukemia and follicular lymphoma after very low dose radioiodine therapy for thyroid diseases. Haematologica 2007;92:e96-7.  Back to cited text no. 13
Ankit J, Premalata CS, Saini KS, Bapsy PP, Sajeevan KV, Singh T, et al. Acute myeloid leukemia following radioactive iodine therapy for papillary carcinoma of the thyroid. Turk J Hematol 2009;26:97-9.  Back to cited text no. 14
Schroeder T, Kuendgen A, Kayser S, Kröger N, Braulke F, Platzbecker U, et al. Therapy-related myeloid neoplasms following treatment with radioiodine. Haematologica 2012;97:206-12.  Back to cited text no. 15
Gilabert M, Prebet T. Acute leukemia arising after radioiodine treatment for thyroid cancer. Haematologica 2012;97:e28-9.  Back to cited text no. 16
Walgraeve D, Verhoef G, Stul M, Cassiman JJ, Mecucci C, Van den Berghe H, et al. Chronic myelogenous leukemia after treatment with 131I for thyroid carcinoma. Report of a case and review of the literature. Cancer Genet Cytogenet 1991;55:217-24.  Back to cited text no. 17
Shimon I, Kneller A, Olchovsky D. Chronic myeloid leukaemia following 131I treatment for thyroid carcinoma: A report of two cases and review of the literature. Clin Endocrinol (Oxf) 1995;43:651-4.  Back to cited text no. 18
Alfiar F, Amato D, Lipton JH. Chronic myeloid leukemia in a woman with papillary carcinoma of the thyroid treated with radioactive iodine. Leuk Lymphoma 1997;27:365-7.  Back to cited text no. 19
Pavithran K, Doval DC. Chronic myeloid leukemia in a man with papillary carcinoma of the thyroid treated with radioactive iodine. Am J Clin Oncol 2005;28:216.  Back to cited text no. 20
Wang KL, Lin LY, Chen PM, Lin HD. Chronic myeloid leukemia after treatment with 131 for thyroid carcinoma. J Chin Med Assoc 2005;68:230-3.  Back to cited text no. 21
Menzel C, Grünwald F, Schomburg A, Palmedo H, Bender H, Späth G, et al. “High-dose” radioiodine therapy in advanced differentiated thyroid carcinoma. J Nucl Med 1996;37:1496-503.  Back to cited text no. 22
Chow SM. Side effects of high-dose radioactive iodine for ablation or treatment of differentiated thyroid carcinoma. J Hong Kong Coll Radiol 2005;8:127-35.  Back to cited text no. 23
de Vathaire F, Schlumberger M, Delisle MJ, Francese C, Challeton C, de la Genardiére E, et al. Leukaemias and cancers following iodine-131 administration for thyroid cancer. Br J Cancer 1997;75:734-9.  Back to cited text no. 24
Lopes Rodrigues C, Corbo R, Proença Martins FP, Barbosa da Fonseca LM, Aranha IP, Gutfilen B. Low dosage of 131iodine effects on chromosomes. Yale J Biol Med 2003;76:109-14.  Back to cited text no. 25
Ramírez MJ, Puerto S, Galofré P, Parry EM, Parry JM, Creus A, et al. Multicolour FISH detection of radioactive iodine-induced 17cen-p53 chromosomal breakage in buccal cells from therapeutically exposed patients. Carcinogenesis 2000;21:1581-6.  Back to cited text no. 26


  [Figure 1], [Figure 2]

  [Table 1]

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1 Iodine-131
Reactions Weekly. 2018; 1715(1): 141
[Pubmed] | [DOI]


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