Acute myeloid leukemia following radioactive iodine therapy for papillary carcinoma of the thyroid/Tiroid papiller karsinomu icin verilen radyoaktif iyot tedavisi sonrasi akut miyeloid losemi.
Abstract: Radioactive iodine (RAI) therapy plays an important role in the management of thyroid malignancies. Leukemia is a very rare complication of radioactive therapy. There are very few case reports with doses below 100 mCi causing leukemia. We report a case of papillary carcinoma of the thyroid treated with 80 mCi RAI who later developed acute myeloid leukemia. Thus, all patients with thyroid carcinoma treated with RAI should undergo periodic hematological examinations irrespective of RAI dose.

Key words: Radioactive iodine, thyroid carcinoma, acute myeloid leukemia

Radyoaktif iyot (RAI) tedavisi tiroid malignitelerinin yonetiminde onemli bir rol oynamaktadir. Losemi, radyoaktif tedavinin cok nadir bir komplikasyonudur. 100mCi altindaki dozlarin losemiye neden oldugunu bildiren cok az olgu raporu vardir. Biz, 80 mCi RAI ile tedavi edilen ve sonrasinda akut miyeoid losemi gelisen bir tiroid papiller karsinom olgusunu bildiriyoruz. Bu nedenle uygulanan RAI dozuna bakilmaksizin, RAI ile tedavi goren butun tiroid karsinomlu hastalarin periyodik hematolojik tetkikleri yapilmalidir.

Anahtar kelimeler: Radyoaktif iyot, tiroid karsinomu, akut miyeloid losemi
Article Type: Case study
Subject: Radiotherapy (Complications and side effects)
Thyroid cancer (Diagnosis)
Thyroid cancer (Care and treatment)
Thyroid cancer (Case studies)
Authors: Ankit, Jain
Premalata, C.S.
Saini, K.V.
Bapsy, P.P.
Sajeevan, K.V.
Singh, Tejinder
Batra, Ullas
Govind, Babu
Dasappa, Lokanatha
Atilli, Suresh
Permeshwar, R.
Pub Date: 06/01/2009
Publication: Name: Turkish Journal of Hematology Publisher: Aves Yayincilik Audience: Academic Format: Magazine/Journal Subject: Health Copyright: COPYRIGHT 2009 Aves Yayincilik ISSN: 1300-7777
Issue: Date: June, 2009
Geographic: Geographic Scope: India Geographic Code: 9INDI India
Accession Number: 202701653
Full Text: Introduction

Radioactive iodine (RAI) is one of the most important modalities in the management of thyroid-related malignancies. All patients who have undergone a total or near-total thyroidectomy for a papillary or follicular carcinoma larger than 1 to 1.5 cm should be considered candidates for RAI ablation(1). RAI ablation decreases tumor recurrence, development of distant metastases and cancer death [2].

Leukemia is a rare complication of RAI therapy [3-6]. In the initial reports [3,6], almost all the cases have occurred after cumulative dosage of more than 800 mCi, in patients more than 50 years of age and with intervals between dosage of RAI less than 12 months.

We now report the occurrence of acute myeloid leukemia in a 45-year-old male 17 months after receiving a total dose of 80 mCi. To our best knowledge, this is the first case of acute myeloid leukemia following RAI therapy for thyroid carcinoma with a dose below 100 mCi, although doses as low as 27 mCi have been reported in relation to acute myeloid leukemia following RAI treatment for hyperthyroidism [7].

Case Report

A 45-year-old male presented to the Nuclear Medicine Department of Kidwai Memorial Institute of Oncology in August 2005 with a history of near-total thyroidectomy for a nodular lesion in the thyroid three months before. The histopathology report was suggestive of papillary carcinoma thyroid. The patient had no past history of radiation exposure. There was no history of thyroid disease in his family. His clinical examination was within normal limits except for the surgical scar on his neck. He underwent the initial workup, which included hemogram, biochemistry, thyroid profile, chest X-ray, abdominal and pelvic ultrasound and histopathological review of slides. All the initial workup was within normal limits and review slides were consistent with papillary carcinoma of the thyroid.

The patient was then subjected to large-dose thyroid scan with 5 mCi of RAI, which showed homogeneous uptake in the thyroid region without any cold areas.

As the patient was an ideal candidate for RAI therapy, he received a single dose of 75 mCi for ablation of residual thyroid tissue as per the institutional policy. Further hospital stay of the patient was uneventful, and two days later suppressive dose of exogenous thyroid hormone was started. The patient was discharged and was advised to return for follow-up after one month.

The patient did not return for follow-up and presented in June 2007 with a one- week history of high-grade fever, bleeding gums and significant weight loss. Laboratory examination revealed a white blood cell count of 24,400/[micro]L (differential count: neutrophils 13%, lymphocytes 25%, and peripheral blasts 50%). Hemoglobin was 8.7 g% and platelet count was 76,000/[micro]L. A bone marrow aspirate and biopsy were consistent with acute myeloid leukemia (AML M5a of French-American-British [FAB] Classification). The blasts were nonspecific esterase-positive. Cytogenetics was suggestive of normal karyotype. The various treatment options were explained to the patient, but he left against medical advice.

Discussion

Leukemia is a very rare complication of RAI therapy, but there are still concerns about its possible carcinogenic effects. Transient leukopenia and thrombocytopenia were observed after RAI administration [8,9]. Bone marrow recovery after RAI treatment is delayed after 45 years of age. Bone marrow suppression after RAI treatment is divided into four grades according to World Health Organization (WHO) classification. The fourth grade is bone marrow aplasia and acute myeloid leukemia. A German cohort studied 107 patients with thyroid carcinoma with bone metastasis. In that study, four patients developed acute myeloid leukemia. These patients received maximum dose of RAI (11.1 GBq) within a very short interval and showed high uptake in bone metastasis [10].

Various mechanisms, like radioiodine-induced sub-lethal damage to bone marrow, which leads to chromosomal aberrations and oncogene activation followed by malignant transformation, are postulated [11,12]. Though acute myeloid leukemia is the commonest observed type of leukemia after RAI treatment [12], there are very few case reports with acute myeloid leukemia developed at doses <100 mCi (Table 1).

There are also case reports of acute lymphoblastic leukemia including Ph+ ALL following RAI therapy [17].

As in the literature, at least six cases including the pre-sent case showed that patients exposed to very low doses of RAI therapy (below 100mCi) can develop leukemia Regular follow-up is mandatory for all these patients irrespective of RAI dose received. As the advantages of RAI therapy have been proven beyond doubt in thyroid malignancies, all patients should receive the benefits of this time-tested therapy. The loss of life caused by recurrence of thyroid carcinoma exceeds that from leukemia by four- to forty-fold [18].

In conclusion, the benefits of RAI therapy outweigh the risk of acute leukemia in patients with papillary carcinoma of the thyroid. However, the patient should be followed regularly both clinically and hematologically for development of leukemia.

Received: January 20, 2008 Accepted: September 10, 2008

Gelis tarihi: 20 Ocak 2008 Kabul tarihi: 10 Eylul 2008

References

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[2.] Taylor T, Specker B, Robbins J, et al. Outcome after treatment of high-risk papillary and non-Hurthle-cell follicular thyroid carcinoma. Ann Intern Med 1998;129:622.

[3.] Edmonds CJ, Smith T. The long-term hazards of treatment of thyroid cancer with radioiodine. Br J Radiol 1986;59:45-51.

[4.] Pochin EE. Leukemia following radioiodine treatment of thyrotoxicosis. Br Med J 1960;2:1545-50.

[5.] Pochin EE. Prospects from the treatment of thyroid carcinoma with radioiodine. Clin Radiol 1967;18:113-35.

[6.] Brincker H, Hansen HS, Anderson AP. Induction of leukemia by i-131 treatment of thyroid carcinoma. Br J Cancer 1973;28:232-7.

[7.] Laurenti L, Salutari P, Sica S, Piccirillo N, Zini G, Zollino M, Leone G. Acute myeloid leukemia after iodine-131 treatment for thyroid disorders. Ann Hematol 1998;76:271-2.

[8.] Alexander C, Bader JB, Schaefer A, Finke C, Krish CM. Intermediate and long-term side effects of high-dose radioiodine therapy for thyroid carcinoma. J Nucl Med 1998;39:1551-4.

[9.] Menzel C, Grunwald F, Schomburg A, Palmedo H, Bender H, Spath G, Biersack HJ. "High-dose" radioiodine therapy in advanced differentiated thyroid carcinoma. J Nucl Med 1996;37:1496-503.

[10.] Petrich T, Widjaja A, Musholt TJ, Hofmann M, Brunkhorst T, Ehrenheim C, Oetting G, Knapp WH. Outcome after radioiodine therapy in 107 patients with differentiated thyroid carcinoma and initial bone metastases: side-effects and influence of age. Eur J Nucl Med 2001;28:203-8.

[11.] Weinberg RA. The action of oncogenes in the cytoplasm and nucleus. Science 1985;230:770-6.

[12.] Chow SM. Side effects of high-dose radioactive iodine for ablation or treatment of differentiated thyroid carcinoma. J HK Coll Radiol 2005;8:127-35.

[13.] Walgraeve D, Verhoef G, Stul M, Cassiman JJ, Mecucci C, Van den Berghe H, Boogaerts M. 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.

[14.] 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 1995;43:651-4.

[15.] Kolade VO, Bosinski TJ, Ruffy EL. Acute promyelocytic leukemia after iodine-131 therapy for Graves' disease. Pharmacotherapy 2005;25:1017-20.

[16.] Beierwaltes WH, Rabbani R, Dmuchowski C, Lloyd RV, Eyre P, Mallettes S. An analysis of "ablation of thyroid remnants" with I-131 in 511 patients from 1947-1984: experience from University of Michigan. J Nucl Med 1984;25:1287-93.

[17.] Piccirillo N, Sora F, Laurenti L, Sica S, Chiusolo P, Leone G. Ph+ acute lymphoblastic leukemia after iodine-131 treatment for thyroid cancer Haematologica 1999;11:1051-2.

[18.] Wong JB, Kaplan MM, Meyer KB, Pauker SG. Ablative radio active iodine therapy for apparently localized thyroid carcinoma. A decision analytic prospective. Endocrinol Metabol Clinc North Am 1990;19:741-60.

Jain Ankit (1), Premalata CS (2), Saini KV (1), Bapsy PP (1), Sajeevan KV (1), Tejinder Singh (1), Ullas Batra (1), Babu Govind (1), Lokanatha Dasappa (1), Suresh Atilli (1), Permeshwar R (3)

(1) Department of Medical Oncology, Kidwai Memorial Institute of Oncology, Bangalore, India

(2) Department of Pathology, Kidwai Memorial Institute of Oncology, Bangalore, India

(3) Department of Nuclear Medicine, Kidwai Memorial Institute of Oncology, Bangalore, India

Address for Correspondence: Ankit Jain, 16th Cross,9th Main House No.23 1st Floor, Ramaswamy Layout, Lakkasandra 560030 Bangalore, India Phone: +91-80-22485876 E-mail: drankitjain@rediffmail.com
Table 1. Case reports of Leukemia with RAI dose below 100mCi

Authors                   Age (yr)/              i-131 dose
                          gender                 (mCi)

Walgraeve D et al. [13]   37/M                    30
Shimon et al. [14]        35/M                    56
Laurenti et al. [7]       45/F                    27
Kolade et al. [15]        51/F                    22.1
Jain et al.               46/M                    80
Beierwaftes [16]          NA                     100

Authors                   Time interval          External
                          from first dose        radiation

Walgraeve D et al. [13]   5 years                -
Shimon et al. [14]        4 years                -
Laurenti et al. [7]       14 months              -
Kolade et al. [15]        27 months              -
Jain et al.               17 months              -
Beierwaftes [16]          1 year                 -

Authors                   Indication for
                          RAI therapy

Walgraeve D et al. [13]   Papillary carcinoma
Shimon et al. [14]        Papillary carcinoma
Laurenti et al. [7]       Hyperthyroidism
Kolade et al. [15]        Hyperthyroidism
Jain et al.               Papillary carcinoma
Beierwaftes [16]          Papillary carcinoma

Authors                   Type of leukemia

Walgraeve D et al. [13]   Chronic myeloid leukemia
Shimon et al. [14]        Chronic myeloid leukemia
Laurenti et al. [7]       Acute myeloid leukemia (FAB M2)
Kolade et al. [15]        Acute promyelocyoc leukemia (FAB M3)
Jain et al.               Acute myeloid leukemia (FAB M5a)
Beierwaftes [16]          Acute granulocyoc leukemia
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