The changes in complete blood count in thyroid cancer patients treated with radioactive iodine ablation therapy / Radyoaktif iyot tedavisi alan tiroid kanserli hastalarda tam kan sayimi degisiklikleri.
Objective: The aim of this study was to evaluate the effect of radioactive iodine (RAI) ablation therapy on the complete blood count (CBC) in thyroid cancer patients.
Materials and Methods: One hundred sixty four patients undergoing RAI ablation therapy after total thyroidectomy were included. CBC results were available from the patients' medical records at the time of ablation and at the 1st, 6th, and 12th months after RAI therapy.
Results: Hemoglobin (Hb), white blood cell (WBC) and platelet (Plt) values were significantly lower than baseline at 1 month after treatment (p<0.0001). Hb and WBC values were increased at the 6th month and at the 1st year. Plt values increased at the 6th month but had decreased again at the Pt year. The values were usually in normal ranges except in the patients with low pretreatment Hb and WBC values.
Conclusion: RAI ablation therapy in thyroid cancer patients is a safe treatment modality without any serious or persistent hematological side effects. (Turk J Hematol 2010; 27: 269-74)
Key words: Radioactive iodine therapy, complete blood count, thyroid cancer
Received: June 1, 2010
Accepted: July 26, 2010
Amac: Bu calismain amaci total tiroidektomi sonrasi artakalan tiroid dokusu icin radyoaktif iyot (RAI) tedavisi alan tiroid kanserli hastalarda tam kan sayimindalci degisimleri degerlendimek.
Yontem ve Gerecler: Total tiroidektomi sonrasi RAI tedavisi almis 164 hasta degerlendirildi. Hastalarin tedaviden once ve tedavi sonrasi 1. ay, 6. ay ve 12. ay hemoglobin (Hb), lokosit (WBC) ve trombosit (Plt) duzeyleri degerlendirildi.
Bulgular: RAI tedavisinden 1 ay sonra Hb, WBC ve Plt degerlerinde anlami bir azalma izlendi. Plt sayisi 6. ayda duzelirken 1. yilda tekrar azaldi. Buna karsilk Hb ve WBC degerlerinde ilk ayda gozlenen azalma 6. ay ve 1. yilda izlenmedi. Ancak izlenen bu degisiklikler tedavi oncesi degerleri dusuk hastalar haric normal sinirlar icindeydi.
Sonuc: Tiroid kanserli hastalarda RAI tedavisi ciddi bir hematolojik yan etkiye yol acmaksizin guvenilir bir tedavi yontemidir. (Turk J Hematol 2010; 27: 269-74)
Anahtar kelimeler: Radioaktif iyod tedavi, tam kan sayimi, tiroid kanseri
Gelis tarihi: 1 Haziran 2010
Kabul tarihi: 26 Temmuz 2010
Treatment of differentiated thyroid cancer (DTC) with radioactive iodine (RAI) is a standard procedure for the ablation of remnant thyroid tissue following surgery and for the treatment of iodine-avid metastases (1). Usually, high doses of RAI (100-150 mCi) are used for total ablation of thyroid remnants. RAI treatments may be repeated especially in metastatic patients, and this delivers high cumulative doses to non-thyroid organs. The side effects of RAI treatment may occur in many areas and organ systems. The most common side effect is a decreased saliva production, but severe long-term side effects are rare. Other organ-specific side effects are found in the lacrimal glands, bone marrow, lungs, and reproductive organs. Incidence of secondary malignancies and leukemia might increase with higher RAI doses (2), (3).
Bone marrow suppression can arise after RAI treatment (4). There are many factors that affect the frequency and severity of bone marrow suppression. These include the prescribed and total cumulative RAI doses, frequency of treatments and clearance rate of RAI therapy, and additively, the patient's bone marrow reserve and degree of bone marrow metastases (2). Although bone marrow suppression with repeated high-dose RAI treatments is reported (5), (6), changes in the peripheral complete blood count (CBC) after an initial RAI ablation treatment is not well defined. Therefore, we retrospectively evaluated the hemoglobin (Hb), platelet (Plt) and white blood cell (WBC) counts before ablation and at the 1st month, 6th month and 1St year following initial RAI ablation treatment.
Materials and Methods
One hundred and sixty-four patients undergoing RAI remnant ablation therapy after total thyroidectomy were retrospectively evaluated. Gender, age and demographic characteristics were recorded. The patient's CBC results were available in the medical records at the time of ablation and at the 1st and 6th months and 1st year after RAI therapy. Patients taking any medications known to affect the CBC; having any hematological conditions; and/or receiving a second dose of RAI during the first-year follow-up or external beam radiotherapy or chemotherapy before RAI therapy or within 1 year after ablation were excluded from the study. None of the patients had bone marrow metastases, but one patient had pulmonary metastases and seven patients had lymph node metastases. Levothyroxine (L-T4) and triiodothyronine (L-T3) treatments were discontinued after 4-6 weeks and 2 weeks, respectively, and a low-iodine diet for 2 weeks was recommended before RAI treatment. None of the patients was prepared for RAI ablation with recombinant human thyroid stimulating hormone (rhTSH). After total thyroidectomy, RAI remnant ablation treatment with standard-high RAI doses [3.7-7.4 GBq (100-200 mCi)] was performed in 6-8 weeks. RAI therapy was administered as follows: 122 patients (74.4%), 37 patients (22.6%), and 5 patients (3%) received 100 mCi, 125-150 mCi, and 175-200 mCi, respectively. L-T4 treatment was restarted after 48 hours. Diagnostic imaging with low-dose RAI (2-5 mCi) was performed within 6-12 months. However, no second RAI treatment or radiotherapy was applied during the one-year follow-up. All blood tests were analyzed with Full Automated CBC analyzer (Beckman Coulter LH-750). Hb reference values were 13-17 g/dl and 11.5-16 g/dl for males and females, respectively. WBC and Plt count reference values were 4.8-10.8 x [10.sup.3]/UL and 130-400 x [10.sup.3]/UL, respectively. Written informed consent was obtained from the patients.
Data are presented as the mean[+ or -]standard deviation (SD); medians with ranges are given when appropriate. Continuous variables were compared using repeated measures variance analysis for changing over time. Bonferroni test was used for post-hoc analysis. CBC values between RAI groups were compared by Student's t test. p<0.05 was considered statistically significant. All statistical analyses were performed using SPSS version 13.01 for Windows.
The mean age of patients (24 males, 68 females) was 47[+ or -] 13 years (range: 22-81 years). The baseline characteristics of the patients are presented in Table 1. Median TSH level was 82 mU/L (range: 32-100 mU/L) because of cessation of L-T4 or L-T3 treatments. Hb (Males/Females), WBC, and Plt values were significantly lower than baseline at 1 month after treatment (p <0.0001). Hb and WBC values had increased at the 6th month and 1St year. The decreases in the Hb levels were not different between the male and female patients. Similarly, it was observed that neutrophil and lymphocyte counts decreased equally. Plt values increased at the 6th month, but decreased again at the 1st year (Table 2, Figure la, b). There was no requirement of blood transfusion or febrile neutropenia occurrence in any of the patients. Although all hematological parameters decreased at the 1st month and for Plt also at the 1st year, the values were usually in normal ranges except for those patients with low pretreatment Hb and WBC values. Before treatment, Hb values were low in 21 patients (12.8%, 8 males, 13 females) while WBC values were low in 7 patients (4.3%); no patients had iron, vitamin B 12 or folate deficiency. The change in Hb and WBC values is probably related to the disease status or the medications used before (Table 3). No significant difference in the decreasing rate was found between patients with low pretreatment and normal pretreatment Hb and WBC counts. Similarly, there was no significant difference when comparing patients receiving different doses of RAI therapy. No complications were observed.
Table 1. Baseline characteristics of patients Characteristics Age 47 [+ or -] 13 Histology PTC 152 (92.7%) FTC 11 (6.7%) HCC 1 (0.6%) TNM Stage I 130 (79.3%) II 20 (12.2%) III 13 (7.9%) IV 1 (0.6%) Administered Activity (MBq/mCi) Mean[+ or -]SD 4144 [+ or -] 851 (112.74 [+ or -] 23) Median 3700 (100) Range 3700-7400 (100-200) Post-Therapy Scan Thyroid remnant 156 (95.1%) Lymph node metastases 7 (4.3%) Pulmonary metastases 1 (0.6%) Bone metastases 0 (0%) PTC: Papillary thyroid cancer; FTC: Follicular thyroid carcinoma; HCC: Thyroid carcinoma, Hurthle cell; TNM: TNM staging system (tumor, node, metastasis) Table 2. CBC changes with RAI therapy Pre-treatment 1st Month 6th Month Hb (g/dl)/M Mean [+ or -] SD 13.7[+ or -]1.9 13.3[+ or 13.5[+ or (a), (b) -]1.8 (c), -]1.9 (d) Median 14 13.6 13.8 Range 9.1-16.8 8.8-15.4 7.9-16 Hb (g/dl)/F Mean [+ or -] SD 13.4[+ or -]1.2 6.7[+ or -]1.9 12.6[+ or (a), (b) (a) -]l.l (c), (d) Median 13.2 6.4 12.8 Range 9.4-16.4 2.5-16.7 8.6-15.2 WBC ([10.sup.3]/[mu]L) Mean [+ or -] SD 12.9[+ or -]1.1 6.5[+ or 13.2[+ or -]1 -]2.6 Median 13 6.1 13 Range 9.6-15.4 3.0-28.6 10.5-15.9 N/L 3.9[+ or -] 3.7[+ or 4[+ or 1.5/2.1 [+ or -]1.5/1.6[+ or -]2.4/1.8[+ or -]0.6 -]0.5 -]0.5 Plt ([10.sup.3]/[mu]L) Mean [+ or -] SD 289[+ or -]71 259[+ or -]57 265[+ or -]62 (a), (f), (g) (h) Median 285 258 265 Range 152-538 142-423 134-422 1st Year Hb (g/dl)/M Mean [+ or -] SD 13.8[+ or -]1.9 Median 14 Range 9.1-16.2 Hb (g/dl)/F Mean [+ or -] SD 6.0[+ or -]1.8 (e) Median 5.8 Range 1.7-12.9 WBC ([10.sup.3]/[mu]L) Mean [+ or -] SD 6.5[+ or -]1.7 Median 6.3 Range 3.3-15.7 N/L 4[+ or -]1.5/1.9[+ or -]0.5 Plt ([10.sup.3]/[mu]L) Mean [+ or -] SD 258[+ or -]65 Median 255 Range 135-498 (a.): pre-treatment-1st month p<0.0001; (b.): pre-treatment-6th month p<0.0001; (c.): 1st month-6th month p<0.0001; (d.): 1st month-1st year p<0.0001; (e.): 1st month-1st year p=0.001; (f.): pre-treatment-6th month p<0.0001; (g.): pre-treatment-lst year p<0.0001; (h.): 6th month-1st year p=0.009. Hb/M: Hemoglobin/males; Hb/F: Hemoglobin/females; WBC: White blood cell; Pit: Platelets; N/L: Neutrophils/lymphocytes Table 3. CBC changes in the patients with low Hb and WBC values Pre-treatment 1st 6th 1st Year Month Month Hb (g/dl)/M Mean [+ or -] SD 11.5[+ or 11.3[+ or 11.3[+ or 12.1[+ or -]1.3 -]1.4 -]1.9 -]1.3 Median 11.7 11.3 11.4 12.2 Range 9.1-12.9 8.8-13 7.9-14.1 10.4-14.1 Hb (g/dl)/F Mean [+ or -] SD 10.7[+ or 10.6[+ or 11.2[+ or 11.8[+ or -]0.7 -]1.1 -]1.1 -]1 Median 11 10.9 11.1 11.8 Range 9.4-11.5 8.6-11.9 9.6-13.4 10.5-14.4 WBC ([10.sup.3]/[mu]L) Mean [+ or -] SD 3.4[+ or -]0.5 3.6[+ or 4.4[+ or 4.2[+ or -]0.9 -]0.5 -]0.7 Median 3.4 3.9 4.4 4.2 Range 2.5-4 1.7-4.4 3.5-5.1 3.3-5.3 Hb/M: Hemoglobin/males; Hb/F: Hemoglobin/females; WBC: White blood cell
[FIGURE 1a OMITTED]
[FIGURE 1b OMITTED]
Bone marrow suppression is a serious and, if not diagnosed, potentially life-threatening complication of RAI treatment. Transient leukopenia, anemia and thrombocytopenia may be observed after RAI administration, but severe cytopenia is usually seen with high doses of RAI (>600 mCi) (7). The World Health Organization classification is used for bone marrow suppression after RAI treatment. While mild and reversible blood count alternations are observed in grade I-II, persistent severe cytopenia and aplasia or acute myeloid leukemia are detected in grade III and grade IV, respectively. Although RAI therapy induces chromosome damage in the lymphocytes, the effect of RAI depends on lymphocyte phenotype and RAI activity. Natural killer cells are most sensitive, followed by B lymphocytes and T-helper lymphocytes. However, these do not result clinically in an immunosuppression (8), (9). Severe and permanent bone marrow suppression was reported by Benua et al. (10) in 8 of 59 patients treated with RAI. In the dosimetric evaluations, six of these eight patients received in excess of 3Gy (300 rads) to the blood. When using 2Gy (200 rads) to the blood as the upper limit, Von Nostrand et al. (11) found that mild transient decreases in blood cell counts were seen in 90% of the patients. We usually applied 100 mCi RAI and the dose usually did not exceed 2Gy.
Hypothyroid patients have an increased serum creatine and decreased glomerular filtration rate. Decreased renal clearance results in increased RAI retention. Therefore, the bone marrow-absorbed dose after treatment with RAI would be expected to be lower for patients given rhTSH, which is protective for hypothyroidism and additionally may reduce the half-life of RAI, than for patients subjected to L-T4 withdrawal (12-14). Molinaro et al. (15) reported recently that RAI ablation treatment is associated with a decline in WBC and Plt that persists for at least one year after ablation without differences between the rhTSH and the L-T4 withdrawal groups. On the other hand, Rosario et al. (16) demonstrated that the decrease in WBC and platelets in the first three months was significantly lower in the rhTSH group than in the L-T4 withdrawal group. This suggests that the transient effects on the bone marrow may be more of a dose-related phenomenon, while the late persistent effects are more influenced by individual susceptibility. In this study, we documented that Hb, WBC, and Plt counts in the first month were decreased, but did not persist for a long time. The patients with low pretreatment Hb and WBC values were not more susceptible to the suppressive effect of the treatment than the patients having normal values. Although statistically significant, the decreases in Hb, WBC and Plt were small and without evidence of clinical importance. Interestingly, Plt counts were slightly decreased at the 1st year, similar to the observation of Molinaro et al. (15), but different from their report, we think that the decreased Plt count was probably associated with the low-dose RAI (2-5 mCi) applied for diagnostic imaging at 6-12 months. Although CBC values were normal after RAI treatment, the statistical results showed that RAI doses were important for bone marrow suppression. Therefore, physicians should be careful regarding additive or overdoses.
Sublethal radiation doses damage bone marrow cells and may lead to leukemia. Acute and chronic myeloid leukemia were reported with RAI treatment, especially in those with bone metastasis. Incidence of leukemia was increased in the patients who received more than 800 mCi, were >45 years and were treated within short intervals. Only very rarely is acute leukemia found in patients receiving a small RAI dose of <300 mCi (17-19). Similarly, we did not observe the development of an acute or chronic myeloid leukemia due to RAI treatment within one year. However, the long-term outcome of RAI therapy may be different from these results.
In conclusion, we suggest that RAI therapy can be associated with slight and reversible changes in Hb, WBC and Plt counts; however, it is a safe treatment modality for ablation without any serious or persistent hematological side effects.
Conflict of interest
No author of this paper has a conflict of interest, including specific financial interests, relationships, and/or affiliations relevant to the subject matter or materials included in this manuscript.
Address for Correspondence: M.D. Bircan Sonmez, Department of Nuclear Medicine, Karadeniz Technical University School of Medicine, Trabzon, Turkey Phone: +90 462 377 57 42 E-mail: email@example.com
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Bircan Sonmez (1), Ismail Dogan (1), Canan Yavruoglu (1), Gamze Can (2), Mehmet Sonmez (3)
(1) Department of Nuclear Medicine, Karadeniz Technical University School of Medicine, Trabzon, Turkey
(2) Department of Public Health, Karadeniz Technical University School of Medicine, Trabzon, Turkey
(3) Department of Hematology, Karadeniz Technical University School of Medicine, Trabzon, Turkey