Mild Decreases in White Blood Cell and Platelet Counts Are Present One Year After Radioactive Iodine Remnant Ablation

Abstract

Background:

Bone marrow suppression after multiple, high-dose radioactive iodine (RAI) therapies is well described. However, changes in the peripheral complete blood count (CBC) that may occur after a single treatment of RAI such as that commonly used for routine remnant ablation is much less well studied. In this retrospective trial, we examined the rate of persistent anemia, leukopenia, and thrombocytopenia 1 year after a single RAI administration.

Methods:

Peripheral blood counts at baseline were compared to those obtained 1 year after RAI remnant ablation in 206 consecutive thyroid cancer patients. Analyses were performed to determine the potential impact of both the method of preparation (recombinant human thyroid stimulating hormone [rhTSH] vs. thyroid hormone withdrawal) and administered activity of ¹³¹I on hemoglobin, white blood cell (WBC), and platelet counts.

Results:

Comparison of the baseline CBC before RAI ablation (median administered activity of approximately 3700 MBq or 100 mCi) with the follow-up CBC done 1 year later demonstrated a statistically significant decline in total WBC (6.7 ± 2.1 × 10⁹ vs. 6.0 ± 1.8 × 10⁹/L, p < 0.001; 9.7% below the reference range at 1-year follow-up) and platelet (272 ± 67 vs. 250 ± 65 × 10⁹/L, p < 0.001; 5.8% below the reference range at 1-year follow-up) with no significant change in hemoglobin (1.40 ± 0.14 vs. 1.40 ± 0.14g/L or 14.0 ± 1.4 vs. 14.0 ± 1.4g/dL; 1.5% below the reference range at 1-year follow-up). There were no significant clinical complications observed during the 1-year follow-up period. The changes in total WBC and platelets were not related to the method of preparation or the administered activity of RAI.

Conclusion:

A single RAI treatment of approximately 3700 MBq (100 mCi) after thyroidectomy is associated with a statistically significant, mild decline in WBC and platelet counts that persists for at least 1 year after ablation. Given the small magnitude of the changes and the lack of clinically significant adverse events, these observations should not decrease the use of RAI ablation in moderate to high-risk patients in whom the benefits of ablation are likely to outweigh these minor risks.

Introduction

R adioactive iodine (RAI) is a commonly used therapeutic modality in patients with differentiated thyroid cancer after thyroidectomy, either for ablation of the postsurgical thyroid remnant or for treatment of recurrent and metastatic disease (1). While high, cumulative administered activities have been associated with an increased risk of secondary malignancies (2,3), life-threatening long-term complications from the usual activities of RAI administered for remnant ablation are very rare.

However, side effects such as salivary gland dysfunction (4,5), nasolacrimal obstruction (6), and reproductive disturbances (5,7) are not infrequently observed in the first several months after RAI ablation. Fortunately, most of these early side effects are self-limited and seldom have long-term clinical implications.

Clinically significant bone marrow suppression and pulmonary fibrosis are rare, but serious, complications that can arise after repeated high-dose RAI treatments (8). For example, a retrospective review of 159 patients given multiple treatments of ¹³¹I (usually 3700–7400 MBq or 100–200 mCi at 3-month intervals) after traditional thyroid hormone withdrawal (THW) demonstrated a transient anemia in 35% (mean cumulative administered activity of 9509 MBq or 257 mCi), transient leukopenia in 10% (mean cumulative activity 12,284 MBq or 332 mCi), and thrombocytopenia in 3% of the patients (mean cumulative activity 17,316 MBq or 468 mCi) (9). The white blood cell (WBC) and platelet counts normalized in all patients by 1 year after completion of therapy, but anemia persisted in 5% of the patients. In addition to cumulative administered activity, the hematopoietic depression was more severe in those patients who were previously treated with external beam irradiation.

Since RAI is cleared from the blood and body more rapidly after recombinant human thyroid stimulating hormone (rhTSH) preparation than traditional hypo-THW (10,11), it is possible that the dose-related side effects of RAI may be less likely to occur after remnant ablation with rhTSH than THW. Indeed a recent study demonstrated that the incidence of early thrombocytopenia developing within the first 2 months after 3700 MBq (100 mCi) RAI ablation was higher in patients prepared with THW than those prepared with rhTSH (21.4% vs. 7%, p = 0.1) (5). Further, the mean decrease in neutrophils (nadir) was also significantly higher in the THW group compared with the rhTSH group (52% vs. 25%, p < 0.01). Six months after ablation, platelet and neutrophil counts had returned to normal in 10 of the 12 patients who have developed early neutropenia or thrombocytopenia. Longer follow-up data are not available.

Despite anecdotal evidence of occasional bone marrow suppression after a single treatment of RAI, the risk of persistent anemia, leukopenia, and thrombocytopenia after an initial ablative treatment of ¹³¹I is not well defined. Therefore, we evaluated the impact of single RAI remnant ablation (after traditional THW or rhTSH-stimulated ablation) on the CBC obtained 1 year after RAI treatment.

Methods

Standard practice at our center for at least the last 20 years requires that all patients undergoing RAI ablation, therapy, or diagnostic scanning have an automated complete blood count (CBC) obtained no more than 1 week before RAI administration. In this retrospective review, we evaluated a consecutive series of 206 thyroid cancer patients undergoing initial RAI remnant ablation (after total thyroidectomy) in whom a CBC was available in the medical record both at the time of ablation (1–3 months after surgery) and at the time of the first follow-up diagnostic whole-body scan approximately 1 year later. Patients were excluded from the study if they were taking any medications known to affect the CBC, if they received a second dose of RAI during the first year of follow-up, if they were known to have any hematological conditions, or if they received external beam radiation therapy and/or chemotherapy before RAI ablation or within 1 year after ablation. This study received approval from our Institutional Research Board.

RAI remnant ablation was performed after either rhTSH or THW preparation as previously described (12,13). In brief, all patients were instructed to follow a low iodine diet before and during treatment. In the hypothyroid group, patients were taken off of levothyroxine 6 weeks (or triiodothyronine 2 weeks) before the diagnostic testing. On the contrary, all patients in the rhTSH group remained on thyroid hormone replacement. They were given 0.9 mg of rhTSH intramuscularly on day 1; a second rhTSH injection (0.9 mg) was given on day 2, followed by a tracer amount of ¹²³I (usually 74–148 MBq or 2–4 mCi) a few hours later. On day 3, the diagnostic scan was obtained in the morning, and the therapeutic dose was administered in the afternoon. All patients returned for posttherapy scan 5–10 days later. The administered activity was selected by the treating physician in conjunction with the nuclear medicine tumor board based on the findings of the diagnostic whole-body scan and the clinicopathological features of each individual case (13). The selection of administered activity was empirically determined in 199 patients and was guided by RAI clearance studies (whole body and blood dosimetry) in only seven patients. Dosimetry calculation was not used to select the administered activity; instead, it was only used to determine the upper limit of RAI that could be safely administered. Each of these seven patients received administered activities well below the maximal tolerable activity defined as the dose that delivers 2 Gy (200 rad) to the blood as an equivalent of bone marrow and whole-body retention of <2960 MBq (<80 mCi) at 48 hours (12).

The primary endpoints of this study were the hematologic changes after 1 year of RAI treatment in thyroid cancer patients.All serum blood tests were performed in the automated hematology laboratories at Memorial Sloan-Kettering Cancer Center using an Automated CBC analyzer (ADVIA 120; Siemens, Deerfield, IL). The following parameters were evaluated in each patient: hemoglobin (Hb) concentration (coefficient of variation = 1.5%), WBC count (coefficient of variation =3.1%), differential count, and platelet count (coefficient of variation =3.1%). The normal value for Hb in males was 1.3–1.7 g/L (13–17 g/dL) and 1.15–1.6 g/L (11.5–16 g/dL) for females. The normal WBC was 4.0 to 11.0 × 10⁹/L, and the normal platelet count was 160 to 400 × 10⁹/L. TSH was determined by a heterogeneous sandwich immunoassay on an Immuno 1 System (Bayer, Tarrytown, NY).

Statistical Analysis

Data are presented as the mean ± standard deviation; medians with ranges are given when appropriate. Continuous variables were compared using paired t-tests, and categorical variables were compared using chi-square analysis. Repeated measures were analyzed using analysis of variance. A p-value of less than 0.05 was considered statistically significant. All statistical analyses were performed using SPSS version 16.0 for Windows.

Results

Clinical characteristics

Pertinent characteristics of the 206 consecutive patients who had a CBC available for review immediately before and a mean of 1.1 ± 0.5 years (range 0.6–1.6 years, median 1.0 year) after initial RAI remnant ablation are presented in Table 1. The majority were females (72.8%) with a mean age of 47 ± 14.6 years at diagnosis. All had undergone total thyroidectomy for predominantly papillary thyroid cancer (68%) or follicular variant of papillary thyroid cancer (26.7%). There were three patients (1.5%) who had follicular thyroid cancer and eight patients (3.9%) who had Hurthle cell thyroid cancer.

Table 1.

Baseline Characteristics of the Trial Patients

Gender
Female	150 (72.8%)
Male	56 (27.2%)
Mean ± SD	47 ± 14.6
Age (years) at diagnosis
Median	44.9
Range	17.4–82.3
Mean ± SD	47 ± 14.6
Age (years) at RAI treatment
Median	44.7
Range	17.4–82.3
Extent of surgery
Total thyroidectomy	206 (100%)
Histology
PTC	140 (68%)
FVPTC	55 (26.7%)
FTC	3 (1.5%)
HCC	8 (3.9%)
TNM stage
I	71%
II	6%
III	23%
IV	0%
Preparation
rhTSH	161 (78%)
THW	45 (22%)
Administered activity rhTSH (MBq/mCi)
Mean ± SD	4662 ± 1591 (126 ± 43)
Median	3996 (108)
Range	1110–11,211 (30–303)
Administered activity THW (MBq/mCi)
Mean ± SD	4144 ± 1702 (112 ± 46)
Median	3774 (102)
Range	1110–11,100 (30–300)
Posttherapy scan
Negative	1 (0.5%)
Result
Thyroid bed only	203 (98.5%)
Pulmonary metastases	2 (1%)

SD, standard deviation; PTC, papillary thyroid cancer; FTC, follicular thyroid cancer; FVPTC, follicular variant of papillary thyroid cancer; HCC, Hurthle cell cancer; RAI, radioactive iodine; THW, thyroid hormone withdrawal; rhTSH, recombinant human TSH.

In our institution, the majority of patients were prepared for RAI ablation with rhTSH (78%). As in our previous reports, rhTSH ablation was offered as compassionate use before specific Food and Drug Administration approval for ablation. Those prepared with THW had a median TSH of 98 mU/L (range 20–364 mU/L) the day before therapeutic RAI treatment. Administered activities were similar in the rhTSH cohort (median 3996 MBq or 108 mCi) and the THW group (median 3774 MBq or 102 mCi). The posttherapy scan revealed pulmonary metastases in two patients (both Stage II).

TNM staging (based on AJCC (American Joint Committee on Cancer) classification, 6th edition) revealed that the majority of patients were Stage I (71%) with a smaller number of Stage II (6%) and Stage III (23%) patients. Because Stage IV patients often required external beam irradiation therapy to focal lesions, systemic therapy, or repeat RAI treatments at 6 months after initial ablation, it is not surprising that no Stage IV patients met the entry criteria for this study.

CBC findings in the full cohort

Results of CBC findings before and after RAI are shown in Table 2. No change in Hb was detected when comparing the preablation value with the value obtained 1 year later. On the contrary, even though the mean and median values remained within the normal reference range, a statistically significant decline in both WBC and platelets counts was seen 1 year after RAI ablation when compared to the preablation values (p < 0.001 for both). However, at the 1-year reevaluation point, no patient had suffered clinical complications from these minor changes in blood counts, and none had severe thrombocytopenia (lowest platelet count at 1-year follow-up was 130 × 10⁹/L) or significant leukopenia (lowest WBC at 1-year follow-up was 3.0 × 10⁹/L). Comparing the preablation CBC with the follow-up CBC done 1 year later revealed that the WBC count was lower in 64% of the patients, and the platelet count was lower in 68% of the patients.

Table 2.

Complete Blood Count Values Before and After Radioactive Iodine Remnant Ablation for All Patients

	Before RAI ablation	1 year after RAI ablation	p-Value
Hb (g/dL)			0.246
Mean ± SD	14.0 ± 1.4	14.0 ± 1.4
Median	14.1	14
Range	10.1–19.9	10.1–18.0
WBC (10⁹/L)			<0.001
Mean ± SD	6.7 ± 2.1	6.0 ± 1.8
Median	6.4	5.8
Range	2.9–21.3	3.0–16.7
Platelet (10⁹/L)			<0.001
Mean ± SD	272 ± 67	250 ± 65
Median	261	247
Range	135–538	130–472

Hb, hemoglobin; WBC, white blood cell.

At the 1-year follow-up point, 9.7% of the patients had WBC count below the reference range, compared to only 4.4% at baseline (p = 0.01). A similar trend was observed with regard to platelet count (5.8% at follow-up vs. 1.5% at baseline line, p = 0.01). The percentage of patients with abnormal Hb level did not change (1.5% at 1-year follow-up and at baseline). Reanalysis of the data excluding those few patients with even minor abnormalities in the baseline CBC evaluation (n = 14 patients) resulted in no significant alterations in the results. WBC at baseline was 6.7 ± 2.0 × 10⁹/L, compared with 6.0 ± 1.8 × 10⁹/L at 1-year follow-up (p < 0.001); baseline platelet was 276 ± 66 × 10⁹/L, and 253 ± 55 × 10⁹/L 1 year later (p < 0.001).

There were 30 patients who had an abnormal CBC at the final follow-up. Among them, 20 patients had WBC below the normal range, 12 had abnormal platelet counts, and 1 had Hb abnormality after 1 year. Only 3 of the 30 patients had both platelet and WBC counts below the reference range, whereas the other 27 had isolated declines in WBC, platelet, or Hb. When examined further, each WBC lineage (neutrophils, basophils, lymphocytes, and eosinophils) showed changes similar to the change in total WBC count without any line appearing more affected than the others (data not shown).

CBC findings analyzed by method of preparation for remnant ablation

The transient period of THW appeared to have little effect on the baseline CBC as no significant differences were detected in the baseline Hb (1.4 ± 0.13g/L or 14 ± 1.3g/dL for rhTSH vs. 1.44 ± 0.15g/L or 14.4 ± 1.5g/dL for THW), WBC (6.8 ± 2.2 × 10⁹/L for rhTSH vs. 6.2 ± 1.5 × 10⁹/L for THW), or platelet counts (276 ± 70 × 10⁹/L for rhTSH vs. 258 ± 55 × 10⁹/L for TWH) drawn before RAI ablation between the patients prepared with THW and those prepared with rhTSH.

Just as when analyzed as a single cohort, analysis based on the method of preparation for RAI revealed no significant impact on the Hb, while statistically significant declines in both the WBC and platelet counts were detected when comparing the baseline counts before ablation with those obtained at 1-year follow-up (see Table 3). Moreover, no significant differences were detected in either the absolute delta changes or the percent changes in Hb, WBC, or platelets when comparing rhTSH preparation with THW.

Table 3.

Complete Blood Count Before and After Radioactive Iodine Based on Method of Preparation: Recombinant Human TSH Versus Thyroid Hormone Withdrawal

Variable	Preparation method	Descriptors	Before RAI ablation	1 year after RAI ablation	Delta	% Change	p-Value a
Hb (g/dL)	rhTSH	Mean ± SD	14.0 ± 1.3	14.0 ± 1.4	0 ± 0.1	0 ± 0.7	0.6
		Median	14	14
		Range	10.1–17.2	10.1–17.3
	THW	Mean ± SD	14.4 ± 1.5	14.2 ± 1.4	−0.2 ± 0.2	−1.5 ± 1.2	0.2
		Median	14.3	13.9
		Range	11.5–19.9	11.1–18.0
WBC (10⁹/L)	rhTSH	Mean ± SD	6.8 ± 2.2	6.1 ± 1.8	−0.5 ± 0.2	−8.5 ± 2.3	0.0001
		Median	6.5	5.9
		Range	2.9–21.3	3.0–16.7
	THW	Mean ± SD	6.2 ± 1.5	5.6 ± 1.3	−0.6 ± 0.2	−10.0 ± 3.0	0.002
		Median	6	5.6
		Range	3.9–9.7	3.3–9.1
Platelet (10⁹/L)	rhTSH	Mean ± SD	276 ± 70	255 ± 69	−21.0 ± 3.4	−6.9 ± 1.0	0.0001
		Median	266	251
		Range	135–538	130–472
	THW	Mean ± SD	258 ± 55	236 ± 47	−22.0 ± 7.0	−6.6 ± 2.6	0.003
		Median	250	222
		Range	152–379	159–355

p-Values compare the baseline count before RAI ablation with the 1-year follow-up count. There was no statistical differences detected when comparing the changes over time between rhTSH preparation and THW for Hb, WBC, or platelet counts.

CBC findings analyzed by administered activity

Over the range of administered activities used in this study, no significant dose–response relationship was found with respect to individual changes (either the absolute change or as a percent change) in Hb, WBC, or platelet counts. Table 4 shows the mean changes in Hb, WBC, and platelet counts when analyzed based on the usual empiric dosing categories. Similarly, when data were analyzed separately for rhTSH and THW groups, wide variations in percent changes in the platelet counts and WBC counts were seen at all levels of administered activities with no clear trend toward an increasing impact of higher doses (data not shown).

Table 4.

Mean Changes in Blood Counts (1 Year After Radioactive Iodine Treatment from Baseline Values) According to Administered Activity of Radioactive Iodine

Administered activity MBq (mCi)	n	Hb a ± SD (g/dL)	WBC a ± SD (10⁹/L)	Platelet a ± SD (10⁹/L)
1110 ± 185 (30 ± 5)	7	−0.4 ± 8	−1.9 ± 1	−60 ± 46
2775 ± 370 (75 ± 10)	19	0.3 ± 1	−0.3 ± 2	−11 ± 44
3700 ± 370 (100 ± 10)	92	−0.2 ± 1	−0.5 ± 2	−16 ± 43
4625 ± 370 (125 ± 10)	6	0.5 ± 0.6	−0.5 ± 3	−16 ± 52
5550 ± 740 (150 ± 20)	71	−0.1 ± 1	−0.8 ± 2	−26 ± 43
7400 (200) or more	11	0.1 ± 0.8	−1 ± 2	−24 ± 43
Total	206	−0.1 ± 1	−0.72	−21 ± 44

p = 0.2 for change in Hb, 0.1 for change in platelets, and 0.4 for change in WBC by analysis of variance.

Further, when the change in platelet count was analyzed by quartiles of administered activity, no significant difference in RAI activity was detected in the patients who had the greatest decline in platelet counts (quartile 1, 4625 ± 1702 MBq or 125 ± 46 mCi) compared with those who had lesser declines (quartile 2, 4440 ± 1591 MBq or 120 ± 43 mCi), no significant decline (quartile 3, 4810 ± 1776 MBq or 130 ± 48 mCi), or even a rise in platelet counts (quartile 4, 4403 ± 1406 MBq or 119 ± 38 mCi). Similarly, when the change in WBC count was analyzed by quartiles, no significant difference was detected in the patients who had the greatest decline in WBC counts (quartile 1, 4625 ± 1961 MBq or 125 ± 53 mCi) compared with those who had lesser declines (quartile 2, 4625 ± 1591 MBq or 125 ± 43 mCi), no significant decline (quartile 3, 4551 ±1628 MBq or 123 ± 44 mCi), or a rise in WBC counts (quartile 4, 4366 ± 1147 MBq or 118 ± 31 mCi).

In addition, there was no significant difference in the administered activities received by those patients who developed a WBC below normal at the 1-year follow-up (4218 ±1443 MBq or 114 ± 39 mCi) compared with those patients in whom the WBC remained within the normal range (4588 ±1628 MBq or 124 ± 44 mCi). Likewise, there was no significant difference in administered activities given to those patients who developed a below normal platelet count at 1 year (4514 ± 1813 MBq or 122 ± 49 mCi) compared with those who maintained a platelet count within the normal range (4551 ±1628 MBq or 123 ± 44 mCi).

Discussion

RAI ablation with administered activities approximating 3700 MBq (100 mCi) is associated with a statistically significant decline in WBC and platelets that persists for at least 1 year after ablation. While statistically significant, the magnitude of decline in both WBC and platelets is small and without evidence of clinical significance. However, significantly more patients had WBC and platelet counts below the normal range 1 year after RAI remnant ablation than at their baseline evaluation before therapy.

Although it is well known that therapeutic ¹³¹I can cause hematopoietic toxicity, as far as we are aware this is the first documentation that ablative RAI results in a persistent, measureable decline in WBC and platelet counts at 1 year after treatment. We were able to make this clinical observation because of the relatively large number of patients treated at our institution and the treatment regimen that calls for hematopoietic monitoring after a single treatment of RAI.

Even though the mild changes in the CBC were not associated with adverse clinical outcomes, the statistically significant decline in WBC and platelet counts is a poignant reminder that RAI ablation, even with relatively moderate administered activity of ¹³¹I, can be associated with persistent effects on the bone marrow for up to 1 year. It is unknown whether these persistent effects could become clinically important in the future if further therapies with potentially bone marrow toxic effects are needed for either progressive thyroid cancer or another disease requiring cytotoxic chemotherapy.

It is difficult to compare our results with the previously published studies because of the differences in dosing regimens and timing of evaluations. In the study of Haynie and Beierwaltes (9), patients were treated every 3 months until no uptake was observed or until the total administered activity of ¹³¹I became “alarmingly large.” Dosimetry was not done, so many patients could have exceeded maximum tolerable activity (MTA), especially in those with large volume RAI avid disease. Despite the differences in dosing regimen, it is reassuring that the WBC and platelet counts had normalized by 1 year after completing therapy. It is quite likely that while the platelet and WBC counts were normal, if the data had been analyzed individually, significant declines in these counts within the normal ranges would have been found. The 5% rate of persistent anemia at 1 year after completion of therapy is probably related to the much higher cumulative administered activity received by these patients as compared to the single 3700 MBq (100 mCi) RAI activity given to our patients.

Over the range of administered activities used in our study, we could not detect a significant dose–response relationship with the subsequent development of abnormal blood counts. As with the development of salivary gland side effects, there appears to be much individual variability in the susceptibility to having a statistically significant decline in both the platelet and WBC counts in response to RAI exposure. Either the threshold for developing alterations in the CBC differs among patients or factors other than administered activity are having a significant impact on the actual bone marrow dose. Alternatively, differences in patients' ability to repair radiation-induced damage could also contribute to differences in susceptibility of an individual to develop persistent abnormalities in the CBC in response to a specific administered activity of radiation. This retrospective study cannot differentiate the cause of the individual dose–response variations.

When analyzed as a full cohort, it is clear that the administered activities used for routine RAI ablation at our center had a much larger influence on subsequent WBC and platelet counts than on Hb. A further difference in individual susceptibility is pointed out by the observation that some patients had an impact only on the WBC, others had changes only in platelet counts, while it was the minority of patients who had abnormalities in both the WBC and platelets. Interestingly, when specific WBC lineage was examined individually, the neutrophils, basophils, lymphocytes, and eosinophils all appeared to demonstrate changes that mirrored the changes in the total WBC count without any line appearing more effected than the others. Incidentally, the relative sparing of red blood cell lineage is a well-known phenomenon with other forms of internally administered radiotherapies as well (14,15).

A several week period of THW appeared to have little, if any, impact on the CBC values obtained immediately before ablation since there were no significant differences detected between patients prepared with THW and rhTSH. This observation allowed us to compare the baseline CBC values obtained (with either THW or rhTSH preparation) with the 1-year follow-up values that were always obtained at the time of rhTSH preparation. If THW would have been associated with abnormalities in the CBC, this could have confounded our observations since the follow-up studies were done on thyroid hormone suppression. But with the lack of impact of THW on the baseline CBC, it seems unlikely that the comparison of the CBC obtained at baseline while hypothyroidism with that obtained at 1-year follow-Eup while subclinically hyperthyroid has significantly impacted our observations.

Since there was no clear dose–response relationship between administered activity and development of alterations in the CBC, it is not surprising that the more rapid clearance of RAI associated with rhTSH preparation did not decrease the likelihood of having a statistically significant decline in WBC or platelet counts. One would only expect the rhTSH prepared cohort to demonstrate fewer alterations if the development of abnormalities in the final CBC was associated with administered activities. Since Rosario et al. (5) demonstrated that mean decrease in neutrophils and platelets in the first 3 months after RAI ablation with 3700 MBq (100 mCi) was significantly lower in the rhTSH group than those prepared with THW, it is likely 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. Since the Rosario study was focused on the early effects after RAI ablation, specific information on the rate of persistent changes or individual changes between baseline and a comparable 1 year follow-up time point were not available.

As with all retrospective reviews, this study has several important limitations. Since we do not routinely obtain CBC measurements in the first few months after RAI ablation, we cannot define the time course of the changes in the CBC over time. Similarly, since our data represent a single time point of follow-up (1 year after ablation), we cannot determine whether the minor changes in the WBC or platelet counts present at 1 year are persistent or whether they either resolve or get worse over time. Since all the patients included in this study were followed at our center, it is unlikely that any of them received cytotoxic therapy unknown to us. However, the potential adverse effects of other medicines, herbal supplements, or other health food products that are often used by cancer patients cannot be adequately assessed in this retrospective study. Because the choice of preparation for RAI ablation was a clinical decision, and not randomized, it is possible that subtle selection bias may cause unrecognized differences in the rhTSH and the THW group. The baseline CBC was collected several weeks after thyroidectomy; therefore, it is not likely that the values were significantly affected by surgery. Finally, we recognize that there is no strict correlation between administered activity and bone marrow dose. However, since data on actual dose to the thyroid and bone marrow were not available, the administered activity was used as a surrogate for the purpose of this study.

In summary, RAI ablation using administered activity approximating 3700 MBq (100 mCi) rarely results in clinically significant bone marrow depression but can be associated with minor changes in platelet and WBC that persist for a year after ablation. Although usually associated with minor changes in the absolute counts, RAI ablation is associated with a significantly higher percentage of patients with WBC and platelet counts below the population reference range at the 1-year follow-up evaluation than seen at the initial evaluation before RAI ablation. While these changes in platelets and WBC appear to have little immediate clinical significance, and the risks associated with these minor changes are unlikely to outweigh the potential benefits of RAI ablation in most patients, they do serve as a cautionary reminder that even the relatively moderate administered activities of RAI (100 mCi) may have persistent, mild effects on the peripheral CBC for at least 1 year after RAI remnant ablation.

Footnotes

Acknowledgments

This work was supported by the International Union against Cancer through a Yamagiwa-Yoshida Memorial International Cancer Study Grant to Dr. E. Molinaro. We would like to thank Drs. Rossella Elisei and Aldo Pinchera for their insights, assistance, and support.

Disclosure Statement

The authors declare that no competing financial interests exist.

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