Abstract 989

Poster Board I-11

Introduction:

One of the risks of childhood cancer treatment is fertility impairment later in life. In the past a large proportion of children with acute lymphoblastic leukemia (ALL) has received cranial irradiation as part of their treatment. The aim of this study was to evaluate whether cranial irradiation negatively affects pituitary regulated gonadal function in male survivors of childhood ALL.

Patients and Methods:

We examined gonadal function, including Inhibin B, LH, FSH, testosterone, and pituitary axis function by measuring TSH, Free-T4 and IGF-I levels in 89 long-term male survivors of childhood ALL after a median follow-up time of 19 year (range 7-34 years).

Results:

Twenty-nine out of 89 male ALL survivors received cranial irradiation. Inhibin, FSH, LH, Testosterone, testicular volume as well as TSH and Free-T4 levels were not different in the cranial irradiated group as compared to the non-irradiated group (table 1). In contrast, IGF-I levels were significantly lower in the cranial irradiated group. Survivors treated with total body irradiation or testicular irradiation had significantly decreased gonadal function based on hormone levels.

Conclusions:

These data show that, in contrast to the negative influence on the growth hormone axis, cranial radiotherapy as part of ALL treatment does not have a deleterious long-term effect on the hypothalamic–pituitary-gonadal axis or pituitary-thyroid axis.

Table 1

Hormone levels according to treatment modality. The two patients treated with orbital irradiation and mediastinal irradiation are not shown. Normal range is given for each hormone. Values given as median and range. Z-scores are given as mean and standard deviation.

Complete groupNo radiotherapyCranial irradiation (med 25 Gy, range 15-30)P-value¥Total body irradiationP-value¥Testicular irradiationP-value¥
Number of patients 87 55 25  4  3  
Age at diagnosis (yrs) 5.0 (0-15) 6.0 (1-15) 4.2 (0.1-14) 0.02 4 (4-12) 0.70 5 (2-5) 0.27 
Age at follow-up (yrs) 25 (18-40) 24 (18-34) 29 (23-40) <0.0001 25 (22-35) 0.25 30 (21-33) 0.11 
Follow-up time (yrs) 19 (7-34) 18 (7-24) 26 (16-34) <0.0001 18 (15-31) 0.13 25 (16-31) 0.01 
Inhibin-B (150-400 ng/l) 155(0-393) 155.5 (67-392) a 177.0 (35-393) 0.85 15 (10-20)* <0.0001 10 (0-10) <0.0001 
Testosterone (10.0-30.0 nmol/l) 16.2(7.7-29.4) 16.6 (7.7-29.4) 16.4 (11.1-20.9) 0.21 12.2 (11.8-16.0) 0.09 11.9 (9.0-17.0) 0.14 
SHBG(10-70 nmol/l) 28.9 (10.6-67.7) 26.2 (10.6-51.4) 31.6 (15.1-51.3) 0.03 22.8 (15.0-40.2) 0.80 47.8 (42.7-67.7)* <0.0001 
LH (1.5-8.0 U/l) 4.0 (0.1-18.9) 3.4 (0.1-8.1) 3.1 (1.3-5.3) 0.38 10.8 (7.7-13.9)* <0.0001 13.9 (8.2-18.9)* 0.08 
FSH (2.0-7.0 U/l) 4.0(1.1-58.7) 3.4 (1.3-14.1) 4.3 (1.1-15.7) 0.14 23.7 (15.9-31.4)* 0.01 48.2 (42.8-58.7)* 0.01 
Testicular volume (>15ml) 20 (2-25) 20.0 (13-25) 20.0 (10-25) 0.79 12.5 (4-13)* 0.02 2.5 (2-3)* <0.0001 
Free T4 (11-25 pmol/l) 14.8 (11.8-22.7) 15.1 (11.6-30.1)b 15.0 (11.8-22.7)c 0.69 12.5 (12.3-12.6)# 0.06 14.8 j 0.79 
TSH (0.4-4.3 mU/l) 1.3 (0.36-3.43) 1.14 (0.37-2.48)d 1.2 (0.46-2.76)e 0.42 1.9 (0.36-3.43) 0.19 0.79 j 0.61 
Height (cm) 178 (163-192) 182 (165-192) 175 (163-189) 0.006 169 (167-184) 0.035 170 (165-186) 0.13 
Body Mass Index 24.1 (17.9-39.6) 23.9 (17.9-39.6) 25.4 (19.2-33.8) 0.04 19.5 (18-24.2) 0.06 20.7 (19.6-21.4) 0.13 
IGF-I (15-47 nmol/l) 24.3 (6.5-54.2) 27.4 (13.1-54.2)h 17.3 (12.8-47.5)i 0.003 20.6 (11.5-32.3) 0.17 7.8 (6.5-23.0) 0.02 
IGF-I (z-scores) −0.49 (1.3) −0.11 (1.1) −0.82 (1.1) 0.02 −0.82 (1.3) 0.24 −2.2 (1.6) 0.01 
Complete groupNo radiotherapyCranial irradiation (med 25 Gy, range 15-30)P-value¥Total body irradiationP-value¥Testicular irradiationP-value¥
Number of patients 87 55 25  4  3  
Age at diagnosis (yrs) 5.0 (0-15) 6.0 (1-15) 4.2 (0.1-14) 0.02 4 (4-12) 0.70 5 (2-5) 0.27 
Age at follow-up (yrs) 25 (18-40) 24 (18-34) 29 (23-40) <0.0001 25 (22-35) 0.25 30 (21-33) 0.11 
Follow-up time (yrs) 19 (7-34) 18 (7-24) 26 (16-34) <0.0001 18 (15-31) 0.13 25 (16-31) 0.01 
Inhibin-B (150-400 ng/l) 155(0-393) 155.5 (67-392) a 177.0 (35-393) 0.85 15 (10-20)* <0.0001 10 (0-10) <0.0001 
Testosterone (10.0-30.0 nmol/l) 16.2(7.7-29.4) 16.6 (7.7-29.4) 16.4 (11.1-20.9) 0.21 12.2 (11.8-16.0) 0.09 11.9 (9.0-17.0) 0.14 
SHBG(10-70 nmol/l) 28.9 (10.6-67.7) 26.2 (10.6-51.4) 31.6 (15.1-51.3) 0.03 22.8 (15.0-40.2) 0.80 47.8 (42.7-67.7)* <0.0001 
LH (1.5-8.0 U/l) 4.0 (0.1-18.9) 3.4 (0.1-8.1) 3.1 (1.3-5.3) 0.38 10.8 (7.7-13.9)* <0.0001 13.9 (8.2-18.9)* 0.08 
FSH (2.0-7.0 U/l) 4.0(1.1-58.7) 3.4 (1.3-14.1) 4.3 (1.1-15.7) 0.14 23.7 (15.9-31.4)* 0.01 48.2 (42.8-58.7)* 0.01 
Testicular volume (>15ml) 20 (2-25) 20.0 (13-25) 20.0 (10-25) 0.79 12.5 (4-13)* 0.02 2.5 (2-3)* <0.0001 
Free T4 (11-25 pmol/l) 14.8 (11.8-22.7) 15.1 (11.6-30.1)b 15.0 (11.8-22.7)c 0.69 12.5 (12.3-12.6)# 0.06 14.8 j 0.79 
TSH (0.4-4.3 mU/l) 1.3 (0.36-3.43) 1.14 (0.37-2.48)d 1.2 (0.46-2.76)e 0.42 1.9 (0.36-3.43) 0.19 0.79 j 0.61 
Height (cm) 178 (163-192) 182 (165-192) 175 (163-189) 0.006 169 (167-184) 0.035 170 (165-186) 0.13 
Body Mass Index 24.1 (17.9-39.6) 23.9 (17.9-39.6) 25.4 (19.2-33.8) 0.04 19.5 (18-24.2) 0.06 20.7 (19.6-21.4) 0.13 
IGF-I (15-47 nmol/l) 24.3 (6.5-54.2) 27.4 (13.1-54.2)h 17.3 (12.8-47.5)i 0.003 20.6 (11.5-32.3) 0.17 7.8 (6.5-23.0) 0.02 
IGF-I (z-scores) −0.49 (1.3) −0.11 (1.1) −0.82 (1.1) 0.02 −0.82 (1.3) 0.24 −2.2 (1.6) 0.01 

¥ p-values as compared to the non-irradiated group

a

n=54, b n=10,c n=21, d n=11,e n=21,f n=1,g n=21,h n=38, i n=21, j n=1

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Disclosures:

No relevant conflicts of interest to declare.

Topics:
cranial irradiation, leukemia, lymphocytic, acute, childhood, pituitary-gonadal axis, survivors, insulin-like growth factor i, follow-up, free thyroxin, hormones, t4 free measurement, testosterone

Author notes

*

Asterisk with author names denotes non-ASH members.

© 2009 by The American Society of Hematology
2009
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