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Leukaemia after I131 therapy for thyroid cancer
LEUKAEMIA A. M. JELLIFFE,
A F T E R ITM T H E R A P Y
M.D., M.R.C.P.,
FOR THYROID
F . F . R . , a n d K. M . J O N E S ,
CANCER
D.Sc., M.R.C.S., L.R.C.P.
From The Middlesex Hospital, London, W. 1 T~E o c c u r r e n c e o f a c u t e m y e l o i d l e u k a e m i a a f t e r the a d m i n i s t r a t i o n o f l a r g e d o s e s o f r a d i o i o d i n e f o r t h y r o i d c a n c e r is n o w w e l l d o c u m e n t e d ( D e l a r u e et al 1952; B l o m et al 1955; S e i d l i n et al 1956; A b b a t t et al 1956). O n e n e w c a s e is r e p o r t e d a f t e r a t o t a l d o s e o f o n l y 400 m C s . CASE HISTORY
without difficulty. A topographical survey at this time showed no detectable uptake in any area of the body. The patient was finally admitted as an emergency on 28th December. For three weeks she hae been unwell, with a persistently raised temperature which had not responded to tetracycline. She was myxoedematous and anaemic and a blood count showed the following findings : Hh. 39 per cent, W.B.C. 600, 26 per cent Polymorphs, 64 per cent Lymphocytes, 16per cent Monocytes, Platelets 45,000. Bone marrow examination showed a generalised hyperplasia with a large number of myeloblasts, and giant and undifferentiated cells were also present. The appearances were compatible with acute myeloblastic leukaemia. The course of the leukaemia was unaffected by treatment which included repeated transfusions, steroids and large doses of thyroid, and the patient died on 12th February. The immediate cause of death was an intracranial haemorrhage. Post mortem examination confirmed the presence of multiple petechial haemorrhages throughout the cerebrum, cerebellum and mid-brain. The bone marrow showed a patchy cellularity with numerous primitive blast cells, confirming the diagnosis of acute myeloblastic leukaemia.
A woman aged seventy-four was admitted elsewhere on 9/11/56 with a history of pain in the right hip of six months duration. X-ray examination of the hip showed a large area of bone destruction in the upper end of the femoral shaft. A biopsy was carried out which revealed a metastatic deposit from a well differentiated adenocarcinoma of the thyroid. Further clinical examination revealed a small nodule in the right lobe of the thyroid which the patient said had been present for at least twenty years. The patient was referred for consideration of treatment with radioiodine. After consultation, it was decided that the deposit in the femur should be stabilised and the thyroid ablated before undertaking this treatment. Before this could be done a pathological fracture occurred through the femoral deposit. This DISCUSSION was stabilised with a MacLaughlin pin and plate on 17th T h e r e is n o d o u b t t h a t r a d i o i o d i n e c a n ocDecember and a total thyroidectomy was carried out ten days later. casionally bring about a most dramatic remission The patient was transferred to the Middlesex Hospital at when widespread metastases from a thyroid cancer the end of the year. On admission, no additional physical are p r e s e n t . T h e p o s s i b i l i t y o f l e u k a e m i a a f t e r t h e abnormalities were found and a full blood count was normal. X-ray examination of the chest showed two large use o f l a r g e t o t a l d o s e s o f I TM as w i t h t h e t w o rounded opacities to the left of the anterior mediastinum, p a t i e n t s r e p o r t e d b y S e i d l i n is n o t surprising, a n d is which were thought to be tumour deposits in lymph nodes. a risk t h a t has to be a c c e p t e d in t h e t r e a t m e n t o f a n TheB.M.R. was + 14 per cent (Robertson Reid Standard). o t h e r w i s e i n e v i t a b l y f a t a l disease. It is m o r e A radioiodine topographical body survey on 2nd January d i s t u r b i n g to see this c o m p l i c a t i o n d e v e l o p i n g a f t e r showed a definite uptake of I T M in the metastases in the femur and chest, and two days later a therapeutic dose of t h e a d m i n i s t r a t i o n o f r e l a t i v e l y s m a l l d o s e s o f 200 mCs of radioiodine was given by mouth. There were no r a d i o i o d i n e . B l o m a n d his c o l l e a g u e s r e p o r t e d a immediate complications apart from some increase in pain patient developing acute myeloid leukaemia one at the fracture site for ten days after the dose. y e a r a f t e r t h e a d m i n i s t r a t i o n o f a d o s e o f 261 m C s . , The patient was discharged, and readmitted on 5th April. a n d o u r p a t i e n t r e c e i v e d o n l y 400 m C s . o v e r f o u r There were no clinical signs of myxoedema, and a topographical survey showed persistent uptake over the regions m o n t h s . Widespread bony metastases were not of the hip and mediastinum. A chest x-ray suggested that p r e s e n t a n d t h e r e is n o r e a s o n to p o s t u l a t e a n u n there had been some diminution in the size of the hilar mass u s u a l l y h i g h s k e l e t a l c o n c e n t r a t i o n o f I TM. of lymph nodes. The blood count was again well within the I f t h e o c c u r r e n c e o f l e u k a e m i a is r e c o r d e d w i t h normal range, and a further dose of 200 mCs was given on increasing frequency after such relatively small 17th April. The patient was kept on maintenance doses of thyroid doses, t h e a u t h o r is p r e p a r e d to a l t e r his p r e s e n t until March 1958, when she was admitted for reassessment. views. W i t h t h e e v i d e n c e at the m o m e n t a v a i l a b l e , An x-ray examination showed that the femoral fracture was the l o g i c a l t r e a t m e n t o f t h e p a t i e n t w i t h w i d e s p r e a d uniting. A topographical survey showed a slight uptake in the upper mediastinum and femur, but the blood platelet m e t a s t a s e s f r o m a w e l l d i f f e r e n t i a t e d a l v e o l a r count had fallen to 160,000 and it was considered that a d e n o c a r c i n o m a , a p p e a r s to be t h y r o i d a b l a t i o n b y further radioiodine was not indicated. Early signs of m e a n s o f s u r g e r y o r r a d i o i o d i n e , f o l l o w e d b y myxoedema were present, the B.M.R. had fallen to 9, and r e p e a t e d d o s e s o f I TM at t h r e e - m o n t h l y i n t e r v a l s , f o r the serum cholesterol was 320 mg. per cent. She was as l o n g as t h e r e is a n y d e t e c t a b l e u p t a k e in t h e b o d y . discharged taking thyroid gr. 5 daily. By June she had improved a great deal, and was getting about the house B e t w e e n the doses, t h e p a t i e n t s h o u l d be m a i n t a i n e d 134
LEUKAEM1A AFTER
11~1 T H E R A P Y F O R T H Y R O I D
o n suppressive doses of t r i - i o d o - t h y r o n i n e or thyroxine. Crile's work suggests that a b o u t one half of these cancers r e s p o n d initially to the suppression of the o u t p u t of pituitary T.S.H. by thyroid a d m i n i s t r a t i o n . If this is so, a n d if leukaemia proves to be a c o m m o n c o m p l i c a t i o n after radioiodine, i t would seem more logical to postpone the use of 1lal until there is n o further response to the m a x i m u m daily dose of thyroxine or thyroid t h a t the patient can tolerate. This type of cancer is often of low grade m a l i g n a n c y , and the patient m a y live for several years w i t h o u t treatment. Such a case should n o t be palliated by a m e t h o d of treatment which is capable o f s h o r t e n i n g life considerably, unless no other m e t h o d is likely to be effective. The appearance of l e u k a e m i a after such low doses of radioiodine emphasises once again the desirability of ablating the thyroid surgically, if this is possible. SUMMARY A new case of leukaemia following radioiodine therapy for thyroid cancer is recorded. The patient received a total of only 400 mCs. of 11~1. Two years
CANCER
135
elapsed between the a d m i n i s t r a t i o n of the initial dose a n d the onset of symptoms. If leukaemia following doses of this order is reported more often i n the future, it is suggested that radioiodine should n o t be the first m e t h o d of t r e a t m e n t advised for metastatic deposits from a well differentiated, alveolar a d e n o c a r c i n o m a of the thyroid. Some of these t u r n o u t s are of extremely low grade malignancy, a n d it is probable that long term remissions c a n be i n d u c e d in m a n y patients with suppressive doses o f thyroid, thyroxine, or trii o d o - t h y r o n i n e . There is n o reason why this form of therapy should reduce the chances of a response to radioiodine t r e a t m e n t at a later date. REFERENCES ABBATT, J. D., FARRAN, H. E. A., & GREENE, R. (1956). Lancet, 1, 782. BLOM, P. S., QUERIDO, A., & LEEKSMA, C. H. W. (1955). Brit J. Radiol. 28, 165. CRILE, G. (1957). Cancer, 10, 1,119. DELARUE, J., TUBIANA, M., & DUTREIX, J. (1952). Bull. Ass. franc. Cancer, 40, 263. SEIDLIN, S. M., SIEGEL,E., YALOW, A. A., & MELAMED,S. (1956). Science, 123, 800.
BOOK REVIEW Atomic Medicine. Edited by CHARLESF. BEHRENS, M.D., Rear Admiral, M.C., U.S. Navy (Ret.); Radiologist, Yates Clinic, Washington, D.C. Third edition. 9 × 6 in. Pp. 705+xiv, fully illustrated. 1959. Baltimore: The Williams & Wilkins Co. (London: Bailliere, Tindall & Cox., Ltd. 120s. THE production of energy by unstable isotopes is attended by the emission of ionising radiations. This association raised a number of important and urgent medical questions when it became possible to mass-produce isotopes for military or civil use. The problem of the biological effects of irradiation had hitherto been of interest only to a number of radiotherapists and other special investigators. It suddenly enlarged into an urgent national research project as soon as it became apparent that the use of isotopes in peace or war may cause irradiation exposure to whole populations. The editor has set out to give an account of the whole field, covering such diverse iterns as the principles of nuclear physics, construction of reactors and bombs, radiobiology, radiation protection, and the clinical use of isotopes.
A great deal of knowledge has accumulated since the previous edition of this book in 1953. Many chapters have therefore been revised or added. Among the contributions of immediate medical interest are those by E. P. Cronkite and his team from Brooklands National Laboratory, They deal with the complex question of acute whole body irradiation injury and this important subject is fully discussed from various aspects, i.e., haematological changes, pathogenesis and protection, diagnosis and treatment of acute radiation disease, and the problem of irradiation from radioactive fallout. The text is based not only on laboratory experiments, but also on the Japanese experiences and the Marshall Island incidents of 1954. The chapters on the biological and clinical use of radio-isotopes give a clear exposition of the general scope, whilst that on clinical isotope technique presents a concise description of basic investigations. The twenty-four chapters have been written by twenty-five authors but there is good integration of the text with little overlap. The production of the book is of a very high standard with clear illustrations and the references at the end of each chapter are given by their full title.--M. HULBERT.
A F T E R ITM T H E R A P Y
M.D., M.R.C.P.,
FOR THYROID
F . F . R . , a n d K. M . J O N E S ,
CANCER
D.Sc., M.R.C.S., L.R.C.P.
From The Middlesex Hospital, London, W. 1 T~E o c c u r r e n c e o f a c u t e m y e l o i d l e u k a e m i a a f t e r the a d m i n i s t r a t i o n o f l a r g e d o s e s o f r a d i o i o d i n e f o r t h y r o i d c a n c e r is n o w w e l l d o c u m e n t e d ( D e l a r u e et al 1952; B l o m et al 1955; S e i d l i n et al 1956; A b b a t t et al 1956). O n e n e w c a s e is r e p o r t e d a f t e r a t o t a l d o s e o f o n l y 400 m C s . CASE HISTORY
without difficulty. A topographical survey at this time showed no detectable uptake in any area of the body. The patient was finally admitted as an emergency on 28th December. For three weeks she hae been unwell, with a persistently raised temperature which had not responded to tetracycline. She was myxoedematous and anaemic and a blood count showed the following findings : Hh. 39 per cent, W.B.C. 600, 26 per cent Polymorphs, 64 per cent Lymphocytes, 16per cent Monocytes, Platelets 45,000. Bone marrow examination showed a generalised hyperplasia with a large number of myeloblasts, and giant and undifferentiated cells were also present. The appearances were compatible with acute myeloblastic leukaemia. The course of the leukaemia was unaffected by treatment which included repeated transfusions, steroids and large doses of thyroid, and the patient died on 12th February. The immediate cause of death was an intracranial haemorrhage. Post mortem examination confirmed the presence of multiple petechial haemorrhages throughout the cerebrum, cerebellum and mid-brain. The bone marrow showed a patchy cellularity with numerous primitive blast cells, confirming the diagnosis of acute myeloblastic leukaemia.
A woman aged seventy-four was admitted elsewhere on 9/11/56 with a history of pain in the right hip of six months duration. X-ray examination of the hip showed a large area of bone destruction in the upper end of the femoral shaft. A biopsy was carried out which revealed a metastatic deposit from a well differentiated adenocarcinoma of the thyroid. Further clinical examination revealed a small nodule in the right lobe of the thyroid which the patient said had been present for at least twenty years. The patient was referred for consideration of treatment with radioiodine. After consultation, it was decided that the deposit in the femur should be stabilised and the thyroid ablated before undertaking this treatment. Before this could be done a pathological fracture occurred through the femoral deposit. This DISCUSSION was stabilised with a MacLaughlin pin and plate on 17th T h e r e is n o d o u b t t h a t r a d i o i o d i n e c a n ocDecember and a total thyroidectomy was carried out ten days later. casionally bring about a most dramatic remission The patient was transferred to the Middlesex Hospital at when widespread metastases from a thyroid cancer the end of the year. On admission, no additional physical are p r e s e n t . T h e p o s s i b i l i t y o f l e u k a e m i a a f t e r t h e abnormalities were found and a full blood count was normal. X-ray examination of the chest showed two large use o f l a r g e t o t a l d o s e s o f I TM as w i t h t h e t w o rounded opacities to the left of the anterior mediastinum, p a t i e n t s r e p o r t e d b y S e i d l i n is n o t surprising, a n d is which were thought to be tumour deposits in lymph nodes. a risk t h a t has to be a c c e p t e d in t h e t r e a t m e n t o f a n TheB.M.R. was + 14 per cent (Robertson Reid Standard). o t h e r w i s e i n e v i t a b l y f a t a l disease. It is m o r e A radioiodine topographical body survey on 2nd January d i s t u r b i n g to see this c o m p l i c a t i o n d e v e l o p i n g a f t e r showed a definite uptake of I T M in the metastases in the femur and chest, and two days later a therapeutic dose of t h e a d m i n i s t r a t i o n o f r e l a t i v e l y s m a l l d o s e s o f 200 mCs of radioiodine was given by mouth. There were no r a d i o i o d i n e . B l o m a n d his c o l l e a g u e s r e p o r t e d a immediate complications apart from some increase in pain patient developing acute myeloid leukaemia one at the fracture site for ten days after the dose. y e a r a f t e r t h e a d m i n i s t r a t i o n o f a d o s e o f 261 m C s . , The patient was discharged, and readmitted on 5th April. a n d o u r p a t i e n t r e c e i v e d o n l y 400 m C s . o v e r f o u r There were no clinical signs of myxoedema, and a topographical survey showed persistent uptake over the regions m o n t h s . Widespread bony metastases were not of the hip and mediastinum. A chest x-ray suggested that p r e s e n t a n d t h e r e is n o r e a s o n to p o s t u l a t e a n u n there had been some diminution in the size of the hilar mass u s u a l l y h i g h s k e l e t a l c o n c e n t r a t i o n o f I TM. of lymph nodes. The blood count was again well within the I f t h e o c c u r r e n c e o f l e u k a e m i a is r e c o r d e d w i t h normal range, and a further dose of 200 mCs was given on increasing frequency after such relatively small 17th April. The patient was kept on maintenance doses of thyroid doses, t h e a u t h o r is p r e p a r e d to a l t e r his p r e s e n t until March 1958, when she was admitted for reassessment. views. W i t h t h e e v i d e n c e at the m o m e n t a v a i l a b l e , An x-ray examination showed that the femoral fracture was the l o g i c a l t r e a t m e n t o f t h e p a t i e n t w i t h w i d e s p r e a d uniting. A topographical survey showed a slight uptake in the upper mediastinum and femur, but the blood platelet m e t a s t a s e s f r o m a w e l l d i f f e r e n t i a t e d a l v e o l a r count had fallen to 160,000 and it was considered that a d e n o c a r c i n o m a , a p p e a r s to be t h y r o i d a b l a t i o n b y further radioiodine was not indicated. Early signs of m e a n s o f s u r g e r y o r r a d i o i o d i n e , f o l l o w e d b y myxoedema were present, the B.M.R. had fallen to 9, and r e p e a t e d d o s e s o f I TM at t h r e e - m o n t h l y i n t e r v a l s , f o r the serum cholesterol was 320 mg. per cent. She was as l o n g as t h e r e is a n y d e t e c t a b l e u p t a k e in t h e b o d y . discharged taking thyroid gr. 5 daily. By June she had improved a great deal, and was getting about the house B e t w e e n the doses, t h e p a t i e n t s h o u l d be m a i n t a i n e d 134
LEUKAEM1A AFTER
11~1 T H E R A P Y F O R T H Y R O I D
o n suppressive doses of t r i - i o d o - t h y r o n i n e or thyroxine. Crile's work suggests that a b o u t one half of these cancers r e s p o n d initially to the suppression of the o u t p u t of pituitary T.S.H. by thyroid a d m i n i s t r a t i o n . If this is so, a n d if leukaemia proves to be a c o m m o n c o m p l i c a t i o n after radioiodine, i t would seem more logical to postpone the use of 1lal until there is n o further response to the m a x i m u m daily dose of thyroxine or thyroid t h a t the patient can tolerate. This type of cancer is often of low grade m a l i g n a n c y , and the patient m a y live for several years w i t h o u t treatment. Such a case should n o t be palliated by a m e t h o d of treatment which is capable o f s h o r t e n i n g life considerably, unless no other m e t h o d is likely to be effective. The appearance of l e u k a e m i a after such low doses of radioiodine emphasises once again the desirability of ablating the thyroid surgically, if this is possible. SUMMARY A new case of leukaemia following radioiodine therapy for thyroid cancer is recorded. The patient received a total of only 400 mCs. of 11~1. Two years
CANCER
135
elapsed between the a d m i n i s t r a t i o n of the initial dose a n d the onset of symptoms. If leukaemia following doses of this order is reported more often i n the future, it is suggested that radioiodine should n o t be the first m e t h o d of t r e a t m e n t advised for metastatic deposits from a well differentiated, alveolar a d e n o c a r c i n o m a of the thyroid. Some of these t u r n o u t s are of extremely low grade malignancy, a n d it is probable that long term remissions c a n be i n d u c e d in m a n y patients with suppressive doses o f thyroid, thyroxine, or trii o d o - t h y r o n i n e . There is n o reason why this form of therapy should reduce the chances of a response to radioiodine t r e a t m e n t at a later date. REFERENCES ABBATT, J. D., FARRAN, H. E. A., & GREENE, R. (1956). Lancet, 1, 782. BLOM, P. S., QUERIDO, A., & LEEKSMA, C. H. W. (1955). Brit J. Radiol. 28, 165. CRILE, G. (1957). Cancer, 10, 1,119. DELARUE, J., TUBIANA, M., & DUTREIX, J. (1952). Bull. Ass. franc. Cancer, 40, 263. SEIDLIN, S. M., SIEGEL,E., YALOW, A. A., & MELAMED,S. (1956). Science, 123, 800.
BOOK REVIEW Atomic Medicine. Edited by CHARLESF. BEHRENS, M.D., Rear Admiral, M.C., U.S. Navy (Ret.); Radiologist, Yates Clinic, Washington, D.C. Third edition. 9 × 6 in. Pp. 705+xiv, fully illustrated. 1959. Baltimore: The Williams & Wilkins Co. (London: Bailliere, Tindall & Cox., Ltd. 120s. THE production of energy by unstable isotopes is attended by the emission of ionising radiations. This association raised a number of important and urgent medical questions when it became possible to mass-produce isotopes for military or civil use. The problem of the biological effects of irradiation had hitherto been of interest only to a number of radiotherapists and other special investigators. It suddenly enlarged into an urgent national research project as soon as it became apparent that the use of isotopes in peace or war may cause irradiation exposure to whole populations. The editor has set out to give an account of the whole field, covering such diverse iterns as the principles of nuclear physics, construction of reactors and bombs, radiobiology, radiation protection, and the clinical use of isotopes.
A great deal of knowledge has accumulated since the previous edition of this book in 1953. Many chapters have therefore been revised or added. Among the contributions of immediate medical interest are those by E. P. Cronkite and his team from Brooklands National Laboratory, They deal with the complex question of acute whole body irradiation injury and this important subject is fully discussed from various aspects, i.e., haematological changes, pathogenesis and protection, diagnosis and treatment of acute radiation disease, and the problem of irradiation from radioactive fallout. The text is based not only on laboratory experiments, but also on the Japanese experiences and the Marshall Island incidents of 1954. The chapters on the biological and clinical use of radio-isotopes give a clear exposition of the general scope, whilst that on clinical isotope technique presents a concise description of basic investigations. The twenty-four chapters have been written by twenty-five authors but there is good integration of the text with little overlap. The production of the book is of a very high standard with clear illustrations and the references at the end of each chapter are given by their full title.--M. HULBERT.