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Extramedullary haematopoiesis in thalassaemia: Results of radiotherapy: A report of three patients
Clinical Oncology (1996) 8:120-122 © 1996 The Royal College of Radiologists
Clinical Oncology
Case Report Extramedullary Haematopoiesis in Thalassaemia: Results of Radiotherapy: A Report of Three Patients K. Pistevou-Gompaki 1, G. Skaragas2, P. Paraskevopoulos ~, K. Kotsa 1 and E. Repanta2 1Theagenion Cancer Center and 2St Paul's Hospital, Thessaloniki, Greece
Abstract. ExtrameduUary haematopoiesis is sometimes encountered in severe anaemia. Rarely, it may cause neurological symptoms, leading to spinal cord or cauda equina compression. Three patients with thalassaemia intermedia, who developed neurological complications, are described. The diagnoses were based on the clinical findings, computed tomography and magnetic resonance imaging. Small doses of radiotherapy (10-20 Gy in 5-10 fractions) relieved symptoms in all of these patients. Our experience supports the role of radiation therapy as a treatment for this complication.
Keywords: Extramedullary haematopoiesis; Radiotherapy; Thalassaemia intermedia
~TRODUCTION Extramedullary haematopoiesis accompanies a number of haematological and chronic medical conditions. Haematopoietic activity occurs most commonly in the spleen, liver and lymph nodes, but may also arise in unusual sites such as the breast, peripheral nerves and epididymis. The dura mater, especially in the region of the thoracic spinal cord, may be a site of extramedullary haematopoiesis. Marrow heterotopia occurs in 15% of patients suffering from thalassaemia major, and to a lesser extent in thalassaemia intermedia, thalassaemia minima and other anaemic conditions [1,2]. Although this pathophysiological response is generally asymptomatic, very rarely it may cause neurological symptoms, even leading to spinal cord compression, due to the pressure exerted by the haematopoietic tissue on the spinal cord. We report on three patients with thalassaemia and spinal cord or cauda equina compression, and discuss the results of radiotherapy. All these patients are currently alive without evidence of local recurrence.
CASE HISTORY 1 This patient was a 34-year-old Greek male, who had been diagnosed with thalassaemia intermedia at the age of 6 years. The genotype of his thalassaemia was /30//3. The patient was transfused every 25-30 days until the age of 14 years, when he underwent splenectomy, which significantly
Correspondence and offprint requests to: Dr K. PistevouGompaki, 2 Gigenon Street, North Kerasia, 57019 Thessaloniki, Greece.
reduced the need for blood transfusions to one or two per year. The pathology reports were consistent with haemosiderosis of the spleen and liver. He presented to us complaining of lower extremity weakness, reduced sensation and an inability to walk. Physical examination revealed pallor, anaemia and mild jaundice. The liver was palpable 6 cm below the right costal margin. There was limited sensory perception below the level of the eighth thoracic vertebra (T8), decreased motor strength, mildly increased tone, symmetrically hyperactive reflexes with bilateral extensor plantar responses, and symmetrical weakness of the lower extremities. Chest radiography showed multiple extensive paravertebral masses. CT scanning revealed a large epidural mass, extending from T6 downwards and completely blocking the spinal cord at the level of T8. The results of blood tests on admission are shown in Table 1. A neurosurgical operation was advised, but the patient refused. The patient was therefore treated with X-ray photons (200 kV) to a dose of 20 Gy in ten fractions through a posterior field (dose calculated at the centre of the masses). By the end of the first week of treatment, there was marked improvement in sensory and motor neurological symptoms. Management also included a transfusion of four units of red blood cells to suppress haematopoietic activity. A follow-up CT scan showed complete disappearance of the lesion. The patient has been followed up for 3 years without evidence of local recurrence.
CASE HISTORY 2 This patient was a 42-year-old Greek male, who was diagnosed with thalassaemia intermedia in childhood. His genotype was [f/ft. The need for blood transfusions was for about one per month until the age of 18 years, when he underwent a splenectomy, during with he received a blood transfusion. Two months later h e developed hepatitis-B infection. He presented to us complaining of lower extremity numbness and weakness, which had appeared 2 months earlier. He was unable to walk. The physical examination revealed pallor, anaemia and mild jaundice. The liver could not be palpated. There was limited sensory perception, decreased motor strength, increased tone, symmetrically hyperactive reflexes with bilateral extensor plantar responses, and symmetrical weakness of the lower extremities. CT scans revealed a paravertebral soft tissue mass compressing the spinal cord in the level of T6-T7 and extending below this level (Fig. la). The results of blood tests on admission are shown in Table 1. The patient refused surgical intervention.
Radiotherapy in ExtrameduUary Haematopoiesis in Thalassaemia
121
Table 1. Haematological findings Patient
Hb (g/dl)
Hct (%)
MCV (fl)
MCH (pg)
MCHC (g/dl)
Ret. x 109/[
HbA2 (%)
HbF (%)
Erythroblasts Ferritin /100 WBC (~/1)
1
10.0 9.5 9.8
32 29 30
76 73 75
22 21 21
28 27 27
109 160 133
6.l 4.9 5.3
30.0 7.9 11.0
400 500 450
2 3
1500 760 860
limited sensory perception and rectal and bladder dysfunction. CT scans revealed a large paravertebtal soft tissue mass extending from L1 to L4, and completely blocking the spinal cord. The results of blood tests on admission are shown in Table 1. The patient was treated with X-ray photons of 200 kV through a simple posterior field, as in the other two patients, and to the same dose. By the end of treatment, both the sensory and motor symptoms were improved. Management also included the transfusion of five units of red blood cells. One month later, clinical examination revealed total remission of the neurological signs, and follow-up CT scans showed a complete disappearance of the lesion. He has been followed up for 4 years without any local recurrence.
DISCUSSION
b
Fig. 1. (a) Paravertebral mass shown on CT scan on admission; (b) Complete resolution of the paravetebral mass after external radiation therapy. He was treated with X-ray photon irradiation at 200 kV, to a dose of 20 Gy in ten fractions through a posterior field. Subsequently, he was transfused with five units of red blood cells. He was markedly clinically improved after the end of the first week of treatment, and also radiologically, as shown on a follow-up CT scan (Fig. lb). He has since been well, and has been followed up for 6 years, without any evidence of local recurrence.
CASE HISTORY 3 This patient was a 19-year-old Greek male, known to have suffered from thalassaemia intermedia since the age of 2 years. The genotype was [3°~ft. His transfusion requirement was one per month. He presented to us with paraparesis,
Intraspinal haematopoiesis remains a rare finding in thalassaemia intermedia. When it does occur, the most common site of extradural involvement is the thoracic spine [1]. Management strategies in such patients have included irradiation, laminectomy, or laminectomy with postoperative irradiation and transfusion therapy [2]. Some patients treated with transfusion alone have improved transiently but developed recurrences later. Spontaneous recovery without therapeutic intervention has also been reported, but may take several months to occur. There is significant morbidity and an associated high frequency of recurrence. Recurrence after surgical decompression may also occur. This is why some authors recommend postoperative irradiation. Haematopoietic tissue is radiosensitive. The radiosensitivity may also vary according to the affected marrow site [3]. The radiation dose administered to our patients was 20 Gy in ten fractions. We gave much thought to whether we should administer less than 20 Gy to the involved areas. According to recent series in the literature, doses given have varied from 10 Gy to 26 Gy [4,5], and, in one report, 30 Gy [6]. We finally decided to use 20 Gy in ten fractions, since both clinical and radiological improvement have been reported with this dosage [4,5]. Radiotherapy should be given with caution, as extramedullary haematopoietic masses constitute a part of the haematopoietic compartment. Although radiation combined with transfusion can suppress extramedullary haematopoiesis and reduce the risk of recurrence, and is also a rapid and effective mode of therapy, our experience with these three patients emphasizes the importance of careful follow-up. The mild course of thalassaemia intermedia may make patients negligent towards their transfusion programme, so they should be closely followed up in order to prevent complications related to the significantly expanded erythron.
References 1. Kaufmann T, Coleman M, Giardina P, et al. The role of radiation therapy in the management of haematopoietie neuro-
122 logic complications in thalassaemia. Acta Haematol 1991 ;85:156-9. 2. Sorshadl OS, Taylor PE, Noyes WD. Extramedullary haematopoiesis, mediastinal masses, spinal cord compression. JAMA 1986;189:343-7. 3. Papavasiliou C, Gouliamos A, Deligiorgi E, et al. Masses of myeloadipose tissue: Radiological and clinical considerations. Int J Radiat Oncol Biol Phys 1990;19:985--93. 4. Papavasiliou C. Clinical expressions of the expansion of the
K. Pistevou-Gompaki bone marrow in the chronic anemias: The role of radiotherapy. Int J Radiat Oncol Biol Phys 1994;28:605-12. 5. Papavasiliou C, Sandilos P. Effect of radiotherapy on symptoms due to heterotopic marrow in thalassaemia. Lancet 1987;1:13-4. 6. Massenkeil G, Wichmann W, Krummenacher F, et al. Reversible Rfickenmarkskompression durch extramedull~ire Blutbildungsherde bei Thalass~mie. Dtsch Med Wochenschr 1993;118:100-6.
Received for publication April 1995 Accepted following revision September 1995
Clinical Oncology
Case Report Extramedullary Haematopoiesis in Thalassaemia: Results of Radiotherapy: A Report of Three Patients K. Pistevou-Gompaki 1, G. Skaragas2, P. Paraskevopoulos ~, K. Kotsa 1 and E. Repanta2 1Theagenion Cancer Center and 2St Paul's Hospital, Thessaloniki, Greece
Abstract. ExtrameduUary haematopoiesis is sometimes encountered in severe anaemia. Rarely, it may cause neurological symptoms, leading to spinal cord or cauda equina compression. Three patients with thalassaemia intermedia, who developed neurological complications, are described. The diagnoses were based on the clinical findings, computed tomography and magnetic resonance imaging. Small doses of radiotherapy (10-20 Gy in 5-10 fractions) relieved symptoms in all of these patients. Our experience supports the role of radiation therapy as a treatment for this complication.
Keywords: Extramedullary haematopoiesis; Radiotherapy; Thalassaemia intermedia
~TRODUCTION Extramedullary haematopoiesis accompanies a number of haematological and chronic medical conditions. Haematopoietic activity occurs most commonly in the spleen, liver and lymph nodes, but may also arise in unusual sites such as the breast, peripheral nerves and epididymis. The dura mater, especially in the region of the thoracic spinal cord, may be a site of extramedullary haematopoiesis. Marrow heterotopia occurs in 15% of patients suffering from thalassaemia major, and to a lesser extent in thalassaemia intermedia, thalassaemia minima and other anaemic conditions [1,2]. Although this pathophysiological response is generally asymptomatic, very rarely it may cause neurological symptoms, even leading to spinal cord compression, due to the pressure exerted by the haematopoietic tissue on the spinal cord. We report on three patients with thalassaemia and spinal cord or cauda equina compression, and discuss the results of radiotherapy. All these patients are currently alive without evidence of local recurrence.
CASE HISTORY 1 This patient was a 34-year-old Greek male, who had been diagnosed with thalassaemia intermedia at the age of 6 years. The genotype of his thalassaemia was /30//3. The patient was transfused every 25-30 days until the age of 14 years, when he underwent splenectomy, which significantly
Correspondence and offprint requests to: Dr K. PistevouGompaki, 2 Gigenon Street, North Kerasia, 57019 Thessaloniki, Greece.
reduced the need for blood transfusions to one or two per year. The pathology reports were consistent with haemosiderosis of the spleen and liver. He presented to us complaining of lower extremity weakness, reduced sensation and an inability to walk. Physical examination revealed pallor, anaemia and mild jaundice. The liver was palpable 6 cm below the right costal margin. There was limited sensory perception below the level of the eighth thoracic vertebra (T8), decreased motor strength, mildly increased tone, symmetrically hyperactive reflexes with bilateral extensor plantar responses, and symmetrical weakness of the lower extremities. Chest radiography showed multiple extensive paravertebral masses. CT scanning revealed a large epidural mass, extending from T6 downwards and completely blocking the spinal cord at the level of T8. The results of blood tests on admission are shown in Table 1. A neurosurgical operation was advised, but the patient refused. The patient was therefore treated with X-ray photons (200 kV) to a dose of 20 Gy in ten fractions through a posterior field (dose calculated at the centre of the masses). By the end of the first week of treatment, there was marked improvement in sensory and motor neurological symptoms. Management also included a transfusion of four units of red blood cells to suppress haematopoietic activity. A follow-up CT scan showed complete disappearance of the lesion. The patient has been followed up for 3 years without evidence of local recurrence.
CASE HISTORY 2 This patient was a 42-year-old Greek male, who was diagnosed with thalassaemia intermedia in childhood. His genotype was [f/ft. The need for blood transfusions was for about one per month until the age of 18 years, when he underwent a splenectomy, during with he received a blood transfusion. Two months later h e developed hepatitis-B infection. He presented to us complaining of lower extremity numbness and weakness, which had appeared 2 months earlier. He was unable to walk. The physical examination revealed pallor, anaemia and mild jaundice. The liver could not be palpated. There was limited sensory perception, decreased motor strength, increased tone, symmetrically hyperactive reflexes with bilateral extensor plantar responses, and symmetrical weakness of the lower extremities. CT scans revealed a paravertebral soft tissue mass compressing the spinal cord in the level of T6-T7 and extending below this level (Fig. la). The results of blood tests on admission are shown in Table 1. The patient refused surgical intervention.
Radiotherapy in ExtrameduUary Haematopoiesis in Thalassaemia
121
Table 1. Haematological findings Patient
Hb (g/dl)
Hct (%)
MCV (fl)
MCH (pg)
MCHC (g/dl)
Ret. x 109/[
HbA2 (%)
HbF (%)
Erythroblasts Ferritin /100 WBC (~/1)
1
10.0 9.5 9.8
32 29 30
76 73 75
22 21 21
28 27 27
109 160 133
6.l 4.9 5.3
30.0 7.9 11.0
400 500 450
2 3
1500 760 860
limited sensory perception and rectal and bladder dysfunction. CT scans revealed a large paravertebtal soft tissue mass extending from L1 to L4, and completely blocking the spinal cord. The results of blood tests on admission are shown in Table 1. The patient was treated with X-ray photons of 200 kV through a simple posterior field, as in the other two patients, and to the same dose. By the end of treatment, both the sensory and motor symptoms were improved. Management also included the transfusion of five units of red blood cells. One month later, clinical examination revealed total remission of the neurological signs, and follow-up CT scans showed a complete disappearance of the lesion. He has been followed up for 4 years without any local recurrence.
DISCUSSION
b
Fig. 1. (a) Paravertebral mass shown on CT scan on admission; (b) Complete resolution of the paravetebral mass after external radiation therapy. He was treated with X-ray photon irradiation at 200 kV, to a dose of 20 Gy in ten fractions through a posterior field. Subsequently, he was transfused with five units of red blood cells. He was markedly clinically improved after the end of the first week of treatment, and also radiologically, as shown on a follow-up CT scan (Fig. lb). He has since been well, and has been followed up for 6 years, without any evidence of local recurrence.
CASE HISTORY 3 This patient was a 19-year-old Greek male, known to have suffered from thalassaemia intermedia since the age of 2 years. The genotype was [3°~ft. His transfusion requirement was one per month. He presented to us with paraparesis,
Intraspinal haematopoiesis remains a rare finding in thalassaemia intermedia. When it does occur, the most common site of extradural involvement is the thoracic spine [1]. Management strategies in such patients have included irradiation, laminectomy, or laminectomy with postoperative irradiation and transfusion therapy [2]. Some patients treated with transfusion alone have improved transiently but developed recurrences later. Spontaneous recovery without therapeutic intervention has also been reported, but may take several months to occur. There is significant morbidity and an associated high frequency of recurrence. Recurrence after surgical decompression may also occur. This is why some authors recommend postoperative irradiation. Haematopoietic tissue is radiosensitive. The radiosensitivity may also vary according to the affected marrow site [3]. The radiation dose administered to our patients was 20 Gy in ten fractions. We gave much thought to whether we should administer less than 20 Gy to the involved areas. According to recent series in the literature, doses given have varied from 10 Gy to 26 Gy [4,5], and, in one report, 30 Gy [6]. We finally decided to use 20 Gy in ten fractions, since both clinical and radiological improvement have been reported with this dosage [4,5]. Radiotherapy should be given with caution, as extramedullary haematopoietic masses constitute a part of the haematopoietic compartment. Although radiation combined with transfusion can suppress extramedullary haematopoiesis and reduce the risk of recurrence, and is also a rapid and effective mode of therapy, our experience with these three patients emphasizes the importance of careful follow-up. The mild course of thalassaemia intermedia may make patients negligent towards their transfusion programme, so they should be closely followed up in order to prevent complications related to the significantly expanded erythron.
References 1. Kaufmann T, Coleman M, Giardina P, et al. The role of radiation therapy in the management of haematopoietie neuro-
122 logic complications in thalassaemia. Acta Haematol 1991 ;85:156-9. 2. Sorshadl OS, Taylor PE, Noyes WD. Extramedullary haematopoiesis, mediastinal masses, spinal cord compression. JAMA 1986;189:343-7. 3. Papavasiliou C, Gouliamos A, Deligiorgi E, et al. Masses of myeloadipose tissue: Radiological and clinical considerations. Int J Radiat Oncol Biol Phys 1990;19:985--93. 4. Papavasiliou C. Clinical expressions of the expansion of the
K. Pistevou-Gompaki bone marrow in the chronic anemias: The role of radiotherapy. Int J Radiat Oncol Biol Phys 1994;28:605-12. 5. Papavasiliou C, Sandilos P. Effect of radiotherapy on symptoms due to heterotopic marrow in thalassaemia. Lancet 1987;1:13-4. 6. Massenkeil G, Wichmann W, Krummenacher F, et al. Reversible Rfickenmarkskompression durch extramedull~ire Blutbildungsherde bei Thalass~mie. Dtsch Med Wochenschr 1993;118:100-6.
Received for publication April 1995 Accepted following revision September 1995