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CASE REPORT

MANAGEMENT OF EXTRAMEDULLARY HAEMATOPOISES INTHALASSAEMIA WITH RADIOTHERAPY: A CASE REPORTAND REVIEW OF LITERATURE

B Thejaswini1, J Bindhu1, R Nanda1, K Aradhana1

Author’s Affiliations: 1Associate prof, Radiation Oncology, Kidwai Memorial Institute of Oncology, Bangalore.Correspondence: Dr. Thejaswini.B, Email: thejaswiniumesh@gmail.com

ABSTRACT

Extramedullary haematopoises (EMH) is a very rare cause for spinal cord compression but is a well de-scribed entity with relation to chronic haemolytic anemias like thalassemia. Radiation therapy has a docu-mented role in the management of this condition. We would like to report a case of a 28 year old manwith underlying thalassemia major presenting with paraparesis and sensory loss, successfully treated withradiotherapy.

Key words: Thalassemia, Extramedullary haematopoises, Spinal cord compression, , Radiotherapy

INTRODUCTIONExtramedullary haematopoises (EMH) is an un-common manifestation in severe thalassemia.Spinal cord compression is a consequence of EMHin the intraspinal epidural space. IntrathoracicEMH tissue most commonly occurs in the post-erior mediastinum and in the lower thoracic paras-pinal area. There is also a postulate that EMH isdue to direct extension from bone marrow by thedevelopment of extramedullary haematopoitic tis-sue from branches of the intercostal veins (3). Thecases most commonly present with paraparesis andsensory defecit rather than paraplegia. We presentone such patient coming with the same patternsuccessfully managed with radiotherapy.

CASE REPORTThis was a 28 year old teacher referred to us forconsideration of radiotherapy in February 2009.He had initially presented with progressive weak-ness, stiffness and parasthesia of both lower limbsof 3 months duration. During the last 2 weeks hehad developed low back pain and ataxia. .Therewere no bladder and bowel dysfunction. There wasno history of fever or previous injury to the back.He was a known case of thalassemia major, diag-nosed in 1996 but on irregular treatment. On ex-amination the patient was of average built withsevere pallor and jaundice. Neurological examina-tion revealed spastic paraparesis (Nurick’s grade 3)of grade 4- to 4+ /5 power and graded sensoryloss below the level of T-3. The bilateral plantar

were extensor and deep tendon reflexes were exag-gerated in both lower limbs.

The MRI of the spine showed a soft tissue masslesion in the epidural space from D3 to D9. Evi-dence of Expansile costovertebral junctions withperifocal thickened soft tissue were seen involvingD3-D10 (Figure 1 & 2)

Figure 1: Axial T2W image showing soft tissueintensity in the epidural and paravertebralspace

Spinal cord edema was present from D2-D10. Thevisualized sternum showed medullary expansion inthe manubrium and body of sternum. The CSFexamination was non contributory.

His haemoglobin was 8 g/dl, haematocrit 26.6%and white blood cell count 3.4 X 109/L. The diffe-rential count was in normal range. Platelets were

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adequate. Peripheral smear showed anisopoikilocy-tosis with microcytosis and hypochromia (Fig 3).

Figure 2: Paramedian T1W Post contrast im-age showing soft tissue intensity in the para-vertebral space

Figure 3: Microscopic Pictograph showingsevere anisopoikilocytosis with microcytic hy-pochromic erythrocytes. Many target cells, da-crocytes and a nucleated erythrocyte seen

A haemoglobin electrophoresis showed an HbF of43.15g/dl and an A band was seen in the E/C re-gion (56.86%) suggestive of Hb E β Thalassaemiamajor. Chest radiography showed reticular patternof bones; feature of haemopoetic disorder. Ultra-sonography showed gross spleenomegaly, thespleen measuring 20 cm and mild hepatomegaly. Inview of the above investigational findings suggest-ing of a severe haemolytic disorder and the typicalMRI findings, a diagnosis of extramedullary hae-matopoiesis with cord compression (D3- D9) sec-ondary to Thalassaemia major was made.

Radiotherapy: He received an equivalent dose of20 Gy over a period of two weeks on telecobaltmachine with conventional fractionation. He tole-rated treatment well and had a remarkable re-sponse within 1 week of treatment.

After 14 Gy of treatment he had subjective im-provement of around 50% in motor weakness,around 80% reduction in pain and sensory deficit.At the time of discharge, he had complete relieffrom pain. He had normal power in lower limbswith residual spasticity and parasthesia. He wasindependent and ambulatory without support. Formanagement of his haemolytic anemia patient hadbeen advised conservative management with bloodtransfusion and hydroxyurea. During the course ofhis treatment there was reduction of Jaundice, totalbilirubin level reduced from 10.8mg/ dL to 1.5mg/ dL at the time of discharge and haemoglobinlevels improved to 8.5 mg/ dL.

At 9 months follow up, he was doing well and re-sumed his work. He had mild residual hypertoniaof both lower limbs and had completely recoveredin terms of neurological deficits (Nurick’s grade 1).After 5 years of treatment with radiotherapy pa-tient reported to us performing his normal routineand has no neurological defecits.

DISCUSSIONParavertebral pseudotumors form a rare complica-tion in a variety of haematological disorders. Thedisorders where extramedullary haematopoises arecommonly seen are thalassaemia, polycythemiarubra vera, myelofibrosis and other hemoglobino-pathies.1,2 The common sites of EMH are the liver,spleen and lymphnodes. It is more rarely seen inkidneys, breast, adrenal gland, dura matter, pleura,retroperitoneal fat, paravertebral gutters, ribs andskin.3-8

The source of masses formed by EMH is contro-versial. One hypothesis suggests that blood form-ing elements are extruded through weakened tra-becular bone into the surrounding tissue wherethey proliferate, this is supported by the radiologi-cal continuity of the epidural mass and intramedul-lary marrow.9

The thoracic spine predisposes to spinal cordcompression due to narrow central canal and li-mited mobility of the thoracic spine. Spinal cordcompression due to epidural haematopoitic tissuehas been documented in 75 cases in literature until2005. EMH associated with thalassemia was firstdescribed by Gatto et al.10

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Table 1: Results of Radiation (single modality) in EMH managementAuthor N RT dose Response Recurrence ratePapavassliov 13 5 8.5 to 24 Gy CR (5) (NA) less than 1 year follow upIssaragrisial 14 9 15-35 CR (8) (3/9) 33%Key : CR – Complete clinical response, NA = No applicable, RR – Relapse rate

The optimal management of EMH with spinalcord compression remains controversial. Thetreatment modalities available ranges from transfu-sions to down regulate erythropoietin to medicalmanagement with hydroyurea and to a more ag-gressive approach with local radiotherapy or sur-gery and/or a combination of these therapies.5,9. Inthis case, radiotherapy was considered the treat-ment of choice and surgical intervention was notfavored in view of risk of severe haemorrhage,long segment of disease and possibility of incom-plete resection.

Radiotherapy has been shown to be effective in themajority of patients with symptomatic EMH.11,12

The mass lesion consisting of haematopoitic tissueappears to be particularly sensitive to ionizing radi-ation and a radiation dose of 10-30 Gy seems ade-quate. Hydroxyurea (HU) is a well known chemotherapeutic agent acts by enhancing the HbF pro-duction and eryhthropoises. In doses of 10-20mg/Kg/ day in an intermittent on continuousschedule has been shown to have sustained haema-tological efficacy with minimal toxicity. Howeverleucopenia and thrombocytopenia have been do-cumented which is usually reversible after a fewdays of discontinuation.5

Surgical decompression provides immediate reliefof the spinal cord compression and also allows ahistological confirmation.8 However when the evi-dence of EMH is clinically confirmed, histologicalproof may not be mandatory.

So we conclude that radiotherapy is an effectivesafe and recommended modality of treatment forspinal cord compression due to EMH. Moderatedose radiotherapy of 20 to 30 Gy has minimal tox-icity, negligible risks and provide rapid and longterm neurological stability. Radiation should beconsidered as the preferred treatment modalitywith subsequent support by other treatments asintensive blood transfusion and hydroxyureatreatment as deemed necessary in EMH with spinalcord compression.

Acknowledgements: We thank Dr. YeshwantPawar, Dept of Radiotherapy and Dr. Manish,Neurosurgeon for their technical assistance andmaterial support.

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