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European Spine Journal

, Volume 19, Issue 6, pp 871–878 | Cite as

Paraspinal extramedullary hematopoiesis in patients with thalassemia intermedia

  • Rachid Haidar
  • Hani Mhaidli
  • Ali T. Taher
Review Article

Abstract

Ineffective erythropoiesis in patients with thalassemia intermedia drives extramedullary hematopoietic tumor formation in several parts of the body. Paraspinal involvement has received increasing attention due to the associated morbidity secondary to spinal cord compression. Although the history and physical examination may help narrow the differential diagnosis, radiographic imaging remains essential to confirm the existence of hematopoietic tissue. Characteristic appearance has been observed mainly on magnetic resonance imaging. Several treatment options have been described, including transfusion therapy, laminectomy, radiotherapy, and the use of fetal hemoglobin inducing agents that decrease the hematopoietic drive. However, the ideal management scheme remains controversial. Until large prospective trials evaluate the efficacy and safety of the available treatment options, both in single and in combination therapy, an individualized approach should be entertained.

Keywords

Thalassemia intermedia Spine Extramedullary hematopoiesis Review 

Notes

Conflict of interest statement

The authors have no conflicts of interest to disclose. This study did not receive external funding.

References

  1. 1.
    Weatherall DJ, Clegg JB (2001) The thalassemia syndromes, 4th edn. Blackwell Scientific Publications, OxfordGoogle Scholar
  2. 2.
    Taher A, Ismaeel H, Cappellini MD (2006) Thalassaemia intermedia: revisited. Blood Cells Mol Dis 37:12–20CrossRefPubMedGoogle Scholar
  3. 3.
    Cromwell LD, Kerber C (1978) Spinal cord compression by extramedullary hematopoiesis in myeloid metaplasia. Radiology 128:118PubMedGoogle Scholar
  4. 4.
    Stahl SM, Ellinger G, Baringer JR (1979) Progressive myelopathy due to extramedullary hematopoiesis: case report and review of the literature. Ann Neurol 5:485–489CrossRefPubMedGoogle Scholar
  5. 5.
    Rice GP, Assis LJ, Barr RM, Ebers GC (1980) Extramedullary hematopoiesis and spinal cord compression complicating polycythemia rubra vera. Ann Neurol 7:81–84CrossRefPubMedGoogle Scholar
  6. 6.
    Cook G, Sharp RA (1994) Spinal cord compression due to extramedullary haemopoiesis in myelofibrosis. J Clin Pathol 47:464–465CrossRefPubMedGoogle Scholar
  7. 7.
    Price F, Bell H (1985) Spinal cord compression due to extramedullary hematopoiesis. Successful treatment in a patient with longstanding myelofibrosis. JAMA 253:2876–2877CrossRefPubMedGoogle Scholar
  8. 8.
    Jackson A, Burton IE (1990) Retroperitoneal mass and spinal cord compression due to extramedullary haemopoiesis in polycythemia rubra vera. Br J Radiol 42:91–92Google Scholar
  9. 9.
    McDonald AC, Cook G, Sharp RA, Bissett D (1993) Spinal cord compression in myelofibrosis—a case report. Acta Oncol 32:692–693CrossRefPubMedGoogle Scholar
  10. 10.
    de Morais JC, Spector N, Lavrado FP, Nobre LF, de Mattos JP, Pulcheri W, Nucci M, Novis S, de Oliveira HP (1996) Spinal cord compression due to extramedullary hematopoiesis in the proliferative phase of polycythemia vera. Acta Haematol 96:242–244CrossRefPubMedGoogle Scholar
  11. 11.
    Haran M, Ni S (2001) Recurrent reversible paraplegia. Lancet 357:1092CrossRefPubMedGoogle Scholar
  12. 12.
    Dore F, Cianciulli P, Rovasio S, Oggiano L, Bonfigli S, Murineddu M, Pardini S, Simonetti G, Gualdi G, Papa G et al (1992) Incidence and clinical study of ectopic erythropoiesis in adult patients with thalassemia intermedia. Ann Ital Med Int 7:137–140PubMedGoogle Scholar
  13. 13.
    Aessopos A, Tassiopoulos S, Farmakis D, Moyssakis I, Kati M, Polonifi K, Tsironi M (2006) Extramedullary hematopoiesis-related pleural effusion: the case of beta-thalassemia. Ann Thorac Surg 81:2037–2043CrossRefPubMedGoogle Scholar
  14. 14.
    Chuang CK, Chu SH, Fang JT, Wu JH (1998) Adrenal extramedullary hematopoietic tumor in a patient with beta-thalassemia. J Formos Med Assoc 97:431–433PubMedGoogle Scholar
  15. 15.
    Kumar A, Aggarwal S, de Tilly LN (1995) Case of the season. Thalassemia major with extramedullary hematopoiesis in the liver. Semin Roentgenol 30:99–101CrossRefPubMedGoogle Scholar
  16. 16.
    Brannan D (1927) Extramedullary hematopoiesis in anemias. Bull Johns Hopkins Hosp 41:104–135Google Scholar
  17. 17.
    Ross P, Logan W (1969) Roentgen findings in extramedullary hematopoiesis. AJR Am J Roentgenol 106:604–613Google Scholar
  18. 18.
    Tsitouridis J, Stamos S, Hassapopoulou E, Tsitouridis K, Nikolopoulos P (1999) Extramedullary paraspinal hematopoiesis in thalassemia: CT and MRI evaluation. Eur J Radiol 30:33–38CrossRefPubMedGoogle Scholar
  19. 19.
    Pantongrag-Brown L, Suwanwela N (1992) Case report: chronic spinal cord compression from extramedullary haematopoiesis in thalassemia BMRI findings. Clin Radiol 46:281–283CrossRefPubMedGoogle Scholar
  20. 20.
    Da Costa JL, Loh YS, Hanam E (1974) Extramedullary hematopoiesis with multiple tumour-simulating mediastinal masses in hemoglobin E-thalassemia disease. Chest 65:210–212CrossRefPubMedGoogle Scholar
  21. 21.
    Lyall A (1935) Massive extramedullary bone marrow formation in a case of pernicious anaemia. J Pathol Bacteriol 41:469–472CrossRefGoogle Scholar
  22. 22.
    Cone SM (1925) Bone marrow occurring in intercostal veins. JAMA 84:1732–1733Google Scholar
  23. 23.
    Cardia E, Toscano S, La Rosa G, Zaccone C, d’Avella D, Tomasello F (1994) Spinal cord compression in homozygous beta thalassemia intermedia. Pediatr Neurosurg 20:186–189CrossRefPubMedGoogle Scholar
  24. 24.
    Amirjamshidi A, Abbassioun K, Ketabchi SE (1991) Spinal extradural hematopoiesis in adolescents with thalassemia. Childs Nerv Syst 7:223–225CrossRefPubMedGoogle Scholar
  25. 25.
    Abbassioun K, Amir-Jamshidi A (1982) Curable paraplegia due to extradural hematopoietic tissue in thalassemia. Neurosurgery 11:804–807CrossRefPubMedGoogle Scholar
  26. 26.
    Parsa K, Oreizy A (1995) Nonsurgical approach to paraparesis due to extramedullary hematopoiesis. J Neurosurg 82:657–660PubMedGoogle Scholar
  27. 27.
    Singhal S, Sharma S, Dixit S, De S, Chander S, Rath GK, Mehta VS (1992) The role of radiation therapy in the management of spinal cord compression due to extramedullary hematopoiesis in thalassemia. J Neurol Neurosurg Psychiatry 55:310–312CrossRefPubMedGoogle Scholar
  28. 28.
    Luyendjik W, Went L, Schaad HD (1975) Spinal cord compression due to extramedullary hematopoiesis in homozygous thalassemia: case report. J Neurosurg 42:212–216CrossRefGoogle Scholar
  29. 29.
    Logothetics J, Constantoulakis M, Exonomidou J, Stefanis C, Hakas P, Augoustaki O, Sofroniadou K, Loewenson R, Bilek M (1972) Thalassaemia major (homozygous eta thalassemia). A survery of 138 cases with emphasis on neurologic and muscular aspects. Neurology 22:249–304Google Scholar
  30. 30.
    Prabhakar S, Chopra J, Khosla VK, Dash S, Banerijee AK (1980) Spinal compression in homozygous beta thalassemia. Surg Neurol 13:351–354PubMedGoogle Scholar
  31. 31.
    Shin KH, Sharma S, Gregoritch SJ, Lifeso RM, Bettigole R, Yoon SS (1994) Combined radiotherapeutic and surgical management of a spinal cord compression by extramedullary hematopoiesis in a patient with hemoglobin E beta thalassemia. Acta Haematol 91:154–157CrossRefPubMedGoogle Scholar
  32. 32.
    Gatto I, Terrana V, Biondi L (1954) Compression of the spinal cord due to proliferation of bone marrow in epidural space in a splenectomized person with Cooley’s disease. Haematologica 38:61–75PubMedGoogle Scholar
  33. 33.
    Cross JN, Morgan OS, Gibbs WN, Cheruvanky I (1977) Spinal cord compression in thalassaemia. J Neurol Neurosurg Psychiatry 40:1120–1122CrossRefPubMedGoogle Scholar
  34. 34.
    Issargisil S, Piankijagum A, Prawase W (1981) Spinal cord compression in thalassemia. Report of 12 cases and recommendations for treatment. Arch Intern Med 141:1033–1036CrossRefGoogle Scholar
  35. 35.
    Luitjes WF, Braakman R, Abels J (1982) Spinal cord compression in a new homozygous variant of beta-thalassemia. Case report. J Neurosurg 57:846–848CrossRefPubMedGoogle Scholar
  36. 36.
    David CV, Balasubramaniam P (1983) Paraplegia with thalassemia. Aust NZ J Surg 53:283–284CrossRefGoogle Scholar
  37. 37.
    Papavasiliou C, Sandilos P (1987) Effect of radiotherapy in symptoms due to heterotopic marrow in beta-thalassemia. Lancet 1:13–14CrossRefPubMedGoogle Scholar
  38. 38.
    Mann KS, Yue CP, Chan KH, Ma LT, Ngan H (1987) Paraplegia due to extramedullary hematopoiesis in thalassemia. Case report. J Neurosurg 66:938–940CrossRefPubMedGoogle Scholar
  39. 39.
    Issardgrisil S, Piankijagum A, Wasi P (1987) Spinal cord compression in thalassemia. Arch Intern Med 141:1033–1036CrossRefGoogle Scholar
  40. 40.
    Jackson DV Jr, Randall ME, Richards F 2nd (1988) Spinal cord compression due to extramedullary hematopoiesis in thalassemia: long-term follow-up after radiotherapy. Surg Neurol 29:388–392Google Scholar
  41. 41.
    Martinez-Rodrigo MA, Sanjuanbenito L, Rodriguez del Barrion E, Martinez-San Millan J, Saldana D (1988) Spinal cord compression secondary to epidural extramedullary hematopoiesis in thalassemia: a clinical case and review of literature. Rev Neurol 27:998–1004Google Scholar
  42. 42.
    Singounas EG, Sakas DE, Hadley DM, Chalevelakis G, Sfakianos G, Raptis S, Karvounis PC (1991) Paraplegia in a pregnant thalassemic woman due to extramedullary hematopoiesis: successful management with transfusions. Surg Neurol 36:210–215CrossRefPubMedGoogle Scholar
  43. 43.
    Hassoun H, Lawn-Tsao L, Langevin ER, Lathi ES, Palek J (1991) Spinal cord compression secondary to extramedullary hematopoiesis: a noninvasive management based on MRI. Am J Hematol 37:201–203CrossRefPubMedGoogle Scholar
  44. 44.
    Kaufmann T, Coleman M, Giardina P, Nisce LZ (1991) The role of radiation therapy in the management of hematopoietic neurologic complications in thalassemia. Acta Haematol 85:156–159CrossRefPubMedGoogle Scholar
  45. 45.
    Chaljub G, Guinto F, Crow W, Kumar R (1991) MRI diagnosis of spinal cord compression in beta thalassemia. Spine 16:583–584CrossRefPubMedGoogle Scholar
  46. 46.
    Mancuso P, Zingale A, Basile L, Chiaramonte I, Tropea R (1993) Cauda equina compression syndrome in a patient affected by thalassemia intermedia: complete regression with blood transfusion therapy. Childs Nerv Syst 9:440–441CrossRefPubMedGoogle Scholar
  47. 47.
    Richter E (1993) Extramedullary hematopoiesis with intraspinal extension in thalassemia. Aktuelle Radiol 3:320–322PubMedGoogle Scholar
  48. 48.
    Dore F, Pardini S, Gaviano E, Longinotti M, Bonfigli S, Rovasio S, Tomiselli A, Cossu F (1993) Recurrence of spinal cord compression from extramedullary hematopoiesis in thalassemia intermedia treated with low doses of radiotherapy. Am J Hematol 44:148CrossRefPubMedGoogle Scholar
  49. 49.
    Lau SR, Chan O, Chow Y (1994) Cord compression due to extramedullary hematopoiesis in a patient with thalassemia. Spine 19:2467–2470CrossRefPubMedGoogle Scholar
  50. 50.
    Gouliamos AD, Plataniotis GA, Michalopoulos ES, Vlahos LS, Papavasiliou CG (1995) Magnetic resonance imaging spinal cord compression in thalassaemia before and after radiation treatment. Clin Radiol 50:504–505CrossRefPubMedGoogle Scholar
  51. 51.
    Lee AC, Chiu W, Tai KS, Wong V, Pech WC, Lau YL (1996) Hypertransfusion for spinal cord compression secondary to extramedullary haematopoiesis. Pediatr Hematol Oncol 13:89–94CrossRefPubMedGoogle Scholar
  52. 52.
    Pistevou Gompaki K, Skaragas G, Papaskevopoulos P, Kotsa K, Repanta E (1996) Extramedullary hematopoiesis in thalassemia, results of radiotherapy: a report of three patients. Clin Oncol 8:120–122CrossRefGoogle Scholar
  53. 53.
    Cianciulli P, Sorrentino F, Morino L, Massa A, Sergiacomi GL, Donato V, Amadori S (1996) Radiotherapy combined with erythropoietin for the treatment of extramedullary hematopoiesis in an alloimmunized patient with thalassemia intermedia. Ann Hematol 72:379–381CrossRefPubMedGoogle Scholar
  54. 54.
    Boyacıgil S, Ardiç S, Tokog˘lu F, Pasaog˘lu E, Karakas HM (1996) Intrathoracic extramedullary haematopoiesis. Australas Radiol 40:179–181CrossRefPubMedGoogle Scholar
  55. 55.
    Coskun E, Keskin A, Suzer T, Sermez Y, Kildaci T, Tahta K (1998) Spinal cord compression secondary to extramedullary hematopoiesis in thalassemia intermedia. Eur Spine J 7:501–504CrossRefPubMedGoogle Scholar
  56. 56.
    Saxon BR, Rees D, Olivieri NF (1998) Regression of extramedullary haemopoiesis and augmentation of fetal haemoglobin concentration during hydroxyurea therapy in beta thalassemia. Br J Haematol 101:416–419CrossRefPubMedGoogle Scholar
  57. 57.
    Cianciulli P, di Toritto TC, Sorrentino F, Sergiacomi L, Massa A, Amadori S (2000) Hydroxyurea therapy in paraparesis and cauda equina syndrome due to extramedullary haematopoiesis in thalassaemia: improvement of clinical and haematological parameters. Eur J Haematol 64:426–429CrossRefPubMedGoogle Scholar
  58. 58.
    Phupong V, Uerpairojkij B, Limpongsanurak S (2000) Spinal cord compression: a rareness in pregnant thalassemic woman. J Obstet Gynaecol Res 26:117–120CrossRefPubMedGoogle Scholar
  59. 59.
    Aliberti B, Patrikiou A, Terentiou A, Frangatou S, Papadimitriou A (2001) Spinal cord compression due to extramedullary hematopoiesis in two patients with thalassemia: complete response with blood transfusion therapy. J Neurol 248:18–22CrossRefPubMedGoogle Scholar
  60. 60.
    Chourmouzi D, Pistevou-Gompaki K, Plataniotis G, Skaragas G, Papadopoulos L, Drevelegas A (2001) MRI findings of extramedullary haemopoiesis. Eur Radiol 11:1803–1806CrossRefPubMedGoogle Scholar
  61. 61.
    Cario H, Wegener M, Debatin KM, Kohne E (2002) Treatment with hydroxyurea in thalassemia intermedia with paravertebral pseudotumors of extramedullary hematopoiesis. Ann Hematol 81:478–482CrossRefPubMedGoogle Scholar
  62. 62.
    Tan TC, Tsao J, Cheung FC (2002) Extramedullary haemopoiesis in thalassemia intermedia presenting as paraplegia. J Clin Neurosci 9:721–725CrossRefPubMedGoogle Scholar
  63. 63.
    Chehal A, Aoun E, Koussa S, Skoury H, Koussa S, Taher A (2003) Hypertransfusion: a successful method of treatment in thalassemia intermedia patients with spinal cord compression secondary to extramedullary hematopoiesis. Spine 28:E245–E249CrossRefPubMedGoogle Scholar
  64. 64.
    Salehi SA, Koski T, Ondra SL (2004) Spinal cord compression in betathalassemia: case report and review of the literature. Spinal Cord 42:117–123CrossRefPubMedGoogle Scholar
  65. 65.
    Zamanizadeh B, Eghbali SS, Taghipour M, Haghnegahdar A, Zare Z (2006) Spinal cord compression secondary to extramedullary hematopoiesis: case report and summary. Neurosurg Q 16:144–146CrossRefGoogle Scholar
  66. 66.
    Malik M, Pillai LS, Gogia N, Puri T, Mahapatra M, Sharma DN, Kumar R (2007) Paraplegia due to extramedullary hematopoiesis in thalassemia treated successfully with radiation therapy. Haematologica 92:e28–e30CrossRefPubMedGoogle Scholar
  67. 67.
    Goerner M, Gerull S, Schaefer E, Just M, Sure M, Hirnle P (2008) Painful spinal cord compression as a complication of extramedullary hematopoiesis associated with β-thalassemia intermedia. Strahlenther Onkol 4:224–226CrossRefGoogle Scholar
  68. 68.
    Moncef B, Hafedh J (2008) Management of spinal cord compression caused by extramedullary hematopoiesis in beta-thalassemia. Inter Med 47:1125–1128CrossRefGoogle Scholar
  69. 69.
    Ileri T, Azik F, Ertem M, Uysal Z, Gozdasoglu S (2009) Extramedullary hematopoiesis with spinal cord compression in a child with thalassemia intermedia. J Pediatr Hematol Oncol 31:681–683CrossRefPubMedGoogle Scholar
  70. 70.
    Fetell MR, Stein BM (1989) Spinal tumors. In: Rowland LP (ed) Merritt’s textbook of neurology, 8th edn. Lea & Febiger, Philadelphia, pp 350–364Google Scholar
  71. 71.
    Dibbern DA, Loevner LA, Lieberman AP, Salhany KE, Freese A, Marcotte PJ (1997) MR of thoracic cord compression caused by epidural extramedullary hematopoiesis in myelodysplastic syndrome. AJNR Am J Neuroradiol 18:363–366PubMedGoogle Scholar
  72. 72.
    Sorsdahl O, Taylor PE, Noyes WD (1964) Extramedullary hematopoiesis, mediastinal masses and spinal cord compression. JAMA 189:343–347PubMedGoogle Scholar
  73. 73.
    Bronn LJ, Paquelet JR, Tetalman MR (1980) Intrathoracic extramedullary hematopoiesis: appearance on 99mTc sulfur colloid marrow scan. AJR Am J Roentgenol 134:1254–1255PubMedGoogle Scholar
  74. 74.
    Oustwani MB, Kurtides ES, Christ M, Ciric I (1980) Spinal cord compression with paraplegia in myelofibrosis. Arch Neurol 37:389–390PubMedGoogle Scholar
  75. 75.
    Guermazi A, Miaux Y, Chiras J (1997) Imaging of spinal cord compression due to thoracic extramedullary haematopoiesis in myelofibrosis. Neuroradiology 39:733–736CrossRefPubMedGoogle Scholar
  76. 76.
    Kalina P, Zaheer W, Drehobl KE (1995) Cord compression by extramedullary hematopoesis in polycythemia vera. AJR Am J Roentgenol 164:1027–1028PubMedGoogle Scholar
  77. 77.
    Wolman IJ, Ortolani M (1969) Some clinical features of Cooley’s anemia patients as related to transfusion schedules. Ann N Y Acad Sci 165:407–414CrossRefPubMedGoogle Scholar
  78. 78.
    Lawson J, Ablow R, Pearson H (1981) The ribs in thalassemia. I the Relationship to therapy. Radiology 140:663–672PubMedGoogle Scholar
  79. 79.
    Yamato M, Fuhrman C (1987) Computed tomography of fatty replacement in extramedullary hematopoiesis. J Comput Assisted Tomogr 11:541–542CrossRefGoogle Scholar
  80. 80.
    Savader S, Otero R, Savader B (1988) MR imaging of intrathoracic extramedullary hematopoiesis. J Comput Assist Tomogr 12:878–880CrossRefPubMedGoogle Scholar
  81. 81.
    Mesurolle B, Sayag E, Meingan P, Lasser P, Duvillard P, Vanel D (1996) Retroperitoneal extramedullary hematopoiesis: sonographic, CT and MR imaging appearance. AJR Am J Roentgenol 167:1139–1140PubMedGoogle Scholar
  82. 82.
    De Klippel N, Dehou MF, Bourgain C, Schots R, De Keyser J, Ebinger G (1993) Progressive paraparesis due to thoracic extramedullary hematopoiesis in myelofibrosis. Case report. J Neurosurg 79:125–127CrossRefPubMedGoogle Scholar
  83. 83.
    Tai SM, Chan JS, Ha SY, Young BW, Chan MS (2006) Successful treatment of spinal cord compression secondary to extramedullary hematopoietic mass by hypertransfusion in a patient with thalassemia major. Pediatr Hematol Oncol 23:317–321CrossRefPubMedGoogle Scholar
  84. 84.
    Bolling T, Schuck A, Rube C, Hesselmann S, Pape H, Dieckmann K, Pöllinger B, Kortmann RD, Speiser-Held I, Meyer FM, Martini C, Asadpour B, Timmermann B, Beck JD, Langer T, Paulides M, Schmidt B, Willich N (2006) Therapy-associated late effects after irradiation of malignant diseases in childhood and adolescence, Feasibility analyses of a prospective multicenter register study. Strahlenther Onkol 182:443–449CrossRefPubMedGoogle Scholar
  85. 85.
    Rades D, Dahm-Daphi J, Rudat V, Schulte R, Stalpers LJ, Veninga T, Hoskin PJ (2006) Is short-course radiotherapy with high doses per fraction the appropriate regimen for metastatic spinal cord compression in colorectal cancer patients? Strahlenther Onkol 182:708–712CrossRefPubMedGoogle Scholar
  86. 86.
    Trott KR, Kamprad F (2006) Estimation of cancer risks from radiotherapy of benign diseases. Strahlenther Onkol 182:431–436CrossRefPubMedGoogle Scholar
  87. 87.
    Olivieri NF, Rees DC, Ginder GD, Thein SL, Brittenham GM, Waye JS, Weatherall DJ (1997) Treatment of thalassemia major with phenylbutyrate and hydroxyurea. Lancet 350:491–492CrossRefPubMedGoogle Scholar
  88. 88.
    Konstantopoulos K, Vagiopoulos G, Kantouni R, Lymperi S, Patriarcheas G, Georgakopoulos D, Fessas P (1922) A case of spinal cord compression by extramedullary haematopoiesis in a thalassaemia patient: a putative role for hydroxyurea? Haematologica 77:352–354Google Scholar

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© Springer-Verlag 2010

Authors and Affiliations

  1. 1.Division of Orthopedic Surgery, Department of SurgeryAmerican University of Beirut Medical CenterBeirutLebanon
  2. 2.Spine ServiceHospital Universitario de Gran CanariaLas PalmasSpain
  3. 3.Division of Hematology and Oncology, Department of Internal MedicineAmerican University of Beirut Medical CenterBeirutLebanon

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