Journal of Neuro-Oncology

, Volume 110, Issue 2, pp 251–256 | Cite as

Central and peripheral nervous system immune mediated demyelinating disease after allogeneic hemopoietic stem cell transplantation for hematologic disease

  • Anna Maria Delios
  • Marc Rosenblum
  • Ann A. Jakubowski
  • Lisa M. DeAngelis
Clinical Study


Immune mediated demyelinating disease (IMDD) after allogeneic hemopoietic stem cell transplant (HSCT) is rare and its etiology unclear. In this retrospective study, we identified patients who underwent HSCT between January 1992 and December 2010 and had IMDD post transplant. A total of 1,484 patients received HSCT and 7 (0.5 %) suffered from IMDD; five were men, and the median age was 54 years (range, 29–64 years). HSCT treated acute myeloid leukemia (n = 5), myelodysplastic syndrome (n = 1), and Waldenström macroglobulinemia (n = 1). All received an HLA matched donor graft, related (6), unrelated (1); from the bone marrow (1), peripheral blood stem cell (6); and T-cell depleted, ex vivo (6) or in vivo (1). The median time from transplant to neurologic symptoms was 120 days (range, 60–390 days). Three had acute demyelinating encephalomyelitis (ADEM), three acute inflammatory demyelinating polyradiculopathy (AIDP) and one autonomic neuropathy. Four of six patients tested had hemopoietic mixed chimerism prior to neurologic symptoms and low CD4+ T-cell counts, median 76 (15–500 cells/μL). Two patients had simultaneous systemic graft versus host disease (GVHD). Two patients with ADEM had a spinal cord or brain biopsy which revealed demyelination. No patients had a viral etiology identified in the cerebrospinal fluid. Patients were treated with IV immunoglobulin, high dose steroids and/or rituximab. Five patients had a significant recovery. Response to immune modulators suggests an immune-based etiology. The incidence of de novo autoimmune disease after HSCT for hematological diseases is rare and may be difficult to differentiate from GVHD.


Allogeneic Stem cell transplant Demyelinating Acute inflammatory demyelinating polyradiculopathy Acute demyelinating encephalomyelitis 


Conflict of interest



  1. 1.
    Brabander C, Cornelissen J, Sillevis Smitt PAE, Vecht ChJ, Van den Bent MJ (2000) Increased incidence of neurological complications in patients receiving allogeneic bone marrow transplantation from alternative donors. J Neurol Neurosurg Psychiatry 68:36–40PubMedCrossRefGoogle Scholar
  2. 2.
    Barba P, Pinana JL, Valcarcel D et al (2009) Early and late neurological complications after reduced-intensity conditioning allogeneic stem cell transplantation. Biol Blood Marrow Transpl 15:1439–1446CrossRefGoogle Scholar
  3. 3.
    Siegal D, Keller A, Xu W et al (2007) Central nervous system complications after allogeneic hematopoietic stem cell transplantation: incidence, manifestations, and clinical significance. Biol Blood Marrow Transpl 13:1369–1379CrossRefGoogle Scholar
  4. 4.
    Sostak P, Padovan CS, Yousry TA, Ledderose G, Kolb L, Straube A (2003) Prospective evaluation of neurological complications after allogeneic bone marrow transplantation. Neurology 60:842–848PubMedCrossRefGoogle Scholar
  5. 5.
    Weber C, Schaper J, Tibussek D et al (2008) Diagnostic and therapeutic implications of neurological complications following paediatric haematopoietic stem cell transplantation. Bone Marrow Transpl 41:253–259CrossRefGoogle Scholar
  6. 6.
    Padovan CS, Gerbitz A, Sostak P et al (2001) Cerebral involvement in graft-versus-host disease after murine bone marrow transplantation. Neurology 56:1106–1108PubMedCrossRefGoogle Scholar
  7. 7.
    Grauer O, Wolff D, Bertz H et al (2010) Neurological manifestations of chronic graft-versus-host disease after allogeneic haematopoietic stem cell transplantation: report from the consensus conference on clinical practice in chronic graft-versus-host disease. Brain 133:2852–2865PubMedCrossRefGoogle Scholar
  8. 8.
    Sakai M, Ohashi K, Ohta K, Yamashita T, Akiyama H, Kisida S et al (2006) Immune-mediated myelopathy following allogeneic stem cell transplantation. Int J Hematol 84:272–275PubMedCrossRefGoogle Scholar
  9. 9.
    Openshaw H, Slatkin NE, Parker PM, Forman SJ (1995) Immune mediated myelopathy after allogeneic marrow transplantation. Bone Marrow Transpl 15(4):633–636Google Scholar
  10. 10.
    Vosz M, Bischof F (2010) Recurrent myelitis after allogeneic stem cell transplantation. Report of two cases. BMC Neurol 10(1):76CrossRefGoogle Scholar
  11. 11.
    Matsuo Y, Kamezaki K, Takesihi S, Takenaka K, Eto T, Nonami A et al (2009) Encephalomyelitis mimicking multiple sclerosis associated with chronic graft-versus host disease after allogeneic bone marrow transplantation. Intern Med 48:1453–1456PubMedCrossRefGoogle Scholar
  12. 12.
    Bulsara KR, Baron PW, Tuttle-Newhall JE, Clavien PA, Morgenlander J (2001) Guillain-Barre syndrome in organ and bone marrow transplant patients. Transplantation 71:1169–1172PubMedCrossRefGoogle Scholar
  13. 13.
    Rodriguez V, Kuehnle I, Heslop HE, Khan S, Krance RA (2002) Guillain-Barre syndrome after allogeneic hematopoietic stem cell transplantation. Bone Marrow Transpl 29:515–517CrossRefGoogle Scholar
  14. 14.
    Mohrmann R, Mah V, Vinters H (1990) Neuropathologic findings after bone marrow transplantation: an autopsy study. Hum Pathol 21(6):630–639PubMedCrossRefGoogle Scholar
  15. 15.
    Saad AG, Alyea EP III, Wen PY, Degirolami U, Kesari S (2009) Graft-versus-host disease of the CNS after allogeneic bone marrow transplantation. J Clin Oncol 27:e147–e149PubMedCrossRefGoogle Scholar
  16. 16.
    King C, Ilic A, Koelsch K, Sarvetnick N (2004) Homeostatic expansion of T-cells during immune deficiency generates autoimmunity. Cell 117:265–277PubMedCrossRefGoogle Scholar
  17. 17.
    Daikeler T, Labopin M, Gioia Di et al (2011) Secondary autoimmune disease occurring after HSCT for an autoimmune disease: a retrospective study of the EBMT autoimmune disease working party. Blood 118:1693–1698PubMedCrossRefGoogle Scholar
  18. 18.
    Sykes M, Nikolic B (2005) Treatment of severe autoimmune disease by stem-cell transplantation. Nature 435:620–627PubMedCrossRefGoogle Scholar
  19. 19.
    El-Sabrout RA, Radovancevic B, Ankoma-Sey V, Van Buren CT (2001) Guillain-Barre syndrome after solid transplantation. Transplantation 71:1311–1316PubMedCrossRefGoogle Scholar
  20. 20.
    Roskrow MA, Kelsey SM, McCarthy M, Newland AC, Monson JP (1992) Selective automatic neuropathy as a novel complication of BMT. Bone Marrow Transpl 10(5):469–470Google Scholar

Copyright information

© Springer Science+Business Media, LLC. 2012

Authors and Affiliations

  • Anna Maria Delios
    • 1
  • Marc Rosenblum
    • 2
  • Ann A. Jakubowski
    • 3
  • Lisa M. DeAngelis
    • 1
  1. 1.Department of NeurologyMemorial Sloan-Kettering Cancer CenterNew YorkUSA
  2. 2.Department of PathologyMemorial Sloan-Kettering Cancer CenterNew YorkUSA
  3. 3.Department of MedicineMemorial Sloan-Kettering Cancer CenterNew YorkUSA

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