Download PDF
Semin Neurol 2010; 30(3): 287-295
DOI: 10.1055/s-0030-1255218
© Thieme Medical Publishers

Neurologic Complications of Hematopoietic Cell Transplantation

Albert Saiz1 , Francesc Graus1
  • 1Service of Neurology and Institut d'Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Hospital Clínic, University of Barcelona, Barcelona, Spain
Further Information

Publication History

Publication Date:
24 June 2010 (online)

    Permissions and Reprints

ABSTRACT

Hematopoietic cell transplantation (HCT) involves the intravenous infusion of hematopoietic progenitor cells from an HLA-matched donor (allogeneic) or from the patient (autologous). Prior to HCT, the recipient is prepared (conditioning) with high-dose chemotherapy or radiotherapy (or both) to destroy defective bone marrow or residual cancer cells. After allogeneic HCT, there is the need for chronic immunosuppression to prevent graft rejection and graft-versus-host disease (GVHD). The frequency and type of neurologic complications depends on the type of HCT, the underlying disease, and the case ascertainment. In this review, the neurologic complications are presented according to the stage of HCT that they are most likely to occur: (1) conditioning—drug-related encephalopathies and seizures or complications secondary to medical procedures; (2) bone marrow depletion—metabolic and drug-related encephalopathies and seizures, septic cerebral infarctions, and hemorrhages; (3) chronic immunosuppression—infections by viruses and opportunistic organisms; and (4) late events—central nervous system (CNS) relapses of the original disease, neurologic complications of GVHD, and second neoplasms.

KEYWORDS

Hematopoietic cell transplantation - immunosuppression - neurotoxicity - subdural hematoma - septic infarction - encephalitis

REFERENCES

  • 1 Armitage J O. Bone marrow transplantation.  N Engl J Med. 1994;  330(12) 827-838
    CrossrefPubMedSearch in Google Scholar
  • 2 Rubin J, Wide K, Remberger M, Gustafsson B. Acute neurological complications after hematopoietic stem cell transplantation in children.  Pediatr Transplant. 2005;  9(1) 62-67
    CrossrefPubMedSearch in Google Scholar
  • 3 Weber C, Schaper J, Tibussek D et al.. Diagnostic and therapeutic implications of neurological complications following paediatric haematopoietic stem cell transplantation.  Bone Marrow Transplant. 2008;  41(3) 253-259
    CrossrefPubMedSearch in Google Scholar
  • 4 Siegal D, Keller A, Xu W et al.. Central nervous system complications after allogeneic hematopoietic stem cell transplantation: incidence, manifestations, and clinical significance.  Biol Blood Marrow Transplant. 2007;  13(11) 1369-1379
    CrossrefPubMedSearch in Google Scholar
  • 5 Wiznitzer M, Packer R J, August C S, Burkey E D. Neurological complications of bone marrow transplantation in childhood.  Ann Neurol. 1984;  16(5) 569-576
    CrossrefPubMedSearch in Google Scholar
  • 6 Patchell R A, White III C L, Clark A W, Beschorner W E, Santos G W. Neurologic complications of bone marrow transplantation.  Neurology. 1985;  35(3) 300-306
    PubMedSearch in Google Scholar
  • 7 Mohrmann R L, Mah V, Vinters H V. Neuropathologic findings after bone marrow transplantation: an autopsy study.  Hum Pathol. 1990;  21(6) 630-639
    CrossrefPubMedSearch in Google Scholar
  • 8 Graus F, Saiz A, Sierra J et al.. Neurologic complications of autologous and allogeneic bone marrow transplantation in patients with leukemia: a comparative study.  Neurology. 1996;  46(4) 1004-1009
    PubMedSearch in Google Scholar
  • 9 Antonini G, Ceschin V, Morino S et al.. Early neurologic complications following allogeneic bone marrow transplant for leukemia: a prospective study.  Neurology. 1998;  50(5) 1441-1445
    PubMedSearch in Google Scholar
  • 10 Bleggi-Torres L F, de Medeiros B C, Werner B et al.. Neuropathological findings after bone marrow transplantation: an autopsy study of 180 cases.  Bone Marrow Transplant. 2000;  25(3) 301-307
    CrossrefPubMedSearch in Google Scholar
  • 11 de Brabander C, Cornelissen J, Smitt P A, Vecht C J, van den Bent M J. Increased incidence of neurological complications in patients receiving an allogenic bone marrow transplantation from alternative donors.  J Neurol Neurosurg Psychiatry. 2000;  68(1) 36-40
    CrossrefPubMedSearch in Google Scholar
  • 12 Barba P, Piñana J L, Valcárcel D et al.. Early and late neurological complications after reduced-intensity conditioning allogeneic stem cell transplantation.  Biol Blood Marrow Transplant. 2009;  15(11) 1439-1446
    CrossrefPubMedSearch in Google Scholar
  • 13 Lieberman F, Gulati S. Intracranial hypotension following bone marrow ‘donation’.  Neurology. 1992;  42 163
    PubMedSearch in Google Scholar
  • 14 Sylvestre D L, Sandson T A, Nachmanoff D B. Transient brachial plexopathy as a complication of internal jugular vein cannulation.  Neurology. 1991;  41(5) 760
    PubMedSearch in Google Scholar
  • 15 DiMaggio J R, Brown R, Baile W F, Schapira D. Hallucinations and ifosfamide-induced neurotoxicity.  Cancer. 1994;  73(5) 1509-1514
    CrossrefPubMedSearch in Google Scholar
  • 16 Posner J B. Side effects of chemotherapy. In: Neurologic Complications of Cancer. New York/Oxford; Oxford University Press 1995: 282-310
    PubMedSearch in Google Scholar
  • 17 Tahsildar H I, Remler B F, Creger R J et al.. Delayed, transient encephalopathy after marrow transplantation: case reports and MRI findings in four patients.  J Neurooncol. 1996;  27(3) 241-250
    CrossrefPubMedSearch in Google Scholar
  • 18 Hoyt R, Szer J, Grigg A. Neurological events associated with the infusion of cryopreserved bone marrow and/or peripheral blood progenitor cells.  Bone Marrow Transplant. 2000;  25(12) 1285-1287
    CrossrefPubMedSearch in Google Scholar
  • 19 Dixit S, Kurle P, Buyan-Dent L, Sheth R D. Status epilepticus associated with cefepime.  Neurology. 2000;  54(11) 2153-2155
    PubMedSearch in Google Scholar
  • 20 Bleggi-Torres L F, de Medeiros B C, Ogasawara V SA et al.. Iatrogenic Wernicke's encephalopathy in allogeneic bone marrow transplantation: a study of eight cases.  Bone Marrow Transplant. 1997;  20(5) 391-395
    CrossrefPubMedSearch in Google Scholar
  • 21 Wade J C, Meyers J D. Neurologic symptoms associated with parenteral acyclovir treatment after marrow transplantation.  Ann Intern Med. 1983;  98(6) 921-925
    PubMedSearch in Google Scholar
  • 22 Gordon B, Lyden E, Lynch J et al.. Central nervous system dysfunction as the first manifestation of multiple organ dysfunction syndrome in stem cell transplant patients.  Bone Marrow Transplant. 2000;  25(1) 79-83
    CrossrefPubMedSearch in Google Scholar
  • 23 Pomeranz S, Naparstek E, Ashkenazi E et al.. Intracranial haematomas following bone marrow transplantation.  J Neurol. 1994;  241(4) 252-256
    CrossrefPubMedSearch in Google Scholar
  • 24 Colosimo M, McCarthy N, Jayasinghe R, Morton J, Taylor K, Durrant S. Diagnosis and management of subdural haematoma complicating bone marrow transplantation.  Bone Marrow Transplant. 2000;  25(5) 549-552
    CrossrefPubMedSearch in Google Scholar
  • 25 Coplin W M, Cochran M S, Levine S R, Crawford S W. Stroke after bone marrow transplantation: frequency, aetiology and outcome.  Brain. 2001;  124(Pt 5) 1043-1051
    CrossrefPubMedSearch in Google Scholar
  • 26 Najima Y, Ohashi K, Miyazawa M et al.. Intracranial hemorrhage following allogeneic hematopoietic stem cell transplantation.  Am J Hematol. 2009;  84(5) 298-301
    CrossrefPubMedSearch in Google Scholar
  • 27 Campbell J N, Morris P P. Cerebral vasculitis in graft-versus-host disease: a case report.  AJNR Am J Neuroradiol. 2005;  26(3) 654-656
    PubMedSearch in Google Scholar
  • 28 Marco de Lucas E, Sábada P, García-Barón P L et al.. Cerebral scedosporiosis: an emerging fungal infection in severe neutropenic patients.  Eur Radiol. 2006;  16 496-502
    CrossrefPubMedSearch in Google Scholar
  • 29 DeLone D R, Goldstein R A, Petermann G et al.. Disseminated aspergillosis involving the brain: distribution and imaging characteristics.  AJNR Am J Neuroradiol. 1999;  20(9) 1597-1604
    PubMedSearch in Google Scholar
  • 30 Jantunen E, Ruutu P, Piilonen A, Volin L, Parkkali T, Ruutu T. Treatment and outcome of invasive Aspergillus infections in allogeneic BMT recipients.  Bone Marrow Transplant. 2000;  26(7) 759-762
    CrossrefPubMedSearch in Google Scholar
  • 31 Schwartz S, Ruhnke M, Ribaud P et al.. Improved outcome in central nervous system aspergillosis, using voriconazole treatment.  Blood. 2005;  106(8) 2641-2645
    CrossrefPubMedSearch in Google Scholar
  • 32 Patterson T F, Kirkpatrick W R, White M et al.. Invasive aspergillosis. Disease spectrum, treatment practices, and outcomes. I3 Aspergillus Study Group.  Medicine (Baltimore). 2000;  79(4) 250-260
    CrossrefPubMedSearch in Google Scholar
  • 33 Shah A K. Cyclosporine A neurotoxicity among bone marrow transplant recipients.  Clin Neuropharmacol. 1999;  22(2) 67-73
    CrossrefPubMedSearch in Google Scholar
  • 34 Hinchey J, Chaves C, Appignani B et al.. A reversible posterior leukoencephalopathy syndrome.  N Engl J Med. 1996;  334(8) 494-500
    CrossrefPubMedSearch in Google Scholar
  • 35 Atkinson K, Biggs J, Darveniza P, Boland J, Concannon A, Dodds A. Cyclosporin-associated central nervous system toxicity after allogeneic bone marrow transplantation.  Transplantation. 1984;  38(1) 34-37
    CrossrefPubMedSearch in Google Scholar
  • 36 Bartynski W S, Zeigler Z, Spearman M P, Lin L, Shadduck R K, Lister J. Etiology of cortical and white matter lesions in cyclosporin-A and FK-506 neurotoxicity.  AJNR Am J Neuroradiol. 2001;  22(10) 1901-1914
    PubMedSearch in Google Scholar
  • 37 Bartynski W S. Posterior reversible encephalopathy syndrome, part 1: fundamental imaging and clinical features.  AJNR Am J Neuroradiol. 2008;  29(6) 1036-1042
    CrossrefPubMedSearch in Google Scholar
  • 38 Furukawa M, Terae S, Chu B C, Kaneko K, Kamada H, Miyasaka K. MRI in seven cases of tacrolimus (FK-506) encephalopathy: utility of FLAIR and diffusion-weighted imaging.  Neuroradiology. 2001;  43(8) 615-621
    CrossrefPubMedSearch in Google Scholar
  • 39 Steg R E, Garcia E G. Complex visual hallucinations and cyclosporine neurotoxicity.  Neurology. 1991;  41(7) 1156
    PubMedSearch in Google Scholar
  • 40 Miyao S, Takano A, Teramoto J, Fujitake S, Hashizume Y. Oculomotor nerve palsy due to intraneural hemorrhage in idiopathic thrombocytopenic purpura: a case report.  Eur Neurol. 1993;  33(1) 20-22
    CrossrefPubMedSearch in Google Scholar
  • 41 Edelson R N, Chernik N L, Posner J B. Spinal subdural hematomas complicating lumbar puncture.  Arch Neurol. 1974;  31(2) 134-137
    CrossrefPubMedSearch in Google Scholar
  • 42 Wen P Y, Alyea E P, Simon D, Herbst R S, Soiffer R J, Antin J H. Guillain-Barré syndrome following allogeneic bone marrow transplantation.  Neurology. 1997;  49(6) 1711-1714
    PubMedSearch in Google Scholar
  • 43 Martino R, Bretagne S, Rovira M et al.. Toxoplasmosis after hematopoietic stem transplantation. Report of a 5-year survey from the Infectious Diseases Working Party of the European Group for Blood and Marrow Transplantation.  Bone Marrow Transplant. 2000;  25(10) 1111-1114
    CrossrefPubMedSearch in Google Scholar
  • 44 Chandrasekar P H, Momin F. Bone Marrow Transplant Team . Disseminated toxoplasmosis in marrow recipients: a report of three cases and a review of the literature.  Bone Marrow Transplant. 1997;  19(7) 685-689
    CrossrefPubMedSearch in Google Scholar
  • 45 Maschke M, Dietrich U, Prumbaum M et al.. Opportunistic CNS infection after bone marrow transplantation.  Bone Marrow Transplant. 1999;  23(11) 1167-1176
    CrossrefPubMedSearch in Google Scholar
  • 46 Martino R, Bretagne S, Einsele H Infectious Disease Working Party of the European Group for Blood and Marrow Transplantation et al. Early detection of Toxoplasma infection by molecular monitoring of Toxoplasma gondii in peripheral blood samples after allogeneic stem cell transplantation.  Clin Infect Dis. 2005;  40(1) 67-78
    CrossrefPubMedSearch in Google Scholar
  • 47 Fischer S A. Emerging viruses in transplantation: there is more to infection after transplant than CMV and EBV.  Transplantation. 2008;  86(10) 1327-1339
    CrossrefPubMedSearch in Google Scholar
  • 48 Cordonnier C, Feuilhade F, Vernant J P, Marsault C, Rodet M, Rochant H. Cytomegalovirus encephalitis occurring after bone marrow transplantation.  Scand J Haematol. 1983;  31(3) 248-252
    CrossrefPubMedSearch in Google Scholar
  • 49 Koc Y, Miller K B, Schenkein D P et al.. Varicella zoster virus infections following allogeneic bone marrow transplantation: frequency, risk factors, and clinical outcome.  Biol Blood Marrow Transplant. 2000;  6(1) 44-49
    CrossrefPubMedSearch in Google Scholar
  • 50 Vu T, Carrum G, Hutton G, Heslop H E, Brenner M K, Kamble R. Human herpesvirus-6 encephalitis following allogeneic hematopoietic stem cell transplantation.  Bone Marrow Transplant. 2007;  39(11) 705-709
    CrossrefPubMedSearch in Google Scholar
  • 51 Wainwright M S, Martin P L, Morse R P et al.. Human herpesvirus 6 limbic encephalitis after stem cell transplantation.  Ann Neurol. 2001;  50(5) 612-619
    CrossrefPubMedSearch in Google Scholar
  • 52 Zerr D M. Human herpesvirus 6 and central nervous system disease in hematopoietic cell transplantation.  J Clin Virol. 2006;  37(S1) S52-S56
    CrossrefPubMedSearch in Google Scholar
  • 53 Provenzale J M, vanLandingham K E, Lewis D V, Mukundan Jr S, White L E. Extrahippocampal involvement in human herpesvirus 6 encephalitis depicted at MR imaging.  Radiology. 2008;  249(3) 955-963
    CrossrefPubMedSearch in Google Scholar
  • 54 Guppy K H, Thomas C, Thomas K, Anderson D. Cerebral fungal infections in the immunocompromised host: a literature review and a new pathogen—Chaetomium atrobrunneum: case report.  Neurosurgery. 1998;  43(6) 1463-1469
    CrossrefPubMedSearch in Google Scholar
  • 55 Hagensee M E, Bauwens J E, Kjos B, Bowden R A. Brain abscess following marrow transplantation: experience at the Fred Hutchinson Cancer Research Center, 1984–1992.  Clin Infect Dis. 1994;  19(3) 402-408
    CrossrefPubMedSearch in Google Scholar
  • 56 Kharfan-Dabaja M A, Ayala E, Greene J, Rojiani A, Murtagh F R, Anasetti C. Two cases of progressive multifocal leukoencephalopathy after allogeneic hematopoietic cell transplantation and a review of the literature.  Bone Marrow Transplant. 2007;  39(2) 101-107
    CrossrefPubMedSearch in Google Scholar
  • 57 Reyes M G, Noronha P, Thomas Jr W, Heredia R. Myositis of chronic graft versus host disease.  Neurology. 1983;  33(9) 1222-1224
    PubMedSearch in Google Scholar
  • 58 Grau J M, Casademont J, Monforte R et al.. Myasthenia gravis after allogeneic bone marrow transplantation: report of a new case and pathogenetic considerations.  Bone Marrow Transplant. 1990;  5(6) 435-437
    PubMedSearch in Google Scholar
  • 59 Amato A A, Barohn R J, Sahenk Z, Tutschka P J, Mendell J R. Polyneuropathy complicating bone marrow and solid organ transplantation.  Neurology. 1993;  43(8) 1513-1518
    PubMedSearch in Google Scholar
  • 60 Sostak P, Padovan C S, Eigenbrod S et al.. Cerebral angiitis in four patients with chronic GVHD.  Bone Marrow Transplant. 2009;  , (Epub ahead of print)
    PubMedSearch in Google Scholar
  • 61 Padovan C S, Bise K, Hahn J et al.. Angiitis of the central nervous system after allogeneic bone marrow transplantation?.  Stroke. 1999;  30(8) 1651-1656
    CrossrefPubMedSearch in Google Scholar
  • 62 Saad A G, Alyea III E P, Wen P Y, Degirolami U, Kesari S. Graft-versus-host disease of the CNS after allogeneic bone marrow transplantation.  J Clin Oncol. 2009;  27(30) e147-e149
    CrossrefPubMedSearch in Google Scholar
  • 63 Ma M, Barnes G, Pulliam J, Jezek D, Baumann R J, Berger J R. CNS angiitis in graft vs. host disease.  Neurology. 2002;  59(12) 1994-1997
    PubMedSearch in Google Scholar
  • 64 Padovan C S, Yousry T A, Schleuning M, Holler E, Kolb H J, Straube A. Neurological and neuroradiological findings in long-term survivors of allogeneic bone marrow transplantation.  Ann Neurol. 1998;  43(5) 627-633
    CrossrefPubMedSearch in Google Scholar
  • 65 Sostak P, Padovan C S, Yousry T A, Ledderose G, Kolb H J, Straube A. Prospective evaluation of neurological complications after allogeneic bone marrow transplantation.  Neurology. 2003;  60(5) 842-848
    PubMedSearch in Google Scholar
  • 66 Cohen J I. Epstein-Barr virus lymphoproliferative disease associated with acquired immunodeficiency.  Medicine (Baltimore). 1991;  70(2) 137-160
    CrossrefPubMedSearch in Google Scholar
  • 67 Nozzoli C, Bartolozzi B, Guidi S et al.. Epstein-Barr virus-associated post-transplant lymphoproliferative disease with central nervous system involvement after unrelated allogeneic hematopoietic stem cell transplantation.  Leuk Lymphoma. 2006;  47(1) 167-169
    CrossrefPubMedSearch in Google Scholar
  • 68 Curtis R E, Rowlings P A, Deeg H J et al.. Solid cancers after bone marrow transplantation.  N Engl J Med. 1997;  336(13) 897-904
    CrossrefPubMedSearch in Google Scholar

Francesc GrausM.D. 

Servei de Neurologia, Hospital Clínic, Villarroel 170

Barcelona 08036, Spain

Email: graus@medicina.ub.es