Semin Neurol 2004; 24(4): 427-434
DOI: 10.1055/s-2004-861537
Copyright © 2004 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

Neurological 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:
07 January 2005 (online)

ABSTRACT

Hematopoietic cell transplantation (HCT) involves the intravenous infusion of hematopoietic progenitor cells from the patient (autologous) or a human leukocyte antigen-matched donor (allogeneic). Before transplantation, the recipient undergoes a conditioning regimen with high-dose chemotherapy or radiotherapy (or both) to destroy a defective bone marrow or residual cancer cells. After allogenic HCT chronic immunosuppression is needed to prevent graft rejection and graft-versus-host disease. The frequency and type of neurological complication depends on the type of HCT, the underlying disease, and the case ascertainment. In this review the neurological 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 relapses of the original disease, neurological complications of graft versus host disease, and second neoplasms.

REFERENCES

  • 1 Armitage J O. Bone marrow transplantation.  N Engl J Med. 1994;  330 827-838
  • 2 Davis D G, Patchell R A. Neurologic complications of bone marrow transplantation.  Neurol Clin. 1988;  6 377-387
  • 3 Openshaw H, Slatkin E N. Neurological complications. In: Thomas ED, Blume KG, Forman SJ Hematopoietic Cell Transplantation Malden MA; Blackwell Scientific Inc 1999: 659-673
  • 4 Patchell R A. Neurological complications of organ transplantation.  Ann Neurol. 1994;  36 688-703
  • 5 Wiznitzer M, Packer R J, August C S, Burkey E D. Neurological complications of bone marrow transplantation in childhood.  Ann Neurol. 1984;  16 569-576
  • 6 Patchell R A, White C L, Clark A W, Beschorner W E, Santos G W. Neurological complications of bone marrow transplantation.  Neurology. 1985;  35 300-306
  • 7 Mohrmann R L, Mah V, Vinters H V. Neuropathologic findings after bone marrow transplantation: an autopsy study.  Hum Pathol. 1990;  21 630-639
  • 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 1004-1009
  • 9 Antonini G, Ceschin V, Morino S et al.. Early neurologic complications following allogeneic bone marrow transplant for leukemia.  Neurology. 1998;  50 1441-1445
  • 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;  25 301-307
  • 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 36-40
  • 12 Snider S, Bashir R, Bierman P. Neurologic complications after high-dose chemotherapy and autologous bone marrow transplantation for Hodgkin's disease.  Neurology. 1994;  44 681-684
  • 13 Lieberman F, Gulati S. Headaches after inadvertent lumbar puncture during bone marrow harvest.  Neurology. 1996;  46 268-269
  • 14 Sylvestre D L, Sandson T A, Nachmanoff D B. Transient brachial plexopathy as a complication of internal jugular vein cannulation.  Neurology. 1991;  41 760
  • 15 DiMaggio J R, Brown R, Baile W F, Schapira D. Hallucinations and ifosfamide-induced neurotoxicity.  Cancer. 1994;  73 1509-1514
  • 16 Posner J B. Side effects of chemotherapy. In: Neurologic Complications of Cancer Philadelphia; FA Davis Company 1995: 282-310
  • 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;  27 241-250
  • 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 1285-1287
  • 19 Dixit S, Kurle P, Buyan-Dent L, Sheth R D. Status epilepticus associated with cefepime.  Neurology. 2000;  54 2153-2155
  • 20 Bleggi-Torres L F, 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;  20 391-395
  • 21 Wade J C, Meyers J D. Neurologic symptoms associated with parenteral acyclovir treatment after marrow transplantation.  Ann Intern Med. 1983;  98 921-925
  • 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 79-83
  • 23 Pomeranz S, Naparstek E, Ashkenazi E et al.. Intracranial hematomas following bone marrow transplantation.  J Neurol. 1994;  241 252-256
  • 24 Colosimo M, McCarthy N, Jayasinghe R, Morton J, Taylor K, Durrant S. Diagnosis and management of subdural hematoma complicating bone marrow transplantation.  Bone Marrow Transplant. 2000;  25 549-552
  • 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 1043-1051
  • 26 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 1597-1604
  • 27 Jantunen E, Piilonen A, Volin L, Parkkali T, Koukila-Kahkola P, Ruutu T. Diagnostic aspects of invasive Aspergillus infections in allogeneic BMT recipients.  Bone Marrow Transplant. 2000;  25 867-871
  • 28 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;  26 759-762
  • 29 Patterson T F, Kirkpatrick W R, White M et al.. Invasive aspergillosis. Disease spectrum, treatment practices, and outcomes.  Medicine. 2000;  79 250-260
  • 30 Shah A K. Cyclosporine A neurotoxicity among bone marrow transplant recipients.  Clin Neuropharmacol. 1999;  22 67-73
  • 31 Reece D E, Frei-Lahr D A, Shepherd J D et al.. Neurologic complications in allogeneic bone marrow transplant patients receiving cyclosporin.  Bone Marrow Transplant. 1991;  8 393-401
  • 32 Hinchey J, Chaves C, Appignani B et al.. A reversible posterior leukoencephalopathy syndrome.  N Engl J Med. 1996;  334 494-500
  • 33 Atkinson K, Biggs J, Darveniza P, Boland J, Concannon A, Dodds A. Cyclosporine-associated central nervous system toxicity after allogeneic bone marrow transplantation.  Transplantation. 1984;  38 34-37
  • 34 Bartynski W S, Zeigler Z, Spearmen 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 1901-1914
  • 35 Casey S O, Sampaio R C, Michel E, Truwit C L. Posterior reversible encephalopathy syndrome: utility of fluid-attenuated inversion recovery MR imaging in the detection of cortical and subcortical lesions.  AJNR Am J Neuroradiol. 2000;  21 1199-1206
  • 36 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;  43 615-621
  • 37 Steg R E, Garcia E G. Complex visual hallucinations and cyclosporine neurotoxicity.  Neurology. 1991;  41 1156
  • 38 Balmaceda C M, Walker R W, Castro-Malaspina H, Dalmau J. Reversal of amphotericin-B-related encephalopathy.  Neurology. 1994;  44 1183-1184
  • 39 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 20-22
  • 40 Edelson R N, Chernik N L, Posner J B. Spinal subdural hematomas complicating lumbar puncture.  Arch Neurol. 1974;  31 134-137
  • 41 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 1711-1714
  • 42 Martino R, Bretagne S, Rovira M et al.. Toxoplasmosis after hematopoietic stem transplantation. Report of a 5-year survey from the Infectious Disease Working Party of the European Group for Blood and Marrow Transplantation.  Bone Marrow Transplant. 2000;  25 1111-1113
  • 43 Chandrasekar P H, Momin F. and the Bone . Marrow Transplant Team. Disseminated toxoplasmosis in marrow transplant recipients: a report of three cases and review of the literature.  Bone Marrow Transplant. 1997;  19 685-689
  • 44 Maschke M, Dietrich U, Prumbaum M et al.. Opportunistic CNS infections after bone marrow transplantation.  Bone Marrow Transplant. 1999;  23 1167-1176
  • 45 Davis D, Henslee P J, Markesbery W R. Fatal adenovirus meningoencephalitis in a bone marrow transplant patient.  Ann Neurol. 1988;  23 385-389
  • 46 Conti D J, Rubin R H. Infection of the central nervous system in organ transplant recipients.  Neurol Clin. 1988;  6 241-260
  • 47 Cordonnier C, Feuilhade F, Vernant J P, Marsault C, Rodet M, Rochant H. Cytomegalovirus encephalitis occurring after bone marrow transplantation.  Scand J Haematol. 1983;  31 248-252
  • 48 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 44-49
  • 49 Mookerjee B P, Vogelsang G. Human herpes virus-6 encephalitis after bone marrow transplantation: successful treatment with ganciclovir.  Bone Marrow Transplant. 1997;  20 905-906
  • 50 Wainwright M S, Martin P L, Morse R P et al.. Human herpesvirus 6 limbic encephalitis after stem cell transplantation.  Ann Neurol. 2001;  50 612-619
  • 51 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 1463-1469
  • 52 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;  19 402-408
  • 53 Coppo P, Laporte J Ph, Aoudjhane M et al.. Progressive multifocal leucoencephalopathy with peripheral demyelinating neuropathy after autologous bone marrow transplantation for acute myeloblastic leukemia (FAB5).  Bone Marrow Transplant. 1999;  23 401-403
  • 54 Re D, Bamborschke S, Feiden W et al.. Progressive multifocal leukoencephalopathy after autologous bone marrow transplantation and alpha-interferon immunotherapy.  Bone Marrow Transplant. 1999;  23 295-298
  • 55 Reyes M G, Noronha P, Thomas W, Heredia R. Myositis of chronic graft versus host disease.  Neurology. 1983;  33 1222-1224
  • 56 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;  5 435-437
  • 57 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 1513-1518
  • 58 Iwasaki Y, Sako K, Ohara Y et al.. Subacute panencephalitis associated with chronic graft-versus-host disease.  Acta Neuropathol (Berl). 1993;  85 566-572
  • 59 Padovan C S, Bise K, Hahn J et al.. Angiitis of the central nervous system after allogeneic bone marrow transplantation.  Stroke. 1999;  30 1651-1656
  • 60 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;  43 627-633
  • 61 Ma M, Barnes G, Pulliam J, Jezek D, Baumann R J, Berger J R. CNS angiitis in graft vs host disease.  Neurology. 2002;  59 1994-1997
  • 62 Sostak P, Padovan C S, Yousry T A, Ledderose G, Kolb H J, Straube A. Prospective evaluation of neurological complications after allogenic bone marrow transplantation.  Neurology. 2003;  60 842-848
  • 63 Cohen J I. Epstein-Barr virus lymphoproliferative disease associated with acquired immunodeficiency.  Medicine. 1991;  70 137-160
  • 64 Curtis R E, Rowlings P A, Deeg J et al.. Solid cancers after bone marrow transplantation.  N Engl J Med. 1997;  336 897-904

Francesc GrausM.D. 

Servei de Neurologia, Hospital Clínic

Villarroel 170

Barcelona 08036, Spain

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