Neurologic Complications of Hematopoietic Cell Transplantation

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.

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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 13 Lieberman F, Gulati S. Intracranial hypotension following bone marrow ‘donation’.  Neurology. 1992;  42 163
• 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
• 15 DiMaggio J R, Brown R, Baile W F, Schapira D. Hallucinations and ifosfamide-induced neurotoxicity.  Cancer. 1994;  73(5) 1509-1514
• 16 Posner J B. Side effects of chemotherapy. In: Neurologic Complications of Cancer. New York/Oxford; Oxford University Press 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(3) 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(12) 1285-1287
• 19 Dixit S, Kurle P, Buyan-Dent L, Sheth R D. Status epilepticus associated with cefepime.  Neurology. 2000;  54(11) 2153-2155
• 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
• 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
• 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
• 23 Pomeranz S, Naparstek E, Ashkenazi E et al.. Intracranial haematomas following bone marrow transplantation.  J Neurol. 1994;  241(4) 252-256
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 33 Shah A K. Cyclosporine A neurotoxicity among bone marrow transplant recipients.  Clin Neuropharmacol. 1999;  22(2) 67-73
• 34 Hinchey J, Chaves C, Appignani B et al.. A reversible posterior leukoencephalopathy syndrome.  N Engl J Med. 1996;  334(8) 494-500
• 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
• 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
• 37 Bartynski W S. Posterior reversible encephalopathy syndrome, part 1: fundamental imaging and clinical features.  AJNR Am J Neuroradiol. 2008;  29(6) 1036-1042
• 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
• 39 Steg R E, Garcia E G. Complex visual hallucinations and cyclosporine neurotoxicity.  Neurology. 1991;  41(7) 1156
• 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
• 41 Edelson R N, Chernik N L, Posner J B. Spinal subdural hematomas complicating lumbar puncture.  Arch Neurol. 1974;  31(2) 134-137
• 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
• 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
• 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
• 45 Maschke M, Dietrich U, Prumbaum M et al.. Opportunistic CNS infection after bone marrow transplantation.  Bone Marrow Transplant. 1999;  23(11) 1167-1176
• 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
• 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
• 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
• 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
• 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
• 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
• 52 Zerr D M. Human herpesvirus 6 and central nervous system disease in hematopoietic cell transplantation.  J Clin Virol. 2006;  37(S1) S52-S56
• 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
• 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
• 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
• 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
• 57 Reyes M G, Noronha P, Thomas Jr W, Heredia R. Myositis of chronic graft versus host disease.  Neurology. 1983;  33(9) 1222-1224
• 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
• 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
• 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)
• 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
• 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
• 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
• 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
• 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
• 66 Cohen J I. Epstein-Barr virus lymphoproliferative disease associated with acquired immunodeficiency.  Medicine (Baltimore). 1991;  70(2) 137-160
• 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
• 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