Abstract
Severe neurologic complications associated with hematopoietic stem cell transplantation (HSCT) have been reported in approximately 14–25% of all pediatric HSCT patients. The majority of severe neurologic events occur within the first 100 days after HSCT. Risk factors for developing severe neurologic events in the context of HSCT include the age of the HSCT recipient (children <3 years old), underlying disease, prior therapy, conditioning regimen, hematopoietic stem cell (HSC) source, unrelated donor, graft versus host disease (GvHD), immunosuppressive agents, metabolic disorders, and prior central nervous system (CNS) infections. The most common causes of developing a severe neurologic complication are medications (particularly calcineurin inhibitors), radiation-induced, hemorrhage-related, immune-mediated, and infection-induced. The most common severe neurologic events are seizures, cerebral vascular events as well as change in consciousness (mental status changes), and encephalopathy/leukoencephalopathy. Severe neurologic events account for 10–15% of all deaths in HSCT patients. Sensory complications such as radiation-induced cataracts, platinum-induced high-frequency hearing loss, and high-dose chemotherapy-induced taste dysfunction are seen quite often in pediatric HSCT recipients. Because pediatric HSCT recipients are still developing, effort needs to be made to minimize neurologic and sensory complications.
References
Kang JM, Kim YJ, Kim JY, Cho EJ, Lee JH, Lee MH, et al. Neurologic complications after allogeneic hematopoietic stem cell transplantation in children: analysis of prognostic factors. Biol Blood Marrow Transplant. 2015;21(6):1091–8
Weber C, Schaper J, Tibussek D, Adams O, MacKenzie CR, Dilloo D, et al. Diagnostic and therapeutic implications of neurological complications following paediatric haematopoietic stem cell transplantation. Bone Marrow Transplant. 2007;41(3):253–9
Uckan D, Cetin M, Yigitkanli I, Tezcan I, Tuncer M, Karasimav D, et al. Life-threatening neurological complications after bone marrow transplantation in children. Bone Marrow Transplant. 2005;35(1):71–6
Maffini E, Festuccia M, Brunello L, Boccadoro M, Giaccone L, Bruno B. Neurologic complications after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2017;23(3):388–97
Faraci M, Lanino E, Dini G, Fondelli MP, Morreale G, Dallorso S, et al. Severe neurologic complications after hematopoietic stem cell transplantation in children. Neurology. 2002;59(12):1895–904
Schmidt K, Schulz AS, Debatin KM, Friedrich W, Classen CF. CNS complications in children receiving chemotherapy or hematopoietic stem cell transplantation: retrospective analysis and clinical study of survivors. Pediatr Blood Cancer. 2008;50(2):331–6
Panosyan EH, Ikeda AK, Chang VY, Laks DR, Reeb CL, Bowles LV, et al. High-dose chemotherapy with autologous hematopoietic stem-cell rescue for pediatric brain tumor patients: a single institution experience from UCLA. J Transp Secur. 2011;2011:740673
Shenoy S, Eapen M, Panepinto JA, Logan BR, Wu J, Abraham A, et al. A trial of unrelated donor marrow transplantation for children with severe sickle cell disease. Blood. 2016;128(21):2561–7
Walters MC, Sullivan KM, Bernaudin F, Souillet G, Vannier JP, Johnson FL, et al. Neurologic complications after allogeneic marrow transplantation for sickle cell anemia. Blood. 1995;85(4):879–84
Woodard P, Helton KJ, Khan RB, Hale GA, Phipps S, Wang W, et al. Brain parenchymal damage after haematopoietic stem cell transplantation for severe sickle cell disease. Br J Haematol. 2005;129(4):550–2
Boelens JJ, Orchard PJ, Wynn RF. Transplantation in inborn errors of metabolism: current considerations and future perspectives. Br J Haematol. 2014;167(3):293–303
Pruitt AA, Graus F, Rosenfeld MR. Neurological complications of transplantation: part I: hematopoietic cell transplantation. Neurohospitalist. 2013;3(1):24–38
Siegal D, Keller A, Xu W, Bhuta S, Kim DH, Kuruvilla J, et al. Central nervous system complications after allogeneic hematopoietic stem cell transplantation: incidence, manifestations, and clinical significance. Biol Blood Marrow Transplant. 2007;13(11):1369–79
Iguchi A, Kobayashi R, Yoshida M, Kaneda M, Watanabe N, Cho Y, et al. Neurological complications after stem cell transplantation in childhood. Bone Marrow Transplant. 1999;24(6):647–52
Caselli D, Rosati A, Faraci M, Podda M, Ripaldi M, Longoni D, et al. Risk of seizures in children receiving busulphan-containing regimens for stem cell transplantation. Biol Blood Marrow Transplant. 2014;20(2):282–5
Vassal G, Deroussent A, Hartmann O, Challine D, Benhamou E, Valteau-Couanet D, et al. Dose-dependent neurotoxicity of high-dose busulfan in children: a clinical and pharmacological study. Cancer Res. 1990;50(19):6203–7
Soni S, Skeens M, Termuhlen AM, Bajwa RP, Gross TG, Pai V. Levetiracetam for busulfan-induced seizure prophylaxis in children undergoing hematopoietic stem cell transplantation. Pediatr Blood Cancer. 2012;59(4):762–4
Beitinjaneh A, McKinney AM, Cao Q, Weisdorf DJ. Toxic leukoencephalopathy following fludarabine-associated hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2011;17(3):300–8
Landier W, Knight K, Wong FL, Lee J, Thomas O, Kim H, et al. Ototoxicity in children with high-risk neuroblastoma: prevalence, risk factors, and concordance of grading scales—a report from the Children’s Oncology Group. J Clin Oncol. 2014;32(6):527–34
Punnett A, Bliss B, Dupuis LL, Abdolell M, Doyle J, Sung L. Ototoxicity following pediatric hematopoietic stem cell transplantation: a prospective cohort study. Pediatr Blood Cancer. 2004;42(7):598–603
Faraci M, Bekassy AN, De Fazio V, Tichelli A, Dini G, Paediatric E, et al. Non-endocrine late complications in children after allogeneic haematopoietic SCT. Bone Marrow Transplant. 2008;41(Suppl 2):S49–57
Cordelli DM, Masetti R, Zama D, Gueraldi D, Rondelli R, Cottone C, et al. Etiology, characteristics and outcome of seizures after pediatric hematopoietic stem cell transplantation. Seizure. 2014;23(2):140–5
Hinchey J, Chaves C, Appignani B, Breen J, Pao L, Wang A, et al. A reversible posterior leukoencephalopathy syndrome. N Engl J Med. 1996;334(8):494–500
Masetti R, Cordelli DM, Zama D, Vendemini F, Biagi C, Franzoni E, et al. PRES in children undergoing hematopoietic stem cell or solid organ transplantation. Pediatrics. 2015;135(5):890–901
Zama D, Masetti R, Cordelli DM, Vendemini F, Giordano L, Milito G, et al. Risk factor analysis of posterior reversible encephalopathy syndrome after allogeneic hematopoietic SCT in children. Bone Marrow Transplant. 2014;49(12):1538–40
Moskowitz A, Nolan C, Lis E, Castro-Malaspina H, Perales MA. Posterior reversible encephalopathy syndrome due to sirolimus. Bone Marrow Transplant. 2007;39(10):653–4
Dicuonzo F, Salvati A, Palma M, Lefons V, Lasalandra G, De Leonardis F, et al. Posterior reversible encephalopathy syndrome associated with methotrexate neurotoxicity: conventional magnetic resonance and diffusion-weighted imaging findings. J Child Neurol. 2009;24(8):1013–8
Zamvar V, Puntis JW. Re: “Posterior reversible encephalopathy syndrome following infliximab infusion”. J Pediatr Gastroenterol Nutr. 2010;50(3):353
Zito JA, Lee CC, Johnson S, Singer A, Vacirca J. Reversible posterior leukoencephalopathy syndrome after rituximab. Am J Emerg Med. 2010;28(4):537.e1–2
Yoshida S, Hayakawa K, Yamamoto A, Kuroda H, Imashuku S. The central nervous system complications of bone marrow transplantation in children. Eur Radiol. 2008;18(10):2048–59
Uderzo C, Bonanomi S, Busca A, Renoldi M, Ferrari P, Iacobelli M, et al. Risk factors and severe outcome in thrombotic microangiopathy after allogeneic hematopoietic stem cell transplantation. Transplantation. 2006;82(5):638–44
Phipps S, Rai SN, Leung WH, Lensing S, Dunavant M. Cognitive and academic consequences of stem-cell transplantation in children. J Clin Oncol. 2008;26(12):2027–33
Willard VW, Leung W, Huang Q, Zhang H, Phipps S. Cognitive outcome after pediatric stem-cell transplantation: impact of age and total-body irradiation. J Clin Oncol. 2014;32(35):3982–8
Gurney JG, Ness KK, Rosenthal J, Forman SJ, Bhatia S, Baker KS. Visual, auditory, sensory, and motor impairments in long-term survivors of hematopoietic stem cell transplantation performed in childhood: results from the Bone Marrow Transplant Survivor study. Cancer. 2006;106(6):1402–8
Freyer DR, Chen L, Krailo MD, Knight K, Villaluna D, Bliss B, et al. Effects of sodium thiosulfate versus observation on development of cisplatin-induced hearing loss in children with cancer (ACCL0431): a multicentre, randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2017;18(1):63–74
Suh DW, Ruttum MS, Stuckenschneider BJ, Mieler WF, Kivlin JD. Ocular findings after bone marrow transplantation in a pediatric population. Ophthalmology. 1999;106(8):1564–70
Kalinina Ayuso V, Hettinga Y, van der Does P, Boelens JJ, Rothova A, de Boer J. Ocular complications in children within 1 year after hematopoietic stem cell transplantation. JAMA Ophthalmol. 2013;131(4):470–5
van Kempen-Harteveld ML, van Weel-Sipman MH, Emmens C, Noordijk EM, van der Tweel I, Revesz T, et al. Eye shielding during total body irradiation for bone marrow transplantation in children transplanted for a hematological disorder: risks and benefits. Bone Marrow Transplant. 2003;31(12):1151–6
Majorana A, Amadori F, Bardellini E, Campus G, Conti G, Strohmenger L, et al. Taste dysfunction in patients undergoing hematopoietic stem cell transplantation: clinical evaluation in children. Pediatr Transplant. 2015;19(5):571–5
Comeau TB, Epstein JB, Migas C. Taste and smell dysfunction in patients receiving chemotherapy: a review of current knowledge. Support Care Cancer. 2001;9(8):575–80
Mattsson T, Arvidson K, Heimdahl A, Ljungman P, Dahllof G, Ringden O. Alterations in taste acuity associated with allogeneic bone marrow transplantation. J Oral Pathol Med. 1992;21(1):33–7
Boer CC, Correa ME, Miranda EC, de Souza CA. Taste disorders and oral evaluation in patients undergoing allogeneic hematopoietic SCT. Bone Marrow Transplant. 2010;45(4):705–11
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2018 Springer International Publishing AG
About this chapter
Cite this chapter
Brown, V.I. (2018). Neurologic and Sensory Complications Associated with HSCT. In: Brown, V. (eds) Hematopoietic Stem Cell Transplantation for the Pediatric Hematologist/Oncologist. Springer, Cham. https://doi.org/10.1007/978-3-319-63146-2_24
Download citation
DOI: https://doi.org/10.1007/978-3-319-63146-2_24
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-63144-8
Online ISBN: 978-3-319-63146-2
eBook Packages: MedicineMedicine (R0)