Abstract
Cerebrovascular complications after hematopoietic stem cell transplantation (HSCT) cause serious morbidity and often contribute to mortality. The incidence, risk factors, and outcome of cerebrovascular disease (CVD) after allogeneic HSCT remain poorly defined. We retrospectively evaluated 459 adult patients who underwent allogeneic HSCT at a tertiary medical center between January 2003 and December 2015. A total of 20 patients (4.4%) developed post-transplant CVD. All cerebrovascular accidents occurred in the first two years post-transplant. The two-year incidences of post-transplant CVD, intracranial hemorrhage, and cerebrovascular infarction were 6.1%, 3.2%, and 3.2%, respectively. The incidence rate of CVD within two years after HSCT was 34.7 (95% CI 22.3 to − 53.7) per 1000 person-years, which was about tenfold higher than the general Taiwanese population. The only significant risk factor associated with post-transplant CVD is prior exposure to three or more courses of high-dose cytarabine. Post-transplant CVD is associated with dismal outcome and early mortality. The median overall survival of patients with post-transplant CVD was markedly reduced compared with those without CVD (8.0 vs. 60.6 months). Most patients with post-transplant CVD died within two months after the CVD events. Our study demonstrates that CVD remains a devastating complication after allogeneic HSCT in the modern era.
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References
Arai Y, Kondo T, Shigematsu A, et al. Increased non-relapse mortality due to high-dose cytarabine plus CY/TBI in BMT/PBSCT for acute lymphoblastic leukaemia in adults. Br J Haematol. 2017;178:106–11.
Fasslrinner F, Schetelig J, Burchert A, et al. Long-term efficacy of reduced-intensity versus myeloablative conditioning before allogeneic haemopoietic cell transplantation in patients with acute myeloid leukaemia in first complete remission: retrospective follow-up of an open-label, randomised phase 3 trial. Lancet Haematol. 2018;5:e161–9.
Maffini E, Festuccia M, Brunello L, et al. Neurologic complications after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2017;23:388–97.
Saiz A, Graus F. Neurological complications of hematopoietic cell transplantation. Semin Neurol. 2004;24:427–34.
Dulamea AO, Lupescu IG. Neurological complications of hematopoietic cell transplantation in children and adults. Neural Regen Res. 2018;13:945–54.
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;13:1369–79.
Dowling MR, Li S, Dey BR, et al. Neurologic complications after allogeneic hematopoietic stem cell transplantation: risk factors and impact. Bone Marrow Transplant. 2018;53:199–206.
American Diabetes A. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2010;33(Suppl 1):62–9.
De Pauw B, Walsh TJ, Donnelly JP, et al. Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin Infect Dis. 2008;46:1813–21.
Glucksberg H, Storb R, Fefer A, et al. Clinical manifestations of graft-versus-host disease in human recipients of marrow from HL-A-matched sibling donors. Transplantation. 1974;18:295–304.
Fine JP, Gray RJ. A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc. 1999;94:496–509.
Hu HH, Sheng WY, Chu FL, et al. Incidence of stroke in Taiwan. Stroke. 1992;23:1237–41.
Chien KL, Sung FC, Hsu HC, et al. Apolipoprotein A-I and B and stroke events in a community-based cohort in Taiwan: report of the Chin-Shan Community Cardiovascular Study. Stroke. 2002;33:39–44.
Lee M, Wu YL, Ovbiagele B. Trends in Incident and recurrent rates of first-ever ischemic stroke in Taiwan between 2000 and 2011. J Stroke. 2016;18:60–5.
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;46:1004–9.
Coplin WM, Cochran MS, Levine SR, Crawford SW. Stroke after bone marrow transplantation: frequency, aetiology and outcome. Brain. 2001;124:1043–51.
Labrador J, Lopez-Anglada L, Perez-Lopez E, et al. Analysis of incidence, risk factors and clinical outcome of thromboembolic and bleeding events in 431 allogeneic hematopoietic stem cell transplantation recipients. Haematologica. 2013;98:437–43.
Bhatt VR, Balasetti V, Jasem JA, et al. Central nervous system complications and outcomes after allogeneic hematopoietic stem cell transplantation. Clin Lymphoma Myeloma Leuk. 2015;15:606–11.
Gooley TA, Chien JW, Pergam SA, et al. Reduced mortality after allogeneic hematopoietic-cell transplantation. N Engl J Med. 2010;363:2091–101.
Barba P, Pinana JL, Valcarcel D, et al. Early and late neurological complications after reduced-intensity conditioning allogeneic stem cell transplantation. Biol Blood Marrow Transplant. 2009;15:1439–46.
Kang JM, Kim YJ, Kim JY, et al. Neurologic complications after allogeneic hematopoietic stem cell transplantation in children: analysis of prognostic factors. Biol Blood Marrow Transplant. 2015;21:1091–8.
Najima Y, Ohashi K, Miyazawa M, et al. Intracranial hemorrhage following allogeneic hematopoietic stem cell transplantation. Am J Hematol. 2009;84:298–301.
Han W, Chen Y, Chen H, et al. Intracranial hemorrhage and mortality in 1461 patients after allogeneic hematopoietic stem cell transplantation for 6-year follow-up: study of 44 cases. Blood. 2013;122:3322–2.
Chow EJ, Mueller BA, Baker KS, et al. Cardiovascular hospitalizations and mortality among recipients of hematopoietic stem cell transplantation. Ann Intern Med. 2011;155:21–32.
Chow EJ, Wong K, Lee SJ, et al. Late cardiovascular complications after hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2014;20:794–800.
Colosimo M, McCarthy N, Jayasinghe R, et al. Diagnosis and management of subdural haematoma complicating bone marrow transplantation. Bone Marrow Transplant. 2000;25:549–52.
Syed FI, Couriel DR, Frame D, Srinivasan A. Central Nervous System Complications of Hematopoietic Stem Cell Transplant. Hematol Oncol Clin North Am. 2016;30:887–98.
Uckan D, Cetin M, Yigitkanli I, et al. Life-threatening neurological complications after bone marrow transplantation in children. Bone Marrow Transplant. 2005;35:71–6.
Sostak P, Padovan CS, Yousry TA, et al. Prospective evaluation of neurological complications after allogeneic bone marrow transplantation. Neurology. 2003;60:842–8.
Narimatsu H, Miyamura K, Iida H, et al. Early central nervous complications after umbilical cord blood transplantation for adults. Biol Blood Marrow Transplant. 2009;15:92–100.
Baker WJ, Royer GL Jr, Weiss RB. Cytarabine and neurologic toxicity. J Clin Oncol. 1991;9:679–93.
Peddi PF, Peddi S, Santos ES, Morgensztern D. Central nervous system toxicities of chemotherapeutic agents. Expert Rev Anticancer Ther. 2014;14:857–63.
Tibussek D, Natesirinilkul R, Sun LR, et al. Severe cerebral vasospasm and childhood arterial ischemic stroke after intrathecal cytarabine. Pediatrics. 2016;137:e20152143.
Bleggi-Torres LF, Werner B, Gasparetto EL, et al. Intracranial hemorrhage following bone marrow transplantation: an autopsy study of 58 patients. Bone Marrow Transplant. 2002;29:29–32.
Mohrmann RL, Mah V, Vinters HV. Neuropathologic findings after bone marrow transplantation: an autopsy study. Hum Pathol. 1990;21:630–9.
Pomeranz S, Naparstek E, Ashkenazi E, et al. Intracranial haematomas following bone marrow transplantation. J Neurol. 1994;241:252–6.
Grauer O, Wolff D, Bertz H, et al. 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 2010;133: 2852–2865.
Chow EJ, Baker KS, Lee SJ, et al. Influence of conventional cardiovascular risk factors and lifestyle characteristics on cardiovascular disease after hematopoietic cell transplantation. J Clin Oncol. 2014;32:191–8.
Chien SH, Liu YC, Liu CJ, et al. Invasive mold infections in acute leukemia patients undergoing allogeneic hematopoietic stem cell transplantation. J Microbiol Immunol Infect. 2018. https://doi.org/10.1016/j.jmii.2018.09.006.
Marr KA. Fungal infections in hematopoietic stem cell transplant recipients. Med Mycol. 2008;46:293–302.
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TAL performed the statistical analysis and wrote the paper. YCL coordinated and designed the study, interpreted data and critically revised the manuscript. The other authors participated in acquisition and analysis of clinical and laboratory data. All authors gave final approval to the manuscript.
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Lin, TA., Gau, JP., Liu, YC. et al. Cerebrovascular disease after allogeneic hematopoietic stem cell transplantation: incidence, risk, and clinical outcome. Int J Hematol 109, 584–592 (2019). https://doi.org/10.1007/s12185-019-02624-y
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DOI: https://doi.org/10.1007/s12185-019-02624-y