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Clinical characteristics and risk factors of Intracranial hemorrhage in patients following allogeneic hematopoietic stem cell transplantation

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Abstract

Intracranial hemorrhage (ICH) is one of the most life-threatening neurological complications after allogeneic hematopoietic stem cell transplantation. Although cerebral complications and its causes after allo-HSCT are well documented, assessment of the incidence and risk factors of intracranial hemorrhage following allo-HSCT are less discussed. A nested case–control study was conducted involving 160 subjects drawn from 2169 subjects who underwent HSCT at Peking University People’s Hospital between 2004 and 2014. Thirty-two patients (1.5 %) with ICH were identified, and 128 controls were matched for age, gender, transplantation type, and time of transplantation. Intracranial hemorrhage was identified by CT scan and/or MRI by searching hospital records. Among the 32 ICH patients, 27 (82.9 %) developed intraparenchymal hemorrhages (IPH), 2 cases (5.7 %) suffered subdural hematomas (SDH), and 3 cases (8.6 %) had multiple hemorrhage lesions in the brain parenchyma. The median time of appearance for cerebral hemorrhages was 147.5 days. Multivariate analysis showed that systemic infections (hazard ratio 2.882, 95 % confidence interval 1.231–6.746), platelet count (5.894, 1.145–30.339), and fibrinogen levels (3.611, 1.528–8.532) were independent risk factors for intracranial hemorrhage among HSCT patients. The cumulative survival rate in the intracranial hemorrhage and control groups were 43.3 and 74.7 % (P = .001), respectively. Intracranial hemorrhage is associated with high mortality and a decreased overall survival rate. Systemic infections, platelet count, and fibrinogen levels were individual independent risk factors.

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References

  1. Guerrero A, Perez-Simon JA, Gutierrez N, Caballero D, Ortin F, Gomez-Sanchez JC, Cacho J, San Miguel JF (1999) Neurological complications after autologous stem cell transplantation. Eur Neurol 41(1):48–50

    Article  CAS  PubMed  Google Scholar 

  2. Saiz A, Graus F (2004) Neurological complications of hematopoietic cell transplantation. Semin Neurol 24(4):427–434. doi:10.1055/s-2004-861537

    Article  PubMed  Google Scholar 

  3. Coplin WM, Cochran MS, Levine SR, Crawford SW (2001) Stroke after bone marrow transplantation—frequency, aetiology and outcome. Brain 124:1043–1051. doi:10.1093/brain/124.5.1043

    Article  CAS  PubMed  Google Scholar 

  4. Saiz A, Graus F (2010) Neurologic complications of hematopoietic cell transplantation. Semin Neurol 30(3):287–295. doi:10.1055/s-0030-1255218

    Article  PubMed  Google Scholar 

  5. Antonini G, Ceschin V, Morino S, Fiorelli M, Gragnani F, Mengarelli A, Iori AP, Arcese W (1998) Early neurologic complications following allogeneic bone marrow transplant for leukemia: a prospective study. Neurol 50(5):1441–1445

    Article  CAS  Google Scholar 

  6. Bleggi-Torres LF, de Medeiros BC, Werner B, Neto JZ, Loddo G, Pasquini R, de Medeiros CR (2000) Neuropathological findings after bone marrow transplantation: an autopsy study of 180 cases. Bone Marrow Transplant 25(3):301–307. doi:10.1038/sj.bmt.1702140

    Article  CAS  PubMed  Google Scholar 

  7. Najima Y, Ohashi K, Miyazawa M, Nakano M, Kobayashi T, Yamashita T, Akiyama H, Sakamaki H (2009) Intracranial hemorrhage following allogeneic hematopoietic stem cell transplantation. Am J Hematol 84(5):298–301. doi:10.1002/ajh.21382

    Article  PubMed  Google Scholar 

  8. Uckan D, Cetin M, Yigitkanli I, Tezcan I, Tuncer M, Karasimav D, Oguz KK, Topcu M (2005) Life-threatening neurological complications after bone marrow transplantation in children. Bone Marrow Transplant 35(1):71–76. doi:10.1038/sj.bmt.1704749

    Article  CAS  PubMed  Google Scholar 

  9. Langholz B, Goldstein L (1996) Risk set sampling in epidemiologic cohort studies. Statistical Science., pp 35–53

    Google Scholar 

  10. Wacholder S, Silverman DT, McLaughlin JK, Mandel JS (1992) Selection of controls in case-control studies: III. Design options. Am J Epidemiol 135(9):1042–1050

    CAS  PubMed  Google Scholar 

  11. Wang Y, Liu DH, Liu KY, Xu LP, Zhang XH, Han W, Chen H, Chen YH, Wang FR, Wang JZ, Sun YQ, Huang XJ (2013) Long-term follow-up of haploidentical hematopoietic stem cell transplantation without in vitro T cell depletion for the treatment of leukemia: nine years of experience at a single center. Cancer 119(5):978–985. doi:10.1002/cncr.27761

    Article  PubMed  Google Scholar 

  12. Wang Y, Chang YJ, Xu LP, Liu KY, Liu DH, Zhang XH, Chen H, Han W, Chen YH, Wang FR, Wang JZ, Chen Y, Yan CH, Huo MR, Li D, Huang XJ (2014) Who is the best donor for a related HLA haplotype-mismatched transplant? Blood 124(6):843–850. doi:10.1182/blood-2014-03-563130

    Article  CAS  PubMed  Google Scholar 

  13. Chang YJ, Huang XJ (2011) Use of G-CSF-stimulated marrow in allogeneic hematopoietic stem cell transplantation settings: a comprehensive review. Clin Transplant 25(1):13–23. doi:10.1111/j.1399-0012.2010.01298.x

    Article  CAS  PubMed  Google Scholar 

  14. Huang XJ (2008) Current status of haploidentical stem cell transplantation for leukemia. J Hematol Oncol 1:27. doi:10.1186/1756-8722-1-27

    Article  PubMed  PubMed Central  Google Scholar 

  15. Chang YJ, Huang XJ (2012) Haploidentical hematopoietic stem cell transplantation with unmanipulated granulocyte colony stimulating factor mobilized marrow and blood grafts. Curr Opin Hematol 19(6):454–461. doi:10.1097/MOH.0b013e3283582322

    Article  CAS  PubMed  Google Scholar 

  16. Zhang XH, Xu LP, Liu DH, Chen H, Han W, Chen YH, Wang FR, Wang JZ, Wang Y, Zhao T, Chen Y, Fu HX, Liu KY, Huang XJ (2013) Epileptic seizures in patients following allogeneic hematopoietic stem cell transplantation: a retrospective analysis of incidence, risk factors, and survival rates. Clin Transplant 27(1):80–89. doi:10.1111/ctr.12000

    Article  PubMed  Google Scholar 

  17. Chang YJ, Zhao XY, Huang XJ (2014) Immune reconstitution after haploidentical hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 20(4):440–449. doi:10.1016/j.bbmt.2013.11.028

    Article  CAS  Google Scholar 

  18. Holler E, Kolb HJ, Greinix H, Perrotin D, Campilho F, Aversa F, Gil L, Cornelissen J, Varanese L, Schacht A, Friese A, Rustige J (2009) Bleeding events and mortality in SCT patients: a retrospective study of hematopoietic SCT patients with organ dysfunctions due to severe sepsis or GVHD. Bone Marrow Transplant 43(6):491–497. doi:10.1038/bmt.2008.337

    Article  CAS  PubMed  Google Scholar 

  19. Langholz B, Richardson D (2009) Are nested case-control studies biased? Epidemiol 20(3):321–329. doi:10.1097/EDE.0b013e31819e370b

    Article  Google Scholar 

  20. Keogh RH, Cox DR (2014) Case-control studies. Cambridge University Press 1st edn. Cambridge, 160-186

  21. Sedgwick P (2014) Nested case-control studies: advantages and disadvantages. BMJ 348(feb14 1):g1532–g1532. doi:10.1136/bmj.g1532

    Article  Google Scholar 

  22. Brandao LR, Kletzel M, Boulad F, Kurtzberg J, Maloney K, Fligman I, Sison CP, Dimichele D (2008) A prospective longitudinal multicenter study of coagulation in pediatric patients undergoing allogeneic stem cell transplantation. Pediatr Blood Cancer 50(6):1240–1246. doi:10.1002/pbc.21473

    Article  PubMed  Google Scholar 

  23. Nagasawa M, Ohkawa T, Endo A, Mitsuiki N, Ono T, Aoki Y, Isoda T, Tomizawa D, Takagi M, Kajiwara M, Morio T, Mizutani S (2013) Early coagulation disorder after allogeneic stem cell transplantation is a strong prognostic factor for transplantation-related mortality, and intervention with recombinant human thrombomodulin improves the outcome: a single-center experience. Int J Hematol 98(5):533–542. doi:10.1007/s12185-013-1443-4

    Article  CAS  PubMed  Google Scholar 

  24. Han TT, Xu LP, Liu DH, Liu KY, Fu HX, Zhao XY, Zhao XS, Huang XJ (2014) Cytomegalovirus is a potential risk factor for late-onset hemorrhagic cystitis following allogeneic hematopoietic stem cell transplantation. Am J Hematol 89(1):55–61. doi:10.1002/ajh.23584

    Article  CAS  PubMed  Google Scholar 

  25. Pihusch M (2004) Bleeding complications after hematopoietic stem cell transplantation. Semin Hematol 41(1 Suppl 1):93–100

    Article  PubMed  Google Scholar 

  26. Rubin J, Wide K, Remberger M, Gustafsson B (2005) Acute neurological complications after hematopoietic stem cell transplantation in children. Pediatr Transplant 9(1):62–67. doi:10.1111/j.1399-3046.2004.00277.x

    Article  PubMed  Google Scholar 

  27. Labrador J, Lopez-Corral L, Vazquez L, Sanchez-Guijo F, Guerrero C, Sanchez-Barba M, Lozano FS, Alberca I, Del Canizo MC, Caballero D, Gonzalez-Porras JR (2015) Incidence and risk factors for life-threatening bleeding after allogeneic stem cell transplant. Br J Haematol 169(5):719–725. doi:10.1111/bjh.13344

    Article  PubMed  Google Scholar 

  28. Teive HA, Funke V, Bitencourt MA, de Oliveira MM, Bonfim C, Zanis-Neto J, Medeiros CR, Zetola VF, Werneck LC, Pasquini R (2008) Neurological complications of hematopoietic stem cell transplantation (HSCT): a retrospective study in a HSCT center in Brazil. Arq Neuropsiquiatr 66(3B):685–690

    Article  PubMed  Google Scholar 

  29. Pihusch R, Salat C, Gohring P, Hentrich M, Wegner H, Pihusch M, Hiller E, Kolb HJ, Ostermann H (2002) Factor XIII activity levels in patients with allogeneic haematopoietic stem cell transplantation and acute graft-versus-host disease of the gut. Br J Haematol 117(2):469–476

    Article  CAS  PubMed  Google Scholar 

Download references

Sources of funding

This work was supported by grants from the National Key Technology Support Program (No. 2012BAI38B03) and the National Natural Science Foundation of China (No. 81270643 and No. 81470363). This work was also supported in part by the Beijing Natural Science Foundation (No. 7132194) and the Specialized Research Fund for the Doctoral Program of Higher Education (No. 20120001110026). All of these grants were received by Xiao-Hui Zhang. The funders had roles in the study design, decision to publish, and preparation of the manuscript.

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    Authors and Affiliations

    1. Peking University People’s Hospital, Institute of Hematology, Beijing, China

      Xiao-Hui Zhang, Qian-ming Wang, Huan Chen, Yu-Hong Chen, Wei Han, Feng-Rong Wang, Jing-Zhi Wang, Yuan-Yuan Zhang, Xiao-Dong Mo, Yao Chen, Yu Wang, Ying-Jun Chang, Lan-Ping Xu & Kai-Yan Liu

    2. Peking University People’s Hospital, Institute of Hematology, Beijing Key Laboratory of HSCT, No. 11, Xizhimen South Street, Xicheng District, Beijing, 100044, China

      Xiao-Jun Huang

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    1. Xiao-Hui Zhang
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    Correspondence to Xiao-Jun Huang.

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    Xiao-Hui Zhang and Qian-ming Wang contributed equally to this work.

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    Supplement Table 1

    Detailed information of ICH patients. (DOCX 24 kb)

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    Zhang, XH., Wang, Qm., Chen, H. et al. Clinical characteristics and risk factors of Intracranial hemorrhage in patients following allogeneic hematopoietic stem cell transplantation. Ann Hematol 95, 1637–1643 (2016). https://doi.org/10.1007/s00277-016-2767-y

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    • DOI: https://doi.org/10.1007/s00277-016-2767-y

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