Annals of Clinical and Experimental NeurologyAnnals of Clinical and Experimental Neurology2075-54732409-2533Research Center of Neurology82110.54101/ACEN.2022.2.4Research ArticleStroke before a haematopoietic stem cell transplantation is a potential risk factor for poor response to therapy in patients with blood cancerPolushinAlexey Yu.<p>Cand. Sci. (Med.), Chief of the chemotherapy and SCT unit for cancer and AID, Head, Laboratory of neurooncology and AID, Raisa Gorbacheva Memorial Research Institute for Pediatric Oncology, Hematology and Transplantation, Associate Professor, Department of neurology</p>alexpolushin@yandex.ruhttps://orcid.org/0000-0001-8699-2482SkibaIaroslav B.<p>Cand. Sci. (Med.), Raisa Gorbacheva Memorial Research Institute for Pediatric Oncology, Hematology and Transplantation, Associate Professor, Department of neurology</p>yaver-99@mail.ruhttps://orcid.org/0000-0003-1955-1032BakinEvgeny A.<p>Cand. Sci. (Tech.), senior researcher, Raisa Gorbacheva Memorial Research Institute for Pediatric Oncology, Hematology and Transplantation, Associate Professor, Department of neurology</p>eugene.bakin@gmail.comhttps://orcid.org/0000-0002-5694-4348VladovskayaMaria D.<p>Cand. Sci. (Med.), Head, Department of hospital registers, senior researcher, Laboratory of neurooncology and AID, Raisa Gorbacheva Memorial Research Institute for Pediatric Oncology, Hematology and Transplantation, Associate Professor, Department of neurology</p>rus-bmt-reg@mail.ruhttps://orcid.org/0000-0002-0215-4623MoiseevIvan S.<p>D. Sci. (Med.), Deputy Director for science, Raisa Gorbacheva Memorial Research Institute for Pediatric Oncology, Hematology and Transplantation, Professor, Professor B.V. Afanasyev Department of hematology, transfusion medicine and transplantation with the course of pediatric oncology</p>moisiv@mail.ruhttps://orcid.org/0000-0002-4332-0114VoznyukIgor A.<p>D. Sci. (Med.), Deputy Director, professor, Department of neurology</p>voznjouk@yandex.ruhttps://orcid.org/0000-0002-0340-4110KulaginAlexander D.<p>D. Sci. (Med.), Director, Raisa Gorbacheva Memorial Research Institute for Pediatric Oncology, Hematology and Transplantation, Head, Professor B.V. Afanasyev Department of Hematology, Transfusion Medi- cine and Transplantation with the Course of Pediatric Oncology</p>kulagingem@rambler.ruhttps://orcid.org/0000-0002-9589-4136Pavlov First Saint Petersburg State Medical UniversitySaint-Petersburg I.I. Dzhanelidze Research Institute of Emergency Medicine3006202216236431702202202032022Copyright © 2022, Polushin A.Y., Skiba I.B., Bakin E.A., Vladovskaya M.D., Moiseev I.S., Voznyuk I.A., Kulagin A.D.2022<p><strong><em>Introduction.</em></strong> More than 50,000 haematopoietic stem cell transplantations (HSCTs) are performed worldwide each year to treat malignant blood cancers, solid tumours, bone marrow aplasia, primary immunodeficiency conditions, autoimmune disorders, and storage disorders. The success of HSCTs depends on many factors, including patient's past medical history.</p>
<p><strong><em>Purpose.</em></strong> To assess the effect of an acute cerebrovascular accident (CVA) that occurred before the HSCT on the transplantation outcome in patients with blood cancer.</p>
<p><strong><em>Materials and methods.</em></strong> We examined the results of 899 transplantations conducted between 2016 and 2018 at the R.M. Gorbacheva Research Institute for Pediatric Oncology, Haematology and Transplantation of the Pavlov First Saint Petersburg State Medical University. We analysed transplantation parameters, as well as donor and recipient characteristics. Apart from intergroup comparisons, pseudo-randomization was performed using the Propensity Score Matching method. The survival rate analysis was conducted using the KaplanMeier estimate and the log rank test.</p>
<p><strong><em>Results.</em></strong> Sixteen patients (1.8%) had cerebrovascular events in their past history before the HSCT: ischaemic stroke in 0.4% of cases and haemorrhagic stroke or intracerebral haemorrhage in 1.4% of cases. Patients with a history of cerebrovascular events included more people with leukaemia (p = 0.02), had more often received an allogenic transplant (р = 0.01), the donors more often had a partial rather than a full HLA match with the recipient (р = 0.06), had a lower body mass index (р = 0.02), and a lower Karnofsky/Lansky score (р = 0.01) than patients in the control group. The presence of a cardiovascular event had a statistically significant association with reduced overall survival rate of HSCT recipients (р = 0.0012).</p>
<p><strong><em>Conclusion.</em></strong> Patients with blood cancer and stroke preceding the transplantation do not typically have any 'classical' risk factors (diabetes mellitus, venous system disorders, decreased cardiac output, significant atherosclerotic changes in precerebral arteries), therefore, secondary prevention guidelines for CVA during treatment of the main disease may not be effective and cannot be relied on. This article discusses the most likely causes of CVA in patients with blood cancer. A history of CVA before HSCT may have a significant effect on the transplantation outcome, but is not a contraindication for this treatment method. Recipient selection is a very important stage in HSCT planning. A multidisciplinary team should find a balance between the indications and contraindications for performing HSCT from an unrelated donor.</p>strokeischaemic strokehaemorrhagic stroketreatment complications in haematological disordersleukaemiaallogenic transplantationlong-term neurological complicationsинсультишемический инсультгеморрагический инсультосложнения лечения гематологических заболеванийлейкозаллогенная трансплантацияпродолжительные неврологические осложнения[Niederwieser D., Baldomero H., Bazuaye N. et al. One and a half million hematopoietic stem cell transplants: continuous and differential improvement in worldwide access with the use of non-identical family donors. Haematologica. 2022; 107(5): 1045–1053. DOI: 10.3324/haematol.2021.279189][Passweg J.R., Baldomero H., Chabannon C. et al. European Society for Blood and Marrow Transplantation (EBMT). Hematopoietic cell transplantation and cellular therapy survey of the EBMT: monitoring of activities and trends over 30 years. Bone Marrow Transplant. 2021; 56(7): 1651–1664. DOI: 10.1038/s41409-021-01227-8][Скиба Я.Б., Полушин А.Ю., Прокудин М.Ю., и др. Остро возникшие симптоматические эпилептические приступы при проведении трансплантации гемопоэтических стволовых клеток. Эпилепсия и пароксизмальные состояния. 2021; 13 (1): 65–82. Skiba Ya.B., Polushin А.Yu., Prokudin М.Yu. et al. Acute symptomatic seizures during haematopoietic stem cell transplantation. Epilepsy and Paroxysmal Conditions. 2021; 13(1): 65–82. (In Russ.) DOI: 10.17749/2077-8333/epi.par.con.2021.049][Афанасьев Б.В., Зубаровская Л.С., Алянский А.Л. и др. Выбор донора при аллогенной трансплантации гемопоэтических стволовых клеток. Российский журнал детской гематологии и онкологии. 2016; 3(3): 30–36. Afanasiev B.V., Zubarovskaya L.S., Alyanskiy A.L. et al. Selection of donor of allogeneic hematopoietic stem cell transplantation]. Russian Journal of Pediatric Hematology and Oncology. 2016; 3(3): 30–36. (In Russ.) DOI: 10.17650/2311-1267-2016-3-3-30-36][Sorror M.L., Maris M.B., Storb R. et al. Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT. Blood. 2005; 106(8): 2912–2919. DOI: 10.1182/blood-2005-05-2004][Sorror M.L., Storb R.F., Sandmaier B.M. et al. Comorbidity-age index: a clinical measure of biologic age before allogeneic hematopoietic cell transplantation. J. Clin. Oncol. 2014; 32(29): 3249–3256. DOI: 10.1200/JCO.2013.53.8157][Cestari D.M., Weine D.M., Panageas K.S. et al. Stroke in patients with cancer: incidence and etiology. Neurology. 2004; 62(11): 2025–2030. DOI: 10.1212/01.wnl.0000129912.56486.2b][Nguyen T., DeAngelis L.M. Stroke in cancer patients. Curr. Neurol. Neurosci. Rep. 2006; 6(3): 187–192. DOI: 10.1007/s11910-006-0004-0][Coplin W.M., Cochran M.S., Levine S.R. et al. Stroke after bone marrow transplantation: frequency, aetiology and outcome. Brain. 2001; 124(Pt 5): 1043–1051. DOI: 10.1093/brain/124.5.1043][Horowitz N., Brenner B. Thrombophilia and cancer. Pathophysiol. Haemost. Thromb. 2008; 36(3–4): 131–136. DOI: 10.1159/000175151][Piatkowska-Jakubas B., Krawczyk-Kuliś M., Giebel S. et al. Use of L-asparaginase in acute lymphoblastic leukemia: recommendations of the Polish Adult Leukemia Group. Pol. Arch. Med. Wewn. 2008; 118(11): 664–669.][Щугарева Л.М., Иова А.С., Иванова О.В., и др. Неврологические осложнения при острой лейкемии у детей. Анналы клинической и экспериментальной неврологии. 2014; 8(4): 60–68. DOI: 10.17816/psaic161 Shchugareva L.M., Iova A.S., Ivanova O.V. et al. Neurological complications in acute leukemia in children. Annals of Clinical and Experimental Neurology. 2014; 8(4): 60–68. (In Russ.) DOI: 10.17816/psaic161][Morris B., Partap S., Yeom K. et al. Cerebrovascular disease in childhood cancer survivors: a Children’s Oncology Group Report. Neurology. 2009; 73(22): 1906–1913. DOI: 10.1212/WNL.0b013e3181c17ea8][Yeh E.T., Bickford C.L. Cardiovascular complications of cancer therapy: incidence, pathogenesis, diagnosis, and management. J. Am. Coll. Cardiol. 2009; 53(24): 2231–2247. DOI: 10.1016/j.jacc.2009.02.050][Zoller B., Ji J., Sundquist J., Sundquist K. Risk of haemorrhagic and ischaemic stroke in patients with cancer: a nationwide follow-up study from Sweden. Eur. J. Cancer. 2012; 48(12): 1875–1883. DOI: 10.1016/j.ejca.2012.01.005][Nishiguchi T., Mochizuki K., Shakudo M. et al. CNS complications of hematopoietic stem cell transplantation. AJR Am. J. Roentgenol. 2009; 192(4): 1003–1011. DOI: 10.2214/AJR.08.1787][Delios A.M., Rosenblum M., Jakubowski A.A. et al. Central and peripheral nervous system immune mediated demyelinating disease after allogeneic hemopoietic stem cell transplantation for hematologic disease. J. Neurooncol. 2012; 110(2): 251–256. DOI: 10.1007/s11060-012-0962-9][Syed F.I., Couriel D.R., Frame D. et al. Central nervous system complications of hematopoietic stem cell transplant. Hematol. Oncol. Clin. North Am. 2016; 30(4): 887–898. DOI: 10.1016/j.hoc.2016.03.009][Dhar R. Neurologic complications of transplantation. Neurocrit. Care. 2018; 28(1): 4–11. DOI: 10.1007/s12028-017-0387-6][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. DOI: 10.1038/sj.bmt.1705905][Kang J.M., Kim Y.J., Kim J.Y. et al. Neurologic complications after allogeneic hematopoietic stem cell transplantation in children: analysis of prognostic factors. Biol. Blood Marrow Transplant. 2015; 21(6): 1091–1098. DOI: 10.1016/j.bbmt.2015.02.007][Cai X., Fu H.X., Mo X.D. et al. Comparison of hemorrhagic and ischemic stroke after allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant. 2020; 55(11): 2087–2097. DOI: 10.1038/s41409-020-0903-8][Del Prete C., Kim T., Lansigan F. et al. The epidemiology and clinical associations of stroke in patients with acute myeloid leukemia: a review of 10,972 admissions from the 2012 National Inpatient Sample. Clin. Lymphoma Myeloma Leuk. 2018; 18(1): 74–77.e1. DOI: 10.1016/j.clml.2017.09.008][Вознюк И.А., Янишевский С.Н., Чечулов П.В. и др. Ишемический инсульт: клинические рекомендации по первичной и вторичной профилактике: методическое пособие для врачей. СПб.; 2018. 32 с. Voznyuk I.A., Yanishevskiy S.N., Chechulov P.V. et al. Ischemic stroke: clinical recommendations for primary and secondary prevention: a methodological guide for doctors. St. Petersburg; 2018. (In Russ.)][Kleindorfer D.O., Towfighi A., Chaturvedi S. et al. 2021 Guideline for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline from the American Heart Association/American Stroke Association [published correction appears in Stroke. 2021; 52(7): e483–e484]. Stroke. 2021; 52(7): e364–e467. DOI: 10.1161/STR.0000000000000375][Zoller B., Ji J., Sundquist J,. Sundquist K. Risk of haemorrhagic and ischaemic stroke in patients with cancer: a nationwide follow-up study from Sweden. Eur. J. Cancer. 2012; 48(12): 1875–1883. DOI: 10.1016/j.ejca.2012.01.005][Bova I., Bornstein N., Korczyn A. Acute infection as a risk factor for ischemic stroke. Stroke. 1996; 27(12): 2204–2206. DOI: 10.1161/01.str.27.12.2204][Sandoval-Montes C., Santos-Argumedo L. CD38 is expressed selectively during the activation of a subset of mature T cells with reduced proliferation but improved potential to produce cytokines. J. Leukoc. Biol. 2005; 77(4): 513–521. DOI: 10.1189/jlb.0404262][Choe C.U., Lardong K., Gelderblom M. et al. CD38 exacerbates focal cytokine production, postischemic inflammation and brain injury after focal cerebral ischemia. PLoS One. 2011; 6(5): e19046.DOI: 10.1371/journal.pone.0019046. Erratum in: PLoS One. 2011; 6(7). DOI: 10.1371/annotation/295c388d-013d-4bb9-b4e4-da8e88317594][Austin P.C., Xin Yu A.Y., Vyas M.V. et al. Applying propensity score methods in clinical research in neurology. Neurology. 2021; 97(18): 856–863. DOI: 10.1212/WNL.0000000000012777]