Cerebrovascular complications of hematopoetic stem cell transplantation in patients with hematologic malignancies

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Abstract

Introduction. Modern transplantation and biological therapy methods are associated with a wide range of adverse events and complications. Incidence and variety of neurological complications mostly depend on myelo- and immunosuppression severity and duration as well as on donor's and recipient's characteristics. The most frequent complications involving the nervous system include neurotoxic reactions, infections, autoimmune and lymphoproliferative diseases, and dysmetabolic conditions as well as cerebrovascular complications that potentially affect transplantation outcomes.

Objective. To evaluate the impact of post-transplantation cerebrovascular events (CVEs) on transplantation outcomes in patients with hematologic malignancies.

Materials and methods. We analyzed 899 transplantations performed at the Raisa Gorbacheva Memorial Research Institute for Pediatric Oncology, Hematology, and Transplantation, Pavlov First Saint Petersburg State Medical University, from 2016 to 2018. We assessed transplantation parameters and donor's and recipient's characteristics by intergroup comparison, pseudo-randomization (propensity score matching), Kaplan–Meier survival analysis, and log-rank tests.

Results. Post-transplantatively, CVEs developed in 2.6% (n = 23) of cases: 13 (1.4%) ischemic strokes and 11 (1.2%) hemorrhagic strokes or intracranial hemorrhages were diagnosed. CVEs developed on days 99.5 ± 39.2 post hematopoetic stem cell transplantation (HSCT). There were more patients with non-malignant conditions in the CVE group as compared to the non-CVE group (21.7% vs 7.9%; p = 0.017). Patients with CVE had a significantly lower Karnofsky index (75.6 ± 21.3 vs 85.2 ± 14.9; p = 0.008). Statistically, we also note some non-significant trends: patients with CVE more often underwent allogenic HSCT (82.6% vs 64.0%; p = 0.077) while donors were more often partially (rather than totally) HLA compatible for recipients (39.1% vs 21.1%; p = 0.33). Patients with CVE more often had a history of venous thromboses (13.3% vs 4.2%; p = 0.077). Post-HSCT stroke decreased post-transplantation longevity by approximately 3 times (331.8 ± 81.6 vs 897.9 ± 25.4 post HSCT; p = 0.0001). In the CVE group, survival during first 180 days post HSCT (landmarks post-HSCT Day+60 and Day+180) was significantly lower as compared to that in the CVE-free group. If CVE developed during first 30 days and 100 days post HSCT, vascular catastrophe did not affect post-HSCT survival significantly.

Conclusion. Whereas ischemic stroke is a long-term HSCT complication (beyond D+100 post transplantation), hemorrhagic stroke is a short-term complication (D0–D+100 post HSCT). CVEs affect survival in patients with hematologic malignancies, especially those developed between D+60 and D+180 post HSCT. History of venous abnormalities, low Karnofsky index at HSCT initiation, and the type of allogenic HSCT, especially from half-matched donors, can be considered as negative outcome risk factors in post-HSCT CVE.

About the authors

Alexey Yu. Polushin

Pavlov First Saint Petersburg State Medical University

Author for correspondence.
Email: alexpolushin@yandex.ru
ORCID iD: 0000-0001-8699-2482

Cand. Sci. (Med.), Head, Scientific and Clinical Center for Transplantation and Cell Therapy in Autoimmune and Neurodegenerative Diseases, Head, Research Laboratory of Neurooncology and Autoimmune Diseases, R.M. Gorbacheva Research Institute of Pediatric Oncology, Hematology and Transplantology; Associate Professor, Department of neurology, First Pavlov State Medical University

Russian Federation, St. Petersburg

Iaroslav B. Skiba

Pavlov First Saint Petersburg State Medical University

Email: yaver-99@mail.ru
ORCID iD: 0000-0003-1955-1032

Cand. Sci. (Med.), Neurologist, R.M. Gorbacheva Research Institute of Pediatric Oncology, Hematology and Transplantology, First Pavlov State Medical University

Russian Federation, St. Petersburg

Evgeny A. Bakin

Pavlov First Saint Petersburg State Medical University

Email: eugene.bakin@gmail.com
ORCID iD: 0000-0002-5694-4348

Cand. Sci. (Tekh.), Senior Researcher, R.M. Gorbacheva Research Institute of Pediatric Oncology, Hematology and Transplantology, First Pavlov State Medical University

Russian Federation, St. Petersburg

Maria D. Vladovskaya

Pavlov First Saint Petersburg State Medical University

Email: rus-bmt-reg@mail.ru
ORCID iD: 0000-0002-0215-4623

Cand. Sci. (Med.), Head, Department of Hospital Registers, Senior Researcher, Research Laboratory of Neurooncology and Autoimmune Diseases, R.M. Gorbacheva Research Institute of Pediatric Oncology, Hematology and Transplantology, First Pavlov State Medical University

Russian Federation, St. Petersburg

Victoria A. Yakovleva

Pavlov First Saint Petersburg State Medical University

Email: 24ro80@gmail.com
ORCID iD: 0000-0002-9839-3169

Cand. Sci. (Med.), Neurologist, R.M. Gorbacheva Research Institute of Pediatric Oncology, Hematology and Transplantology, First Pavlov State Medical University

Russian Federation, St. Petersburg

Ivan S. Moiseev

Pavlov First Saint Petersburg State Medical University

Email: moisiv@mail.ru
ORCID iD: 0000-0002-4332-0114

D. Sci, (Med.), Hematologist, Deputy Director for Scientific Work, R.M. Gorbacheva Research Institute of Pediatric Oncology, Hematology and Transplantology, Professor, B.V. Afanasyev Department of Hematology, Transfusion Medicine and Transplantation with the Course of Pediatric Oncology, First Pavlov State Medical University

Russian Federation, St. Petersburg

Stanislav N. Yanishevskiy

Pavlov First Saint Petersburg State Medical University; S.M. Kirov Military Medical Academy; Almazov National Medical Research Centre

Email: stasya71@yandex.ru
ORCID iD: 0000-0002-6484-286X

D. Sci. (Med.), Head, Research Laboratory of Neurology and Neurorehabilitation, Professor, Department of Neurology and Psychiatry, Chief Researcher, Research Institute of Technologies for Predicting the Risk of Cardiovascular Complications, Center for Personalized Medicine, V.A. Almazov National Medical Research Center; Associate professor, Department of Nervous Diseases, S.M. Kirov Military Medical Academy

Russian Federation, St. Petersburg; St. Petersburg; St. Petersburg

Igor A. Voznyuk

Pavlov First Saint Petersburg State Medical University; S.M. Kirov Military Medical Academy

Email: voznjouk@yandex.ru
ORCID iD: 0000-0002-0340-4110

D. Sci. (Med.), Professor, Department of Neurology, First Pavlov State Medical University; Professor, Department of Nervous Diseases, S.M. Kirov Military Medical Academy

Russian Federation, St. Petersburg; St. Petersburg

Alexander D. Kulagin

Pavlov First Saint Petersburg State Medical University

Email: kulagingem@rambler.ru
ORCID iD: 0000-0002-9589-4136

D. Sci. (Med.), Professor, Director, R.M. Gorbacheva Research Institute of Pediatric Oncology, Hematology and Transplantology, Head, B.V. Afanasyev Department of Hematology, Transfusion Medicine and Transplantation with the Course of Pediatric Oncology, First Pavlov State Medical University

Russian Federation, St. Petersburg

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Supplementary files

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2. Fig. 1. Covariate balance at pseudo-randomization of CVE patients post HSCT.

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3. Fig. 2. Patient survival post group pseudo-randomization at 30 (A), 60 (B), 100 (C), and 180 (D) days post HSCT.

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Copyright (c) 2023 Polushin A.Y., Skiba I.B., Bakin E.A., Vladovskaya M.D., Yakovleva V.A., Moiseev I.S., Yanishevskiy S.N., Voznyuk I.A., Kulagin A.D.

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