Neurological complications following pediatric allogeneic hematopoietic stem cell transplantation: Risk factors and outcome

Irina Zaidman; Tamar Shaziri; Dina Averbuch; Ehud Even-Or; Yael Dinur-Schejter; Adeeb NaserEddin; Rebecca Brooks; Bella Shadur; Aharon Gefen; Polina Stepensky

doi:10.3389/fped.2022.1064038

Neurological complications following pediatric allogeneic hematopoietic stem cell transplantation: Risk factors and outcome

Front Pediatr. 2022 Dec 2:10:1064038. doi: 10.3389/fped.2022.1064038. eCollection 2022.

Authors

Irina Zaidman^{1

2}, Tamar Shaziri¹, Dina Averbuch^{1

3}, Ehud Even-Or^{1

2}, Yael Dinur-Schejter², Adeeb NaserEddin², Rebecca Brooks^{1

4}, Bella Shadur^{5

6}, Aharon Gefen^{7

8}, Polina Stepensky^{1

2}

Affiliations

¹ Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.
² Department of Bone Marrow Transplantation and Cancer Immunotherapy, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
³ Department of Pediatrics, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
⁴ Pediatric Intensive Care Unit, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
⁵ Immunology Division, Garvan Institute of Medical Research, Sydney, NSW, Australia.
⁶ St Vincent's Clinical School, University of New South Wales, Sydney, NSW, Australia.
⁷ Division of Pediatric Hematology Oncology and Bone Marrow Transplantation, Ruth Rappaport Children's Hospital, Rambam Medical Center, Haifa, Israel.
⁸ Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.

Abstract

Background: Allogeneic hematopoietic stem cell transplantation (HSCT) is an efficient treatment for numerous malignant and nonmalignant conditions affecting children. This procedure can result in infectious and noninfectious neurological complications (NCs).

Objective: The objective of the study is to examine the incidence, risk factors, and outcomes of NCs in pediatric patients following allogeneic HSCT.

Methods: We performed a retrospective study of 746 children who underwent 943 allogeneic HSCTs in two large pediatric hospitals in Israel from January 2000 to December 2019.

Results: Of the pediatric patients 107 (14.3%) experienced 150 NCs. The median follow-up was 55 months. Noninfectious NCs were more common than infectious NCs (81.3% vs. 18.7%). Factors significantly associated with type of NC (infectious vs. noninfectious) were underlying disease (immunodeficiency vs. malignant and metabolic/hematologic disease) (p-value = 0.000), and use of immunosuppressive agent, either Campath or ATG (p-value = 0.041). Factors with a significant impact on developing neurological sequelae post-NC were number of HSCT >1 (p-value = 0.028), the use of alemtuzumab as an immunosuppressive agent (p-value = 0.003), and infectious type of NC (p-value = 0.046). The overall survival rate of whole NC-cohort was 44%; one-third of all mortality cases were attributed to the NC. The strongest prognostic factors associated with mortality were older age at HSCT (p-value = 0.000), the use of alemtuzumab as an immunosuppressive agent (p-value = 0.004), and the existence of neurological sequelae (p-value = 0.000). Abnormal central nervous system imaging (p-value = 0.013), the use of alemtuzumab as an immunosuppressive agent (p-value = 0.019), and neurological sequelae (p-value = 0.000) had statistically significant effects on neurological cause of death.

Conclusion: Infectious and noninfectious NCs are a significant cause of morbidity and mortality following allogeneic HSCT in children. Further research is required to better understand the risk factors for different NCs and their outcomes regarding sequelae and survival.

Keywords: abnormal imaging; hematopoietic stem cell transplantation; neurological complications; neurological sequelae; pediatric malignant and nonmalignant diseases; survival.