Central Nervous System Disorders Following Hematopoietic Stem Cell Transplantation

NCT04737785 | Completed

• 1 other identifier: 8414(0)136
• Study Type: observational
• Target: 252
• Locations: 11 countries
• Sites: 21

Brief Summary

All patients undergoing allogeneic or autologous HSCT at the participating centres will be observed. Once a diagnosis of CNS disorder is made, additional data will be reported for these patients. We will identify clinical and diagnostic characteristics such as cerebrospinal fluid (CSF) and neuroimaging patterns, risk factors, response to treatment (including novel antifungal agents such as isavuconazole) and outcome. In addition, risk factors for CNS disorders after allogeneic and autologous HSCT will be analyzed using a prospectively assessed matched control group. In the future, this study might be the basis for an interventional trial (e.g. using a prophylactic approach).

Conditions

Central Nervous System Infections; Central Nervous System Complication; Infectious Disease of Nervous System; Blood Disease; Blood Cancer; Infection

Outcome Measures

Primary Outcomes (4)

• Clinical characteristics of infectious and non-infectious CNS disorders following allogeneic or autologous HSCT

  Clinical characteristics to be analysed: * Recipient/donor sex * Recipient/donor age (at HSCT) * Primary diagnosis * Status of the primary disease at the time of HSCT - remission (partial or complete) /relapse /relapse including CNS involvement/progression, stable disease, unknown) * Prior CNS radiotherapy * Prior intrathecal (antineoplastic) treatment * Prior (antineoplastic) treatment (especially 'novel drugs´) * Pre-existing medical conditions * Recipient/donor serostatus of CMV, EBV, HHV-6, HSV, VZV, Toxoplasma spp. * Type of transplant (allogeneic vs. autologous) * Type of donor (MRD vs. haploidentical donor vs. other donor type) * Stem cell source (CB vs. BM vs. PB) * Type of conditioning (RIC vs MAC) * TCD (yes vs. no), ATG (yes vs. no), alemtuzumab (yes vs. no) * Acute and chronic GvHD (at day 0, including grade) * ECOG performance status at different time points * Concomitant infections * Selected peripheral blood parameters

  32 months

• Diagnostic characteristics of infectious and non-infectious CNS disorders following allogeneic or autologous HSCT

  Diagnostic characteristics analyzed: * Recipient´s age at onset of the CNS disorder (day 0) * Date of symptom onset of the CNS disorder * Type of symptoms (e.g. seizures, hemiplegia, paraplegia, paresis, psychosis, vomiting, confusion/altered consciousness, fever) * Date of diagnosis of the CNS disorder (e.g. CSF analysis) * Clinical diagnosis of CNS infection (e.g. encephalitis, meningitis, meningoencephalitis, myelitis, abscess, leukoencephalopathy) * Clinical diagnosis of non-infectious CNS disorder (e.g. metabolic/drug-induced disorder, posterior reversible encephalopathy syndrome, bleeding, thrombosis, ischemic stroke, CNS relapse of a underlying malignancy) * Time interval between HSCT and symptom onset * Time interval between symptom onset and diagnosis * Antimicrobial prophylaxis prior to onset of CNS disorder * Level of likelihood of the type of CNS disorder:

  32 months

• Efficacy of CNS treatment for different types of CNS disorders

  Efficacy measured as: * CNS cured with neurological sequelae * CNS cured without neurological sequelae * CNS symptoms improved * CNS symptoms stabilized * deteriorating * death because of CNS disorder * death because of other cause Treatments analyzed: * Antimicrobials * Steroids * Surgical treatment * Reduction of immunosuppression * Other treatment Types of CNS disorders: * infectious * non-infectious

  30 days

• Survival

  alive or death, including date, cause of death, CNS disorder-related death vs. other death cause at the different study points

  32 months

Secondary Outcomes (6)

• Incidence of infectious and non-infectious CNS disorders after HSCT

  32 months

• Timing of infectious and non-infectious CNS disorders after HSCT

  32 months

• Distribution of infectious and non-infectious CNS disorders after HSCT

  32 months

• Impact of development of CNS disorders on overall survival

  32 months

• Risk factors for CNS disorders after allogeneic and autologous HSCT using a prospectively assessed matched control group

  32 months

Study Arms (2)

Case group

HSCT recipients who developed a CNS disorder after HSCT

Control group

HSCT recipients whom did not develop a CNS disorder

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

HSCT patients of any age with any underlying disease for which the transplant is given.

You may qualify if:

• Case group:
• received allogeneic or autologous HSCT between January 1st, 2021 and December 31st, 2022
• develop an infectious (any CTCAE grade) or relevant (CTCAE \>1°) non-infectious CNS disorder after HSCT in this period.
• Control group:
• received allogeneic or autologous HSCT between January 1st, 2021 and February 28th, 2023

You may not qualify if:

• Patients with missing essential Med-A data
• Patients not giving informed consent to report data to EBMT prior to initiation of transplant procedures

Sponsors & Collaborators

• European Society for Blood and Marrow Transplantation: lead

Study Sites (22)

The Children's Hospital at Westmead

Westmead, Australia

Location

Instituto de Cancerologia S.A

Medellín, Colombia

Location

Hopital St. Louis

Paris, 75010, France

Location

Carl-Thiem-Klinikum

Cottbus, Germany

Location

Jena University Hospital

Jena, Germany

Location

University Children's Hospital

Würzburg, Germany

Location

Central Hospital of Southern Pest

Budapest, Hungary

Location

Hadassah University Hospital

Jarusalem, Israel

Location

Institute G. Gaslini

Genova, Italy

Location

Ospedale San Martino

Genova, Italy

Location

Clinica di Oncoematologia Pediatrica

Padua, Italy

Location

Universita Cattolica S. Cuore

Rome, Italy

Location

University Hospital, Collegium Medicum UMK

Bydgoszcz, Poland

Location

University Children's Hospital in Krakow

Krakow, Poland

Location

The Medical University of Warsaw

Warsaw, Poland

Location

Raisa Gorbacheva Research Institute for Oncology

Saint Petersburg, 197022, Russia

Location

Hospital Santa Creu i Sant Pau

Barcelona, Spain

Location

Hospital Univ. 12 de Octubre

Madrid, Spain

Location

Niño Jesus Children's Hospital

Madrid, Spain

Location

University Hospital La Fe

Valencia, Spain

Location

Centre Ntl de greffe de MO de Tunis

Tunis, Tunisia

Location

Hacettepe University Children's Hospital

Antalya, Turkey (Türkiye)

Location

MeSH Terms

Conditions

Central Nervous System Infections; Hematologic Diseases; Hematologic Neoplasms; Infections

Condition Hierarchy (Ancestors)

Central Nervous System Diseases; Nervous System Diseases; Hemic and Lymphatic Diseases; Neoplasms by Site; Neoplasms

Study Officials

• Martin Schmidt-Hieber, Dr

  Carl-Thiem-Klinikum, Clinic for Hematology and Oncology, Cottbus, Germany

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Target Duration: 3 Months
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 14, 2021
• First Posted: February 4, 2021
• Study Start: January 1, 2021
• Primary Completion: June 30, 2023
• Study Completion: August 1, 2024
• Last Updated: August 27, 2024

Record last verified: 2024-08

Locations

AU (1); PL (3); RU (1); ES (4); TU (1); CO (1); HU (1); FR (1); DE (3); IL (1); IT (4)