Central Nervous System Disorders Following Hematopoietic Stem Cell Transplantation: a Prospective Observational Trial From the Infectious Diseases Working Party and the Transplant Complications Working Party of the European Society for Blood and Marrow Transplantation
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 252
- 试验地点
- 22
- 主要终点
- Efficacy of CNS treatment for different types of CNS disorders
研究概览
简要总结
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).
详细描述
For each case patient (i.e. HSCT recipient with a CNS disorder) two control patients (1:2 allocation) should be analysed prospectively with the aim to get more insights into risk factors for CNS disorders. Hereby, the two patients transplanted subsequently to the corresponding case patient should be included as controls if they survive and do not develop a CNS disorder until the inclusion time point. Inclusion time points of controls should be determined by using the same delay between transplant and the onset of the CNS disorder of the corresponding case patient. Controls should also be stratified by centre, HSCT type (i.e. allogeneic vs. autologous) and age (adults vs. paediatrics). As for cases with CNS disorders, controls should also be evaluated regularly until last follow-up. To avoid bias and to estimate the incidence of infectious vs. non-infectious CNS disorders in autologous and allogeneic HSCT recipients accurately centres should also report patients with CNS disorders not included in this study (e.g. due to lack of informed consent or essential Med-A data). Centres are additionally asked by the data management office in Leiden/Netherlands for these data on a regularly basis.
Primary objectives
- Clinical and diagnostic characteristics of infectious and non-infectious CNS disorders following allogeneic or autologous HSCT
- Outcome 30 days after CNS disorder onset (cured vs. improved vs. stabilized vs. worsened vs. died due to CNS disorder vs. died by other cause)
Secondary objectives
- Incidence, timing, and distribution of infectious and non-infectious CNS disorders after HSCT
- Impact of development of CNS disorders on overall survival
- Risk factors for CNS disorders after allogeneic and autologous HSCT using a prospectively assessed matched control group
- Efficacy of treatment for different types of CNS disorders
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •who survive and do not develop a CNS disorder until the inclusion time point (day 0, defined as the same delay between transplantation and CNS disorder onset of the corresponding case)
排除标准
- •Patients with missing essential Med-A data
- •Patients not giving informed consent to report data to EBMT prior to initiation of transplant procedures
结局指标
主要结局
Efficacy of CNS treatment for different types of CNS disorders
时间窗: 30 days
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
Clinical characteristics of infectious and non-infectious CNS disorders following allogeneic or autologous HSCT
时间窗: 32 months
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
Survival
时间窗: 32 months
alive or death, including date, cause of death, CNS disorder-related death vs. other death cause at the different study points
Diagnostic characteristics of infectious and non-infectious CNS disorders following allogeneic or autologous HSCT
时间窗: 32 months
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:
次要结局
- Incidence of infectious and non-infectious CNS disorders after HSCT(32 months)
- Impact of development of CNS disorders on overall survival(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)
- Risk factors for CNS disorders after allogeneic and autologous HSCT using a prospectively assessed matched control group(32 months)
- Efficacy of treatment for different types of CNS disorders(32 months)