Dataset Information

Neurologic complications after allogeneic transplantation: a meta-analysis.

ABSTRACT:

Objective

Neurologic adverse events remain challenging complications with poor morbidity and mortality post adult allogeneic hematopoietic cell transplantation (allo-HCT) for hematologic diseases. We conducted a systematic review and meta-analysis to determine their spectrum, incidence, and impact on survival.

Methods

We searched MEDLINE, COCHRANE, EMBASE through March 2019 for all types of primary studies. Two independent reviewers screened, extracted data, and assessed risk of bias (RoB).

Results

We identified 552 eligible studies describing 57.972 patients; one randomized controlled trial, two case-control, 17 prospective, 86 retrospective cohort studies, 21 case series, and 425 case reports. RoB ranged from fair to high although case series were low-risk. The majority of studies traced infectious or drug-related neurologic manifestations. Infectious complications were present in 2.7% (95% CI 1.9-3.6) and 3.3% (95% CI 0.8-7.1) of patients in retrospective and prospective cohort studies, respectively. In retrospective studies, 3.4% (95% CI 2.1-4.9) of patients suffered from drug-related neurologic events. In prospective cohorts the equivalent incidence was 13% (95% CI 4.2-24.8). Neurologic complications had a detrimental impact on survival.

Interpretation

Our study highlights the wide spectrum and significant impact of neurologic complications on survival post allo-HCT. This systematic review summarizes existing data and provides the necessary background information for every physician involved in the management of these patients.

SUBMITTER: Gavriilaki M

PROVIDER: S-EPMC6801165 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Publications

Neurologic complications after allogeneic transplantation: a meta-analysis.

Gavriilaki Maria M Mainou Maria M Gavriilaki Eleni E Haidich Anna-Bettina AB Papagiannopoulos Sotirios S Sakellari Ioanna I Anagnostopoulos Achilles A Kimiskidis Vasilis V

Annals of clinical and translational neurology 20190927 10

<h4>Objective</h4>Neurologic adverse events remain challenging complications with poor morbidity and mortality post adult allogeneic hematopoietic cell transplantation (allo-HCT) for hematologic diseases. We conducted a systematic review and meta-analysis to determine their spectrum, incidence, and impact on survival.<h4>Methods</h4>We searched MEDLINE, COCHRANE, EMBASE through March 2019 for all types of primary studies. Two independent reviewers screened, extracted data, and assessed risk of b ...[more]

PMID: 31560177

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Project description:BACKGROUND:Chronic graft-versus-host disease (cGVHD) is a major factor of morbidity and mortality for allogeneic stem cell transplantation (aSCT). The skin and internal organ involvement is the most common systemic complication of cGVHD and closely resembles systemic sclerosis (SSc). Circulating lymphocytes characterize the autoimmune nature of both conditions. Therefore we hypothesized that the common clinical manifestation (systemic organ and skin injury) and the common underlying players (lymphocytes) justify the combined meta-analysis of these diseases. RESULTS:The aSCT and SSc datasets were uploaded from Gene Expression Omnibus (GEO), a public functional genomics data repository. The available microarray studies of peripheral blood mononuclear cells (PBMCs) and isolated lymphocytes were limited to well established microarray platforms (Affymetrix, Agilent, Canvac, and Illumina) and experimental settings with ?10 patients per group. The resulting pools of data were merged by unique gene identifier and analyzed by the expression genome-wide association studies (eGWAS) coupled with the subtraction of the cGVHD+ and cGVHD- molecular signatures. The eGWAS was applied to 47 and 50 lymphocyte profiles from aSCT and SSc patients, respectively. The identified 35 candidates were represented by 8 known cGVHD genes (including CXCR4, LTBR and PML) and 28 new candidate genes (including SEPX1 and DNJGB1). The further mutual subtraction of cGVHD+ and cGVHD- candidates and pathway analysis identified a list of 25 genes. Seven of these genes belong to the fibroblast development and function pathway, consisting of the well known cGVHD genes CCND1, JUN, and FOS, and the new molecular targets MMP2, FOSB, TNFAIP8, and DUSP1. These genes become primary candidates for a potential link of systemic effects of cGVHD and SSc. CONCLUSIONS:We designed a new approach for meta-analysis by combining data from different diseases using common clinical manifestation as a linker. This allowed us to power up the insufficient standalone meta-analysis of aSCT microarray studies, by adding SSc samples to the data pool. This new method has successfully identified novel molecular targets for systemic effects of both aSCT and SSc. We believe that this approach is generalizable and can be applied to an array of diseases with common clinical manifestations.

Project description:Despite recent advances, multiple myeloma (MM) remains incurable. However, the appearance of allogeneic stem cell transplantation (allo-SCT) through graft-versus-myeloma effect provides a potential way to cure MM to some degree. This systematic review aimed to evaluate the outcome of patients receiving allo-SCT and identified a series of prognostic factors that may affect the outcome of allo-SCT.We systematically searched PubMed, Embase, and the Cochrane Library from 2007.01.01 to 2017.05.03 using the keywords 'allogeneic' and 'myeloma'.A total of 61 clinical trials involving 8698 adult patients were included. The pooled estimates (95% CI) for overall survival (OS) at 1, 2, 3 and 5 years were 70 (95% CI 56-84%), 62 (95% CI 53-71%), 52 (95% CI 44-61%), and 46 (95% CI 40-52%), respectively; for progression-free survival were 51 (95% CI 38-64%), 40 (95% CI 32-48%), 34 (95% CI 27-41%), and 27 (95% CI 23-31%), respectively; and for treatment-related mortality (TRM) were 18 (95% CI 14-21%), 21 (95% CI 17-25%), 20 (95% CI 13-26%), and 27 (95% CI 21-33%), respectively. Additionally, the pooled 100-day TRM was 12 (95% CI 5-18%). The incidences of grades II-IV acute graft-versus-host disease (GVHD) and chronic GVHD were 34 (95% CI 30-37%) and 51 (95% CI 46-56%), respectively. The incidences of relapse rate (RR) and death rate were 50 (95% CI 45-55%) and 51 (95% CI 45-57%), respectively. Importantly, disease progression was the most major cause of death (48%), followed by TRM (44%). The results failed to show an apparent benefit of allo-SCT for standard risk patients, compared with tandem auto-SCT. In contrast, all 14 trials in our study showed that patients with high cytogenetic risk after allo-SCT had similar OS and PFS compared to those with standard risk, suggesting that allo-SCT may overcome the adverse prognosis of high cytogenetic risk.Due to the lack of consistent survival benefit, allo-SCT should not be considered as a standard of care for newly diagnosed and relapsed standard-risk MM patients. However, for patients with high-risk MM who have a poor long-term prognosis, allo-SCT may be a strong consideration in their initial course of therapy or in first relapse after chemotherapy, when the risk of disease progression may outweigh the transplant-related risks. A large number of prospective randomized controlled trials were needed to prove the benefits of these therapeutic options.

Dataset Information

Neurologic complications after allogeneic transplantation: a meta-analysis.

Objective

Methods

Results

Interpretation

Publications

Neurologic complications after allogeneic transplantation: a meta-analysis.

Similar Datasets

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