Pediatric Patients with Extramedullary Leukemia Involving the Central Nervous System Have a Superior Outcome.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 920-920
Author(s):  
Donna Johnston ◽  
Todd Alonzo ◽  
Robert Gerbing ◽  
Beverly Lange ◽  
William G. Woods
Keyword(s):  
Central Nervous System ◽  
Bone Marrow ◽  
Overall Survival ◽  
Nervous System ◽  
Leukemia Cells ◽  
Relapse Risk ◽  
Cns Disease ◽  
Cns Relapse ◽  
Significant Difference ◽  
The Central Nervous System

Abstract Purpose: Extramedullary leukemia (EML), formally known as chloroma, is discrete collections of leukemia cells outside of the bone marrow. EML is often seen within the central nervous system (CNS) and these are often treated in a similar fashion as leukemia cells within the cerebral spinal fluid (CSF). We previously demonstrated that the presence of leukemia cells within the CSF (CNS leukemia) does not affect overall survival. We sought to determine the outcome of patients with central nervous system EML and compare these patients with those with CNS disease and non CNS EML. Methods: Patients enrolled on Children’s Cancer Group protocols 2861, 2891, 2941 and 2961 being treated for de novo acute myeloid leukemia (AML) with intensive timing chemotherapy were classified for the presence of CNS disease as CNS1 (<5 wbc in the CSF without blasts), CNS2 (<5 wbc in the CSF with blasts), or CNS3 (≥ 5 wbc in the CSF with blasts), as well as EML in the CNS (eg orbit, brain, etc) or non-CNS EML (eg skin, lung, etc). These patient’s outcomes were then analyzed. Results: A total of 1459 patients treated with intensive timing chemotherapy were analyzed in this study. At diagnosis, 1113 (76%) were CNS1, 143 (13%) CNS2, 154 (11%) CNS3, 48 (3%) had CNS EML, 57 (4%) had a non-CNS EML, and only 6 patients (0.4%) with CNS EML had CNS3 status. Patients with CNS EML had a significantly higher overall survival from study entry compared to patients with non-CNS EML (83% vs 38%, p<0.001), and compared to CNS3 patients (83% vs 50%, p<0.001). The patients with CNS EML also had a significantly higher event free survival compared to patients with non-CNS EML (65% vs 34%, p<0.001), and compared to CNS3 patients (65% vs 34%, p<0.001). There was no significant difference in relapse risk, bone marrow relapse, isolated CNS relapse, or EML relapse comparing patients with CNS EML and non-CNS EML. CNS EML patients had a significantly lower relapse risk compared to CNS3 patients (29% vs 49%, p=0.025). There was not a significant difference in bone marrow relapse, isolated CNS relapse, or EML relapse comparing these 2 groups of patients. Conclusion: Patients with extramedullary leukemia involving the CNS had a significantly better survival than patients with non-CNS EML or patients with CNS leukemia at diagnosis. This should reassure clinicians caring for these often challenging patients.

scholarly journals The Central Nervous System Microenvironment Influences the Leukemia Transcriptome and Enhances Leukemia Chemo-Resistance

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1515-1515
Author(s):  
Jeffrey Gaynes ◽  
Leslie Jonart ◽  
Jordan Naumann ◽  
Edward Zamora ◽  
Nathan Gossai ◽  
...  
Keyword(s):  
Gene Expression ◽  
Central Nervous System ◽  
Bone Marrow ◽  
Nervous System ◽  
Choroid Plexus ◽  
Leukemia Cells ◽  
Self Renewal ◽  
Cns Relapse ◽  
Leukemia Development

Abstract Central nervous system (CNS) relapse is a significant cause of treatment failure among patients with acute lymphoblastic leukemia (ALL). Isolated CNS relapse occurs in ~3-8% of children with leukemia and accounts for 30-40% of initial relapses in some clinical trials. In addition, CNS-directed therapies are associated with seizures, secondary neoplasms, encephalopathy, and long-term endocrine, developmental, neurovascular, and cognitive deficits. While many studies have demonstrated that interactions between leukemia cells and components of the bone marrow microenvironment influence leukemia development, maintenance, and chemo-resistance, the role of the CNS microenvironment in leukemia is less well studied. To investigate the influence of the CNS niche in leukemia, we asked whether the CNS niche could impart unique and functionally important gene expression changes in leukemia cells. We transplanted NALM-6 human, pre-B leukemia cells into NSG mice without prior irradiation to avoid perturbing the bone marrow and CNS niches. After systemic leukemia development the mice were euthanized and leukemia cells were isolated from the bone marrow and CNS microenvironments. Gene expression profiling of ~700 cancer-associated genes (NanoString® Technology) identified 36 leukemia genes differentially expressed (30 up-regulated and 6 down-regulated; fold change ≥ 2 and FDR<0.05) in leukemia cells in the CNS microenvironment relative to the bone marrow. Furthermore, functional annotation revealed the up-regulated genes were involved in known leukemia and cancer pathways including MAPK, RAS, and apoptosis. We elected to further examine the gene PBX1 as it is a transcription factor with known roles in hematopoiesis, leukemia, and cancer biology. PBX1 contributes to Evi-1 mediated leukemia development in a murine model of leukemia and is a partner with TCF3 in the t(1;19) translocation that occurs in ~5% of pre-B ALL. Interestingly, this translocation is also associated with an increased risk for CNS relapse. We confirmed PBX1 mRNA up-regulation in leukemia cells either isolated from the CNS or in leukemia cells co-cultured with CNS-derived, murine choroid plexus cells by quantitative PCR. Supporting the generalizability of these results, additional human B-cell leukemia lines SEM and REH also exhibited PBX1 mRNA up-regulation in leukemia cells isolated from the murine CNS niche. Western blots of NALM-6 and SEM leukemia cells isolated from the mouse CNS as well as from leukemia cells co-cultured ex vivo with choroid plexus cells also showed PBX1 up-regulation at the protein level. Finally, culture of leukemia cells in either choroid plexus cell conditioned media or human cerebral spinal fluid (CSF) had minimal effects on PBX1 protein levels, suggesting that direct cell contact, rather than a soluble factor(s), contributes to PBX1 up-regulation in leukemia cells. Following confirmation of PBX1 up-regulation in leukemia cells within the CNS microenvironment, we next ectopically expressed PBX1, or GFP as a control, in leukemia cells to identify functional consequences of PBX1 expression in leukemia cells. Leukemia cells expressing PBX1 exhibited decreased sensitivity to cytarabine relative to control cells as measured by both proliferation and apoptosis assays. Furthermore, shRNA targeting PBX1, but not control shRNA, prevented PBX1 up-regulation in leukemia cells when co-cultured with choroid plexus cells and modestly, but significantly, attenuated the ability of choroid plexus cells to protect leukemia cells from cyatabine-induced apoptosis. Finally, although PBX1 had no effect on leukemia proliferation, it caused enhanced colony-forming ability in semi-solid media, consistent with increased leukemia self-renewal properties. Together these results suggest PBX1 up-regulation in leukemia cells may contribute to both leukemia self-renewal properties and chemo-resistance in the CNS niche. In summary, we believe this work illustrates the unique and functionally important effect that the CNS microenvironment has on leukemia cells. More comprehensive analyses of the leukemia transcriptome, genome, and proteome in the CNS niche will build upon this foundation and provide a more detailed understanding of the role of the CNS niche in leukemia biology. Finally, this approach may identify targetable CNS niche-mediated mechanisms of leukemia chemo-resistance and self-renewal. Disclosures No relevant conflicts of interest to declare.

scholarly journals Cell-Free DNA As a Biomarker for Acute Lymphoblastic Leukemia Relapse in the Central Nervous System

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 7-8
Author(s):  
Meghan Haney ◽  
Henry Moore ◽  
Shilpa Sampathi ◽  
Yelena Chernyavskaya ◽  
Tom Badgett ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Bone Marrow ◽  
Nervous System ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Leukemia Cell ◽  
Cns Disease ◽  
The Central Nervous System ◽  
Cell Clonality ◽  
Over Time

Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer, with a relapse rate of 15%. The presence of lymphoblasts in the central nervous system (CNS) is a negative prognostic indicator and a frequent site of disease relapse. CNS disease is defined as more than five white blood cells in the cerebrospinal fluid (CSF) with positive lymphoblast cytomorphology. Often leukemic blasts are detected by flow cytometry of the CSF prior to reaching the five white blood cell threshold, requiring repeat lumbar punctures at 2-4 week intervals until the arbitrarily defined clinical criteria for diagnosis are met. Additionally, more than 50% of autopsied brains from ALL patients show evidence of CNS disease, despite non-detectable CNS involvement via cytology of CSF. These data suggest that patients may be harboring CNS disease before it expands enough to be clinically diagnosed. We have developed a new assay that may allow for earlier detection of CNS disease and relapse by quantifying cell-free, circulating tumor DNA (ctDNA) in the CSF. ctDNA is a proven biomarker of relapse and metastasis in solid tumors in pre-clinical testing; however, its utility at predicting CNS disease in ALL has not been examined. We examined two possible methods for using ctDNA as a biomarker: leukemia cell clonality and DNA methylation profiling. We collected bone marrow aspirate, blood, and CSF samples from 11 newly diagnosed patients prior to the start of chemotherapy treatment to use as a training data set. ctDNA was isolated from blood and CSF samples at diagnosis and throughout treatment. Genomic DNA was isolated from bone marrow and peripheral blood mononuclear cell (PBMC) samples at diagnosis. For leukemia cell clonality assays, Invivoscribe Lymphotrack PCR assays combined with MinION (Oxford Nanopore Technologies) sequencing were used to identify the VDJ sequence of the immunoglobulin (B-ALL) or T-cell receptor (T-ALL) rearrangements in the clones comprising each leukemia. Throughout the course of treatment, ctDNA samples were run on the MinION sequencer, examining the abundance of major clones present and ctDNA quantification was done on patient plasma and CSF samples over time. While this assay relies on patient specific VDJ sequencing, we are also in the process of developing a more universal assay that utilizes recurrent methylation changes in T-ALL or B-ALL, compared to normal PBMCs. We performed methylation sequencing on 3 control PBMC samples and 7 ALL patient samples to identify differentially methylated regions (DMRs) present specifically in ALL samples. This sequencing identified 9,222 DMRs present in the ALL samples. These sites were then compared with publicly available datasets, yielding 55 overlapping regions and 19 specific overlapping methylation sites commonly present in ALL samples and not in PBMCs. We are now in the process of validating these differentially methylated sites by droplet digital polymerase chain reaction (ddPCR) to come up with a panel of biomarkers to track ALL disease over time. The end goal of our study is to develop an assay to rapidly detect relapse and CNS disease in ALL that is more sensitive and less invasive than the current clinical assays. Earlier detection of relapse and CNS disease will provide patients with more treatment options, which may ultimately improve patient outcome. Results will ultimately be correlated with patient response to therapy, the presence of CNS disease, and overall outcomes as determined by standard clinical diagnostic procedures. Disclosures No relevant conflicts of interest to declare.

Mitoxantrone Improves the Outcome of Children with Central Nervous System (CNS) Involvement at First Relapse of Acute Lymphoblastic Leukemia (ALL)-Results of the International ALLR3 Study

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3303-3303
Author(s):  
Ashish Narayan Masurekar ◽  
Catriona Anne Parker ◽  
Satarupa Choudhuri ◽  
Carly Leighton ◽  
Jeremy Hancock ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Bone Marrow ◽  
Nervous System ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Cns Involvement ◽  
Cns Disease ◽  
Off Label ◽  
Cns Relapse ◽  
Time To Relapse

Abstract Abstract 3303 Introduction: Despite improvement in frontline therapy in childhood acute lymphoblastic leukemia (ALL), central nervous system (CNS) relapse remains a significant clinical problem. The ALLR3 trial (ISCRTN 45724312) was designed specifically to address this issue with the use of drugs known to penetrate the CNS. The trial incorporated a randomization between Mitoxantrone and Idarubicin during induction. Mitoxantrone showed an early benefit in all patients resulting in closure of the randomization in December 2007 (ASH Annual Meeting Abstracts, Nov 2009; 114:3390). Subsequently all patients now receive Mitoxantrone. Here we report on the outcome of patients with isolated CNS relapse (iCNSr) or combined CNS relapse (involvement of CNS and bone marrow, cCNSr). Methods: CNS involvement was defined as ≥5 WBC/μl with morphological evidence of blasts in the cerebrospinal fluid (CSF). Combined relapse (cCNSr) was defined as CNS disease with ≥ 5% blasts in the bone marrow. Time to relapse was classified as, Very Early: within 18 months of first diagnosis; Early: after 18 months of first diagnosis but within 6 months of stopping therapy and Late: more than 6 months after stopping therapy. All patients received 3 blocks of chemotherapy. Subsequently, allogenic stem cell transplant (allo-SCT) was offered to all very early relapses (iCNSr & cCNSr), early iCNSr (irrespective of immunophenotype), all T-cell cCNSr (irrespective of time to relapse) and early or late pre-B cCNSr that had a minimal residual disease level of ≥ 104 at the end of induction. All other patients were offered chemotherapy and cranial radiotherapy. Results: Of a total of 330 relapsed patients, 102 (31%) had CNS involvement. Of these 63 (62%) had iCNSr and 39 (38%) had cCNSr. The incidence of CNS disease was higher in males (M:F, CNS relapses 2.5:1 vs all relapses 1.5:1). CNS relapses had a higher proportion of T-cell disease (pre B:T CNS relapses 3.6:1 vs all relapses 7.8:1]. The number of patients presenting in very early, early and late phases were 19 (19%), 55 (54%) and 28 (27%) respectively. All late iCNSr patients were males. Almost all late relapses (iCNSr and cCNSr) (27/28) were of a pre B phenotype. At the end of induction phase, 91/102 (89%) achieved complete remission (CR) and 82/102 (80%) remained in CR after 3 blocks of chemotherapy. The estimated 3-year overall survival (OS) and progression free survival (PFS) for all patients with CNS disease was 45.5% (95%CI 32.9, 58.0) & 43.4% (95%CI 32.0, 54.7) respectively. There were no significant differences in survival with respect to site of the disease (combined vs isolated), gender or immunophenotype (pre B vs T). As shown in Table 1, CNS relapse patients who received Mitoxantrone had a significantly improved outcome when compared to those who received Idarubicin. This was most evident in those who had i) iCNSr, ii) pre-B phenotype and iii) allo-SCT, when analyzed on an intention to treat basis. This represents a considerable improvement in outcome compared to the results obtained in these sub-groups of patients in the previous UK ALLR2 study (Roy A et.al. Br. J. Haem. 2005;130:67-75). Conclusion: Mitoxantrone is highly effective in children with relapsed pre B ALL who have CNS involvement. As there were no other differences between patients treated on Mitoxantrone or Idarubicin, effective systemic therapy is as important as CNS directed therapy, if not more, in treating patients with CNS relapse. Disclosures: Off Label Use: Most drugs used in this protocol are off label as the majority of drugs used in childhood ALL are not liscensed for use in children.

Mammalian Bone Marrow Acetylcholinesterase

1982 ◽  
Vol 40 ◽  
pp. 44-45
Author(s):  
Ezzatollah Keyhani
Keyword(s):  
Central Nervous System ◽  
Bone Marrow ◽  
Nervous System ◽  
Common Property ◽  
Extracellular Medium ◽  
The Central Nervous System ◽  
The Common ◽  
Mammalian Bone

Acetylcholinesterase (EC 3.1.1.7) (ACHE) has been localized at cholinergic junctions both in the central nervous system and at the periphery and it functions in neurotransmission. ACHE was also found in other tissues without involvement in neurotransmission, but exhibiting the common property of transporting water and ions. This communication describes intracellular ACHE in mammalian bone marrow and its secretion into the extracellular medium.

PENENTUAN NILAI PARAMETER LIPOFILITAS SENYAWA 4-KLOROBENZOILTIOUREA DAN UJI POTENSIASI TERHADAP TIOPENTAL PADA MENCIT PUTIH (Mus musculus)

2019 ◽  
Vol 4 (1) ◽  
pp. 1
Author(s):  
Dini Kesuma
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Electronic Properties ◽  
Mus Musculus ◽  
Log P ◽  
P Value ◽  
Lead Compounds ◽  
Significant Difference ◽  
Central Nervous System Depressant ◽  
The Central Nervous System

Synthesis of the 4-chlorobenzoylthiourea compound was carried out by acylating thiourea with 4-chlorobenzoyl chloride. The 4-chlorobenzoylthiourea compound  will increase the lipophilic and the electronic properties other than the lead compounds of benzoylthiourea in order to, by expectation, raise the central nervous system depressant as well. The lipophilic would affect the ability of the compounds in penetrating biological membranes, which is highly dependent on the solubility of the drug within lipid/water. Log P is the most common method used in determining the parameter value. This experiment was to mix two dissolvents (octanol and water) which are immissible. The both levels of the compounds were carefully observed by a spectrophotometer UV-Vis. From the test, the result of log P value of the 4-chlorobenzoylthiourea compound was 2.32, while the theoretical log P value of the compounds, by using the π Hansch-Fujita method is 1.62 and the f Rekker-Mannhold method is 2.225. Consequently, the result of the test shows that there is a significant difference between the progress experiment and both theoretical log P methods. Moreover, in the test of the central nervous system depressant through the potentiation test to thiopental using mice indicates that the 4-chlorobenzoylthiourea compound have potentiation effects to thiopental compared to the lead compounds of benzoylthiourea.

scholarly journals Pharmacogenetics of the Central Nervous System—Toxicity and Relapse Affecting the CNS in Pediatric Acute Lymphoblastic Leukemia

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2333
Author(s):  
Judit C. Sági ◽  
András Gézsi ◽  
Bálint Egyed ◽  
Zsuzsanna Jakab ◽  
Noémi Benedek ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Acute Lymphoblastic Leukemia ◽  
Gene Polymorphisms ◽  
Lymphoblastic Leukemia ◽  
Toxic Encephalopathy ◽  
Inverse Association ◽  
Central Nervous System Toxicity ◽  
Cns Relapse ◽  
The Central Nervous System

Despite improving cure rates in childhood acute lymphoblastic leukemia (ALL), therapeutic side effects and relapse are ongoing challenges. These can also affect the central nervous system (CNS). Our aim was to identify germline gene polymorphisms that influence the risk of CNS events. Sixty single nucleotide polymorphisms (SNPs) in 20 genes were genotyped in a Hungarian non-matched ALL cohort of 36 cases with chemotherapy related acute toxic encephalopathy (ATE) and 544 controls. Five significant SNPs were further analyzed in an extended Austrian-Czech-NOPHO cohort (n = 107 cases, n = 211 controls) but none of the associations could be validated. Overall populations including all nations’ matched cohorts for ATE (n = 426) with seizure subgroup (n = 133) and posterior reversible encephalopathy syndrome (PRES, n = 251) were analyzed, as well. We found that patients with ABCB1 rs1045642, rs1128503 or rs2032582 TT genotypes were more prone to have seizures but those with rs1045642 TT developed PRES less frequently. The same SNPs were also examined in relation to ALL relapse on a case-control matched cohort of 320 patients from all groups. Those with rs1128503 CC or rs2032582 GG genotypes showed higher incidence of CNS relapse. Our results suggest that blood-brain-barrier drug transporter gene-polymorphisms might have an inverse association with seizures and CNS relapse.

Primary Leptomeningeal Gliomatosis in Children and Adults: A Morphological and Molecular Comparative Study With Literature Review

Neurosurgery ◽  
2015 ◽  
Vol 78 (3) ◽  
pp. 343-352 ◽  
Author(s):  
Arnault Tauziede-Espariat ◽  
Andre Maues de Paula ◽  
Melanie Pages ◽  
Annie Laquerriere ◽  
Emilie Caietta ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Overall Survival ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Clinical Symptoms ◽  
Malignant Gliomas ◽  
Leptomeningeal Gliomatosis ◽  
Molecular Features ◽  
The Central Nervous System ◽  
The Mean

Abstract BACKGROUND: Primary leptomeningeal gliomatosis (PLG) is a poorly recognized tumor of the central nervous system. OBJECTIVE: To describe the histopathological, immunohistochemical, and molecular features of PLG. METHODS: Results of our multicentric retrospective study of 6 PLG cases (3 pediatric and 3 adult) were compared with literature data. RESULTS: The mean age was 54.7 years for adults and 8.7 years for children, with 3 males and 3 females. Clinical symptoms were nonspecific. Cerebrospinal fluid analyses showed a high protein level often associated with pleocytosis but without neoplastic cells. On neuroimaging, diffuse leptomeningeal enhancement and hydrocephalus were observed, except in 1 case. PLG was mostly misinterpreted as infectious or tumoral meningitis. The first biopsy was negative in 50% of cases. Histopathologically, PLG cases corresponded to 1 oligodendroglioma without 1p19q codeletion and 5 astrocytomas without expression of p53. No immunostaining for IDH1R132H and no mutations of IDH1/2 and H3F3A genes were found. Overall survival was highly variable (2-82 months) but seems to be increased in children treated with chemotherapy. CONCLUSION: This study shows the difficulties of PLG diagnosis. The challenge is to achieve an early biopsy to establish a diagnosis and to begin a treatment, but the prognosis remains poor. PLG seems to have a different molecular and immunohistochemical pattern compared with intraparenchymal malignant gliomas.

scholarly journals Evaluation of The Effectiveness and Side Effects of Radiotherapy in Patients With Primary Nervous System Lymphoma. A Single Center Experience

2020 ◽  
Vol 7 ◽  
Author(s):  
Timur Koca ◽  
Aylin Fidan Korcum ◽  
Yasemin Şengün ◽  
Melek Gamze Aksu ◽  
Mine Genç
Keyword(s):  
Central Nervous System ◽  
Overall Survival ◽  
Nervous System ◽  
Side Effects ◽  
Disease Free Survival ◽  
Central Nervous System Lymphoma ◽  
Field Size ◽  
High Dose ◽  
Free Survival ◽  
Significant Difference

Aim: In this study, we aimed to evaluate the overall and progression-free survival, the radiotherapy process and the early and late adverse effects in patients who underwent radiotherapy (RT) for primary nervous system lymphoma in our clinic.Method: Between January 2010 and September 2019, 16 patients who received radiotherapy due to primary central nervous system lymphoma in our clinic were examined according to their statistically significant differences in terms of survival and side effects.Results: The median disease-free survival of the patients was 6 months, and the median overall survival was 12.5 months. 18.75% of the patients could not receive chemotherapy but only radiotherapy. Radiotherapy doses were range from 2600 to 5000 cGy. When patients were evaluated in terms of radiotherapy dose, field size and chemotherapy, no statistically significant difference in overall survival was detected. Cognitive disorders were observed as the most common late side effects while the most common acute side effects in patients were headaches.Conclusion: In the treatment of primary central nervous system lymphoma, changes in radiotherapy portals and radiotherapy doses can be predicted in patients who received high-dose methotrexate chemotherapy or not. Furthermore, it has been considered that more comprehensive studies are needed to increase the success of treatment and provide standardization in treatment, especially in patients with elderly and comorbid diseases.

Efficacy of PD-1 or PD-L1 inhibitors and central nervous system metastases in advanced cancer: a meta-analysis

2021 ◽  
Vol 21 ◽  
Author(s):  
Minyong Peng ◽  
Shan Li ◽  
Hui Xiang ◽  
Wen Huang ◽  
Weiling Mao ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Overall Survival ◽  
Cell Death ◽  
Nervous System ◽  
Programmed Cell Death ◽  
Future Research ◽  
Significant Heterogeneity ◽  
Cns Metastases ◽  
Hazard Ratios ◽  
Significant Difference

<P>Background: Little is known about the efficacy of programmed cell death protein-1 (PD-1) or programmed cell death-ligand 1 (PD-L1) inhibitors in patients with central nervous system (CNS) metastases. <P> Objective: Assess the difference in efficacy of PD-1 or PD-L1 inhibitors in patients with and without CNS metastases. <P> Methods: From inception to March 2020, PubMed and Embase were searched for randomized controlled trials (RCTs) about PD-1 or PD-L1 inhibitors. Only trails with available hazard ratios (HRs) for overall survival (OS) of patients with and without CNS metastases simultaneously would be included. Overall survival hazard ratios and their 95% confidence interval (CI) were calculated, and the efficacy difference between these two groups was assessed in the meantime. <P> Results: 4988 patients (559 patients with CNS metastases and 4429 patients without CNS metastases) from 8 RCTs were included. In patients with CNS metastases, the pooled HR was 0.76 (95%CI, 0.62 to 0.93), while in patients without CNS metastases, the pooled HR was 0.74 (95%CI, 0.68 to 0.79). There was no significant difference in efficacy between these two groups (Χ=0.06 P=0.80). <P> Conclusion: With no significant heterogeneity observed between patients with or without CNS metastases, patients with CNS metastases should not be excluded from PD-1 or PD-L1 blockade therapy. Future research should permit more patients with CNS metastases to engage in PD-1 or PD-L1 blockade therapy and explore the safety of PD-1 or PD-L1 inhibitors in patients with CNS metastases.</P>

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