Asian variant intravascular large B-cell lymphoma with highly suspected central nervous system involvement: A case report.

BACKGROUND: Intravascular large B-cell lymphoma (IVLBCL) is a rare subtype of extranodal lymphoma. In particular, the Asian variant of IVLBCL is characterized by hemophagocytic lymphohistiocytosis along with bone marrow involvement. However, central nervous system (CNS) involvement is uncommon in this variant compared to the Western variant. Here, we report a case of typical Asian variant IVLBCL with highly suspected CNS involvement and discuss the nature of the disease and its genetic aberration. CASE SUMMARY: A 67-year-old female patient complained of gradually worsening cognitive impairment. While hospitalized, she developed a high fever and showed marked bicytopenia. Intracranial imaging revealed a suspected leptomeningeal disease. Although no malignant cells were found in the cerebrospinal fluid (CSF), the protein and lactate dehydrogenase levels in CSF were increased. Bone marrow examination revealed an increased number of hemophagocytic histiocytes, and 18F-fluorodeoxyglucose (FDG) positron emission tomography with computerized tomography scan revealed increased FDG uptake in both adrenal glands, the liver, and the right ethmoid sinus. A tissue biopsy showed atypical large lymphoid cells with prominent nucleoli in the vessels, and the tumor cells were positive for CD20, BCL2, BCL6, and IRF4/MUM1. In addition, targeted sequencing identified MYD88, TET2, and PIM1 mutations. Consequently, we diagnosed the patient with the Asian variant of IVLBCL with highly suspected CNS involvement. CONCLUSION: Suspicion of IVLBCL and immediate diagnosis lead to timely treatment. Moreover, careful CNS examination at diagnosis is recommended.

Current Treatment Patterns and the Role of Upfront Autologous Stem Cell Transplantation in Patients with Peripheral T-Cell Lymphoma: A Korean Nationwide, Multicenter Prospective Registry Study (CISL 1404).

PURPOSE: We conducted a nationwide, multicenter, prospective registry study for newly diagnosed patients with peripheral T-cell lymphoma (PTCL) to better define the clinical characteristics, treatment patterns, survival outcomes, and the role of upfront autologous stem cell transplantation (ASCT) in these patients. Materials and Methods: Patients with PTCL receiving chemotherapy with curative intent were registered and prospectively monitored. All patients were pathologically diagnosed with PTCL. RESULTS: A total of 191 patients with PTCL were enrolled in this prospective registry study. PTCL, not otherwise specified (PTCL-NOS) was the most common pathologic subtype (n=80, 41.9%), followed by angioimmunoblastic T-cell lymphoma (AITL) (n=60, 31.4%). With a median follow-up duration of 3.9 years, the 3-year progression-free survival (PFS) and overall survival (OS) rates were 39.5% and 60.4%, respectively. The role of upfront ASCT was evaluated in patients who were considered transplant-eligible (n=59). ASCT was performed as an upfront consolidative treatment in 32 (54.2%) of these patients. There were no significant differences in PFS and OS between the ASCT and non-ASCT groups for all patients (n=59) and for patients with PTCL-NOS (n=26). However, in patients with AITL, the ASCT group was associated with significantly better PFS than the non-ASCT group, although there was no significant difference in OS. CONCLUSION: The current study demonstrated that the survival outcomes with the current treatment options remain poor for patients with PTCL-NOS. Upfront ASCT may provide a survival benefit for patients with AITL, but not PTCL-NOS.

Outcomes in Refractory Diffuse Large B-Cell Lymphoma: Results from Two Prospective Korean Cohorts.

PURPOSE: Diffuse large B-cell lymphoma (DLBCL) is the most common hematologic malignancy worldwide. Although substantial improvement has been achieved by the frontline rituximab-based chemoimmunotherapy, up to 40%-50% of patients will eventually have relapsed or refractory disease, whose prognosis is extremely dismal. MATERIALS AND METHODS: We have carried out two prospective cohort studies that include over 1,500 DLBCL patients treated with rituximab plus CHOP (#NCT01202448 and #NCT02474550). In the current report, we describe the outcomes of refractory DLBCL patients. Patients were defined to have refractory DLBCL if they met one of the followings, not achieving at least partial response after 4 or more cycles of R-CHOP; not achieving at least partial response after 2 or more cycles of salvage therapy; progressive disease within 12 months after autologous stem cell transplantation. RESULTS: Among 1,581 patients, a total of 260 patients met the criteria for the refractory disease after a median time to progression of 9.1 months. The objective response rate of salvage treatment was 26.4%, and the complete response rate was 9.6%. The median overall survival (OS) was 7.5 months (95% confidence interval, 6.4 to 8.6), and the 2-year survival rate was 22.1%±2.8%. The median OS for each refractory category was not significantly different (p=0.529). CONCLUSION: In line with the previous studies, the outcomes of refractory DLBCL patients were extremely poor, which necessitates novel approaches for this population.

Usefulness of Genetic Aberration and Shorter Telomere Length in Myelodysplastic Syndrome: A Pilot Study.

OBJECTIVE: We aimed to evaluate the clinical usefulness of genetic aberration and shorter telomere length (TL) in individuals with myelodysplastic syndrome (MDS). METHODS: A targeted sequencing panel with 49 genes and TL measurement by quantitative real-time polymerase chain reaction were performed for 46 subjects. RESULTS: According to the revised International Prognostic Scoring System (IPSS-R) subtypes, the mutation frequency was 33.3%, 57.9%, and 100% in the very low/low, intermediate, and very high/high risk groups, respectively. A shorter telomere was detected in 43.5%. We defined group 1 as IPSS-R-high or -very high risk, group 2 as having 1 or more genetic aberrations, group 3 as having a shorter TL, and group 4 as having a longer TL than the age-matched reference. Group 1 and group 2 showed an adverse prognosis. The TL was not strongly correlated with MDS prognosis. However, it may be related to a poor long-term prognosis. CONCLUSION: Genetic variation and shorter TL may be helpful in reclassifying non-high-risk groups.

The new diagnostic criteria for myelodysplasia-related acute myeloid leukemia is useful for predicting clinical outcome: comparison of the 4th and 5th World Health Organization classifications.

Mutations in myelodysplasia-related (MR) genes, rather than morphological features, have been included in the diagnostic criteria of the new 5th World Health Organization (WHO) classification for myelodysplastic syndrome (MDS)-associated acute myeloid leukemia (AML). This study compares the clinical relevance of the new criteria with those of the previous version. In a cohort of 135 patients with newly diagnosed AML, the MDS-related AML patients were classified according to the 5th and 4th edition of the WHO classification (AML, myelodysplasia-related [AML-MR5th] and AML with myelodysplasia-related changes [AML-MRC4th], respectively). The median age of the patients was 70.4 years. MR gene mutations were found in 48 patients (35.6%). Sixty-one patients (46.6%) were diagnosed with AML-MRC4th, while 71 patients (53.0%) were diagnosed with AML-MR5th. Patients with AML-MR5th were significantly older with significantly lower treatment response rate, higher recurrence rate, and shorter relapse-free survival after chemotherapy, whereas AML-MRC4th patients did not show any association with the treatment outcome. Overall, the following prognostic factors for survival were identified: age over 75 years, antecedent MDS or MDS/myeloproliferative neoplasm, chromosome 5 or 7 abnormalities, and KRAS and ZSZR2 mutations. The 5th WHO classification is more useful for predicting the treatment response of patients with AML-MR than the previous version. Among the MR genes, ZSZR2 mutations were found to be independent prognostic factors affecting survival.

Sequential eradication of Helicobacter pylori as a treatment for immune thrombocytopenia in patients with moderate thrombocytopenia: a multicenter prospective randomized phase 3 study.

Due to several issues, standard treatments are not recommended for asymptomatic patients with moderate immune thrombocytopenia (ITP). Since platelet responses are reported in some patients with Helicobacter pylori (H. pylori)-positive ITP after eradication, we conducted a multicenter, phase 3 study to evaluate the safety and efficacy of recently established sequential eradication for these patients having moderate thrombocytopenia. Persistent or chronic ITP patients with platelet count (30 × 103 ~ 80 × 103/µL) and confirmed active H. pylori infection were randomly assigned to a treatment and a control group. The former received 10-day sequential treatment. Eradication was assessed by urea breath test at 3 months after treatment. Primary endpoint was the overall platelet response rate at 3 months in successfully eradicated treatment group and control group. Secondary endpoints were platelet response time, H. pylori eradication success rate, etc. The patient enrollment terminated early because of the change of national insurance and treatment guideline for H. pylori-positive patients in Korea during the study. Of the 28 H. pylori-positive ITP patients, 17 were randomized to the treatment group, and eradication was achieved for 15 (88.2%) at 3 months, and seven in control group after withdrawal. Statistically, significant difference in platelet response rates between the two groups were observed (p = 0.017). Our study verifies that H. pylori eradication was an effective ITP treatment for patients with H. pylori-associated moderate ITP. This sequential eradication regimen showed not only a high H. pylori eradication rate, but also a remarkable platelet response for ITP patients. Trial registration number and date of registration for these prospectively registered trials is ClinicalTrials.gov number, NCT03177629 and June 6, 2017.

Safety and efficacy of nilotinib in adult patients with chronic myeloid leukemia: a post-marketing surveillance study in Korea.

Background: Nilotinib is a tyrosine kinase inhibitor approved by the Ministry of Food and Drug Safety for frontline and 2nd line treatment of Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML). This study aimed to confirm the safety and efficacy of nilotinib in routine clinical practice within South Korea. Methods: An open-label, multicenter, single-arm, 12-week observational post-marketing surveillance (PMS) study was conducted on 669 Korean adult patients with Ph+ CML from December 24, 2010, to December 23, 2016. The patients received nilotinib treatment in routine clinical practice settings. Safety was evaluated by all types of adverse events (AEs) during the study period, and efficacy was evaluated by the complete hematological response (CHR) and cytogenetic response. Results: During the study period, AEs occurred in 61.3% (410 patients, 973 events), adverse drug reactions (ADRs) in 40.5% (271/669 patients, 559 events), serious AEs in 4.5% (30 patients, 37 events), and serious ADRs in 0.7% (5 patients, 8 events). Furthermore, unexpected AEs occurred at a rate of 6.9% (46 patients, 55 events) and unexpected ADRs at 1.2% (8 patients, 8 events). As for the efficacy results, CHR was achieved in 89.5% (442/494 patients), and minor cytogenetic response or major cytogenetic response was achieved in 85.8% (139/162 patients). Conclusion: This PMS study shows consistent results in terms of safety and efficacy compared with previous studies. Nilotinib was well tolerated and efficacious in adult Korean patients with Ph+ CML in routine clinical practice settings.

Short-chain fluorocarbon-based polymeric coating with excellent nonwetting ability against chemical warfare agents.

The ongoing concerns and regulations on long-chain fluorinated compounds (C8 or higher) for nonwetting coatings have driven the market to search for sustainable alternative chemistries. In this study, a copolymeric coating containing short-chain fluorinated groups was synthesized to achieve excellent nonwetting ability against hazardous chemical warfare agents (CWAs). A copolymer of 1H,1H,2H,2H-perfluorooctyl methacrylate (PFOMA) and ethylene glycol dimethacrylate (EGDMA, crosslinker) was directly coated onto a textile fabric via initiated chemical vapor deposition. The p(PFOMA-co-EGDMA) coating shows a rough-textured morphology with a bumpy, raspberry-like structure leading to high contact angles (θ water > 150° and θ dodecane = 113.8°) and a small water shedding angle (<5°). Moreover, the p(PFOMA-co-EGDMA) coating was further analysed for application in military fabrics: air permeability, tensile strength, and safety against toxic perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS). Outstanding nonwetting was noticeably achieved against different CWAs, including bis(2-chloroethyl)sulfide (HD), pinacolyl methylfluorophosphonate (GD), and O-ethyl S-(2-diisopropylaminoethyl)methylphosphonothioate (VX) (θ HD = 119.1°, θ GD = 117.0°, and θ VX = 104.1°). The coating retained its nano-structuration and nonwetting ability for water and n-dodecane despite being subjected to 250 cycles of Martindale abrasion and harsh chemicals (NaOH and HCl). The robustness and scalable straightforward preparation route of the coating make it an ideal approach for designing durable next-generation CWA nonwetting coatings for fabrics with favorable health and environmental properties.

A case report of nilotinib-induced irreversible interstitial lung disease.

RATIONALE: Nilotinib is a second line tyrosine kinase inhibitor to treat patients with chronic myeloid leukemia after imatinib resistance or intolerance. Drug related pulmonary complication is known to be rare. We discuss a case of nilotinib-induced interstitial lung disease presenting with nonspecific interstitial pneumonia on the unilateral lung. PATIENT CONCERNS: A 46-year-old man with chronic-phase chronic myeloid leukemia presented with cough and weight loss for 2 months. He had been treated with nilotinib for 52 months. DIAGNOSIS: Computed tomography scan showed right lung dominant consolidations, ground glass opacities and traction bronchiectasis. Bronchoalveolar lavage fluid analysis revealed no evidence of infection or malignancy. Surgical lung biopsy specimen was consistent with fibrosing nonspecific interstitial pneumonia. The patient was diagnosed with nilotinib induced interstitial lung disease. INTERVENTIONS: Corticosteroid treatment was initiated with prednisolone (50 mg daily) and slowly tapered down for 2 months. OUTCOMES: Cough improved after the course of corticosteroid treatment. However, fibrotic lung lesions persisted. Reinitiation of nilotinib resulted in the worsening of lung lesions. LESSONS: We report a case of irreversible interstitial lung disease that caused by nilotinib. Clinicians should have suspicion of this potential pulmonary complication in patients with respiratory symptoms and abnormal radiologic findings during nilotinib treatment, albeit rarely.

Pegfilgrastim Prophylaxis Is Effective in the Prevention of Febrile Neutropenia and Reduces Mortality in Patients Aged ≥ 75 Years with Diffuse Large B-Cell Lymphoma Treated with R-CHOP: A Prospective Cohort Study.

PURPOSE: Febrile neutropenia (FN) can cause suboptimal treatment and treatment-related mortality (TRM) in diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP). MATERIALS AND METHODS: We conducted a prospective cohort study to evaluate the effectiveness of pegfilgrastim prophylaxis in DLBCL patients receiving R-CHOP, and we compared them with the PROCESS cohort (n=485). RESULTS: Since January 2015, 986 patients with DLBCL were enrolled. Pegfilgrastim was administered at least once in 930 patients (94.3%), covering 90.3% of all cycles. FN developed in 137 patients (13.9%) in this cohort (23.7% in the PROCESS cohort, p<0.001), and 4.2% of all cycles (10.2% in the PROCESS cohort, p<0.001). Dose delay was less common (≥3 days: 18.1% vs. 23.7%, p=0.015; ≥5 days: 12.0% vs. 18.3%, p=0.023) in this cohort than in the PROCESS cohort. The incidence of TRM (3.2% vs. 5.6%, p=0.047) and infection-related death (1.8% vs. 4.5%, p=0.004) was lower in this cohort than in the PROCESS cohort. The 4-year overall survival (OS) and progression-free survival (PFS) rates of the two cohorts were not different (OS: 73.0% vs. 71.9%, p=0.545; PFS: 69.5% vs. 68.8%, p=0.616). However, in patients aged ≥75 years, the 4-year OS and PFS rates were higher in this cohort than in the PROCESS cohort (OS: 49.6% vs. 33.7%, p=0.032; PFS: 44.2% vs. 30.3% p=0.047). CONCLUSION: Pegfilgrastim prophylaxis is effective in the prevention of FN and infection-related death in DLBCL patients receiving R-CHOP, and it also improves OS in patients aged ≥75 years.

E-Cadherin and Angiopoietin-2 as Potential Biomarkers for Colorectal Cancer With Peritoneal Carcinomatosis.

BACKGROUND/AIM: E-Cadherin has been implicated in cell-cell adhesion, and soluble E-cadherin is involved in angiogenesis and resistance to anti-angiogenic therapy in several cancer types. This study aimed to investigate the expression and clinical significance of soluble E-cadherin and other angiogenesis-related factors in plasma and malignant ascites of colorectal cancer (CRC) in patients with peritoneal carcinomatosis (PC). MATERIALS AND METHODS: Multiplex enzyme-linked immunosorbent assay was performed on 95 body fluid samples (57 plasma and 38 malignant ascites) from patients with CRC. The status of E-cadherin and angiopoietin-2 (AGNPT2) was retrospectively evaluated by immunohistochemistry in primary CRC and paired metastatic peritoneal tissues or cell blocks of malignant ascites of 30 patients with peritoneal metastases of CRC. RESULTS: The expression levels of soluble E-cadherin and ANGPT2 in plasma samples were significantly increased in patients with PC compared with those without. E-Cadherin concentration was significantly lower and ANGPT2 concentration was significantly higher in malignant ascites than plasma samples. Expression of E-cadherin was strongly positive, whilst that of ANGPT2 was negative in primary colorectal tissues, metastatic peritoneal tissues, and cell blocks of malignant ascites by immunohistochemistry. High levels of soluble E-cadherin or ANGPT2 in ascites were negatively associated with overall survival in patients with CRC with malignant ascites. CONCLUSION: Our findings suggest that soluble E-cadherin and ANGPT2 may be surrogate biomarkers for clinical outcome in patients with PC from CRC.

The Prognostic Ability of RAS Pathway-Related Gene Mutations in Patients with Myeloid Neoplasms Treated with Hypomethylating Agents.

INTRODUCTION: This study aimed to identify genetic predictors of treatment response and survival in patients with myeloid neoplasms treated with hypomethylating agents (HMAs). METHODS: We performed next-generation sequencing on bone marrow aspiration samples of 59 patients diagnosed with acute myeloid leukemia (AML), myelodysplastic syndrome with excess blasts-2, or chronic myelomonocytic leukemia and treated with decitabine or azacitidine as a frontline therapy. RESULTS: A single gene with the most common mutations was TP53 (14 of 59 patients), and mutations in RAS pathway-related genes including KRAS, NRAS, FLT3, PTPN11, CBL, and KIT were found in 28.8% of patients. The overall response rate to HMAs was 33.9%. Predictive factors for a poor response were an age >75 years (p = 0.007), 3 or more gene mutations (p = 0.004), mutations in RAS pathway-related genes (p = 0.033), and a mutated NRAS gene (p = 0.042). An age >75 years (hazard ratio 2.946), diagnosis of AML (hazard ratio 2.915), and mutations in NRAS (hazard ratio 4.440) were identified as poor prognostic factors for survival. CONCLUSION: In conclusion, mutations in RAS pathway-related genes were predictors of a poor response to HMAs. Particularly, mutated NRAS was associated with inferior survival rates.

Diagnosis and treatment of chronic myelomonocytic leukemia.

Chronic myelomonocytic leukemia (CMML) is a clonal disorder of hematopoietic cells and is a complex of heterogeneous conditions with both myeloproliferative and myelodysplastic features. The diagnosis of CMML is made using morphologic criteria including monocyte-dominant leukocytosis, dysplastic changes, and increased blasts in the bone marrow. Recently, the identification of monocyte subtypes in peripheral blood using multiparameter flow cytometry has been actively studied. Chromosomal abnormalities are the basis of CMML risk stratification, and mutations in several genes including ASXL1 are known to be important not only for the diagnosis and treatment of this disease but also for predicting its prognosis. The standard treatment principles for CMML have not yet been clearly defined; however, hypomethylating agents are mainly considered the frontline therapy in most cases. Although allogeneic hematopoietic stem cell transplantation has limited applications owing to its toxicity, it still plays an important role as the only curative treatment option. Researchers are continuing to develop new drugs for CMML treatment and to prove their clinical usefulness. This review summarizes what is known to date on the diagnosis, treatment, and prognostic factors of CMML and presents future directions by analyzing recent research trends.

Comparison of Bleeding, Hematoma, Pain, and Discomfort After Bone Marrow Examination With or Without Sandbag Compression.

PURPOSE: A safe and effective hemostatic care is necessary after bone marrow examination to minimize bleeding, pain, and discomfort. However, a standardized hemostatic care protocol following bone marrow examination has not been established. The purpose of this study was to investigate the differences in bleeding, hematoma, pain, and discomfort by the hemostatic method used following bone marrow examination. METHODS: This study was carried out with a pre-test/post-test nonequivalent control group design. Sixty-four patients undergoing bone marrow examination at the hemato-oncology ward in a tertiary hospital in South Korea were assigned to an intervention (n = 30) and comparison group (n = 34). The intervention group was treated using a compression dressing alone, while the comparison group received a compression dressing followed by sandbag compression. Both groups received two hours of bedrest. Bleeding, hematoma, pain, and discomfort were measured at one and two hours after the biopsy. RESULTS: No significant differences in the occurrence of bleeding between the groups at one and two hours after bone marrow examination were observed, and no participant developed hematoma. The intervention group had significantly lower pain than the comparison group two hours after the bone marrow examination as well as lower discomfort one hour and two hours after the bone marrow examination (p < .05). CONCLUSION: Applying only compression dressing after a bone marrow examination is effective in reducing pain and discomfort without measurable differences in bleeding and hematoma, suggesting that compression dressings alone could be effective in lowering pain and discomfort following bone marrow examination.

Phase II Trial of Postoperative Adjuvant Gemcitabine and Cisplatin Chemotherapy Followed by Chemoradiotherapy with Gemcitabine in Patients with Resected Pancreatic Cancer.

PURPOSE: Despite curative resection, the 5-year survival for patients with resectable pancreatic cancer is less than 20%. Recurrence occurs both locally and at distant sites and effective multimodality adjuvant treatment is needed. MATERIALS AND METHODS: Patients with curatively resected stage IB-IIB pancreatic adenocarcinoma were eligible. Treatment consisted of chemotherapy with gemcitabine 1,000 mg/m2 on days 1 and 8 and cisplatin 60 mg/m2 on day 1 every 3 weeks for two cycles, followed by chemoradiotherapy (50.4 Gy/28 fx) with weekly gemcitabine (300 mg/m2/wk), and then gemcitabine 1,000 mg/m2 on days 1 and 8 every 3 weeks for four cycles. The primary endpoint was 1-year disease-free survival rate. The secondary endpoints were disease-free survival, overall survival, and safety. RESULTS: Seventy-four patients were enrolled. One-year disease-free survival rate was 57.9%. Median disease-free and overall survival were 15.0 months (95% confidence interval [CI], 11.6 to 18.4) and 33.0 months (95% CI, 21.8 to 44.2), respectively. At the median follow-up of 32 months, 57 patients (77.0%) had recurrence including 11 patients whose recurrence was during the adjuvant treatment. Most of the recurrences were systemic (52 patients). Stage at the time of diagnosis (70.0% in IIA, 51.2% in IIB, p=0.006) were significantly related with 1-year disease-free survival rate. Toxicities were generally tolerable, with 53 events of grade 3 or 4 hematologic toxicity and four patients with febrile neutropenia. CONCLUSION: Adjuvant gemcitabine and cisplatin chemotherapy followed by chemoradiotherapy with gemcitabine and maintenance gemcitabine showed efficacy and good tolerability in curatively resected pancreatic cancer.

Effects of Video-Based Information Provision Using a Smart Pad on Patients Undergoing Bone Marrow Biopsy.

The purpose is to determine the effect of video-based information provision using a smart pad on uncertainty, anxiety, physiological parameters, pain, and educational satisfaction among patients hospitalized for a bone marrow biopsy. This study was done with a pre-/posttest nonequivalent control group design. The subjects were 65 patients in the hematology-oncology ward of a university hospital in Cheongju, South Korea, who underwent a bone marrow biopsy between August 2017 and May 2018. Thirty volunteers were allocated to the control group and 35 volunteers to the intervention group. The experimental group showed significantly lower uncertainty and significantly greater satisfaction with education than did the control group. No significant difference was observed in anxiety, systolic and diastolic blood pressure, pulse, and pain. Video-based information provision using a smart pad was effective for lowering uncertainty among patients receiving a bone marrow biopsy, as well as for boosting their sense of educational satisfaction.

Distinct tumor immune microenvironments in primary and metastatic lesions in gastric cancer patients.

This study compared the tumor immune microenvironments (TIMEs) of primary gastric cancer (PGC) and paired metastatic gastric cancer (MGC). CD4+ and CD8+ T-cell density and PD-L1 expression were evaluated by multiplex immunohistochemistry, DNA mismatch repair (MMR) by immunohistochemistry, and immune-related genes by RNA sequencing. Twenty-three patients who underwent surgical treatment for PGC and MGC were enrolled in this study. CD8+ T-cell, PD-L1+ cell, and PD-L1+CK+ cell densities were significantly lower in MGC than PGC. PD-L1 positivity using a combined positive score (≥ 1%) and deficient MMR were observed in 52.2% and 8.7% of PGC samples, respectively, whereas both occurred in only 4.3% of MGC samples. The most frequent TIME types were inflamed (34.8%) and adaptive immune resistance (34.8%) in PGC, and immune desert (65.2%) and immunological ignorance (73.9%) in MGC. In transcriptome analysis, the expression of the T-cell inflamed gene set and co-stimulatory gene module was down-regulated in MGC compared to PGC. The total CD8+ T-cell density was an independent prognostic marker in both PGC and MGC (univariate P = 0.002, multivariate P = 0.006). Our result suggest that the TIME of metastatic tumors was less immunologically active compared to that of primary tumors in gastric cancer patients.