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Primary central nervous system lymphoma (PCNSL) remains a disease with poor outcome and high recurrence rate. We retrospectively analyzed the clinical data of 243 immunocompetent patients with PCNSL in Beijing Tiantan Hospital. The median age of PCNSL patients was 57 years (range 10-95 years). For induction therapy, 94.7% of patients received high-dose methotrexate (HD-MTX) containing regimens, and 59.3% received rituximab, which increased over time. The overall response rate was 72.8%, with 58.8% achieving complete response. With a median follow-up of 27.0 months (95% confidence interval 23.6-30.4), the median progression-free survival (PFS) time was 14.0 months (95% CI 9.45-18.55), and the 2-year PFS rate was 33.2%. The median overall survival (OS) was not reached (NR), with an estimated overall survival rate at 4 years of 61.6%. Among 95 patients who completed sequential consolidation chemotherapy with either pemetrexed or etoposide plus cytarabine, the median PFS was 28 months (95% CI 17.11-38.89), and the estimated overall survival at 4 years was 78.7%. In conclusion, HD-MTX based induction chemotherapy with non-myeloablative sequential consolidation chemotherapy is an alternative feasible treatment option.

Background It has been indicated that abnormal glucose metabolism mediated by hypoxia‐inducible factor 1α (HIF‐1α) played an essential role in the development of solid tumor. However, there were rare studies about the role of them in primary central nervous system lymphoma (PCNSL). Objective To investigate the protein levels of HIF‐1α, glucose transporter 1 (GLUT1), and hexokinase 2 (HK2) in PCNSL and whether their levels are associated with prognostic factors. Methods Expression of HIF‐1α, GLUT1, and HK2 in 39 tumor tissues was evaluated by immunohistochemical stainning. The correlation of the expression of HIF‐1α with the protein level of GLUT1 and HK2 was investigated. In addition, the association between these protein expression levels and clinical parameters and prognosis was analyzed. Results In the tumor specimens of PCNSL, positive stainings of HIF‐1α, GLUT1, and HK2 were in 23 patients (58.97%), 25 patients (64.1%), and 26 patients (66.67%), respectively, which were associated with the expression level of lactic dehydrogenase (LDH), but not with age, gender, number of lesion, ECOG score, or deep structure. The expression of HIF‐1α was positively correlated with the expression of GLUT1 (p, There was a hypoxic microenvironment, and HIF‐1α was involved in the regulation of glycolysis pathway in PCNSL. GLUT1 might be a potential marker for shorter PFS in PCNSL.

Introduction Secondary central nervous lymphoma(SCNSL) was defined as lymphoma involvement of both within and outside CNS at initially diagnosis or CNS relapse of a systemic disease. The prognosis of SCNSL was poor and the most appropriate treatment remained unestablished. Methods We conducted a retrospective study addressing the feasibility of R-MIADD regimen which comprised rituximab, high dose methotrexate, ifosfamide, cytarabine, liposomal formulation of doxorubicin, dexamethasone in 19 consecutive SCNSL patients. Results Nineteen SCNSL patients with newly diagnosed CNS lesions were included with median age of 58 years (range 20 to 72 years). Eleven out of 19(57.9%) patients achieved complete remission(CR) and 2(10.5%) patients achieved partial remission by the end of induction treatment, the overall response rate (ORR) was 68.4%. The median follow-up time after the onset of CNS was 11.1 (3.2-35.5) months, the median progression-free survival after CNS was 28.0 months (95% CI: 11.0-44.9), and the median overall survival after CNS were 34.5months, by the time of this report, 8 patients remained CR. Treatment-related deaths was found in only one patient. Conclusions This is the largest series of SCNSL patients in China, and these date underscore the feasibility and efficacy of R-MIADD as induction treatment of SCNSL, further investigation is warranted.

Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis is the most common type of infection-associated HLH. Previous studies were focused on pediatric EBV-HLH patients, therefore there lack of adult data.We performed a retrospective analysis of 133 EBV-HLH patients (≥14 years old) in Beijing Friendship Hospital from March 2009 to April 2016 to evaluate the clinical manifestation and the effects and prognosis of existing regimens of EBV-HLH in adult and adolescents.Of these patients, 91 male and 42 female cases had a median age of 26 (14-77) years. EBV-DNA load on admission was at a median of 6.6E + 05 IU/ml. The one-year mortality of these patients was 78%. 112 patients received the HLH-94/04 regimen as the initial treatment, 52 patients (46.43%) had response. Of the 6 patients who received the L-DEP regimen as the initial treatment, 5 patients (83.33%) had response. The rest 15 patients received initial treatment without etoposide, 5 cases achieved PR. 69 refractory or relapsed patients received DEP or L-DEP regimen, 55 (79.71%) cases had response. In addition, who received the L-DEP regimen, with the overall response rate significantly higher than the DEP regimen (88.37% VS 65.38%, P = 0.031). 36 out of 133 EBV-HLH patients eventually received allo-HSCT, with the overall survival rate of 52.78%. In summary, EBV-HLH is a highly lethal disease.DEP/L-DEP was a good salvage treatment. L-DEP might be a more effective first-line initial regimen than HLH-94/04 regimen for EBV-HLH. Finally, allo-HSCT is an effective radical treatment for EBV-HLH.

A major cause of hemophagocytic lymphohistiocytosis (HLH) is malignant neoplasms of the blood system, among which NK/T cell lymphoma is one of the most common risk factors. Patients with NK/T cell lymphoma hemophagocytic lymphohistiocytosis (NK/T-LAHS) have a worse prognosis and higher mortality. We aimed to explore the factors that affect the prognosis of NK/T-LAHS.Clinical data of 42 patients with NK/T-LAHS diagnosed by Beijing Friendship Hospital from June 2008 to June 2016 were analyzed retrospectively. The survival time was counted until 1 August 2016.For the 42 NK/T-LAHS patients, 1-month survival rate was 48.9%, 2-month survival rate was 36.7%, 3-month survival rate was 28.8%, 6-month survival rate was 23.0%, and 12-month survival rate was 15.4%. NK/T-LAHS patients who underwent allogeneic hematopoietic stem cell transplantation (Allo-HSCT) (p = 0.000), exhibited peripheral blood Epstein-Barr virus (EBV)-positivity (p = 0.004), and achieved overall response (OR) remission after initial induction therapy (p = 0.007) had statistical significance.NK/T-LAHS is a disease of poor prognosis and high mortality. NK/T-LAHS patients who achieved OR remission after the initial induction therapy had a better prognosis than non-remission patients and Allo-HSCT was an effective way to prolong the survival of NK/T-LAHS patients. However, EBV positivity in peripheral blood was a poor prognostic factor in NK/T-LAHS patients.

Objectives: Encouraging progress has been made in application of splenectomy in the treatment of relapsed hemophagocytic lymphohistiocytosis (HLH) of unknown cause. The aim was to determine the roles of lymphocyte subpopulations and inflammatory cytokines in splenectomy.Methods: We retrospectively analyzed changes in lymphocyte subpopulations and levels of inflammatory cytokines at different time-points before and after splenectomy in the patients with relapsed HLH of unknown cause, as well as the correlations between these changes and the disease prognosis.Results: During the period from June 2006 to June 2016, we enrolled 107 patients with relapsed HLH of unknown cause, of whom 29 were treated with splenectomy. Among the 29 patients, 7 cases were non-Hodgkin lymphomas based on spleen pathology, 1 case withdrew and the remaining 21 non-lymphoma cases were available for analysis. Results showed a significant increase in both percentage of CD16+CD56+ NK cells (P = 0.003) and NK cell activity (P = 0...

Background This study investigated the clinical characteristics of primary hemophagocytic lymphohistiocytosis (HLH) in adults, including immunological markers, pedigree findings, and conditions of allogeneic hematopoietic stem cell transplantation (Allo-HSCT). Methods The study included clinical data of 18 adult patients with primary HLH treated in our center from June 2010 to January 2017. Results Of these 18 cases, pathogenic variants were found in the following genes: PRF1 (n = 11), UNC13D (n = 5), SH2D1A (n = 2), RAB27a (n = 1), and LYST (n = 2). One patient had pathogenic variants in both PRF1 and UNC13D genes, one patient had pathogenic variants in both LYST and UNC13D genes and another patient had pathogenic variants in both PRF1 and SH2D1A genes. Additionally, 3 of the 18 cases involved homozygous pathogenic variants, while 2 cases involved hemizygous pathogenic variants. The remaining 13 cases involved compound heterozygous pathogenic variants. The natural killer (NK) cell activity test was conducted in all 18 cases where 14(77.8%)patients showed reduction in NK cell activity. Furthermore, this article presents 3 representative results of the pedigree findings from 12 patients who underwent family surveys. The 8 patients who underwent Allo-HSCT had a median survival of 27.2 months, as compared with the median survival of 7 months for the10 patients who did not undergo Allo-HSCT, a significant difference between the two groups of patients (p = 0.006). Conclusion PRF1 was one of the most commonly mutated gene in adult patients with primary HLH. Family surveys and immunological markers were important for the HLH diagnosis and the selection of an appropriate donor. Allo-HSCT was an effective therapy for adult primary HLH.

Encouraging progress has been made in application of splenectomy in the treatment of relapsed hemophagocytic lymphohistiocytosis (HLH) of unknown cause. The aim was to determine the roles of lymphocyte subpopulations and inflammatory cytokines in splenectomy.We retrospectively analyzed changes in lymphocyte subpopulations and levels of inflammatory cytokines at different time-points before and after splenectomy in the patients with relapsed HLH of unknown cause, as well as the correlations between these changes and the disease prognosis.During the period from June 2006 to June 2016, we enrolled 107 patients with relapsed HLH of unknown cause, of whom 29 were treated with splenectomy. Among the 29 patients, 7 cases were non-Hodgkin lymphomas based on spleen pathology, 1 case withdrew and the remaining 21 non-lymphoma cases were available for analysis. Results showed a significant increase in both percentage of CD16Splenectomy can improve clinical symptoms and survival of patients with relapsed HLH of unknown cause. The mechanism is likely related to the changes in percent NK cells and cytokines (IL-21 and IL-1α) after surgery.

Background Epstein–Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) is the most frequent subtype of secondary HLH triggered by infections. Previous studies have shown that ~30 % or more of patients with EBV-HLH do not respond to standard therapy. This study investigated the efficacy and safety profile of a modified DEP regimen in combination with PEG-aspargase (L-DEP) as a salvage therapy for refractory EBV-HLH. Methods In this study from October 2014 to October 2015, 28 patients with refractory EBV-HLH received a L-DEP regimen at the Beijing Friendship Hospital, Capital Medical University. Treatment efficacy and adverse events were evaluated at 2 and 4 weeks after L-DEP treatment. Results Median EBV-DNA concentrations before and 2 weeks after receiving the L-DEP regimen were 9.6 × 105 (1.5 × 104 − 1 × 109) copies/mL and 2.2 × 105 (3.8 × 102 − 1.2 × 107) copies/mL, respectively; the post-treatment values were significantly lower than that of the pretreatment (P = 0.048). Nine of the 28 study patients achieved complete response (CR) and 15 partial response (PR), resulting in an overall response rate of 85.7 % (CR+PR). Four patients who did not achieve response died within 4 weeks of receiving L-DEP. Thirteen of the 24 patients who achieved partial or complete response received subsequent allogenic hematopoietic stem cell transplantation (allo-HSCT). Ten of these 13 patients survived until 1 March 2016. The major adverse effects of the L-DEP regimen were high serum amylase concentrations, abnormal liver function, and coagulation disorders. Conclusions This study suggests that L-DEP is a safe and effective salvage therapy prior to allo-HSCT for refractory EBV-HLH and increases the possibility of such patients receiving allo-HSCT. A prospective multicenter large-scale clinical trial that aims to validate the L-DEP regimen for refractory EBV-HLH is currently underway (ClinicalTrails.gov Identifier: NCT02631109).

Background: With advances in theinterventional field, the choice between coronary artery bypass grafting (CABG) and percutaneous coronary intervention with drug-eluting stents (PCI-DES) for the diabetic subset with left main (LM) and/or multivessel disease (MVD) remains consistently controversial. Methods and results: We conducted a systematic review of randomized controlled trials (RCTs) and observational controlled trials (OCTs) comparing the two strategies for the diabetic subset with LM and/or MVD. PubMed, EMBASE, CENTRAL databases, Google Scholar and SinoMed were systematically searched for eligible studies without language and publica­tion restrictions. We identified 19 trials (4 randomized and 15 nonrandomized), enrolling 5,805 patients in OCTs and 3,060 patients in RCTs, respectively. PCI-DES was associated with higher mortality compared with CABG (11.7% DES vs. 9.1% CABG, RR 1.23, 95% CI 1.00–1.53, p = 0.06). Patients after PCI-DES had higher prevalence of myocardial infarction (MI) when compared with CABG (8.5% DES vs. 4.6% CABG, RR 1.68, 95% CI 1.20–2.37, p = 0.003). PCI-DES patients were at substantially lower risk of stroke (2.0% DES vs. 3.9% CABG, RR 0.51, 95% CI 0.39–0.67, p < 0.00001), but at several-fold higher risk of repeat revascularization (19.0% DES vs. 6.3% CABG, RR 2.95, 95% CI 2.46–3.55, p < 0.00001). The OCT patients risked a lower mortality as compared to the RCT patients (9.6% OCTs vs. 11.9% RCTs, RR 0.81, 95% CI 0.71–0.92, p = 0.001). Conclusions: CABG for patients with diabetes mellitus and LM and/or MVD had advan­tages over PCI-DES in all-cause death, nonfatal MI, and repeat revascularization, but the substantial disadvantage in nonfatal stroke. The high-selected patients (RCTs) risked a higher mortality than the real-world patients (OCTs).

Epstein-Barr virus-associated hemophagocytic lymphohistocytosis (EBV-HLH) is the most frequent subtype of secondary HLH with infectious triggers. In addition to meet the HLH-2004 diagnostic criteria, the diagnosis of EBV-HLH requires the evidence of EBV infection and exclusion of primary HLH and lymphoma-associated HLH. The prognosis of EBV-HLH is generally dismal. To assess the efficacy of current treatment protocols in adult and adolescent patients with EBV-HLH, we retrospectively analyzed 171 HLH patients presented at our institution from March 2009 to April 2016. Of those, 133 patients were EBV-HLH; 35 patients were lymphoma-associated HLH; 3 of 68 patients who underwent genetic test were diagnosed with primary HLH including one with homozygous mutation in UNC13D, one with homozygous mutation in RAB27A, and one with hemizygous mutation in SH2D1A. The rest of the 68 patients exhibited various levels of genetic defects. Of the 133 EBV-HLH patients, 91 male and 42 female cases (2.2:1) were aged between 14 - 77 years with a median age of 26 years. EBV-DNA load on admission was at a median of 6.6 × 105 copies/ml (range: from 5.0 × 103 - 7.8 × 109 copies/ml). One-year mortality rate for them was 66.4%. One hundred and twelve cases were initially treated by HLH-94 or HLH-2004 regimen. Of those, 52 cases (46.4%) had response including 22 cases (19.6%) of complete response (CR) and 30 cases (26.8%) of partial response (PR). Six patients received L-DEP regimen as initial treatment, of which 5 cases had response consisting 3 cases of CR and 2 cases of PR. The overall response rate (ORR) was 83.3%. The rest 15 patients received initial treatment without etoposide, 5 patients (33.3%) achieving PR and 10 patients (66.7%) showing no response. Sixty-nine refractory or relapsed cases received DEP or L-DEP regimen, ORR of which was 79.7%. For those cases, 26 cases received DEP regimen, of which 17 cases (65.4%) had response including 5 cases of CR and 12 cases of PR. Forty-three patients received L-DEP as salvage therapy, of which 38 cases (88.4%) had response including 13 cases of CR (30.2%) and 25 cases of PR (58.1%). Compared to DEP treatment, who received L-DEP had a higher effective rate (65.4% versus 88.4%, p=0.031). Of 133 EBV-HLH patients, only 36 patients received allogeneic hematopoietic stem cell transplantation, the survival rate was 61.1%. In conclusion, EBV-HLH is a fatal disease. Our results indicate DEP or L-DEP is an effective salvage therapy. Additionally, L-DEP may be a more effective therapy than HLH-94/2004 regimen to be used as an initial treatment. Finally, allogeneic hematopoietic stem cell transplantation is an effective approach for the treatment of EBV-HLH. Disclosures No relevant conflicts of interest to declare.