In this prospective, multicenter, Phase 2 clinical trial (NCT02987244), patients with peripheral T-cell lymphomas (PTCLs) who had responded to first-line chemotherapy with cyclophosphamide, doxorubicin or epirubicin, vincristine or vindesine, etoposide, and prednisone (Chi-CHOEP) were treated by autologous stem cell transplantation (ASCT) or with chidamide maintenance or observation. A total of 85 patients received one of the following interventions: ASCT (n = 15), chidamide maintenance (n = 44), and observation (n = 26). estimated 3 PFS and OS rates were 85.6 Clinical trial registration: clinicaltrial.gov, NCT02987244. Registered 8 December 2016, http://www.clinicaltrials.gov/ct2/show/NCT02987244 .

Supplementary Data from Tislelizumab for Relapsed/Refractory Classical Hodgkin Lymphoma: 3-Year Follow-up and Correlative Biomarker Analysis

BACKGROUND:Myeloablative chemotherapy supported by autologous stem cell transplantation (ASCT) is an option for primary central nervous system lymphoma (PCNSL) in both the relapse setting and as postremission consolidation, but the level of evidence in this field is still low. MATERIAL AND METHODS:We retrospectively analyzed 47 HIV-negative PCNSL patients from 2010 to 2021. To assess the outcomes in patients undergoing ASCT. RESULTS:Of the 47 patients, the median age was 51 (range, 21-77) years, and 28 (59.6%) were male. After induction, 33 (70.2%) patients achieved complete remission, and 6 (12.8%) patients achieved partial remission. At a median follow-up of 21.4 months (95% CI 8.86-33.95), the median progression-free survival (PFS) was 23.3 months (95% CI 14.87-31.73), and the 4-year PFS rate was 14.6%. The median overall survival (OS) time was 62.4 months (95% CI 41.93-82.87), and the 4-year OS rate was 71.5%. Among 20 patients who received ASCT (10 consolidation, 10 salvage), the 4-year PFS and 4-year OS rates were 57.3% and 71.2%, respectively. In the multivariate analysis, ASCT therapy (hazard ratio [HR] 0.16, P=0.016) and early remission (HR 0.12, p=0.003) were found to be independent prognostic factors for a longer PFS. Two treatment-related deaths occurred in patients with multiple relapses before ASCT. Pancytopenia and diarrhea were the most common adverse events. CONCLUSIONS:ASCT offers potential long-term PFS with good tolerability for patients with PCNSL. Our retrospective cohort adds to the currently available literature and identifies disease status after induction as a significant factor affecting survival.

OBJECTIVE:To analyze the clinical characteristics and risk factors of invasive fungal infection (IFI) occurenced in patients with acute leukemia (AL) during treatment in tropical regions.METHODS:The clinical data of 68 AL patients admitted to the Hainan Hospital of PLA General Hospital from April 2012 to April 2019 was retrospectively analyzed. Logistic regression analysis was used to analyze the factors affecting the occurrence of IFI in AL patients.RESULTS:Among the 68 patients, 44 were acute myeloid leukemia, 24 were acute lymphoblastic leukemia, 39 were male, 29 were female and the median age was 41(13-75) years old. The 68 patients received 242 times of chemotherapy or hematopoietic stem cell transplantation(HSCT), including 73 times of initial chemotherapy or inducting chemotherapy after recurrence, 14 times of HSCT, 155 times of consolidating chemotherapy. Patients received 152 times of anti-fungal prophylaxis, including 77 times of primary anti-fungal prophylaxis and 75 times of secondary anti-fungal prophylaxis. Finally, the incidence of IFI was 31 times, including 24 times of probable diagnosis, 7 times of proven diagnosis, and the total incidence of IFI was 12.8%(31/242), the incidence of IFI in inducting chemotherapy was 24.66%(18/73), the incidence of IFI in HSCT patients was 28.57% (4/14), the incidence of IFI in consolidating chemotherapy was 5.80% (9/155). Multivariate analysis showed that inducting chemotherapy or HSCT, the time of agranulocytosis ≥7 days, risk stratification of high risk were the independent risk factors for IFI in AL patients during treatment in tropical regions.CONCLUSION:The incidence of IFI in patients with AL in the tropics regions is significantly higher than that in other regions at homeland and abroad. Anti-fungal prophylaxis should be given to the patients with AL who have the high risk factors of inducting chemotherapy or HSCT, time of agranulocytosis ≥7 days and risk stratification of high risk.

Abstract Purpose: Tislelizumab is an anti–programmed cell death protein 1 (anti–PD-1) monoclonal antibody specifically designed to minimize binding to Fcγ receptors (FcγR). Patients and Methods: Here, we present the extended 3-year follow-up of a phase II study of tislelizumab in 70 patients with relapsed/refractory classical Hodgkin lymphoma (cHL) who failed or were ineligible for autologous stem cell transplantation. Results: With a median follow-up of 33.8 months, the overall response rate by the independent review committee was 87.1%, and the complete response (CR) rate was 67.1%. Responses were durable as shown by a median duration of response of 31.3 months, and median progression-free survival (PFS) of 31.5 months. The 3-year PFS and overall survival rates were 40.8% and 84.8%, respectively. Treatment-related adverse events (TRAEs) of any grade occurred in 97.1% of patients; the grade ≥3 TRAE rate was low (31.4%), and only 8.6% of patients experienced adverse events leading to treatment discontinuation. Correlative biomarker analysis showed that FcγRΙ-expressing macrophages had no observed impact on either the CR rate or PFS achieved with tislelizumab, which may be potentially related to its engineered Fc region. Conclusions: With extended follow-up, tislelizumab yielded long-term benefits and demonstrated a favorable safety profile for patients with relapsed/refractory cHL. This trial was registered at clinicaltrials.gov as NCT03209973.

目的:探讨bcl-2抑制剂维奈克拉+FLAG+伊达比星（IDA）方案对第1次异基因造血干细胞移植（allo-HSCT）后复发的急性髓系白血病（AML）治疗效果和安全性及第1次allo-HSCT后复发患者的治疗选择。方法:回顾性分析解放军总医院海南医院2018年7月收治的1例复发难治AML患者的诊疗过程，并复习相关文献。结果:患者，女性，23岁，诊断为AML，经过诱导化疗及巩固化疗后复发，挽救化疗无效，遂在复发状态下进行第1次allo-HSCT；移植后4个月患者再次复发，在给予挽救性治疗无效的情况下给予维奈克拉+FLAG+IDA方案治疗，达完全缓解（CR），流式细胞术检测微小残留病（MRD）阴性，遂给予第2次allo-HSCT，并于+60天给予地西他滨+维奈克拉巩固治疗。随访至移植后3个月余时，患者仍为CR和MRD阴性。结论:分子靶向药物维奈克拉与FLAG+IDA方案联合对第1次allo-HSCT后复发的AML患者安全、有效，且耐受性良好。第2次allo-HSCT可以作为年轻的第1次allo-HSCT后复发AML患者的有效治疗选择。

Background: YF-H-2015005, a novel CXCR4 antagonist, has been proven to increase the quantities of circulating hematopoietic stem cells (HSCs), which results in an adequate collection of HSCs in non-Hodgkin lymphoma (NHL) patients. Methods: This was a multicenter, double-blind, randomized (1:1), placebo-controlled phase III clinical trial. All patients received granulocyte colony-stimulating factor (G-CSF) for up to 8 consecutive days. YF-H-2015005 or placebo was administrated on the evening of day 4 and continued daily for up to 4 days. Apheresis was conducted 9–10 h after each dose of YF-H-2015005 or placebo. The primary endpoint was the proportion of NHL patients procuring ≥5 × 10 6 /kg CD34 + HSCs within ≤4 apheresis sessions. Results: In total, 101 patients with NHL were enrolled. The proportions of patients achieving primary endpoint were 57 and 12% in YF-H-2015005 and placebo groups, respectively ( P < 0.001). Moreover, a higher proportion of YF-H-2015005-treated patients reached a minimum target collection of ≥2 × 10 6 /kg CD34 + HSCs in ≤4 apheresis days compared to placebo-treated patients (86 vs. 38%, P < 0.001). Furthermore, the median time to collect ≥2 or 5 × 10 6 /kg CD34+ HSCs were 1 and 3 days in YF-H-2015005-treated patients, but 4 days and not reached in placebo-treated patients, respectively. No severe treatment emergent adverse events were observed in both YF-H-2015005 treatment and placebo groups. Conclusions: YF-H-2015005 plus G-CSF regimen was a tolerable combination with high efficacy, which might be used to rapidly mobilize and collect HSCs in NHL patients.

Objective: To assess the efficacy and safety of the novel histone deacetylase inhibitor, chidamide, in combination with cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone (Chi-CHOEP) for untreated peripheral T-cell lymphoma (PTCL). Methods: A prospective, multicenter, single arm, phase 1b/2 study was conducted. A total of 128 patients with untreated PTCL (18–70 years of age) were enrolled between March 2016 and November 2019, and treated with up to 6 cycles with the Chi-CHOEP regimen. In the phase 1b study, 3 dose levels of chidamide were evaluated and the primary endpoint was determination of the maximum-tolerated dose and recommended phase 2 dose (RP2D). The primary endpoint of the phase 2 study was 2-year progression-free survival (PFS). Results: Fifteen patients were enrolled in the phase 1b study and the RP2D for chidamide was determined to be 20 mg, twice a week. A total of 113 patients were treated at the RP2D in the phase 2 study, and the overall response rate was 60.2%, with a complete response rate of 40.7%. At a median follow-up of 36 months, the median PFS was 10.7 months, with 1-, 2-, and 3-year PFS rates of 49.9%, 38.0%, and 32.8%, respectively. The Chi-CHOEP regimen was well-tolerated, with grade 3/4 neutropenia occurring in approximately two-thirds of the patients. No unexpected adverse events (AEs) were reported and the observed AEs were manageable. Conclusions: This large cohort phase 1b/2 study showed that Chi-CHOEP was well-tolerated with modest efficacy in previously untreated PTCL patients.

Objective To analyze the characteristics, prognosis and risk factors of bloodstream infection in patients with hematological malignancies in the tropics, so as to provide evidence for the prevention and treatment of bloodstream infection. Methods The clinical features, blood culture results and prognosis of patients with bloodstream infection in patients with hematological malignancies admitted to Hainan Hospital of PLA General Hospital were retrospectively studied. Results The most common primary infection site of the 81 patients with hematological malignancies was lung (46.91%), followed by PICC (11.11%). The detection rate of Gram-positive bacteria and Gram-negative bacteria in the blood culture was 60.98% and 30.02%, respectively. Coagulase-negative staphylococci was the most common Gram-positive bacteria resulting in bloodstream infection in our study. Of the Gram-negatives, Klebsiella pneumoniae (34.38%) was predominant, followed by Escherichia coli (18.75%) and Pseudomonas aeruginosa (18.75%). Gram-positive bacteria was highly sensitive (100%) to vancomycin, linezolid and tigecycline. Study showed that Gram-negative bacteria had low sensitive to quinolones, in particular, the resistance rate of Escherichia coli to quinolones was as high as 83.33%. In terms of overall survival (OS), the 30-days OS of patients with Gram-negative and Gram-positive septicemia was 77.42% and 92.00%, respectively. There was no statistically significant difference between the two groups. Multivariate analysis revealed that septic shock (P=0.001, RR=269.27) was an independent risk factor for 30-day mortality, and remission status (P=0.027, RR=0.114) was an independent predictor of a favourable outcome of bloodstream infection in patients with hematological malignancies. Conclusion Gram-positive bacteria are the main pathogens causing bloodstream infections in patients with hematological malignancies in the tropics. Improving the care of PICC is an important measure to reduce the incidence of bloodstream infection in patients with hematological malignancies in the tropics. A correct treatment relieving disease and effective prevention and treatment of septic shock can reduce mortality of patients with bloodstream infection in patients with hematological malignancies in the tropics.

We report the case of a 23-year-old man with a medical history of idiopathic thrombocytopenic purpura (ITP) and newly diagnosed with the Epstein-Barr virus (EBV)-positive multiple-site extramedullary plasmacytoma (EMP), which involves the respiratory system. The patient was referred to our hospital because of progressive nasal congestion and nasal mass. Nasopharyngoscopy and bronchoscopy were performed. The biopsy pathological hematoxylin and eosin (HE) staining indicated plasma cell myeloma, and further immunohistochemistry CD99(+), CD79a(+), CD38(+), MUM-1(+), and Lambda(+) confirmed the diagnosis. The patient's bone marrow was normal, and hypercalcemia, renal insufficiency, anemia, evident bone lesions were not observed. Serum immunoglobulin quantification, serum protein electrophoresis, and blood and urine light chain quantification were all within the normal range. The serum immunofixation electrophoresis was negative, and the serum-free light chain was normal. These results could rule out multiple myeloma (MM) and prove to be EMP involving the nasal cavity, main bronchus, lung, and left hip. No desired effect was achieved after receiving PAD (bortezomib, adriamycin, and dexamethasone) and VRD (bortezomib, lenalidomide, and dexamethasone) treatments. Even if the tumor was remarkably relieved after receiving the 2-course CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) regimen, secondary resistance to CHOP unfortunately occurred in this case. We attempted to apply epigenetic therapy in the treatment of refractory multiple EMP. Although no complete remission (CR) was achieved, the maximum standard uptake value (SUVmax) in tumor lesions was significantly lower than before, and the patient's symptoms significantly improved. The patient tolerated decitabine and chidamide. We speculated that epigenetic drugs have potential effect in the treatment of multiple-site EMP.

Objective:To explore programmed death(PD)-1 inhibitor in treatment of patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) combined central nervous system (CNS) involvement, and review relevant literature.Methods:In April 2019, two patients with R/R DLBCL combined CNS involvement after autologous stem cell transplantation (auto-HSCT) who admitted to Department of Hematology, First Medical Center of Chinese PLA General Hospital were selected as research subjects. These 2 patients were treated with a variety of regimens based on PD-1 inhibitor camrelizumab (200 mg/time, once every 2 weeks). Retrospective analysis method was conducted to collect relevant clinical data and efficacy of these patients receiving camrelizumab treatment, and reviewed relevant literature. The follow-up data of this study was as of June 30, 2019. This study was in line with World Medical Association Declaration of Helsinki revised in 2013, and informed contents were obtained from all subjects. Results:① Patient 1 was male and 50 years old. He presented with " left eye pain for 1 month" and was diagnosed as DLBCL in February 2017. Then, he experienced DLBCL relapse in CNS after first-line R-CHOP(rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone) chemotherapy and received auto-HSCT in October 2018. Unfortunately, he experienced DLBCL relapse in CNS and systemic in March 2019. Patient 2 was female and 44 years old. She presented with " swollen tonsillar for 1 month" and was diagnosed as DLBCL in July 2016. She experienced her first relapse after first-line R-CHOP chemotherapy. She achieved a second complete remission (CR) after second-line R-DICE(rituximab, dexamethasone, ifosfamide, cisplatin and etoposide) chemotherapy. Auto-HSCT was also performed for her in May 2018. But she experienced relapse again in December 2018. ② Patient 1 received a total of 13 times camrelizumab based regimens. And a partial remission (PR) was achieved after 10 times of camrelizumab treatment. Finally, unconfirmed CR (CRu) was confirmed in patient 1 after 13 times of camrelizumab treatment. As of the end of follow-up, this patient was still in good remission. However, no improvement was shown after 5 times of camrelizumab treatment in patient 2, and she eventually died due to progression of lymphoma 12 months after the second recurrence. ③ After receiving 4 times camrelizumab treatment, camrelizumab was detected in serum and cerebrospinal fluids samples of patient 1, at concentrations of 34 968.86 and 494.57 ng/mL, respectively. The concentration of camrelizumab in serum sample of patient 2 was 26 538.14 ng/mL. But camrelizumab wasn′t detected in her cerebrospinal fluids sample. ④ According to current literature, there was no predictive biomarker for efficacy of PD-1 inhibitors for patients with R/R DLBCL. With the exception that PD-1 inhibitors showed promising results in some selected types of lymphoma, the response rate of patients with R/R DLBCL who received PD-1 inhibitor monotherapy was very low. Combination therapy incorporating a PD-1 inhibitor seemed to be a rational approach for R/R DLBCL.Conclusions:It is advisable to detect concentration in serum and cerebrospinal fluids samples from R/R DLBCL patients using PD-1 inhibitors. The presence of PD-1 inhibitor in cerebrospinal fluids may serve as a biomarker for its efficacy for R/R DLBCL patients with CNS involvement. Whether there is a direct correlation between cerebrospinal concentration in cerebrospinal fluid and curative effect needs to be further confirmed.

e19507 Background: Tislelizumab is a humanized IgG4 monoclonal antibody with high affinity/specificity for programmed cell death protein 1 (PD-1). It was engineered to minimize binding to Fc-γ receptors on macrophages, thereby decreasing antibody-dependent phagocytosis, a potential mechanism of T-cell clearance and resistance to anti–PD-1 therapy. Tislelizumab therapy was highly active in autologous stem cell transplant (ASCT)-failed or ineligible patients with R/R cHL ( Leukemia. 2020;34:533). Here we report results from up to 3 years follow-up. Methods: This asingle-arm, multicenter phase 2 study (NCT03209973) of 200 mg tislelizumab administered intravenously to patients (pts) with R/R cHL every 3 weeks until progressive disease (PD) or unacceptable toxicity. Patients were eligible if they: failed to achieve a response or progressed after ASCT, or: received ≥2 lines of prior systemic chemotherapy for cHL and were ineligible for ASCT. Primary endpoint was overall response rate (ORR) assessed by an independent review committee (IRC) per Lugano criteria ( J Clin Oncol. 2014;32:3059). Secondary endpoints were progression-free survival (PFS), duration of response (DOR), complete response (CR) rate, and time to response (TTR) per IRC, safety, and tolerability. Results: Pts (N=70) from 11 centers in China were enrolled and treated; characteristics have been previously reported. As of the data cutoff date (Nov 2, 2020), median follow-up was 33.8 months (range, 3.4-38.6). Pts still on treatment at the end of study (n=33; 47.1%) entered a long-term extension study. Efficacy data is presented in the Table below. In the 13 pts who received prior ASCT, 11 (84.6%) achieved CR. The most common treatment-emergent adverse events (AEs; ≥30%) were pyrexia (57.1%), upper respiratory tract infection (38.6%), hypothyroidism (37.1%), and increased weight (34.3%). Treatment-related grade ≥3 AEs (≥2 pts) were pneumonitis, hypertension, neutropenia, lipase increased, weight increased, and increased creatine phosphokinase (CPK; 2.9% each). Immune-related AEs were reported in 32 pts (45.7%), with grade ≥3 AEs in 8 pts (11.4%): pneumonitis (4) and skin adverse reactions, nephritis, lipase increased, and blood CPK increased (1 each). AEs led to treatment discontinuation in 6 pts (8.6%). Conclusions: Long-term follow-up of R/R cHL pts treated with tislelizumab further demonstrated the substantial therapeutic activity and continued PFS benefit. There were no new safety concerns identified for long-term treatment with tislelizumab. Clinical trial information: NCT03209973. [Table: see text]

OBJECTIVE:To analyze the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for treatment of acute leukemia in the tropical area.METHODS:Twelve acute leukemia patients who were underwent allo-HSCT from April 2013 to November 2018 in Hainan Hospital of Chinese PLA General Hospital were selected, including 5 cases of acute lymphoblastic leukemia (ALL) and 7 case of acute myeloid leukemia (AML). Three cases received HLA matched sibling hematopoietic stem cell transplantation, 8 cases received haploidentical hematopoietic stem cell transplantation, 1 cases received partially mismatched unrelated hematopoietic stem cell transplantation. Pretreatment regimen: 9 cases received modified BU/CY+ATG pretreatment regimen, 3 cases received BU/CY pretreatment regimen. Graft-versus-host disease (GVHD) prevention regimen: all patients received cyclosporine A, mycophenolate mofetil combined with short-term methotrexate regimen. The clinical efficacy of allo-HSCT in treatment of acute leukemia in the tropical area was analyzed by detecting hematopoietic reconstitution, GVHD, infection, relapse and survival after transplantation.RESULTS:All the 12 patients achieved granulocyte reconstruction and megakaryocyte reconstruction. The median time of granulocyte reconstruction was 11.5 (6-14) days, and the median time of megakaryocytic reconstruction was 12.5 (10-22) days. Within 100 days after transplantation, the acute GVHD occurved in 8 cases, including 6 cases of Ⅱ-Ⅳ degree acute GVHD and 2 cases of Ⅲ-Ⅳ degree acute GVHD, 11 cases survived more than 100 days after transplantation, and the chronic GVHD occurred in 1 case, which was mildly limited. Pulmonary infection occurred in 7 cases, cytomegaloviremia occurred in 6 cases, EB viremia occurred in 6 cases, and hemorrhagic cystitis occurred in 5 cases. 2 cases relapsed and eventually died, and the remaining 10 patients survived without disease until the date of follow-up. The median follow-up time was 4 (1-68) months, 83.3% (10/12) survived without disease, and 16.7% (2/12) relapsed.CONCLUSION:Allo-HSCT is an effective method for the treatment of acute leukemia in adults. Leukemia patients should be transplanted as soon as possible after remission. The incidence of pulmonary fungal infection in transplanted patients in tropics is high, therefore the prevention and treatment of fungal infection should be strengthened.

Background: Tislelizumab, a humanized immunoglobulin 4 monoclonal anti-programmed cell death protein 1 (anti-PD-1) antibody, has an engineered Fc region that minimizes binding to Fcγ receptor (FcγR) on macrophages, thereby abrogating antibody-dependent phagocytosis (ADCP)-induced T-cell clearance. Tislelizumab demonstrated an overall response rate of 87.1% with a high complete response (CR) rate (62.9%) and was generally well tolerated in a phase 2 study in Chinese patients with relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL) (BGB-A317-203 study; clinicaltrials.gov identifier: NCT03209973). The present study explored the underlying mechanism of action (MOA) of tislelizumab and its potential contribution to the high CR rate associated with it in patients with R/R cHL. Methods: Seventy patients with confirmed R/R cHL were included in this study. Tissue samples were collected at baseline for biomarker testing. Forty-one samples were evaluable for multiple immunohistochemistry (mIHC) assays, and 36 samples were evaluable for gene expression profiling (GEP). For programmed death-ligand 1 (PD-L1), CD8 (cytotoxic T-cell marker), CD68 (macrophage pan-marker), CD64 (FcγRΙ), and CD30, mIHC samples were stained using Opal 7-Color IHC kit. Spatial analysis for the markers was conducted using HALO software. GEP utilized the HTG EdgeSeq Precision Immuno-Oncology panel. Genes expressed differentially in CR and non-CR were identified using the Lima R Bioconductor package. Gene signature score was calculated by the gene set variation analysis method. Median value across the biomarker population was used as the cutoff to define biomarker high versus low group. Differential biomarker tests between CR and non-CR were conducted by Wilcoxon rank-sum test. Results: For anti-PD-1 antibodies with a functional Fc, the Fc/FcγR interaction resulted in macrophage-induced T-cell clearance and dampened anti-tumor activity, while tislelizumab activity was not affected by macrophages in the mouse cancer model (Zhang T, et al. Cancer Immunol Immunother. 2018;67:1079-1090). In cHL clinical samples, we observed a similar CR rate for tislelizumab in FcγRΙ+ macrophages (CD68+CD64+) high versus low group (71.4% vs 60%, P=0.85 by Fisher-test). In the CD8+ T-cell high microenvironment where ADCP-induced T-cell clearance is more likely, neither the total number of CD68+/CD64+ cells (CR rate 86.6% for high vs 85.7% for low, n.s. by Fisher-test) nor the average number of CD68+CD64+ cells within 30 µm of CD8+ T cells (85.7% vs 80%, n.s. by Fisher-test) were observed to affect the CR rate. Additional tumor microenvironment components that may contribute to the high CR rate were also explored. We found that FcγRΙ+ and CD8+ cell percentage by mIHC were higher in CR patients (P=0.04 and P=0.08, CR vs non-CR). GEP results show that the tumor inflammation gene signature (TIS) (eg, CD8A, CCL5, PD-L1, IDO1, IFNG, CXCL9) were higher in CR patients (CR vs non-CR, P=0.04). Specific gene/gene signatures were associated with CR for different histology subtypes. In the mixed cellular subtype, CD8+ T cells by mIHC (P=0.0004) and the TIS gene signature by GEP (P=0.007) showed a larger difference between CR and non-CR. In the nodular sclerosis subtype, the extracellular matrix and fibroblast-related gene signature (eg, ICAM, COL1As, ITGAs, PDGFRB) were higher in CR patients (P=0.04, CR vs non-CR). Conclusions: Tislelizumab demonstrated a high CR rate regardless of the FcγRΙ expressing macrophage abundance in the cHL tumor microenvironment, which may be a functional consequence of its engineered Fc region and may differentiate its MOA from the MOAs of other anti-PD-1 agents. CD8+ T-cell abundance and tumor inflammatory gene signatures in the microenvironment may be associated with higher CR rate for cHL patients treated with tislelizumab. Disclosures Wang: BeiGene Co., Ltd.: Current Employment, Current equity holder in private company. Zhang:BeiGene Co., Ltd.: Current Employment, Current equity holder in private company. Liu:BeiGene Co., Ltd.: Current Employment, Current equity holder in private company. Zhang:BeiGene Co., Ltd.: Current Employment, Current equity holder in private company. Shen:BeiGene Co., Ltd.: Current Employment, Current equity holder in private company. Wang:BeiGene Co., Ltd.: Current Employment, Current equity holder in private company. Yang:BeiGene Co., Ltd.: Current Employment, Current equity holder in private company. Guo:BeiGene Co., Ltd.: Current Employment, Current equity holder in private company.

OBJECTIVE:To investigate the clinical characteristics of relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) and the factors affecting overall survival (OS) time.METHODS:The clinical data of 14 R/R DLBCL patients admitted to the Hainan Hospital of Chinese PLA General Hospital from April 2012 to March 2019 were analyzed retrospectively and the overall response rate (ORR) after the end of different treatments was estimated. Kaplan-Meier method was used to describe the survival curve, and Log-rank test was used to compare whether different survival curves showed statistically different.RESULTS:There were 8 males and 6 females with a median age of 51 (26-75) years old and the median course of treatment before R/R was 7 (4-13). Finally, 11 patients achieved remission, 6 patients of which showed complete remission, and 5 patients showed partial remission, with the median ORR duration at 2.5 (0-51) months. All patients in the group of ibrutinib combined with second-line chemotherapy achieved remission (4/4), it was equivalent to the high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (HDC-AHSCT) group (4/4), which was significantly higher than that of the other second-line group (3/6). The median OS time of patients was 17 (6-76) months. The survival of patients receiving ibrutinib combined with second-line chemotherapy and HDC-AHSCT was significantly better than that of patients not receiving ibrutinib combined with second-line chemotherapy and HDC-AHSCT. Normal lactate dehydrogenase, IPI score＜3 at diagnosis, and CR/PR after treatment could improve the survival time of patients.CONCLUSION:The duration of remission for R/R DLBCL patients is short and the prognosis is very poor. The survival time of patients with high level of lactate dehydrogenase, IPI score≥3 at diagnosis and SD/PD after treatment is significantly shortened. Ibrutinib combined second-line chemotherapy and HDC-AHSCT can improve the efficacy and survival of R/R DLBCL patients.

Primary adrenal lymphoma (PAL) is a rare entity of lymphoma with dismal prognosis using systemic chemotherapy. More clinical reports are needed to guide the treatment for PAL.We performed a retrospective analysis of 20 patients diagnosed with PAL who presented to our center between January 2005 and January 2014.Median age at presentation was 48 years (range: 27-73) with a male-to-female ratio of 7:3. Bilateral and right-sided adrenal involvement were seen in 11 of 20 and 7 of 20 patients, respectively. Adrenal insufficiency (AI) was seen in 6 of 10 evaluated patients. Diffuse large B cell lymphoma (DLBCL) was the most common immunophenotype (85.0%). Two patients died due to rapid disease progression before treatment. Two patients received autologous stem cell transplantation as consolidation therapy. All patients received prophylactic intrathecal chemotherapy. The estimated 5-year overall survival (OS) and progression-free survival (PFS) were 52.5% [95% confidence interval (95% CI: 28.2-72.0)] and 53.2% (95% CI: 29.0-72.5), respectively.These findings suggest that PAL should always be considered in differential diagnosis of adrenal mass with AI. Despite the contrasting previous reports, long-term prognosis of PAL is not necessarily inferior to that of non-Hodgkin lymphoma in general.

目的 探讨肝脾γδ-T细胞淋巴瘤(hepatosplenic gamma-delta T-cell lymphoma,HSTCL)的临床表现、病理学特征、免疫表型特点与临床治疗.方法 回顾性分析2012年11月-2015年4月本中心收治的4例肝脾γ δ-T细胞淋巴瘤患者临床资料并文献复习.结果 男性3例,年龄分别为18岁、49岁、63岁;女性1例,34岁;均有肝脾大、骨髓受累.脾中肿瘤细胞弥漫浸润脾索及脾窦,细胞中等大小,核仁不明显;免疫组化CD3阳性,Bcl-2阳性,B系相关抗原阴性,细胞毒性颗粒标记TIA-1可阳性.骨髓中髓窦受累并扩张,肿瘤细胞小至中等大小,核仁不明显或有1～2个可辨别的核仁,核浆比例升高;免疫分型均表达CD3和TCR γ δ,部分CD2及CD7阳性,可表达NK细胞抗原CD16、CD56,均不表达CD4、CD8、CD57.49岁男性患者放弃治疗,3例接受化疗患者2例因感染死亡,其中1例行异基因造血干细胞移植并复发.4例患者从有临床症状到确诊时间分别为20 d、16个月、5个月、19个月,确诊到死亡时间分别为7个月、3个月、2个月、2个月.结论 肝脾γδ-T细胞淋巴瘤骨髓受累时可借助免疫分型明确诊断;该型淋巴瘤对化疗多耐药,预后差.

Prognosis is poor for patients with relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL) after failure of or who are ineligible for autologous stem cell transplant. We evaluated the efficacy and safety of tislelizumab, an investigational anti-PD-1 monoclonal antibody, in phase 2, single-arm study in Chinese patients with R/R cHL. The primary endpoint was overall response rate as assessed by an independent review committee, according to the Lugano 2014 Classification. Seventy patients were enrolled in the study and received at least one dose of tislelizumab. After median follow-up of 9.8 months, 61 (87.1%) patients achieved an objective response, with 44 (62.9%) achieving a complete response (CR). The estimated 9-month progression-free survival rate was 74.5%. Most common grade ≥3 adverse events (AEs) were upper respiratory tract infection and pneumonitis. Infusion-related reactions occurred in 27 (38.6%) patients, and 27 patients (38.6%) experienced an immune-related AE, the most common of which was thyroid dysfunction. Eleven (15.7%) patients experienced at least one treatment-emergent AE leading to dose interruption or delay. No deaths occurred due to AEs. Treatment of patients with R/R cHL with tislelizumab was generally well tolerated and resulted in high overall response and CR rates, potentially translating into more durable responses for these patients.

Background: Chidamide is a novel benzamide class of histone deacetylase (HDAC) inhibitor. In a pivotal phase 2 trial with refractory or relapsed peripheral T-cell lymphoma (PTCL), chidamide produced ORR 28% with CR 14% leading to its approval by the China Food and Drug Administration in 2014 for refractory or relapsed PTCL. We sought to assess the safety, tolerability and efficacy of the novel histone deacetylase inhibitor chidamide in combination with CHOEP (cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone) (Chi-CHOEP) for previously untreated PTCL.