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Background Myelomatous pleural effusion (MPE), as a presentation of extramedullary infiltration of multiple myeloma (MM), is rare and currently associated with poor outcomes without effective therapy. The potential value of cytokine detection in pleural effusion to MPE has not been reported to date. Case presentation We herein report a case of refractory and relapsed multiple myeloma that developed bilateral MPE due to disease progression caused by intolerance to various chemotherapy regimens. Cytomorphology and flow cytometry were adopted for diagnosis confirmation. Chemotherapy containing immunomodulators combined with thoracic catheterization drainage was applied to the patient, showing a certain therapeutic effect. During the course of disease, the change of cytokine profile in pleural effusion was monitored by cytometric bead array (CBA) technology, revealing that cytokines related to tumor load such as interleukin 6 (IL-6) and interleukin 10 (IL-10) in pleural effusion decreased with the improvement of disease, while other cytokines such as interleukin 2 (IL-2), interleukin 4 (IL-4), interleukin 17A (IL-17A), tumor necrosis factor α (TNF-α), interferon γ (IFN-γ), granzyme A, granzyme B, perforin and granulysin increased with the improvement of disease. Conclusion There is a prospect that cytokine level in pleural effusion may indicate treatment response of MPE, and in light of this case, immunomodulators may be utilized in treating patients suffering MPE. Due to limitations of our single case, we urge more groups to evaluate the potential role of cytokine profile in MPE.

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.

Junhui Xu,* Mangju Wang,* Ye Shen, Miao Yan, Weiwei Xie, Bingjie Wang, Huihui Liu, Xinan Cen Department of Hematology, Peking University First Hospital, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xinan CenDepartment of Hematology, Peking University First Hospital, No. 8 Xi Shi Ku Street, Xi Cheng District, Beijing, 100034, People’s Republic of ChinaTel +86-10-83575746Email cenxn@bjmu.edu.cnBackground: Amyloid light-chain amyloidosis (AL amyloidosis) is commonly associated with multiple myeloma. However, the clinical characteristics and prognosis of symptomatic and smoldering multiple myeloma with AL amyloidosis are not particularly clear.Methods: Patients with symptomatic and smoldering multiple myeloma in the Peking University First Hospital registry from 2010 to 2018 were studied. The clinical and laboratory information was collected from first presentation to death or until the last available clinical follow-up. The patients’ survival and outcomes were analyzed, and the relationship between the clinical parameters and survival was also assessed.Results: Compared with symptomatic multiple myeloma patients without AL amyloidosis, patients with AL amyloidosis had higher incidence of BNP≧700pg/mL (P< 0.001), ALP> 187.5IU/L (P=0.032) and ALB< 25g/L (P< 0.001). Similarly, compared with smoldering multiple myeloma patients without AL amyloidosis, patients with AL amyloidosis had higher incidence of BNP≧700pg/mL (P=0.030) and Alb< 25g/L (P=0.024). The existence of AL amyloidosis, especially those with the heart involvement, was related to shorter long-term survival of symptomatic and smoldering multiple myeloma according to univariate analyses. Renal involvement and gastrointestinal tract involvement had an impact on the prognosis of smoldering multiple myeloma but not on the symptomatic multiple myeloma. Cox regression model for overall survival detected BNP≧700pg/mL in symptomatic multiple myeloma having independent poorer prognostic significance (HR=2.455, P=0.004). Interestingly, BNP at diagnosis was significantly correlated with cardiac amyloidosis (r=0.496, P< 0.001). Cox regression model for overall survival detected the presence of AL amyloidosis in smoldering multiple myeloma having independent poorer prognostic significance (HR=8.741, P=0.002).Conclusion: AL amyloidosis is an independent poor prognostic factor for not only symptomatic multiple myeloma but also smoldering multiple myeloma. It is mainly because of involvement of important organs, especially the heart. AL amyloidosis probably has a greater impact on the prognosis of smoldering multiple myeloma than on the symptomatic multiple myeloma.Keywords: symptomatic multiple myeloma, smoldering multiple myeloma, AL amyloidosis, poor prognostic factor

Introduction: Daratumumab is a human IgGκ monoclonal antibody targeting CD38 with a direct on-tumor and immunomodulatory mechanism of action. In phase 3 clinical studies, the addition of daratumumab to standard-of-care regimens consistently demonstrated a significant progression-free survival (PFS) benefit and improved depth of response, including minimal residual disease-negativity, in patients (pts) with newly diagnosed MM or RRMM. In the primary analysis of the phase 3 CASTOR study (median follow-up: 7.4 mo), D-Vd reduced the risk of disease progression or death by 61% (median PFS, not reached [NR] vs 7.2 mo; hazard ratio [HR], 0.39; 95% confidence interval [CI], 0.28-0.53; P Methods: Eligible pts in LEPUS and CASTOR received ≥1 prior line of therapy and were randomized 2:1 in LEPUS and 1:1 in CASTOR to 8, 21-day cycles of V (1.3 mg/m2 SC) on Days 1, 4, 8, and 11, and d (20 mg, PO or IV) on Days 1, 2, 4, 5, 8, 9, 11, and 12 ± D (16 mg/kg IV) given QW for Cycles 1-3, Q3W for Cycles 4-8, and Q4W thereafter. The primary endpoint for both studies was PFS. Results: A total of 211 (D-Vd, n=141; Vd, n=70) pts in LEPUS and 498 (D-Vd, n=251; Vd, n=247) pts in CASTOR were randomized. The median (range) age was 61 (28-82) years for Chinese and 64 (30-88) years for global pts. In general, baseline characteristics were similar between Chinese and global pts and balanced between treatment arms, with the exception of median body weight (LEPUS: 67 kg; CASTOR: 76 kg). Chinese and global pts both received a median of 2 prior lines of therapy; 79% and 66% received prior V, 27% and 28% were refractory to lenalidomide, and 64% and 32% were refractory to their last prior line of therapy, respectively. After a median follow up of 8.2 months in LEPUS and 7.4 months in CASTOR, a consistent PFS benefit of D-Vd vs Vd was demonstrated in the pooled analysis set across age (60 mL/min) subgroups (Table 1). Median time to progression was also consistently prolonged with D-Vd vs Vd across pooled pt subgroups. Among response evaluable pts, D-Vd improved overall response rate, rate of very good partial response or better, and rate of complete response or better (Table 2) and prolonged median duration of response vs Vd in all pt subgroups. Additional data, including PFS2, from the pooled subgroups analysis will be presented at the meeting. The safety profile of D-Vd was generally consistent across pts in LEPUS and CASTOR. Grade 3/4 treatment-emergent adverse events (TEAEs; D-Vd/Vd) occurring at a ≥5% frequency with D-Vd vs Vd in both Chinese and global pts included thrombocytopenia (51%/37%; 45%/33%), lymphopenia (44%/29%; 10%/3%), neutropenia (16%/6%; 13%/4%), and hypertension (12%/3%; 7%/1%). 49%/38% of Chinese and 42%/34% of global pts had ≥1 serious TEAEs. TEAEs leading to treatment discontinuation occurred in 4%/3% of Chinese and 7%/9% of global pts, and TEAEs leading to death occurred in 4%/10% of Chinese and 5%/6% of global pts. Rates of infusion-related reactions (IRRs) were similar for D-Vd across studies (LEPUS: 38%; CASTOR: 45%); most occurred during the first infusion and the majority were grade 1/2. Conclusions: D-Vd demonstrated a clinical benefit, including significantly improved PFS, in pooled Chinese and global pts with RRMM who received ≥1 prior line of therapy, regardless of age, cytogenetic risk status, or renal function. The safety profile of D-Vd was consistent across all pts, and no new safety concerns were identified. These results support the use of D-Vd in Chinese pts with RRMM. Disclosures Jin: The First Affiliated Hospital of Zhejiang University: Current Employment. Spencer:Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Cilag GmbH: Consultancy, Honoraria, Research Funding, Speakers Bureau. Weisel:Roche: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria; Adaptive: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; GlaxoSmithKline: Honoraria. Mateos:Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Adaptive: Honoraria, Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Honoraria; Regeneron: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees. Nooka:Adaptive Technologies: Consultancy, Honoraria; Spectrum Pharmaceuticals: Consultancy; Oncopeptides: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; GlaxoSmithKline: Consultancy, Honoraria, Other: Personal Fees: Travel/accomodations/expenses, Research Funding; Karyopharm Therapeutics, Adaptive technologies: Consultancy, Honoraria, Research Funding. Qi:Janssen: Current Employment, Current equity holder in publicly-traded company; Johnson and Johnson: Current equity holder in publicly-traded company. Sun:Janssen: Current Employment, Current equity holder in publicly-traded company. Gai:Janssen: Current Employment, Current equity holder in publicly-traded company. Liu:Janssen: Current Employment, Current equity holder in publicly-traded company. Yang:Janssen: Current Employment, Current equity holder in publicly-traded company.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematologic malignancy arising from plasmacytoid dendritic cell precursors. The disease typically manifests in the skin, but it also evolves into a leukemic phase or can be complicated by other myeloid malignancies, especially myelomonocytic tumors. The association between these neoplasms is not fully elucidated. We report a case of BPDCN with a history of cytopenia that was supposed to be chronic myelomonocytic leukemia. The patient received intensive chemotherapy and achieved complete remission, but soon relapsed. The successive occurrence of myelomonocytic neoplasm and BPDCN is in accordance with the fact that they evolve from a common cell origin with a multilineage potential for myelomonocytic and plasmacytoid dendritic cell differentiation. This case may shed further light on the mystery of biology and the histogenesis of BPDCN.

Background Universal gene targets are in persistent demand by real‐time quantitative polymerase chain reaction (RT‐qPCR)‐based methods in acute leukemia (AL) diagnosis and monitoring. Human Krüppel‐like factor 3 (hKLF3), a newly cloned human transcription factor, has proved to be a regulator of hematopoiesis. Methods Sanger sequencing was performed in bone marrow (BM) samples from 17 AL patients for mutations in hKLF3 coding exons. hKLF3 expression in peripheral blood (PB) and BM samples from 45 AL patients was dynamically detected by RT‐qPCR. PB samples from 31 healthy donors were tested as normal controls. Results No mutation was sequenced in hKLF3 coding exons. hKLF3 expression in PB of AL was significantly lower than that in healthy donors [0.30 (0.02‐1.07) vs 1.18 (0.62‐3.37), P, In the present study, we investigated the expression of hKLF3 in acute leukemia patients by both Sanger sequencing and RT‐qPCR. ROC analyses indicated excellent efficacy of hKLF3 expression in PB samples for the diagnosis of AML. In addition, a significantly converse correlation between inhibition of hKLF3 expression in peripheral blood and increased leukemic burden was observed.

Objective T cell lymphomas are associated with an aggressive worse prognosis. This study is designed to assess T cell lymphomas using 18F-FDG PET/CT. Methods Sixty-four patients with newly diagnosed T cell lymphomas underwent PET/computed tomography (PET/CT) scans, 47 cases who were fully followed up were retrospectively reviewed and analyzed. Overall survival (OS) and progression-free survival (PFS) were recorded for prognosis. We measured the maximum standardized uptake value (SUVmax) in all cases, analyzed the correlation between SUVmax and survival and other clinicopathologic parameters. Kaplan-Meier log-rank tests were then used to compare the survival of high and low PET/CT parameter groups, and multivariate Cox proportional hazards regression analysis was carried out to identify predictors of OS and PFS. Results With a median follow-up of 26.5 (range 0.7-117.5) months, the 1-, 2- and 3-year OS were 75.6, 61.7 and 49.2%, and PFS were 49.3, 39.9 and 29.9%, respectively in 47 patients. Among them, 33 cases progressed with a median time of 9.5 (0.7-115.0) months, and 26 patients died with a median survival time of 26.5 (0.7-117.5) months. Multivariate analysis showed the following independent prognostic factors for OS: age >60 years (P = 0.002), SUVmax >9.7 (P = 0.009) and extranodal involvement of more than one site (P = 0.018). In addition, lactate dehydrogenase level (P = 0.003) and B symptoms (P = 0.018) were independent risk factors for PFS. Conclusion Pretherapy SUVmax may serve as an independent predictor of outcome in patients with newly diagnosed T cell lymphomas.

Background Multiple myeloma is a disease of the older people, whose prognoses are highly heterogeneous. The International Myeloma Working Group (IMWG) proposed a geriatric assessment (GA) based on age, functional status and comorbidities to discriminate between fit and frail patients. Given the multidimensional nature of frailty and the relatively recent exploration of frailty in the field of MM, reaching a consensus on the measurement of frailty in MM patients remains challenging. Objective We sought to assess the feasibility of performing a comprehensive GA (CGA) in older MM patients in a real-world and multicentre setting and to evaluate their baseline CGA profiles. Results We studied 349 older patients with newly diagnosed MM (age range, 65–86 years). Our results showed that a CGA is feasible for older MM patients. Using the IMWG-GA criteria, we identified significantly more frail patients in our cohort comparing to in the IMWG cohort (43% vs 30%, P = 0.002). In the IMWG-GA ‘fit’ group, risk of malnutrition, depression and cognitive impairment remains. The median follow-up time was 26 months (range 1–38). The median overall survival (OS) was 34.7 months, and the estimated 3-year OS rate was 50%. A high MNA-SF score (MNA-SF ≥ 12), low GDS score (GDS ≤ 5) and high CCI score (CCI ≥ 2) can be used to predict the OS of older patients with newly diagnosed MM. This study is registered at www.clinicaltrials.gov (NCT03122327). Conclusions Our study justifies the need for a CGA in older patients with newly diagnosed MM.

Ye Shen,* Jinping Ou,* Bingjie Wang, Lihong Wang, Junhui Xu, Xinan Cen Department of Hematology, Peking University First Hospital, Beijing, 100034, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xinan CenDepartment of Hematology, Peking University First Hospital, No. 8, Xishiku Street, Xicheng District, Beijing, 100034, People’s Republic of ChinaEmail cenxn@bjmu.edu.cnBackground: This study assessed the clinical characteristics of gastrointestinal bleeding (GIB), obstruction (GIO), and perforation (GIP) in patients with primary gastrointestinal diffuse large B-cell lymphoma (PGI-DLBCL) and the influence on long-term survival.Methods: A retrospective analysis was performed of 148 patients with PGI-DLBCL admitted to Peking University First Hospital from August 1994 to May 2018. The clinical characteristics of GIB, GIO, and GIP before and after chemotherapy were recorded. The associated overall survival and progression-free survival were analyzed.Results: Among 148 patients, 56.8% had gastrointestinal complications (GICs), including GIB, GIO, GIP, and multiple complications, and 22.6% of them occurred after chemotherapy, mostly during the first 4 cycles. The most common clinical manifestations of patients with GICs were abdominal pain or discomfort (79.8%), hematemesis or melena (22.6%), and abnormal bowel habits (17.9%). Patients with Eastern Cooperative Oncology Group (ECOG) score ≥ 2, tumor mass ≥ 10 cm, or intestinal involvement had significantly higher risk of severe GICs as initial manifestations. Among 130 patients who received chemotherapy, B symptoms, tumor mass ≥ 10 cm, and Lugano stage (IIE, IV) strongly correlated with GICs after chemotherapy (P < 0.05). Rituximab did not increase the risk of GICs. GICs which occurred before or after chemotherapy reduced the objective response rate at the end of chemotherapy. The prognosis of patients was significantly worsened by GIP, GIB, or multiple complications after chemotherapy (P < 0.05). GIB at presentation or GIO before or after chemotherapy had no prognostic value (both P > 0.05).Conclusion: GICs adversely affect the quality of life, prolong the length of hospitalization, and shorten the long-term survival of patients with PGI-DLBCL.Keywords: diffuse large B-cell lymphoma, gastrointestinal complication, bleeding, obstruction, perforation

Background Daratumumab plus bortezomib/dexamethasone (D-Vd) significantly improved outcomes versus Vd in patients with relapsed or refractory multiple myeloma (RRMM) in the phase 3 CASTOR study. We report the results of a prespecified interim analysis of the phase 3 LEPUS study of D-Vd versus Vd in Chinese patients with RRMM. Patients and Methods Chinese patients with ≥ 1 prior line of therapy were randomized 2:1 to receive 8 cycles (21 days/cycle) of bortezomib (1.3 mg/m2 subcutaneously) and dexamethasone (20 mg orally/intravenously) ± daratumumab (16 mg/kg intravenously). The primary endpoint was progression-free survival (PFS). Results A total of 211 patients were randomized (D-Vd, 141; Vd, 70). After an 8.2-month median follow-up, D-Vd significantly prolonged PFS versus Vd (median, not reached vs. 6.3 months; hazard ratio, 0.28; 95% confidence interval, 0.17-0.47; P Conclusion These data support the use of D-Vd in Chinese patients with RRMM.

Background Multiple myeloma causes different types of renal injury. C3 glomerulonephritis (C3GN) is characterised by an abnormal deposition of complement C3 in the glomeruli due to abnormal activation of the alternative pathway of the complement system. While the association between C3GN and multiple myeloma has been well established, mild renal injury by C3GN in multiple myeloma patients with high levels of light chain has not been reported. Case presentation A 55-year-old Chinese man presented with proteinuria. Combined with immunofixation electrophoresis, bone marrow biopsy, and renal biopsy, he was diagnosed with IgA-type multiple myeloma accompanied by C3GN and light chain proximal tubulopathy without crystal deposits. Although he had a higher level of lambda serum-free light chain, the renal injury in this patient was mild. After treatment with four courses of BD, one course of PAD, and autologous stem cell transplantation, he achieved a very good partial hematologic response with stable renal function. Conclusions In multiple myeloma, the light chain reaches a certain level and persists, resulting in C3GN renal impairment. Early diagnosis and early intensive treatment are critical for the prognosis of such patients.

Objective Serum free light chain (FLC) level is closely associated with the functional state of B lymphocytes, and many studies have shown that delayed reconstitution of B lymphocytes contributed to chronic graft-versus-host disease (cGVHD). This study assessed the predictive value of FLC levels in serum collected early after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for cGVHD. Methods Sixty-two patients who had undergone allo-HSCT were retrospectively reviewed. The correlations between the FLC levels and the development of cGVHD were explored. Results Of the 62 patients, 33 cases developed cGVHD, with the prevalence of 53.2%. With Seattle classification, 19 cases had limited cGVHD while 14 cases contracted extensive cGVHD. While with NIH classification, 17 cases had mild cGVHD, 6 cases moderate cGVHD, and 10 cases severe cGVHD. Multivariant statistical analysis showed that the FLC levels were not associated with all severities of cGVHD but were correlated with the development of extensive or moderate to severe cGVHD (P = .01 and .038, respectively). Conclusions Serum FLC levels early after HSCT may reflect the functional state of B-cell reconstitution. Patients with low serum FLC Level early post-allo-HSCT tend to develop extensive cGVHD or moderate to severe cGVHD.

To investigate the characteristic changes of the plasma cytokine profile in Chinese patients with idiopathic multicentric Castleman diseases (iMCD).The plasma samples from 22 patients with confirmed diagnosis of iMCD were collected before treatments; Specimens from 17 patients with newly diagnosed multiple myeloma, 10 non Hodgkin's lymphoma, and 15 healthy donors were used as control. Seventeen kinds of cytokines were measured by cytokine beads array (CBA) and ELISA respectively.Six cytokines were measured by ELISA. The concentrations of IL-2, IL-6, IL-21 and VEGF were significantly higher in the plasma of iMCD patients than those of the healthy donors (P＜0.01) and the level of IL-21 was highest in the iMCD group. There was no significant difference in the levels of IL-1β and IL-4 between the iMCD and healthy donor groups. Thirteen cytokines were measured by CBA assay, besides IL-6 level was confirmed to be higher in iMCD group than that in healthy controls (P＜0.01）, IL-12-p70 and IL-33 levels were also higher in iMCD group than those in control group (P＜0.05）, no significant difference of the rest cytokines was found between iMCD and the control group.IL-6 and VEGF has shown to involved in the pathogenesis of iMCD, the results of preliminary study imply the role of IL-2 、IL-21、IL-12-p70 and IL-33 in this rare lymphoproliferative disease. Further studies are needed to elucidate the mechanism of these cytokines, which may shed some light on the identification of novel therapeutic targets against iMCD.特发性多中心型Castleman病患者细胞因子谱特征的初步分析.研究我国特发性多中心型Castleman病（idiopathic multicentric castleman disease,iMCD）患者血浆中细胞因子谱的特征性改变.收集22例确诊iMCD患者治疗前的血浆标本，并以17例初发多发性骨髓瘤（MM）、10例非霍奇金淋巴瘤（NHL）及15例健康供者血浆标本作为对照，应用细胞因子磁珠阵列(cytokine beads array,CBA)和ELISA 2种方法，检测17种细胞因子的浓度.ELISA法检测的6种细胞因子中，iMCD患者的IL-2，IL-6，IL-21和VEGF的血浆水平均明显高于正常对照（ P＜0.01），且IL-21水平在iMCD组最高；IL-1β和IL-4水平与正常对照无差异。CBA法检测13种细胞因子浓度结果显示，iMCD患者的IL-6、IL-33和IL-12-p70水平均明显高于正常对照（P＜0.01），其余细胞因子与正常对照相比均无显著差异（P＞ 0.05）.除了已知的IL-6和VEGF可能参与了iMCD的发生发展外，IL-2 、IL-21、IL-12-p70和IL-33的作用值得进一步探讨，相关研究可能发现iMCD治疗的新型靶点.

Immortalized cell lines are useful for deciphering the pathogenesis of acute leukemia and developing novel therapeutic agents against this malignancy. In this study, a new human myeloid leukemia cell line YBT-5 was established. After more than 1-year cultivation from the bone marrow of a patient with acute monocytic leukemia, YBT cell line was established. Then a subclone, YBT-5, was isolated from YBT using single cell sorting. Morphological and cytogenetical characterizations of the YBT-5 cell line were determined by cytochemical staining, flow cytometry analysis, and karyotype analysis. Molecular features were identified by transcriptomic analysis and reverse transcription-polymerase chain reaction. To establish a tumor model, 5 × 106 YBT-5 cells were injected subcutaneously in nonobese diabetic/severe combined immune-deficiency (NOD/SCID) mice. DOT1L has been proposed as a potential therapeutic target for KMT2A-related leukemia; therefore, to explore the potential application of this new cell line, its sensitivity to a specific DOT1L inhibitor, EPZ004777 was measured ex vivo. The growth of YBT-5 does not depend on granulocyte-macrophage colony-stimulating factor. Cytochemical staining showed that α-naphthyl acetate esterase staining was positive and partially inhibited by sodium fluoride, while peroxidase staining was negative. Flow cytometry analysis of YBT-5 cells showed positive myeloid and monocytic markers. Karyotype analysis of YBT-5 showed 48,XY,+8,+8. The breakpoints between KMT2A exon 10 and exon 11 (KMT2A exon 10/11) and MLLT3 exon 5 and exon 6 (MLLT3 exon 5/6) were identified, which was different from all known breakpoint locations, and a novel fusion transcript KMT2A exon 10/MLLT3 exon 6 was formed. A tumor model was established successfully in NOD/SCID mice. EPZ004777 could inhibit the proliferation and induce the differentiation of YBT-5 cells. Therefore, a new acute monocytic leukemia cell line with clear biological and molecular features was established and may be used in the research and development of new agents targeting KMT2A-associated leukemia.

To investigate the clinical manifestations pathologic features, treatment options and prognosis of patients with bone lymphoma.The clinical characteristics, pathologic features, treatment and prognosis of 34 BL patients diagnosed by histopathologic method or/and PET-CT and treated in first hospital of peking university from January 2004 to April 2018 were analyzed retrospectively.The median age of 34 BL patients was 56 years old, the male and female ratio was 1.43∶1 (24 /10). Among 34 patients, the patients with primary bone lymphoma(PBL) were 8 cases, the patients with secondary bone lymphoma(SBL) was 26 cases, the PBL and SBL ratio was 0.31∶1. Bone lymphoma lacks typical systemic symptoms, and its onset began mostly from bone pain and pathologic bone fracture. The most frequent pathological type of bone lymphoma in our study was diffuse large B-cell lymphoma (DLBCL), accounting for 55.88%. At present, the conventional treatment for bone lymphoma includes chemotherapy, or chemotherapy combined with radiotherapy and surgery, as well as hematopoietic stem cell transplantation. The average and median OS time of BL patients were 349 years and 3 years respectively, meanwhile the OS rate for three years and two years were 56.25% and 78.16%, respectively. Factors that affect survival of BL patients were PBL and SBL classification, pathological type, blood LDH level, and treatment methods.Bone lymphoma is usually concealed onset，an adequate and adequate combination therapy can improve the survival rate and transplantation therapy plays an important role. Primary bone lymphoma is rare, the prognosis of patients with primary bone lymphoma is good, whereas the prognosis of patients with secondary bone lymphoma is poor.真实世界骨淋巴瘤的病理特征、治疗选择与患者预后评估.探讨骨淋巴瘤的临床特点、病理特征、治疗方法和患者预后.回顾性分析北京大学第一医院2004年1月至2018年4月收治的34例骨淋巴瘤患者的临床特征、病理特点、治疗及预后.34例骨淋巴瘤患者的中位年龄为56 岁，男、女性别比例为1.43∶1。原发性骨髓瘤（PBL） 8例，继发性骨髓瘤（SBL） 26例，PBL与SBL之比为0.31∶1。PBL患者常无明显的全身症状，多因骨痛或病理性骨折起病。病理类型以DLBCL最多，占55.88%。目前骨淋巴瘤的治疗方法为化疗，或化疗辅以放疗或手术，有条件者行造血干细胞移植治疗。本研究中骨淋巴瘤患者平均生存期为3.49年，中位生存期为3年， 3年生存率为82.14%。影响生存期的因素有PBL和SBL分类、病理类型、血LDH水平和治疗方法.骨淋巴瘤起病隐匿，选择足量、充分的联合治疗手段可提高患者的生存率，原发性骨淋巴瘤少见且预后较好，继发性骨淋巴瘤预后差.

To investigate the expression of CD160 on the surface of human natural killer (NK) cells and its possible relationship with hematological malignancies.CD160 expression on human leukemia cell line NK92 cells was confirmed by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. The proliferation characteristics and cell surface markers of this cell line were determined. Cytotoxicity of NK92 against 2 human myeloid leukemia cell lines, K562 and THP-1 was analyzed ex vivo. CD160 blocking antibody CL1-R2 was employed to clarify its role in NK cell mediated cytolysis. Then, the expression of CD160 on NK cells in peripheral blood from various patients with hematological malignancies were measured by flow cytometry.The mRNA and protein levels of CD160 expressions on NK92 cells were confirmed by RT-PCR and Western blot, respectively. The flow cytometry results demonstrated that the strong positive expression of CD160 could be detected on the NK92 cell surface. NK92 could effectively kill K562 and THP-1 cells, while the cytolysis effect was abrogated in the presence of CD160 blocking antibody CL1-R2. The high levels of HVEM were expressed on both target cells, but the HLA class I molecules were absent on K562. The expression of CD160 on CD3The cytolysis function of human NK cells is mediated partially by CD160 molecule. The decrease of CD160 expression on NK cells from patients with various hematological malignancies implies that down-regulation of CD160 expression may be a novel mechanism of tumor immune escape.

To analyze the incidence of bone marrow involvement in patients with different pathological types of lymphoma.The results of bone marrow tests including bone marrow aspiration(BMA), flow cytometry detection, bone marrow biopsy(BMB) andThe incidence of bone marrow involvement (BMI ) in the patients with NHL was much higher than that in patients with HL [32.6 %(201/616) vs 15%(13/86)](P0.05). For patients with NHL, the incidence of bone marrow involvement in B-cell lymphoma was higher than that in T-cell lymphoma (37.0% vs 22.6%)(P0.05). According to different pathological types, the incidences of BMI in the patient with mantle cell lymphoma, hepatosplenic T-cell lymphoma, diffuse large B-cell lymphoma (DLBCL) and follical lymphoma (FL) were 88% (25/22), 100% (5/5), 21.8% (56/257), and 38.5% (15/39) , respectively.The incidence of bone marrow involvement varies in different pathological types of lymphoma.Bone marrow assessment has significant importance for stading of newly diagnosed lymphoma patients.

To assess the safety and efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in treating patients with relapsed and refractory lymphoma.Thirty-one consecutive patients with relapsed or refractory lymphoma received allo-HSCT. Used conditioning regimens included conditioning based on BEAM regimen(12 cases), conditioning based on modified Bu/Cy regimen(11 cases), conditioning based on Cy/TBI regemen(6 cases) and conditioning of Bu/Cy regimen(1 case). For provention of GVHD, the MMF was used on the basis of classcal protocol consisting of CsA combined with MTX. The infused HSC included the HLA-matched related HSC(11 cases), HLA nonidentical related HSC(13 cases) and HLA-matched unrelated HSC(6 cases). The bone marrow plus peripheral blood HSC were infused in 21 cases, while only peripheral blood HSC were infused in 9 cases. Among the 31 cases of relapse/refractory lymphoma, 18 patients were male and 13 were female, 4 cases were Hodgkin's lymphoma and 27 cases were non-Hodgkin's lymphoma. ALL of the 31 patients were qualified, as they were not in complete remission (CR) or in advanced stage at the time of transplantation.Twenty-seven evaluable patients showed the engraftment of both neutrophil and platelet at a median of 12 days(range 10-20) and 13 days(range 9-34) respectively, 9 cases developed II-IV aGVHD, and cGVHD was observed in 3 patients, 5 patients can not achieve CR at 3 months after transplantation, and 6 patients relapsed after CR, the median follow-up of all the 31 patients after transplantation was 11.5 months (ranged, 0-141 months), and the 2-year OS was 46.1%±9.5% with median survival of 40 (9-141) months in the 15 survivors. The age (P0.05), disease status before transplantation (P=0.020) and remission after transplantation(P=0.000) were significantly related with survival. Cox's proportional hazards regression model analysis showed that the age (P=0.041) and disease statue (P=0.020) before allo-HSCT were independent predictive factors for survival.Allo-HSCT is an optimal treatment strategy for the patients with relapsed and refractory lymphoma who failed to most, if not all, available options.

The shortage of HLA-identical siblings or unrelated donors has restricted the application of hematopoietic stem cell transplantation (HSCT). Few studies have systematically assessed survival and chronic health conditions (CHCs) in the same cohort of patients after HLA-mismatched/haploidentical (mismatched) family donor transplantation. In the present study, we retrospectively analyzed the survival of 127 adult patients receiving either HLA-matched (71 cases) or HLA-mismatched (56 cases) family donor transplantation. Of 127 patients, 81 patients survived at least 2 years after HSCT and were still alive until the present investigation. We evaluated the CHCs in 76 survivors (41 matched and 35 mismatched). CHC-related information was scored according to the Bone Marrow Transplant Survivor Study questionnaire. There was no significant difference in overall survival or disease-free survival between HLA-matched and -mismatched transplant recipients. The CHCs were less severe in HLA-mismatched recipients than in matched cohorts. Multivariate analysis identified that age over 40 years at transplantation and presence of chronic graft-versus-host disease were independent risk factors for CHCs, while anti-thymocyte globulin-containing conditioning regimens might be protective. However, HLA disparity was not crucial for either the survival rate or CHCs. In conclusion, HLA-mismatched family donor transplantation can achieve comparable therapeutic effects to HLA-identical sibling transplantation.

Background: Multiple Myeloma (MM) is a disease of the elderly, whose prognoses are highly heterogeneous. Hence International Myeloma Working Group (IMWG) proposed geriatric assessment (GA) in 2015, including daily activity and comorbidity status, to better discriminate between fit and frail patients (Palumbo et al, 2015). However, IMWG recruited patients from clinical trials instead of real world practices. Therefore we studied GA in elderly MM patients consecutively in China, along with other perspectives which are known to be problematic in elderly population that were previously left unnoticed, such as nutrition status, risk of cognitive impairment, risk of depression, and quality of life. Aim: Our study centers on the feasibility to perform a more comprehensive geriatric assessment (cGA) in elderly MM patients, current cGA status in elderly MM patients in China, and the cGA difference between Chinese patients and patients in the IMWG study. Method: From August 2017 to April 2019, we continuously recruited 336 newly diagnosed elderly (age ≥ 65) MM patients from 21 centers in China. cGA was performed at diagnosis, after treatment cycle 1, after cycle 4, and 1 year after treatment. cGA includes physical conditions (ECOG), activities of daily living (ADL), instrumental ADL (IADL), mini-nutritional assessment (MNA-SF), geriatric depression scale (GDS), mini-mental state examination (MMSE), quality of life (SF-36) and Charlson comorbidity index (CCI). Staging was assessed at baseline (International Staging System (ISS) & Revised ISS) and hematological responses were evaluated along with each cGA timepoint. Results: We pool-analyzed data of 336 newly-diagnosed elderly MM patients. The median age was 70 (range 65-88) and 25.5% of patients were older than 75 years. 336 (100%) patients were able to complete cGA, and median assessment time was 40 minutes (range 20-70). Upon diagnosis, only 34% and 37.5% of patients had full ADL and IADL respectively. 38.5% of patients had moderate to high risk of depression (GDS ≥ 6). 13.2% of patients were malnourished (MNA-SF ≤ 7), while 46.3% of patients were at risk of malnutrition (8 ≤ MNA-SF ≤ 11). 41% of patients had at least one comorbidity (CCI ≥ 1). 45.7% of patients had moderate to intermediate risk of cognitive impairment (MMSE ≤ 26). Grouping by IMWG-GA index, our study identified 59.9% patients in frail group (vs 39% in IMWG study), 15.8% in intermediate (vs 31% in IMWG) and 24.3% in fit (vs 30% in IMWG). 69% of patients received proteasome inhibitor-containing regimens and 20.7% of patients received lenalidomide-containing regimens. Best hematological responses in fit and intermediate groups were better than responses in frail group (≥ PR rate: 88.5% in fit, 94.4% in intermediate vs 77.5% in frail). Median follow up time was 10 months. To date, 215 (64%) patients have finished the cGA after cycle 1; 164 (48.8%) patients have finished the cGA after cycle 4; 91 (27.1%) patients has finished all 4 planned cGA and improvements in cGA were observed in the majority of these patients. Conclusion: Our study showed significant CGA heterogeneity in elderly MM patients. Even in the IMWG-GA "fit" group, nutrition, depression and cognitive impairment remain problems. Frail patients took up a larger proportion in Chinese elderly MM patients compared to IMWG study. Our study strongly justifies the necessity for cGA in elderly patients with MM, more so in the real world MM patients than in the clinical trials. Disclosures No relevant conflicts of interest to declare.

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. Patients and methods: This was a prospective, multicenter, single-arm Phase 1b - 2 clinical trial conducted exclusively in China. In the phase 1b study, three dose levels of chidamide were explored. In the phase 2 portion, patients were treated at the RP2D. The primary endpoint of the Phase 1b was determination of the maximum tolerated dose (MTD), dose limiting toxicities (DLT) and RP2D. The primary endpoint of the phase 2 study was determination of the overall response rate (ORR). Results: A total of 82 patients were enrolled between March 2016 and Dec 2017 at 17 sites across China. The cutoff date for the analysis was July 2018. In phase 1b dose-escalation study, 15 patients were treated and the second dose cohort (20 mg biw) was declared the MTD and thus the RP2D. Subsequently, 67 patients were enrolled and treated at the RP2D in the phase 2 part of the study. Overall, among 82 enrolled patients in the entire phase 1b/2 study, the median number of cycles per person was five (range 1-8) and the relative dose intensity was 75.4%. The most common toxicities in the Phase 1b/2 study included leucopenia, anemia, and neutropenia. No reactivation of Epstein-Barr virus or Hepatitis B virus was observed. For entire phase 1b/2 study of 82 patients, the ORR was 68.3% with a CR rate of 43.9%. In the phase 2 part of the study, the ORR was 73.2% with 47.8% CR. with a median follow-up of 12.7 months (range 0.3-30.8 months), the median PFS for entire phase 1b/2 study was 17.4 months and the 1-year PFS was 52.9%. The median OS had not yet been reached, and the 1-year OS was 74.5%. In the phase 2 study, the median PFS was 17.4 months and the 1-year PFS was 53.6%. The median OS had not yet been reached, and the 1-year OS was 76.3%. Conclusion: Chi-CHOEP is an effective and feasible novel regimen for untreated PTCL. These data warrant further investigation in a randomized phase 3 study. This trial was registered at www.clinicaltrials.gov as #NCT02987244. Disclosures No relevant conflicts of interest to declare.

To analyse the clinical features and prognostic significance of cross-lineage antigen expression in patients with acute myeloid leukemia(AML) in order to establish individualized treatment for a better outcome and prognosis.A total of 227 cases (exduding M3) were detected by flow cytometry for immune phenotype. The CD7(-)CD56(-)CD19(-) AML served as control. The clinical features, treatment response and prognosis of CD7(+) group, CD56(+) group and CD19(+) group were compared.The detection rate of CD56(+),CD7(+) and CD19(+) in AML was 15.9%, 25.1% and 11.0%, respectively. There were no differences between CD56(+) AML, CD7(+) AML, CD19(+) AML, and CD56(-)CD7(-)CD19(-) AML in the proportion of blast cells, white blood cell count, hemoglobin level, platelet count and MDS transformed AML rate. The CR after the first course chemotherapy and cumulative CR in CD56(+) AML patients were lower than those in the control group (20.0% vs 58.1%, P=0.0099; 73.3% vs 87.5%, P=0.04). The median time of CR in CD56(+) AML was longer than that in the control group (118 days vs 46 days, P=0.04). The PFS time and OS time of CD56(+) AML were shorter than those in the control group (245 days vs 580 days, P=0.037; 494 days vs 809 days, P=0.04). The CR after the first course chemotherapy and cumulative CR in CD19(+) AML patients were higher than those in the control group(75.0% vs 58.1%, P=0.46; 100% vs 87.5%, P=0.02). The median time of CR in CD19(+) AML was shorter than that in the control group (28 days vs 46 days, P=0.02). The PFS time and OS time of CD19(+) AML tended to be longer than those in the control group (P=0.13, P=0.07, respectively). The median PFS and OS were not reached at the time of last follow-up. The CR after the first course chemotherapy, cumulative CR and median time to CR in CD7(+) AML patients were not different from those in the control group (53.1% vs 58.1%, P=0.67; 87.1% vs 87.5%, P=0.44; 50 days vs 46 days, P=0.44). No differences of PFS and OS were observed between CD7(+) AML and the control.CD56(+) AML patients respond poorly to treatment, frequently relapse after complete remission and have a low survival rate. These patients need more intensive chemotherapy or in combination with other treatments. The interval of MRD detection should be shortened to find out relapse earlier. CD19(+) AML patients have a good treatment outcome and often accompanies with AML1/ETO fusion gene, which is known to be a good prognostic marker. Aberrant expression of CD7 on AML cells is not a poor prognostic factor in this study.

To study the relationship between surface markers of CD56 and CD19 and karyotypes and prognosis in multiple myeloma.A total of 126 cases of newly diagnosed multiple myeloma in the first hospital of Peking university from 2011 to 2015 were enrolled in this study. Cytogenetic abnormalities and immunophenotypes were detected by using fluorescence in situ hybridization and flow cytometry respectively before chemotherapy. Bone marrow smear was used for detection of abnormal plasma cell infiltration. By combining with their basic data, the relationship between immunophenotypes, cytogenetics and prognosis of MM was analyzed.(1) The median of myeloma cells in the 126 patients was 0.24（0.01-0.97）; the median of myeloma cells in 116 patients who have immunophenotype datas was 0.25（0.01-0.97）； the median of myeloma cells in CD19 positive patients was 0.11（0.01-0.53）; the median of myeloma cells in CD19 negative patients was 0.26（0.01-0.97）. The median of myeloma cells in CD19 positive patients was much lower than that in CD19 negative patients（P=0.036）. (2)In 116 patients detected by the immunophenotype, the myeloma cells expressed CD19,CD20,CD56 and CD117. Compared with CD56 negative patients(45/116,38.79%),CD56 positive patients(71/116,61.21%) had a clearly favorable disease outcome（OS was 53.0 month vs 31.0 month,P=0.016; PFS was 37.5 months vs 18.4 months, P=0.036）. (3)CD19 positive patients was 16.38%（19/116）,CD19 negative patients was 83.62%（97/116）； CD19 positive MM and CD19 negative MM had no difference in OS and PFS. (4)CD117 positive rate in CD19 positive patients was 42.11%(8/19), the CD117 positive rate in CD19 negative patients was 18.57%(18/97), the CD19 expression positively correlated with CD117 expression. (5)FISH detection was done for 67 newly diagnosed MM patients, 8 patients showed normal karyotypes(11.94%), 59 patients had abnormal karyotypes(88.06%). The most common abnormal karyotypes were IgH rearragement which occurred in 47 patients(70.15%). Other abnormal karyotypes included 1q21+, del(13q14),del(13q14.3),del(17p13) . These abnormal karyotypes occurred in 37 patients（55.22%）,31 patients（46.27%）,33 patients（49.25%） and 13 patients（19.40%） respectively. In comparison with CD19 negative MM patients, the incidence rate of 1q21+ and del(13q14.3) was significantly lower in CD19 positive patients(1q21+:33.33% vs 61.54%,P=0.016; del(13q14.3): 33.33% vs 53.85%,P=0.043）.The prognosis of CD56 positive MM patients is better than that of CD56 negative MM patients, CD19 negative MM has more abnormal karyotypes and bone marrow infiltration,but they have no statistical prognostic differences.

Histologic transformation (HT) is a frequent event in the clinical course of patients with indolent lymphoma with dismal outcome. The diagnosis of HT is based on clinical manifestation, PET-CT and pathologic biopsy, and the latter is a golden standard for HT. There are contradictory data about the impact of initial management on the risk of transformation. Patients who present with HT did not receive R-CHOP or chemotherapy-naive, should receive this regimen. For the subset of patients received R-CHOP prior to HT, the second line chemotherapy for DLBCL should be adopted. Consolidation with HDT-ASCT should be considered for the suitable young patients. The radio-immunotherapy and novel drugs showed a bright perspective for the patients with HT.

The aim of the present study was to explore the effect of different X-ray doses on the proliferation and cytotoxic activity of peripheral blood mononuclear cells (PBMCs), particularly lymphocytes, in order to assess whether this reduces the incidence of graft vs. host disease (GVHD) while preserving the graft vs. tumor (GVT) effect in patients with hematological malignancies following hematopoietic stem cell transplantation (HSCT). PBMCs from healthy donors were irradiated with X-rays at doses of 0, 2.5, 5, 7.5, 10, 15, 25 or 50 Gy, and their proliferative activity was determined using a WST-8 assay kit. The cytotoxic activity of non-irradiated PBMCs and PBMCs irradiated with 7.5 Gy X-rays was tested in the leukemic cell line K562 and its Adriamycin-resistant strain K562A using a lactate dehydrogenase assay. The clinical data of 7 patients who received 7.5 Gy X-ray-irradiated PBMC infusions following autologous HSCT were analyzed. PBMCs irradiated with ≥7.5 Gy X-rays exhibited a complete inhibition of proliferation. PBMCs irradiated with 7.5 Gy X-rays exhibited significantly increased cytotoxic activity towards K562 cells compared with K562A cells (P0.05). Based on the in vitro data, clinical data from patients who received 7.5 Gy X-ray-irradiated PBMC infusions following HSCT between January 2005 and January 2013 were assessed retrospectively. A total of 7 patients were included in the current study. The majority achieved various degrees of remission following donor lymphocyte infusion (DLI) and none suffered from GVHD. This indicates that 7.5 Gy-irradiated PMBCs have a potential application in DLI for the treatment of patients following HSCT. However, further studies on larger patient cohorts are required to assess the clinical potential of 7.5 Gy-irradiated PBMCs for preserving the GVT effect while avoiding GVHD following HSCT.

Summary Introduction The relative expression of T cell receptor (TCR) beta variable (TRBV) and TCR diversity was compared between recipients receiving human leukocyte antigen (HLA)-mismatched transplants and those receiving HLA-matched transplants, using granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood stem cells and bone marrow as grafts. Methods The kinetics of the relative expression of TRBV family members were analyzed using real-time quantitative PCR. Additionally, the association of TRBV clonotype with acute graft-versus-host disease (aGVHD) was determined by cloning and sequence analysis of the CDR3 region. Results The TCR diversity in recipients receiving HLA-mismatched transplants was significantly lower than in those receiving HLA-matched transplants at 1 month and 2 months after hematopoietic stem cell transplantation (HSCT) (both P

The Epstein-Barr virus (EBV) is thought to be one of tumorigenic viruses, which can be detected in many kinds of lymphomas, such as extranodal NK/T-cell lymphoma and Burkitt lymphoma. Those EBV positive lymphomas are also called EBV-associated lymphomas. Some studies showed that patients with EBV-associated lymphoma had a worse prognosis. Dysfunction of T cells may contribute to failure of immune surveillance and tumorigenesis. Therefore, this study was aimed to investigate T cell dysfunction in patients with EBV-associated lymphoma. Peripheral blood was collected from 20 patients with EBV-associated lymphoma and 10 healthy donors (healthy EBV seropositive donors) at the Peking University First Hospital. First, the phenotypes and ratios of PBMCs were analyzed using flow cytometry. Compared with healthy donors, the proportion of CD3+ T cells were little lower in the patients, but had no significantly difference (healthy donors vs patients, 47.82±6.85% vs 34.43±3.63%, p=0.09). The ratios of CD4+ T cells / CD8+ T cells were significantly decreased in the patients, the proportion of CD4+ T cells in CD3+ T cells were decreased (healthy donors vs patients, 59.40±3.84% vs 29.46±2.84%, p Disclosures No relevant conflicts of interest to declare.

Clonal expansion of T cells after allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been observed, but their characteristics remain to be fully elucidated. We report here that CD8(+) T cells were the dominant T lymphocytes seen and T-cell repertoire diversity decreased dramatically during the first 3 months after allo-HSCT. Patients with GVHD grade II - IV had significantly lower T-cell repertoire diversity compared with non-GVHD patients. TCR beta variable gene (TCRBV) subfamily 8, 5.1, 5.2, 4, and 13 were the five most frequently expanded subfamilies among these patients. Among the 49 over-expanded clones identified, clonotype "TCR3-5" and "TCR18-5" were isolated from four patients with HLA-A2 allele and skin GVHD. Their frequencies correlated well with skin symptoms (i.e. rash). Moreover, they were detected in donors but not detected in recipients before transplantation. Lastly, three common TCRBV CDR3 motifs shared by T cells related with GVHD were discovered: TGDS, GLAG, and GGG. These findings suggest that TCR spectratyping is helpful for revealing GVHD-related T cells and may have utility in early diagnosis.

This study was purposed to investigate the EBV infection status of lymphoma patients from January 2008 to April 2012 in the First Hospital of Peking University. All the candidates have been detected for EBV which was either peripheral blood EBV DNA or ISH EBER in pathology from January 2008 to April 2012. The information on their sex, age, pathological type, peripheral blood EBV DNA and ISH EBER was collected, the positive rate of different EBV tests was studied, and the different characteristics of the EBV(+) and EBV(-) group were also explored. And Kaplan-Meier and Cox survival analysis was applied to investigate the EBV's effect on overall survival of these patients. The results showed that among 169 lymphoma patients, the positive rates of EBV EBER in extranodal NK/T cell lymphoma, angioimmunoblastic T cell lymphoma and peripheral T-cell lymphoma were 84.8%, 72.7% and 40.0%, respectively, and were ranged as the top three. The positive rate of EBV in DLBCL was relatively lower (16.7%) than that in above three types of lymphoma. The positive rate of peripheral blood EBV DNA of the elderly EBV(+) DLBCL was 50%. One out of 10 HL patients was subjected to EBER detection, the result of which was positive. The positive rate of peripheral blood EBV DNA of HL was 10%. Both the T cell lymphoma proportion and the rate of B symptom were higher in EBV(+) group than in EBV(-) group. In all the EBER(+) cases, the difference of OS between EBV(+) and EBV(-) patients was statistically significant. In multiple-factor survival analysis, peripheral blood EBV DNA positive was an independent risk factor for poor prognosis in the patients with lymphoma. It is concluded that EBV is closely related to extranodal NK/T cell lymphoma, angioimmunoblastic T cell lymphoma and peripheral T-cell lymphoma. Peripheral blood EBV DNA positive is an independent risk factor for poor prognosis in lymphoma patients.

This study was aimed to investigate the clinical manifestation, pathological features, treatment and related prognosis factors of primary mediastinal large B cell lymphoma (PMLBCL). The clinical data of 29 PMLBCL patients admitted in Peking University First Hospital were summarized and the related factors were analyzed retrospectively from January 2000 to November 2013. The results showed that 29 patients with the median age 32 were all pathologically diagnosed as PMLBCL. The main clinical features included mediastinal bulk mass (72.4%), superior vena caval syndrome (51.7%), dyspnea (62.1%), serous membrane fluid (48.3%), with 62.1% extranodal invasion and 62.1% extra-thoracic involvement. According to Ann-Arbor stage, 16 patients (55.1%) were classified to stage I/II and 13 patients (44.9%) to stage III/IV, 12 patients (41.4%) had B symptoms. Among the 29 patients, 2 patients failed to be followed and the others were followed for the median time of 29 months, 17 patients achieved CR, 5 patients achieved PR, 1 patient replaced and 4 patients died of disease progression. The 5-year overall survival rate (OS) was 85.2%, in which RCHOEP regimen group patients had OS 94.4% and CHOEP group patients had OS 75%; 8 patients underwent auto-HSCT and 1 patients underwent allo-HSCT who kept in CR state. Univariate analysis by log-rank test showed albumin level and LDH ≥ 2ULN, the initial therapy response and IPI score were prognostic factors , but neither were independent prognostic factors by Cox Regression Model. It is concluded that PMLBCL has distinct clinical features. RCHOEP chemotherapy regimen can achieve satisfactory results, but needs to be explored by further clinical trials.

Summary This study retrospectively collected the clinical and laboratory data of 114 patients with Castleman disease (CD) from a single medical centre. Clinical classification identified 62 patients (54·4%) with unicentric Castleman disease and 52 (45·6%) with multi-centric Castleman disease. Pathological classification revealed 68 cases (59·6%) of hyaline vascular variant, 16 (14·1%) mixed cellular variant (Mix) and 30 (26·3%) plasmacytic variant. Clinical complications occurred in 69 CD patients, including 37 cases of paraneoplastic pemphigus (PNP) and 25 cases with renal complications. Haematological involvement, pleural effusion and/or ascites and POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes) were also found. Univariate analysis showed that presence of clinical complications and PNP were both risk factors relating to CD patient survival. Prognostic factors showing P

This study was aimed to analyze the clinical and pathological characteristics of patients with primary extranodal lymphoma (PENL). A total of 236 patients with PENL were enrolled to evaluate the clinical and pathological features. The clinical data of 236 patients with PENL confirmed by pathological and immunohistochemical methods between January 2001 and March 2012 were analyzed retrospectively. The results indicated that: (1)236 patients with PENL accounted for 40.7% of lymphoma over the same period. Median age was 55 years old (from 16 to 91 years old) . There were 153 males and 83 females(ratio 1.8: 1). (2)The common sites of involvement were gastrointestinal tract, nasal cavity, tonsil, mediastinum, skin, spleen, testis, bone and soft tissue, central nervous system, which accounted for 30.1% (71/236), 10.6% (25/236), 8.9% (21/236), 5.9% (14/236), 5.1% (12/236), 4.7% (11/236), 4.2% (10/236) , 4.2% (10/236) , 3.0% (7/236) respectively. (3)Symptoms of PENL did not have special characteristics, however its signs usually manifested with the enlargement or mass of organs, which accounted for 66.9% (158/236) in this study. (4)According to WHO classification of tumours of haematopoietic and lymphoid tissues in 2008, the common pathological type of gastrointestinal lymphoma was diffuse large B-cell lymphoma, mucosa-associated lymphoid tissue lymphoma; the common pathological type of nasal lymphoma was extranodal NK/T cell lymphoma; the common pathological type of tonsillar lymphoma, testicular lymphoma, CNS lymphoma was diffuse large B-cell lymphoma. It is concluded that the primary extranodal lymphoma is not rare, it is alert to PENL while organs enlarge or mass forms, so that clinical physician should pay attention to tissue biopsy.

To study the prognostic implications of hematopoietic cell transplantation-specific comorbidity index (HCT-CI) on non-relapse mortality (NRM) and overall survival (OS) in patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT).Clinical data of 161 cases received allo-HSCT from July 2003 to November 2010 were analyzed retrospectively. The prognostic significance of HCT-CI, age, sex, conditioning regimens, disease status before transplantation, graft source and the degree of HLA matches for NRM and OS was conducted by COX regression model. The prognostic impact of HCT-CI on NRM and OS was performed in all patients under different disease status before transplantation.Of the 161 cases with allo-HSCT, 3-year NRM and OS were 26.4% and 61.4% respectively. NRM at 3 years in patients with HCT-CI score 0, 1-2 and ≥3 were 14.9%, 24.5% and 52.7% respectively. And OS at 3 years were 68.9%, 64.6% and 34.7% respectively. There were significant differences between HCT-CI score 0 and ≥3 groups for NRM and OS (P0.01). High-risk disease status before transplantation (NRM: RR=3.35, P0.01;OS: RR=3.53, P0.01) and HCT-CI score≥3 (NRM: RR=6.85, P0.01;OS: RR=3.77, P0.01)were independent risk factors by COX regression model. In the subgroup analysis according to disease status, high score of HCT-CI was associated with poor OS (P0.01) and high NRM (P0.01) in patients with low-risk, but not in those with high-risk disease status.HCT-CI score and disease status before transplantation are independent risk factors for patients received allo-HSCT. HCT-CI score have prognostic implication for NRM and OS in patients with low-risk disease status, but not in high-risk group.

To summarize the incidence of various adverse reactions in the clinical application of L-asparaginase (L-Asp), and to analyze the cause of hepatic encephalopathy in three cases.The complete data of 23 patients in our department from December 2009 to December 2010 were collected. Their blood ammonia levels, transaminase, serum albumin and blood coagulation function before, during and after the L-Asp application were assayed.(1) All patients had elevated blood ammonia level after the L- Asp application. This occurred 2 days after the beginning of treatment and the median time to reach peak level (ranged from 194 to 446 μmol/L, with a median value of 300 μmol/L) was 4 days. It returned to normal level after a median time of 5 days (ranged 3-7 days) with drug withdrawal. Of the 23 patients studied, 3 developed hepatic encephalopathy. (2) All patients appeared lower blood fibrinogen, 10 cases (43.5%) with lower fibrinogen only, while 13 cases (56.5%) with both prolonged APTT and lower fibrinogen. The lowest level of fibrinogen was detected at 1 week after drug application. Of the 23 patients, 14 (60.9%) had mild lower blood fibrinogen (1-2 g/L), and 9 (39.1%) had significantly lower fibrinogen (0-1 g/L). (3) Six cases (26.1%) had slightly elevated level of transaminase (2 times the upper limits of normal), 8 (34.8%) appeared hypoalbuminemia.As the incidence of elevated blood ammonia levels was high in the application of L-Asp, the level of blood ammonia should be closely monitored to avoid the occurrence of hepatic encephalopathy, especially in elderly patients and patients with previous liver disease or long-term heavy drinking. L-Asp can also lead to low fibrinogen level, hypoalbuminemia and abnormal transaminase. Monitoring the blood coagulation function and liver function is required and, if necessary, plasma infusion and liver protection therapy are required.

This study was purposed to analyze the clinical characteristics and prognostic factors in patients with primary gastrointestinal non-Hodgkin's lymphoma (PGI-NHL). The pathological data of 101 PGI-NHL patients admitted in our hospital in the past 15 years were analyzed retrospectively. The results showed that 101 patients with PGI-NHL accounted for 14.49% of NHL in the same period, there were 64 males, 37 females, the range of ages was from 18 to 87 years old, median age was 61 years old; in disease distribution, the stomach PGI-NHL accounted for 58.42%, intestine PGI-NHL accounted for 39.60%, multiple GI involvements (MGI) accounted for 1.98%; in pathological type, diffuse large B cell lymphoma (DLBCL) accounted for 66.34%, mucosa-associated lymphoid tissue (MALT) lymphoma accounted for 17.82%, mantle cell lymphoma (MCL) accounted for 3.96%, enteropathy-associated T cell lymphoma (EATL) accounted for 7.92%, extra-nodal nasal type NK/T cell lymphoma accounted for 1.98%, follicular lymphoma (FL) accounted for 0.99%, small lymphocyte lymphoma (SLL) accounted for 0.99%. Eighty-nine out of 101 patients were followed up (49 cases live, 40 cases dead), data of the 12 patients were lost; the median survival time was 29 months (1 - 173). The three-year OS and five-year OS were 58.4% and 52.6% respectively. Univariate analysis revealed that the factors affecting OS included sex (P = 0.004), lesion site (P = 0.002), tumor size (P = 0.011), clinical Lugano staging for gastrointestinal non-Hodgkin's lymphoma (P = 0.003), IPI score (P = 0.000), pathological cell phenotype (P = 0.001), and pathological type (P = 0.006), their differences were statistically significant (P0.05). Multivariate Cox regression analysis indicated that clinical Lugano staging for gastrointestinal non-Hodgkin's lymphoma, IPI score, pathological type were independent prognostic risk factors affecting OS. It is concluded that clinical Lugano staging for gastrointestinal non-Hodgkin's lymphoma, IPI score and pathological type are independent risk factors affecting OS.

This study was purposed to investigate the role of NK-alloreactivity and donor-inhibiting or activating KIR gene in predicting prognosis under unmanipulated allogeneic blood and marrow transplantation. A modified polymerase chain reaction sequence specific primers (PCR-SSP) method was used to typing KIR and HLA genotype of donors and recipients. The relationship between donor activating or inhibitory KIR and recipient HLA genotypes on event free survival (EFS), cumulative incidence of malignant relapse and transplant-related mortality (TRM) were investigated retrospectively in 67 patients undergoing hematopoietic stem cell transplantation. The results showed that no effect of 'KIR/HLA mismatched' was detected on acute graft-versus-host disease (aGVHD) and relapse. The EFS of KIR/HLA mismatched group was lower, especially KIR2DL1/HLA-C2 mismatched group (44.8% vs 69.2%, P = 0.043). However, EFS was better for the presence of donor-activating KIR2DS2 (81.3% vs 52.6%, P = 0.052), and the relapse rate was significantly lower for the presence of this genotype (7.7% vs 34.2%, P = 0.05). EFS was worse in patients homozygous for group 1 HLA-C (C1) when donor carries the activating KIR2DS1 (KIR2DS1 positive/HLA-C2-negative group, P = 0.028), and the incidence of aGVHD in this group was significantly higher than that in any other groups (P = 0.028). In multivariate analysis, advanced disease stage, more than two donor-activating KIR, donor KIR2DS2-negative genotype were associated with an reduced disease-free survival (HR = 3.34, 2.19, 3.18;and P = 0.005, 0.053, 0.066). Donor KIR2DS2-negative genotype were also associated with an increased risk of relapse (HR = 6.72, 9.43; and P = 0.019, 0.047). And donor KIR2DS1 positive/recipient HLA-C2 negative group was the only risk factor of TRM (HR = 3.27, 95% CI 1.78 - 9.06, P = 0.023). It is concluded that missing ligand for the donor inhibitory KIR has weak effect on the outcome of unmanipulated HSCT. The activating KIR play an important role in the EFS, relapse and TRM after HSCT. Donor KIR2DS1-positive/recipient HLA-C2-negative group and donor KIR2DS1 gene negative predict poor prognosis. Analysis of KIR genotype and its ligand is important for the selection of best donor and prognostic evaluation in unmanipulated allogeneic HSCT.

This study was aimed to investigate whether incorporation of rituximab into high-dose chemotherapy with autologous peripheral blood stem cell transplantation (auto-PBSCT)could improve the survival of patients with diffuse large B-cell lymphoma (DLBCL), and evaluate the safety of this regimen.Twenty-five patients (age, 17 - 61 yrs) with DLBCL were treated with a sequential chemotherapy for remission induction, intensive chemotherapy for mobilization of stem cells, and high-dose chemotherapy followed by auto-PBSCT. Among 25 patients, 22 cases were at IV Ann Arbor stage, 60% cases with B symptom, and 10 cases with intermediate-high risk and 2 cases with high risk when evaluated by International Prognostic Index (IPI). The high-dose chemotherapy included BEAM regimen for 21 patients, and TBI conditioning regimen for 4 patients. Each patient received infusion of rituximab at a dose of 375 mg/m(2) for 2 times, each at peripheral blood stem cell mobilization and peripheral stem cell infusion.20 patients achieved complete remission (CR) before transplantation. After high-dose chemotherapy and auto-PBSCT, 92% patients achieved CR. At a median follow-up of 45 months, the estimated 3-year overall survival (OS) and progression-free survival (PFS) were 78.9% and 75.9%, respectively, for all patients; while those were 87.4% and 82.4% for patients achieved CR before auto-PBSCT. Multivariate analysis by Cox regression revealed that failure to achieving CR before auto-PBSCT was an independent prognostic factor affecting OS, while factor affecting PFS was IPI scores. Rituximab was generally well tolerated with few side-effects.Our results suggested that the addition of rituximab to high-dose chemotherapy followed by auto-PBSCT was effective and safe for patients with DLBCL.

To study the chronic health conditions (CHC) in long-term survival recipient after hematopoietic stem cell transplantation (HSCT).The CHC of 101 cases survived for more than 1 year after HSCT were collected according to Bone Marrow Transplant Survivor Study (MBMTSS) questionnaire. The differences of the incidence and severity of CHC between auto-HSCT and allo-HSCT, HLA-matched and HLA-mismatched family donors HSCT were compared, and risk factors related to chronic health conditions were analyzed retrospectively in family donor HSCT.Of the 101 HSCT survivors, 48.5% reported one or more chronic health conditions, and 83.7% of which were mild to moderate. The CHC in HLA-matched related donors HSCT were more serious than in HLA-mismatched related donors HSCT. The percentage of CHC total score above 3 in allo-HSCT recipients (32.1%) was higher than that in auto-HSCT ones (10.0%). The percentage of CHC total score 1-2, 3-4, and above 5 in HLA-matched family donors HSCT were 23.5%, 29.4%, and 14.7%, respectively, being significantly higher than those in HLA-mismatched ones (15.6%, 15.6%, and 6.2%, respectively). CHC was mainly related to chronic graft-versus-host disease (cGVHD). Single variable analysis showed that younger age at time of transplantation, HLA fully matched, the use of antithymocyte globulin (ATG) in the conditioning regimens were favorable for CHC. COX-regression Model showed that age was the only independent risk factor for predicting the CHC in family donor HSCT.The chronic health conditions after HSCT is mild to moderate, these complications in HLA-matched related donor HSCT are more serious than those in HLA-mismatched related donor HSCT. The age at transplantation is the only independent risk factor for chronic health conditions.

To investigate the risk factor for cytomegalovirus (CMV) viremia and its impact on the survival of patients after allogeneic hematological stem cell transplantation (allo-HSCT).Quantitative fluorescence PCR was used to examine the quantity of CMV in mononuclear cells. All patients were tested weekly after allo-HSCT within 3 months. Univariate and multivariate analysis were used to determine the risk factors of CMV viremia. Five-year overall survival rate was compared and analyzed between the patients with or without CMV viremia.The incidence of CMV viremia was 72.1% (132/183). Of which, 59.1% (78/132) occurred post one month after transplantation, 40.9% (54/132) occurred within one month and 27.9% (51/183) sustained negative within three months. Two cases were clearly diagnosed as CMV disease with a incidence of 1.1%. Both univariate and multivariate analysis indicated that transplant methods and blood cyclosporine A (CsA) concentration were significantly correlated with CMV viremia. When pairwise compared the results between the different transplant methods, significant differences of CMV viremia were found between human leukocyte antigen (HLA) matched sibling and HLA mismatched relatives, unrelative donor or cord blood (all P values0.05). There was no significant difference between HLA mismatched relatives and unrelative donor or cord blood. Further analysis showed that the incidence of CMV viremia was much higher in those who had used antithymocyte globulin (ATG) then those not used ATG. The Kaplan-Meier survival curve showed there was no significant difference between the groups with and without CMV viremia.The incidence of CMV viremia after allo-HSCT is 72.1%. Administration of ATG during conditioning regimen and blood CsA concentration300 µg/L are the main risk factors for CMV viremia. There is no significant effect of CMV viremia on the cumulative overall survival, while prompt treatment of CMV viremia is a crucial way to prevent CMV disease.

To investigate the treatment of primary amyloidosis with high-dose melphalan and autologous hematopoietic stem cell transplantation to further examine the survival, hematologic response, and improvement of amyloid-related organ dysfunction.Retrospective analysis of 20 patients with primary amyloidosis treated with autologous hematopoietic stem cell transplantation. The status of major organ function before transplantation, mobilization programs and conditioning regimen as possible risk factors for survival were also investigated.Of 20 cases, 11 out of 15 evaluable cases achieved hematologic response, among them, 6 got complete remission (CR, 40%) and 5 partial remission (PR, 33%). The median onset time was 3.0 months (1.5 - 4.0 months) and 4 months (3 - 5 months), respectively after transplantation. The overall hematologic response was 73%. The 11 hematologic responders also had kidney responses. The median time to achieve kidney response was 3 months (2 - 6 months). The 3-year overall survival of the cohort of cases was 71.4%. The major causes of death were heart failure, renal dysfunction and gastrointestinal bleeding. G-CSF alone could obtain satisfactory mobilization results and most of patients well tolerated to the conditioning regimen of melphalan doses from 140 mg/m(2) to 200 mg/m(2).Treatment of primary amyloidosis with high-dose melphalan followed by autologous peripheral blood stem cell transplantation produced high efficacy. The cardiovascular system involvement, renal dysfunction and the abnormality of coagulation function before transplantation may be the risk factors for survival.

The chemotactic movement of T lymphocytes mediated by chemokines and their receptors plays an important role in the pathogenesis of graft-versus-host disease (GVHD) post-allogeneic hematopoietic stem cell transplantation (allo-HSCT). CCR7 and CXCR3 are two receptors associated with the development of GVHD. Bortezomib, a proteasome inhibitor, was recently found to prevent GVHD in a mouse model and to decrease the production of Th1 cytokines. Here, we report that bortezomib differentially regulates the expression of CXCR3 and CCR7 on T cells; it significantly decreases CXCR3 expression on T cells as well as its CD4(+)/CD8(+) subsets in a dose-dependent manner, while it does not significantly affect CCR7 expression on T cells and subsets. Moreover, the secretion of CXCL9 by activated T cells is also increasingly downregulated with increasing concentrations of bortezomib. Meanwhile, bortezomib inhibits T-cell chemotactic movements toward CXCL9 in a dose-dependent manner, but has no effect on CCL19-induced T-cell chemotaxis. Additionally, it was found that bortezomib treatment also prompts T-lymphocyte apoptosis through activation of caspase-3 and its downstream PARP cleavage in a dose- and time-dependent manner. These results suggest that bortezomib may act as a suppressor of GVHD by downregulating T-cell chemotatic movement toward GVHD target organs, as well as by inducing apoptosis.

To evaluate the image of SPECT/PET (18)F-FDG in monitoring response to therapy for lymphoma patients.A retrospective study was performed in 83 SPECT/PET studies for 70 patients with lymphoma from 1998 to 2008 in our hospital. The risk factors for survival rate were analyzed by univariate analysis.Forty patients received SPECT/PET after 2 - 4 cycles of chemotheraphy, the median PFS in patients with positive and negative group were 5.5 months and 15.5 months, 2-year PFS were 12.5% and 66.8%; the median OS were 12.5 months and 17 months, and 1-year OS were 28.8% and 94.1%, respectively, all being of significant difference between two groups (P = 0.003). Forty-three patients performed posttreatment SPECT/PET, the median PFS in patients with positive and negative group were 10 months and 23 months, the 2-year PFS were 23.3% and 83.2%; the median OS were 17 months and 27 months and the 2-year OS were 60.0% and 100% respectively, all being of significant difference (P = 0.001).SPECT/PET has significant value in monitoring response to therapy and predicting prognosis for patients with lymphoma.

To investigate the efficacy and treatment outcome of different induction regimens, and different post-remission therapies for adult acute promyelocytic leukemia (APL).The outcome of 73 patients with newly diagnosed APL were retrospectively analyzed. According to the induction regimens, the patients were divided into three groups: chemotherapy-only (14 cases group I), all-trans retinoic acid (ATRA) or combined with chemotherapy (33 cases group II), and ATRA combined with arsenic trioxide (As(2)O(3)) (26 cases group III). The complete remission (CR) rate and the time to CR (TTC) were analyzed. After CR, the patients were divided into 2 groups for post-remission therapies: one with sequential treatment of chemotherapy/ATRA/As(2)O(3) and the other with alternative treatment of chemotherapy/ATRA. The overall survival (OS), disease free survival (DFS) and relapse rate were compared between these two groups. Patients induced CR with both ATRA and As(2)O(3), and then sequentially treated with chemotherapy/ATRA/As(2)O(3) (group A), and those induced CR with ATRA or As(2)O(3) alone and then with non-chemotherapy/ATRA/As(2)O(3) sequentially (group B) were also analyzed and compared for CR, OS and DFS.(1) For induction treatment, the CR rate in ATRA and As(2)O(3) combination group was 100%, in ATRA combined with chemotherapy group was 78.8%, and in chemotherapy-only group was 57.1% (P = 0.030). The median TTC in ATRA with As(2)O(3) combination group was 26 (13 - 40) days being the shortest among the three groups. (2) For the post-remission treatment, 3-year OS rates in group I and group II were (95.7 ± 4.3)% and (68.6 ± 11.2)% (P0.05), and 3-year DFS rates were (79.0 ± 9.5)%, and (32.9 ± 15.5)%, respectively (P0.01). The relapse rate was 14.8% in group I, and 50.0% in group II (P = 0.011). (3) The CR, 3-year OS and DFS rates in group A were all 100%. The CR rate in ATRA or As(2)O(3) alone induced group was 72.9%, and 3-year OS was (72.3 ± 9.1)% (P0.05).For adult APL induction with ATRA and As(2)O(3) combination can obtain a higher CR rate, and shorter TTC. The post-remission treatment with sequential chemotherapy, ATRA and As(2)O(3) results in a lower relapse rate, and significantly improves OS and DFS. The ATRA and As(2)O(3) combination induction with the sequential post-remission therapy is the best strategy for APL treatment.

The aim of this study was to analyze the risk factors of hemorrhagic cystitis (HC) after hematopoietic stem cell transplantation (HSCT). The data of 188 transplant patients treated from July 2003 to August 2009 in Peking University First Hospital were studied. The patients were followed up to 180 days after HSCT. Clinical records of the total 188 cases and the 150 cases underwent allogeneic HSCT out of 188 cases were analyzed by using a Cox regression model respectively. The results indicated as follows: (1) 51 of 188 patients developed HC (27.12%). Univariate analysis showed that sex (male RR = 1.673, p = 0.076), allogeneic HSCT (RR = 1.848, p = 0.061) were related to HC, and allogeneic HSCT (RR = 4.508, p = 0.037) was the independent risk factor for HC by multivariate analysis. (2) HC occurred in 32.67% (49/150) patients who underwent allogeneic HSCT, with 42 cases of grade II-IV HC (28.00%). For the incidence of grade II-IV HC, univariate analysis revealed mismatched related donor/matched unrelated donor (RR 2.444, p = 0.018), CMV viruria (RR 2.059, p = 0.021) and CMV positive in serum and urine at the same time (RR 2.497, p = 0.003) were risk factors. The following factors, as conditioning with Fludarabine (Flu) (RR 0.504, p = 0.059) and TBI (RR 0.185, p = 0.095), were associated with a decreased tendency of II-IV HC at age of 26 - 40 (compared with age ≤ 25 or ≥ 41, RR 0.454, p = 0.056). Some others, as conditioning with CTX (RR2.015, p = 0.063), the application of ATG (RR 2.343, p = 0.054) and CMV viremia (RR 2.123, p = 0.088), were associated with an increased tendency of II-IV HC by univariate analysis. Multivariate analysis demonstrated that CMV positive in serum and urine at the same time (RR 2.269, p = 0.008), conditioning without Flu (RR = 2.106, p = 0.040) were the independent risk factor for grade II-IV HC. And the application of ATG (RR = 2.154, p = 0.083) was related to the tendency of higher incidence of grade II-IV HC. It is concluded that the incidence of HC is high in patients underwent allogeneic HSCT. CMV positive in serum and urine at the same time, while conditioning without Flu are the independent risk factors of grade II-IV HC. Application of ATG is related to the increased trend of grade II-IV HC.

The aim of this study was to evaluate the application value of SPECT/PET (18)F-FDG imaging in patients with lymphoma and its significance in monitoring relapse of this disease. A retrospective analysis of 71 SPECT/PET examinations was performed in patients with lymphoma diagnosed by pathologic and immunohistochemistry means from 1998 to 2008 in Peking university first hospital. The results showed that 28 patients underwent SPECT/PET before initial therapy, the accuracy of SPECT/PET and CT were 100% and 81.7% respectively. The diagnostic sensitivity of SPECT/PET and CT for foci were 85.7% and 53.5% respectively, and there was significant difference between them (p = 0.003). The diagnostic sensitivity of SPECT/PET and CT for extranodal foci were 91.3% and 56.5% respectively, there was significant difference also between them (p = 0.007). 32 patients underwent 43 SPECT/PET for monitoring relapse during follow up. The positive predictive value and negative predictive value of SPECT/PET for relapse were 100% and 92.9% respectively. The relapse were found by SPECT/PET in 6 patients more early than appearance of clinical symptoms and physical signs as well as laboratory examination, imaging examination. In conclusion, SPECT/PET has significant value in diagnosing and monitoring relapse for patients with lymphoma.

To monitor blood cells EBV-DNA copies by quantitative Epstein-Barr virus (EBV) polymerase chain reaction after hematopoietic stem cell transplantation (HSCT) and to evaluate its implication.EBV-DNA copies of peripheral blood mononucleated cells (PBMNCs) were detected by fluorescence quantitative PCR once a week since conditioning regimen from fifty one patients received HSCT. Correlation between development of lymphoproliferative disorders (LPD) and EBV-DNA copies and influence factors of EBV reactivation were analyzed.The cumulative incidence of EBV viremia was 58.8%. EBV reactivation occurred (39.6 +/- 23.5) days after HSCT, later than that of cytomegalovirus (CMV) reactivation (25.0 +/- 15.1) days (P0.01). HLA mismatch (P0.01), use of antithymocyte globulin (ATG) (P0.01), age less than twenty (P0.001) were factors for EBV reactivation, (93.3% vs 48.1%, 92.3% vs 18.7%, and 100% vs 53.1%, respectively). EBV related post-transplant lymphoproliferative disorders (EBV-PTLD) occurred only in 4 out of 30 (13.3%) EBV reactivation patients, whose EBV DNA load maintained over 10(6) copies/ml for at least two weeks (4 out of 13 cases). The median survival time of EBV-PTLD patients was 19.5 (11 - 75) days.EBV reactivation occurs frequently after HSCT, especially in those received HLA mismatch grafts, used antithymocyte globulin or aged under twenty. Patients with EBV loads over 10(6) copies/ml, especially lasting over two weeks, appear to have an increased risk for PTLD, and pre-emptive therapy may be of clinical useful.