Objective: To evaluate the tolerance and safety of a human-mouse chimeric anti-CD20 monoclonal antibody IBI301 in Chinese patients achieved objective response with CD20⁺ B-cell non-Hodgkin’s lymphoma (NHL). Methods: Nine patients with CD20⁺ B-cell NHL received dose-escalating IBI301 infusions (250 mg/m², n=3; 375 mg/m², n=3; 500 mg/m², n=3, respectively). The data of all patients were collected for safety analyses. The median exposures of 125 mg/m², 375 mg/m², 500 mg/m² dose groups were 243, 690 and 980 mg, respectively. Safety and tolerability were evaluated by monitoring adverse events (AE). The ratios of CD19⁺, CD20⁺ B cells and the levels IgG and IgM were detected to evaluate the pharmacodynamics. Results: Totally 52 events of AE were observed, including 18 events of AE in 125 mg/m² group, 14 events of AE in 375 mg/m² group and 20 events of AE in 500 mg/m² group, respectively. There were 26 adverse reactions of 52 cases of AE, 22 reactions were judged to be probably related to IBI301, and 4 reactions were not probably related to IBI301, all disappeared or returned to baseline levels. Common AE in this study included decreased WBC, upper respiratory infection, decreased neutrophil count, dyspepsia, hyperuricemia, paresthesia, oral mucositis and dizziness. No patients quitted or trial discontinued. No severe AE (SAE) were reported. No dose-limiting toxicity (DLT) events were observed in the study. The ratio of CD20⁺ and CD19⁺ B cells decreased in all subjects. There was no significant changes of the levels of IgG and IgM. Conclusions: The single dose of IBI301 injection was well tolerated, and the AE occurred in the patients recovered. No SAE were reported, No DLT events were observed in the study. The IBI301 caused an elimination of the peripheral CD20-expressing B cells in all patients. Clinical trial registration Chinadrugtrials, CTR20140762.

Objective: To observe the material basis and mechanism of action of Kai-Xin-San (KXS) in regulating antidepression of neurotrophic factors. Methods: KXS eluted by ethanol on macroporous resin was prepared. The antidepressive effect of different components was compared by tailing suspension test and forced swimming test of mice. The levels of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in hippocampus were determined by ELISA. The rat astrocyte glioma C6 cell line and the rat adrenal pheochromocytoma PC12 cell line were used to evaluate the effects of different ethanol elution sites on the expression of NGF and BDNF and the differentiation of PC12 cells.Results: All of the ethanol elution components from KXS exerted anti-depressive effects by shorting the immobile time of tailing suspension and forced swimming of mice and 70％ ethanol elution components exerted best efficacy. This site also could increase expressions of NGF and BDNF on C6 glioma cell line. The 10％ ethanol elution site had the strongest ability to promote PC12 cell differentiation. Ginsenosides were the main effectuve ingredients for promoting the expression of neurotrophic factors. Conclusion: Regulation of neurotrophic factors might be the prominent action mechanism of KXS exerting anti-depressive effects.

OBJECTIVETo analyse the incidence, clinical features, prognosis of bone-related extramedullary disease （bEMD） and its relationship with strict EMD (sEMD) in MM patients.

METHODSThe records of 834 consecutive newly diagnosed patients with MM in our hospital between 1993 and 2013 were retrospectively reviewed.

RESULTS①Among 834 patients at diagnosis, 32 cases (3.8%) showed bEMD, and 40 cases (4.8%) showed sEMD. Patients with bEMD at presentation showed significant lower level of lactate dehydrogenase (180.9 U/L vs 299.2 U/L, P=0.034) and higher overall response rate (ORR) (95.7% vs 66.7%, P=0.009) compared with sEMD patients. While the above two parameters were comparable between patients with bEMD and without EMD. ②As to the prognosis of patients without autologous hematopoietic stem cell transplantation (auto-HSCT), the overall survival (OS) of patients with sEMD, bEMD and without EMD was 14.0, 37.5, and 38.0 months, respectively. The time to progression (TTP) of the three groups was 11.5, 27.0, and 22.0 months, respectively. Compared to the patients with sEMD, the outcomes (both OS and TTP) of the other two groups was significantly better (P<0.05). Patients with bEMD at presentation was comparable to the patients without EMD, but the two groups were better than the patients with sEMD. ③The incidence of bEMD during follow-up was 0.5%. The OS of patients with sEMD, bEMD and without EMD during follow-up was 26.0, 17.0, and 40.0 months, respectively. The TTP of the three groups was 13.0, 11.0, and 25.0 months, respectively. The outcomes (both OS and TTP) of patients with bEMD at relapse/progression showed no significant difference as compared with the other two groups (P>0.05).

CONCLUSIONThe clinical features of MM patients with bEMD are different from the patients with sEMD. Outcomes of this population is significantly better than the latter, and is comparable to the patients without EMD. It suggests that bEMD alone has no negative prognostic significance in MM patients.

Bone Diseases ; China ; Hematopoietic Stem Cell Transplantation ; Humans ; Incidence ; Longitudinal Studies ; Multiple Myeloma ; Neoplasm Recurrence, Local ; Prognosis ; Retrospective Studies

OBJECTIVETo observe the clinical and biological characteristics of Non-IgM-secreting lymphoplasmacytic lymphoma (LPL) and draw the differences between non-IgM LPL and Waldenström macroglobulinemia (WM).

METHODSRecords of 13 patients with non-IgM LPL were retrospectively analyzed between January 2000 and December 2013. The cytogenetic aberrations were detected by fluorescence in situ hybridisation (FISH).

RESULTSIn the cohort, 7 males and 6 females with a median age of 63 years (range 43 to 74), two patients were IgA secreting, 6 with IgG secreting and 5 patients without monoclonal globulin. The major complaint at diagnosis included anemia associated symptom (53.8%), mucocutaneous hemorrhage and superficial lymphadenopathy (15.4%). Eight patients had B symptom at diagnosis. All of the 13 patients had bone marrow involvement and anemia, and 10 patients had 2 or 3 lineage cytopenia. In 5 patients with available immunophenotypic data, all expressed CD19, CD20, CD22 and CD25, but missed the expression of CD10, CD103 and CD38. Two cases had CD5 or sIgM positive alone. Another 2 patients were CD23 or CD11c positive and 3 patients were FMC7 positive. Cytogenetic aberrations had been detected by FISH in 7 patients, but only two (28.6%) patients had aberrations with del(6q).

CONCLUSIONThe clinical and biological characteristics had no significantly difference between non-IgM LPL and WM.

Adult ; Aged ; Antigens, CD ; Chromosome Aberrations ; Female ; Humans ; Immunoglobulin M ; In Situ Hybridization, Fluorescence ; Integrin alpha Chains ; Leukemia, Lymphocytic, Chronic, B-Cell ; Male ; Middle Aged ; Retrospective Studies ; Waldenstrom Macroglobulinemia

OBJECTIVETo investigate the outcomes of autologous stem cell transplantation (ASCT) for patients with aggressive peripheral T-cell lymphoma (PTCLs) in advanced stage.

METHODSThe clinical data of 25 patients in complete remission (CR) with aggressive PTCLs received ASCT from May 1997 to June 2013 were retrospectively analyzed.

RESULTS① Of the 25 cases, 16 were unspecified PTCL (PTCL-U), 4 with angioimmunoblastic T cell lymphoma (AITL), 3 with anaplastic large cell lymphoma (ALCL) and 2 with hepatosplenic T cell lymphoma (HSTL), with a median age of 30(12-54) years old. Ratio of male to female is 16∶9. The distribution of stages was 8 cases with stage Ⅲ and 17 patients with stage Ⅳ. Nine patients presented with bone marrow involvement. Before ASCT, 18 patients were in CR1 and 7 patients were in CR2. ②Two patients with HSTL in stage ⅣB and IPI score 4/5 in CR1 relapsed and died within 12 months after ASCT. At a median follow-up of 38 (range 14-110) months, the estimated 3-year probability of PFS and OS for the other 23 patients was (63.1 ± 10.5)% and (71.8 ± 9.9)%, respectively. The patients in first CR had a better survival than the patients in second CR. The 3-year probability of PFS were (74.9 ± 11.0)% vs (33.3 ± 19.2)% (P=0.092) and OS were (80.2 ± 10.4)% vs (50.0 ± 20.4)% (P=0.043), respectively. The 3-year probability of PFS and OS were (40.0 ± 17.4)% and (53.3 ± 17.3)% in bone marrow involvement patients and the corresponding figure were (77.9 ± 11.3)% and (84.4 ± 10.2)% in non- bone marrow involvement patients.

CONCLUSIONASCT could improve the survival of aggressive PTCLs. Non CR1 status and bone marrow involvement had negative influence on OS in patients with aggressive PTCLs treated by ASCT. The prognosis was very poor in patients with HSTL and satisfactory regimens should be investigated.

Adolescent ; Adult ; Child ; Female ; Hematopoietic Stem Cell Transplantation ; Humans ; Lymphoma, Large-Cell, Anaplastic ; Lymphoma, T-Cell, Peripheral ; Male ; Middle Aged ; Neoplasm Staging ; Prognosis ; Remission Induction ; Retrospective Studies ; Transplantation, Autologous ; Young Adult

Objective:This study aimed to compare the clinical efficacy and prognosis between rituximab plus fludarabine and cyclophosphamide (FCR) and fludarabine and cyclophosphamide (FC) regimens for patients with chronic lymphocytic leukemia (CLL). Methods:The clinical data of 58 patients with CLL treated with FCR or FC regimens from December 2002 to January 2012 were analyzed retrospectively. Therapy efficacy and prognosis were compared between the two groups. Results:Among the 58 pa-tients, 27 (44.4%) experienced complete remission (CR) in the FCR group and 31 patients (19.4%) experienced CR in the FC group (P=0.039). The overall response rate (ORR) of the FCR group was higher than that of the FC group (81.5%and 51.6%, respectively, P=0.017). Fourteen patients achieved MRD-negative rating after therapy. PFS and OS in MRD-negative patients were superior compared with the MRD-positive group (P=0.000, 0.003). The proportion of MRD-negative patients in the FCR group was higher than that in the FC group (37.0%and 12.9%, respectively, P=0.032). PFS in high-risk genetic patients was lower than that in low-risk genetic patients (P=0.011, 0.027). The OS time between the two groups did not exhibit any difference. Conclusion:FCR produced a high CR and ORR in patients with CLL. Many patients in the FCR group were responsive to the treatment. Thus, FCR could be a more effective regimen than FC for patients with CLL.

OBJECTIVETo explore the immunophenotypic characteristics of CD5⁺ B cell lymphoproliferative disorders (B-LPD) of Chinese patients.

METHODSImmunophenotyping of bone marrow and (or) of peripheral blood was performed in patients with B-LPD by four color multiparameter flow cytometry analysis using a panel of monoclonal antibodies, and the patients clinical data were retrospectively analyzed. The difference in immunophenotypes and the related clinical features were retrospectively analyzed. Fluorescence in situ hybridization (FISH) for t(11;14) detection was applied to diagnose or exclude mantle cell lymphoma.

RESULTS(1)A total 260 CD5⁺ B-LPD patients were enrolled in this study, including 186 chronic lymphocytic leukemia (CLL), 40 mantle cell lymphoma (MCL), other B-LPD including 5 splenic marginal zone lymphoma (SMZL), 2 B-cell prolymphocytic leukemia (B-PLL), 3 hairy cell leukemia (HCL). The other 26 cases (10%)were not classified and defined as unclassified B-LPD (BLPD-U). MCL patients were all positive for t(11;14) detected by FISH, while all the BLPD-U patients were negative for t(11;14). (2) All patients expressed CD19, CD20 and CD5. According to the immunophenotypic score system, 186 CLL patients scored 4-5, 99.5% of patients with CD23⁺, 11.3% with sIgM⁺, 10.2% with FMC7⁺, 44.1% with CD22⁺ and 51.1% with CD11c⁺. MCL patients scored 2-3, with 50% expressing CD23 and sIgM, 81.6% expressing FMC7, 92.1% expressing CD22 and 5.3% expressing CD11c. In aspect of BLPD-U and other B-LPD, the expression of CD23, sIgM, FMC7, CD22 and CD11c were 73.1% and 50%, 34.6% and 50%, 88.5% and 100%, 92.3% and 90%, 69.2% and 70%, respectively. (3)In comparison of CLL with MCL, there was a significant difference in the expression of CD23, sIgM, FMC7, CD22 and CD11c between the two groups (P<0.01). Between MCL and BLPD-U, similar expression type of CD23, sIgM, FMC7 and CD22 was found except CD11c, which was highly expressed in BLPD-U (P<0.001). The difference of CD11c expression was also statistically significant between MCL and other B-LPD (P<0.01). In comparison of MCL with other B-LPD, there was a significant difference in the expression of CD11c (P<0.01). The expression of CD23 and sIgM in MCL are 7%-21% and 82%-100% respectively in Western population, while the expression of other immunophenotypic markers is similar with our study.

CONCLUSIONThe significant high incidence of CD23 and low incidence of sIgM compared to the Western population was observed in Chinese patients, and CD11c coud serve as a useful marker to distinguish MCL from CLL and other CD5⁺ B-LPD.

Adult ; Aged ; Aged, 80 and over ; Cell Count ; Female ; Flow Cytometry ; methods ; Humans ; Immunophenotyping ; Leukemia, Lymphocytic, Chronic, B-Cell ; immunology ; Lymphoma, Mantle-Cell ; immunology ; Lymphoproliferative Disorders ; immunology ; Male ; Middle Aged ; Retrospective Studies

OBJECTIVETo explore the feasibility and diagnostic implication of BRAF V600E mutation identified by high-resolution melting (HRM) assay in patients with hairy cell leukemia (HCL).

METHODSThe V600E mutation of BRAF exon 15 in four HCL patients were detected by HRM assay and patients' clinical data were retrospectively analyzed.

RESULTSAll four HCL patients were positive for the BRAF V600E mutation, which were identical to the results of DNA sequencing.

CONCLUSIONThe HRM assay for BRAF V600E mutation provides a useful tool to aid the laboratory diagnosis of HCL with easy operability, accuracy, and low cost.

Adult ; Aged ; DNA Mutational Analysis ; Female ; Humans ; Leukemia, Hairy Cell ; diagnosis ; genetics ; Male ; Middle Aged ; Mutation ; Polymerase Chain Reaction ; methods ; Proto-Oncogene Proteins B-raf ; genetics

BACKGROUNDWaldenström macroglobulinemia (WM) is an uncommon lymphoid malignancy. The characteristics and prognosis of WM have never been systematically studied in the East.

METHODSWe analyzed the clinical characteristics and the prognostic factors of 90 Chinese WM patients, and compared them with the Western reports.

RESULTSThe median age was 62 years old with a male-to-female ratio of 3.74. The most common symptoms at diagnosis were fatigue (77.8%) and bleeding (20%), while only 6 patients (6.7%) were asymptomatic. In the univariate analysis, age >62 years, thrombocytopenia, leucopenia, cytopenias ≥ 2, and high risk on the international prognostic scoring system for WM were the adverse risk factors, but only age >62 years and ≥ 2 cytopenias were the independent prognostic factors in the multivariate analysis. Using age <62 years and ≥ 2 cytopenias, three significantly different prognostic groups could been distinguished, with 5-year overall survival of 71.6%, 48.6%, and 17.0% (P < 0.001).

CONCLUSIONDistinct characteristics exist in WM in China compared to the West and we describe a new simple prognostic model for newly diagnosed WM patients.

Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Prognosis ; Risk Factors ; Waldenstrom Macroglobulinemia ; diagnosis ; mortality