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Soils on the Qinghai-Tibetan Plateau (QTP) have distinct physical properties from agricultural soils due to weak weathering and strong erosion. These properties might affect permafrost dynamics. However, few studies have investigated both quantitatively. In this study, we selected a permafrost site on the central region of the QTP and excavated soil samples from 20 cm to 200 cm. We measured soil porosity, thermal conductivity, saturated hydraulic conductivity and matric potential in the laboratory. Finally, we ran a simulation model replacing default sand or silty clay parameters with different combinations of these measured parameters. Results showed that gravel content (diameter > 2 mm) was ~ 55 % on average in soil profile; soil porosity was less than 0.3; saturated hydraulic conductivity ranged from 0.004–0.03 mm s−1; saturated matric potential ranged from −14 to −604 mm. When default sand or silty clay parameters were substituted with these measured values, the model errors of soil temperature, soil liquid water content, active layer depth and permafrost lower boundary were reduced. The root mean squared errors of active layer depths simulated using measured parameters, and the default sand and silty clay parameters were about 0.28, 1.06, 1.83 m, respectively. Among these measured parameters, porosities, which were much smaller than soil textures used in land surface models, played a dominant role in reducing model errors. We also demonstrated that soil water dynamic processes should be considered, rather than using static properties under frozen and unfrozen soil states as in most permafrost models. We concluded that it is necessary to consider the distinct physical properties of soil and water dynamics on the QTP when simulating dynamics of permafrost in this region. It is important to develop methods for systematic measuring physical properties of gravelly soil and to develop a spatial dataset for porosity because of its importance in simulating permafrost dynamics in this region.

The increased risk of Richter transformation (RT) in patients with chronic lymphocytic leukaemia (CLL) due to Epstein-Barr virus (EBV) reactivation during immunosuppressive therapy with fludarabine other targeted agents remains controversial. Among 31 RT cases classified as diffuse large B-cell lymphoma (DLBCL), seven (23%) showed EBV expression. In contrast to EBV

Multiple myeloma (MM) is a genetically heterogeneous disease with diverse clinical characteristics and outcomes. Recently, multiplex ligation-dependent probe amplification (MLPA) has emerged as an effective and robust method for the detection of cytogenetic aberrations in MM patients. In the present study, MLPA analysis was applied to analyze cytogenetics of CD138 tumor cells of 59 MM samples, and its result was compared, retrospectively, with the interphase fluorescence in situ hybridization (iFISH) data. We firstly established the normal range of each of the 42 diagnostic probes using healthy donor samples. A total of 151 aberrations were detected in 59 patient samples, and 49/59 cases (83.1%) harbored at least one copy number variation. Overall, 0-7 aberrations were detected per case using MLPA, indicating the heterogeneity and complexity of MM cytogenetics. We showed the high efficiency of MLPA and the high congruency of the two methods to assess cytogenetic aberrations. Considering that MLPA analysis is not reliable when the aberration only exits in a small population of tumor cells, it is essential to use both MLPA and iFISH as complementary techniques for the diagnosis of MM.

As the largest high-altitude permafrost region in the world, the Qinghai–Tibetan Plateau (QTP) has experienced pronounced warming, which may exert a profound effect on ecosystem's CO 2 emissions due to the large amounts of organic carbon in the permafrost soil. In this study, response of ecosystem respiration to short-term experimental warming was investigated in the alpine meadow ecosystem of a permafrost site on the QTP during the 2012 growing season. The results showed that cumulative growing season ecosystem CO 2 emissions were 277.09 and 325.33 g C m − 2 for the control and warming plots, respectively. Thus, a 2.18 °C increase in ground surface temperature and a 0.62 °C increase in soil temperature prompted a 17.41% increase in the ecosystem's CO 2 emissions. The relationships between temporal variations in ecosystem respiration and soil temperature can be described through exponential equation. Soil temperature accounted for 50 and 64% of the variations in ecosystem respiration on a diurnal scale, and 71 and 84% of the variations in ecosystem respiration on a seasonal scale in the control and warming plots, respectively. Moreover, the temperature sensitivity (i.e. apparent Q 10 values) of the ecosystem respiration rates was significantly higher in the warming plots than in the control plots. Our results indicate that the effect of warming promoted CO 2 emissions of the alpine meadow ecosystem at a permafrost site on the QTP, and that soil temperature is the key factor controlling ecosystems' CO 2 emissions. In addition, while ecosystem respiration provides positive feedback on the rise in temperature through an increase in temperature sensitivity under warming conditions, at least in the short term, this feedback may be partially offset by an increase in above- and belowground biomass caused by warming.

Purpose: Accumulating evidence indicates that intratumor heterogeneity is prevalent in multiple myeloma and that a collection of multiple, genetically distinct subclones are present within the myeloma cell population. It is not clear whether the size of clonal myeloma populations harboring unique cytogenetic abnormalities carry any additional prognostic value. Experimental Design: We analyzed the prognostic impact of cytogenetic aberrations by fluorescence in situ hybridization at different cutoff values in a cohort of 333 patients with newly diagnosed myeloma and 92 patients with relapsed myeloma. Results: We found that nearly all IgH-related arrangements were observed in a large majority of the purified plasma cells; however, 13q deletion, 17p deletion, and 1q21 amplification appeared in different percentages within the malignant plasma cell population. Based on the size of subclones carrying these cytogenetic aberrations, the patients were divided into four groups: 0%–10%, 10.5%–20%, 20.5%–50%, and >50%. Receiver-operating characteristics analysis was applied to determine the optimal cutoff value with the greatest differential survival and showed that the most powerful clone sizes were 10% for 13q deletion, 50% for 17p deletion, and 20% for 1q21 gains, which provided the best possible cutoffs for predicting poor outcomes. Conclusions: Our study indicated that the impact of clone size on prognostic value varies between specific genetic abnormalities. Prognostic value was observed for even a subgroup of plasma cells harboring the cytogenetic aberration of 13q deletion and 1q21 gains; however, 17p deletion displayed the most powerful cutoff for predicting survival only if the predominant clones harbored the abnormality. Clin Cancer Res; 21(9); 2148–56. ©2015 AACR.

Alpine grassland and permafrost occupy about two thirds and one half of the total area of the Qinghai-Tibetan Plateau (QTP), respectively. Soil water, which can be affected by permafrost thawing and precipitation, is important for vegetation growth in this region. It is therefore vital to consider the effects of both thawing and precipitation when studying the effect of climate warming on alpine grassland on the QTP. In this study, we examined two adjacent basins, one semiarid and the other semihumid, in the northeastern section of the QTP. We used remote sensing data to compare fractional vegetation cover (FVC) and the relationships between FVC and land surface temperature (LST) in different types of frozen ground; the samples were analogous to a chronosequence of climate warming and permafrost thawing. Our analysis produced three significant results: (1) the FVCs of the semihumid basin were significantly greater than those of the semiarid basin for most types of frozen ground (p < 0.05); (2) th...

Precipitation is one of the important water supplies in the arid and semiarid regions of northwestern China, playing a vital role in maintaining the fragile ecosystem. In remote mountainous area, it is difficult to obtain an accurate and reliable spatialization of the precipitation amount at the regional scale due to the inaccessibility, the sparsity of observation stations, and the complexity of relationships between precipitation and topography. Furthermore, accurate precipitation is important driven data for hydrological models to assess the water balance and water resource for hydrologists. Therefore, the use of satellite remote sensing becomes an important means over mountainous area. Precipitation datasets based on station data or pure satellite data have been increasingly available in spite of several weaknesses. This paper evaluates the usefulness of three precipitation datasets including TRMM 3B43_V6, 3B43_V7, and Asian Precipitation Highly Resolved Observational Data Integration Towards Evaluation with rain gauge data over Tianshan mountainous area where precipitation data is scarce. The results suggest that precipitation measurements only provided accurate information on a small scale, while the satellite remote sensing of precipitation had obvious advantages in basin scale or large scale especially over remote mountainous area.

Gravel is common in soil profiles of alpine grassland on the Qinghai-Tibetan plateau (QTP). However, little is known about the effect of gravel on soil and vegetation properties. In this study, we investigated the gravel content in the topsoil (0–40 cm) at three sites with different surface gravel mulch and analyzed the influence of gravel on soil organic carbon (SOC), soil total nitrogen (TN), fractional vegetation cover (FVC), and aboveground biomass (AGB). Results showed that (1) gravel content was the highest in sites with high surface gravel mulch, and the lowest in sites with light surface gravel mulch; (2) gravel was significantly negatively correlated with SOC, TN, FVC and AGB, and (3) gravel of 2–20 mm in size was the most important factor determining soil and vegetation properties. Our results suggested that the presence of gravel in the soil profile is not beneficial to soil nutrition sequestration and vegetation growth of alpine grassland on the QTP and should be considered in ecosystem modeling studies.

Purpose: PR1 is a human leukocyte antigen (HLA)-A2 nonameric peptide derived from neutrophil elastase (NE) and proteinase 3 (P3). We have previously shown that PR1 is cross-presented by solid tumors, leukemia, and antigen-presenting cells, including B cells. We have also shown that cross-presentation of PR1 by solid tumors renders them susceptible to killing by PR1-targeting immunotherapies. As multiple myeloma is derived from B cells, we investigated whether multiple myeloma is also capable of PR1 cross-presentation and subsequently capable of being targeted by using PR1 immunotherapies. Experimental Design: We tested whether multiple myeloma is capable of cross-presenting PR1 and subsequently becomes susceptible to PR1-targeting immunotherapies, using multiple myeloma cell lines, a xenograft mouse model, and primary multiple myeloma patient samples. Results: Here we show that multiple myeloma cells lack endogenous NE and P3, are able to take up exogenous NE and P3, and cross-present PR1 on HLA-A2. Cross-presentation by multiple myeloma utilizes the conventional antigen processing machinery, including the proteasome and Golgi, and is not affected by immunomodulating drugs (IMiD). Following PR1 cross-presentation, we are able to target multiple myeloma with PR1-CTL and anti-PR1/HLA-A2 antibody both in vitro and in vivo. Conclusions: Collectively, our data demonstrate that PR1 is a novel tumor-associated antigen target in multiple myeloma and that multiple myeloma is susceptible to immunotherapies that target cross-presented antigens. Clin Cancer Res; 24(14); 3386–96. ©2018 AACR.

Primary bone (PB) diffuse large B-cell lymphoma (DLBCL) is rare and has a favorable prognosis, but the underlying biological mechanisms remain unknown. In this study we analyzed the clinicopathologic features of 160 patients with PB-DLBCL in comparison with 499 nonosseous DLBCL. Compared with patients with nonosseous DLBCL and secondary involvement of bone by DLBCL, PB-DLBCL patients less frequently had elderly age, B-symptoms, elevated serum lactate dehydrogenase levels, and high International Prognostic Index at diagnosis, more frequently had germinal center (GC) subtype (approximately 90%) and complete remission, and had significantly better survival. The 5-year progression-free and overall survival rates of PB-DLBCL patients were 80% and 93%, respectively, superior to both GC B-cell-like (GCB) and activated B cell-like subtypes of DLBCL. Further stratifying nonosseous DLBCL cell-of-origin subtypes by clinical factors showed that PB-DLBCL had similar survival rates as the centrocyte-origin (CC) subtype of DLBCL-GCB classified by the B-cell-associated gene signature algorithm. To better understand the favorable outcome of PB-DLBCL patients, gene expression profiling and microRNA profiling were performed in a small subset of PB-DLBCL. The gene expression profiles of PB-DLBCL resembled those of nonosseous DLBCL-GCB-CC, but were distinct from other DLBCL cell-of-origin especially the centroblast-origin (CB) subtype. Compared with DLBCL-GCB-CB, PB-DLBCL and DLBCL-GCB-CC also had much higher levels of miR-125a-3p, miR-34-3p, and miR-155-5p, and significantly lower levels of miR-17-5p and miR-17-3p. These results demonstrated that PB-DLBCL is clinically distinct, and the cell-of-origin of PB-DLBCL stems from centrocytes in the GC, that are biologically attributed for the favorable prognosis of PB-DLBCL.

B-cell chronic lymphoproliferative disorders (B-CLPD) comprise several entities with indolent clinical manifestations but heterogeneous survival. Cytogenetic aberrations are now the standard prognostic predictors in chronic lymphocytic leukemia (CLL) but have been less investigated in other subtypes of B-CLPD. In this study, we detected cytogenetic aberrations by fluorescence in situ hybridization (FISH) in 875 B-CLPD patients, based on a panel probes locating at 13q14, 11q22, 17p13 and CEP12. We identified del17p acted as the independent adverse cytogenetic predictor for overall survival (OS) in CLL. Del13q, del11q and del17p were adverse factors for OS in Waldenstrom's macroglobulinemia in the univariate analysis but lost their role in the multivariate analysis. Trisomy 12 acted as an independent poor factor for both marginal zone lymphoma (MZL) and unclassified B-CLPD (BCLPD-U) subtype. Del17p did not impact survival in MZL and BCLPD-U patients. These contrasting results indicate different roles of the same cytogenetic aberrations in the pathogenesis of each B-CLPD subtype. As del17p contributed to the poorest survival in CLL and desired extraordinary treatment strategy, the imitation of CLL strategy to other B-CLPD with del17p should be carefully advocated based on this study.

Objective To summarize and investigate the characteristics of nodal marginal zone lymphoma (NMZL).strongMethod/strongThe clinical data and laboratory characteristics of of NMZL patients admitted in our hospital between January 2002 and September 2013 were analyzed retrospectively.strongResults/strongTwenty-four patients were enrolled in the study. The median age was 54.4 (28-70) years,and the male/female ratio was 1:1. Most of the patients (95%) had bone marrow involvement,40.9% (9/22) had elevated lactate dehydrogenase level,8.3% (2/24) had the positive expression of hepatitis C virus antibody,33.3% (6/18) had positive autoimmune antibodies,and 33.3% (8/24) had monoclonal immunoglobulins in the serum. All of the patients expressed CD19 and CD20 cell markers,whereas none of them expressed CD10 cell marker. The positive rate of CD5 marker was 10% (1/10),the positive rate of CD23 marker was 50% (5/10),whereas no patient had the expressions of both CD5 and CD23 at the same time. The total overall remission rate was 81.25%,and the total complete remission rate was 56.2%. The separate overall remission and complete remission rate had increasing trends in rituximab subgroup than subgroups without using rituximab(P=0.136,P=0.262).strongConclusion/strongNMZL has a low incidence and can be seen in both males and females. It often invades bone marrow. Rituximab may increase the response rate and even improve the progression free survival.

Background Diffuse large B-cell lymphoma (DLBCL) of leukemic phase is a rare clinical manifestation, but is highly prevalent with central nervous system involvement (CNSI). Little is known about this rare clinical observation. Methods We reviewed the clinical characteristics of 40 DLBCL patients with leukemic phase identified by flow cytometry and analyzed BCL2 and MYC aberrations by fluorescence in situ hybridization. Results The median age of these 40 patients was 46 years (range, 15–75) with 19 men patients. All patients had bone marrow involvement, and fourteen (35.0%) had CNSI. There were respectively 14 patients (35.0%) had the BCL2 or MYC gain/amplification and nine of them (22.5%) simultaneously had both aberrations. Compared to those without CNSI, CNSI was found more commonly in male patients (71.4 vs. 34.6%, p = 0.046), in those with IPI scores of 4–5 (57.1% vs. 11.5%, p = 0.001), and in those with elevated serum LDH (100 vs. 61.5%, p = 0.007) and both MYC and BCL2 rearrangement (88.9 vs. 19.4%; p = 0.000). BCL2 and MYC rearrangements were the sole independent factor correlated with CNSI. Conclusion It is possible that both BCL2 and MYC gene aberrations may contribute to the high incidence of CNSI observed in leukemic phase of patients with DLBCL.

Patients with chronic lymphocytic leukemia (CLL) with 13q deletion as the sole cytogenetic abnormality usually have a favorable outcome, but the frequency of the 13q14 deletion and its impact on the outcome of other B-cell chronic lymphoproliferative disorders (BCLPDs) remain unclear. To further characterize this aberration, we investigated the prognostic significance of 13q deletion in 541 patients with BCLPDs. We performed fluorescence in situ hybridization (FISH) studies with 13q locus-specific LSI-D13S25 and LSI-RB1 probes. 52.1% of the patients with CLL harbored 13q deletion, which was significantly higher than that of other BCLPDs (p < 0.001). The size of 13q deletion was heterogeneous in both CLL and other BCLPDs. However, the distribution of cases with different deletion sizes showed no significant difference between the two groups. Whereas 13q deletion was a favorable prognostic factor in CLL, a large deletion of 13q was associated with poor prognosis in terms of time to first therapy (p = 0.020), progression-free survival (p = 0.05) and overall survival (p = 0.002) in BCLPD cases other than CLL. In conclusion, the deletion of 13q varied in size both in CLL and in other BCLPDs and adversely influenced the prognosis of patients with other BCLPDs.

Freeze/thaw (F/T) processes can be quite different under the various land surface types found in the complex tundra of the Arctic, such as polygonal tundra (wet center and dry rims), ponds, and thermokarst lakes. Proper simulation of these different processes is essential for accurate prediction of the release of greenhouse gases under a warming climate scenario. In this study we have incorporated the water layer into a dynamic organic soil version of the Terrestrial Ecosystem Model (DOS-TEM), having first verified and validated the model. Results showed that (1) the DOS-TEM was very efficient and its results compared well with analytical solutions for idealized cases, and (2) despite a number of limitations and uncertainties in the modeling, the simulations compared reasonably well with in situ measurements from polygon rims, polygon centers (with and without water), and lakes on Samoylov Island, Siberia, indicating the suitability of the DOS-TEM for simulating the various F/T processes. Sensitivity tests were performed on the effects of water depth and our results indicated that both water and snow cover are very important in the simulated thermal processes, for both polygon centers and lakes. We therefore concluded that the polygon rims and polygon centers (with various maximum water depths) should be considered separately, and that the dynamics of water depth in both polygons and lakes should be taken into account when simulating thermal processes for methane emission studies.

Normal plasma cells (PCs) are either undetectable or outnumbered by the myelomatous PC compartment in bone marrow of multiple myeloma (MM). However, residual normal PCs have been detected in a minority of symptomatic MM patients with superior survival. The number of normal PCs is also an important factor to identify monoclonal gammopathy of undetermined significance (MGUS)-like MM. We speculate that the polyclonal serum IgM level in non-IgM myelomas may reflect the number of residual normal PCs. Here we investigated the prognostic relevance of polyclonal serum IgM level in a series of 485 newly diagnosed symptomatic MM (NDMM) patients. Our results showed that symptomatic MM patients with polyclonal IgM more than 0.5g/L displayed a favorable baseline clinical feature, together with a significantly lower frequency of high-risk cytogenetic abnormalities. This group of patients had a significantly prolonged progression-free survival (PFS) and overall survival (OS) regardless of thalidomide or bortezomib therapy. Furthermore, the superior outcome was independent of the depth of response. Our findings suggest that polyclonal IgM level is capable of identifying a group of symptomatic MM patients with distinct clinicobiological characteristics and favorable survival, similar with MGUS-like MM.

Aberrant expression of microRNAs in chronic lymphocytic leukemia (CLL) has been reported to be associated with clinical outcome and improve prognostic stratification. The aim of this study was to explore the association of miR-29c expression with clinical parameters and survival in 53 Chinese patients with CLL. We showed that the miR-29c expression level decreased significantly from early to advanced clinical stages, and was significantly lower in patients with β(2)-microglobulin higher than 3.5 mg/L or with disease progression or death. With the cut-off determined by receiver operating characteristic (ROC) curve analysis, optimizing concordance with immunoglobulin heavy chain (IgVH) mutation status, miR-29c negative and positive groups were defined as including 17 and 36 patients, respectively. The miR-29c negative group had a higher percentage of patients with trisomy 12 or deletion of 11q or 17p (70.6% vs. 34.3%; p = 0.014) compared to the miR-29c positive group. The median progression-free survival and overall survival of the miR-29c negative group were 21 and 92 months, respectively, significantly shorter than in the miR-29c positive group (both not reached; p = 0.002 and p = 0.042, respectively), and miR-29c down-regulation was an independent prognostic factor for PFS. In conclusion, down-regulation of miR-29c is associated with higher tumor burden and significantly predicts short survival in Chinese patients with CLL.

Sex-determining region Y-box 11 (SOX11) is an important diagnostic marker in mantle cell lymphoma (MCL). However, the direct oncogenic mechanisms and downstream effector pathways implicated in SOX11-driven transformation remain poorly understood. In the present study, we analyzed SOX11 expression in B-NHL, and used lentivirus-mediated RNA interference targeting SOX11 to investigate the resulting changes in cellular processes and the underlying mechanisms in MCL cell lines. We found that patients with higher SOX11 expression have superior overall survival (OS) and progression-free survival (PFS) compared to those with lower SOX11 expression. SOX11 silencing promotes proliferation and inhibiting apoptosis of MCL cell through caspase-9-3-7-PARP signaling, and desensitizes MCL cell to bortezomib. Conclusively, our data suggest that SOX11 represents a useful prognostic marker in mantle cell lymphoma.

Background: B-cell chronic lymphoproliferative disorders (BCLPD) are a heterogeneous group of mature B-cell malignancies characterized by monoclonal proliferation in the bone marrow (BM) or peripheral blood (PB). The overlapped clinical features and the lack of individual diagnostic markers make diagnosis challenging, especially in patients who have difficulty to get adequate non-BM biopsy specimens or patients manifest as leukemic onset without nodes-involvement. It is necessary to explore novel methods to make precise diagnostic classification and prognostic prediction through simply PB/BM examination. Methods and results: A total of 1592 patients with newly diagnosed BCLPD were enrolled from January 1998 to December 2016, of which chronic lymphocytic leukemia (CLL) accounted for 39%, leukemic marginal zone lymphoma (l-MZL)occupied 13%, and Waldenstrom's macroglobulinemia/ lymphoplasmacytic lymphoma (LPL/WM), leukemic follicular lymphoma (l-FL) and mantle cell lymphoma (l-MCL) were 13%, 9% and 8%, respectively. There are 14% patients failed to fit into any of the categories and remaining unclassified which defined as BCLPDU. The median age at diagnosis was 58 years old. The male/female ratio of all BCLPD patients was 1.84:1. Male predominance was pronounced in WM/LPL, l-MCL and HCL with a M/F ratio of 2.5-2.7, while with balance gender in l-MZL and l-FL. FISH analyses were performed in 1234 patients. 17p and 11q deletion were most common in l-MCL (36% and 17%), while 13q deletion and trisomy 12 were most frequent in CLL (35% and 21%). Patients with 17p deletion showed significantly adverse survival in CLL and l-MCL (p A total of 665 patients had been successfully amplified the IGHV-IGHD-IGHJ rearrangements. Based on a cut-off value of 98% homology, the IGHV mutated proportion in patients with l-MCL was 48.6%, which was higher than other BCLPDs, following CLL 33.3% and l-MZL 28.6%, while most of WM and l-FL were unmutated. The most frequent rearrangement in l-MZL were IGHV1-2*01, which was seldom found in other subtypes. Also, DH2-2 and VH3-7 were mainly found in CLL and l-MCL respectively. Besides, we have identified several stereotyped IGH CDR3 which were specific for the certain BCLPD subtype. About 23% unclassified patients could acquire further diagnosis according to the special mutation status, VDJ rearrangements or stereotyped CDR3 sequencing. With a median follow-up of 50.3 months, 522 patients (38.0%) had disease progression or died. Patients with lMCL have a significant worse survival than other entities, with a 3-year overall survival (OS) rate of 58%. Following , patients with WM/LPL had relatively poorer prognosis with a 5-year OS rate of 68.2%, while the prognosis for l-MZL, l-FL and CLL were relatively favourable, with a 5-year OS of 80%.The OS of the B-CLPD had improved over time due to the emergence of immunotherapy and novel (3-year OS improved from 82.1% to 92.2%). The improvement of l-MCL and WM was obvious but not for CLL and l-MZL. Conclusion: Non-BM biopsy specimens are not available for part of BCLPD patients. Overlapped magnification of BM/PB brings on difficulties in differential diagnosis. Besides morphology and immunophenotype, comprehensive analysis of FISH, karyotype, IGHV, MYD88 or BRAF mutation and other molecular examination might contribute to further differential diagnosis and prognostic prediction. Moreover, it might provide advice for the initial time and strategy of treatment. Disclosures No relevant conflicts of interest to declare.

OBJECTIVE: To record and describe the current status of real world treatment and outcome of patients with high risk multiple myeloma by retrospective ,single-center, non-interventional, observational study METHODS: The data were collected from the CAMS&PUMC estimated real-world outcomes in high-risk multiple myeloma patients between January 2013 to June 2017. RESULTS: A total of 160 patients were enrolled. Of these patients, 1 case discontinued treatment with complications. 52 cases had not received standardized first-line treatment (9 cases of traffic inconvenience, 40 cases were unable to bear treatment costs, and 3 cases were refused consolidation / maintenance therapy after induction). In 107 patients received standardized treatment, the median age 56 years (31-77), 37 and 70 did and did not undergo stem cell transplantation (SCT) at any time during treatment, respectively. In these 37 patients, 4 patients received double auto stem cell transplantation(ASCT), 2 cases of allogeneic hematopoietic stem cell transplantation (allo-SCT), and the other 31 received single ASCT. Immunological subtype IgA was found in 21 cases (19.6%), IgG in 42 cases (39.3%), IgD in 18 cases (16.8%), and light chain in 23 cases (21.4%), non secretory 3 cases(2.8%).The proportion of IgD subtypes was significantly higher than that of MM patients in the same period (5.8%).Non parosteal extramedullary myeloma was found in 24 cases (22.4%), primary plasma cell leukemia in 12 cases (11.2%). 9.3%(10 cases) of the patients had received bortezomib-based therapy without thalidomide/lenalidomide, 8.4%(9 cases) had received thalidomide/lenalidomide-based therapy without bortezomib, and 82.2%(88 cases) had received bortezomib plus thalidomide/ lenalidomide-based therapy as frontline treatment, respectively. After a median follow-up of 22.31 months, the median disease-free survival (PFS) and overall survival (OS) were 28.52 and 48.10 months, respectively. Although there was no difference in OS between the treatment regimens, the SCT group had a better survival benefit than the non SCT group. The median PFS in the two group was 46.78 months vs 24.84 months (p=0.037), the SCT group had not reached the median OS, but the median OS in the non SCT group was 43.30 months, and the SCT group could obtain longer survival time than the non SCT group, p=0.012.However, the PFS of single, double and allo-SCT in the SCT group was 46.78, 19.32 and 54.51 months respectively (P single vs double = 0.770, P single vs allo = 0.547, P double vs allo = 0.317), and the three subgroups had not reached the median OS. CONCLUSION: The results of our study suggest that there are significant differences in the treatment regimen used in the real world for the therapy of high risk MM. About 1/3 of high-risk MM patients can not adhere to the standard treatment. Patients who received transplantation were only 34.6% of the patients in the standard treatment. Patients with high-risk MM who receive hematopoietic stem cell transplantation can obtain longer remission time and have significant survival benefits even in the novel drugs era. This diversity provides references for treatment recommendations. Moreover, our results provide real world data for clinical benefits. Disclosures No relevant conflicts of interest to declare.

[1] Soil surface temperature is a critical boundary condition for the simulation of soil temperature by environmental models. It is influenced by atmospheric and soil conditions and by vegetation cover. In sophisticated land surface models, it is simulated iteratively by solving surface energy budget equations. In ecosystem, permafrost, and hydrology models, the consideration of soil surface temperature is generally simple. In this study, we developed a methodology for representing the effects of vegetation cover and atmospheric factors on the estimation of soil surface temperature for alpine grassland ecosystems on the Qinghai-Tibetan Plateau. Our approach integrated measurements from meteorological stations with simulations from a sophisticated land surface model to develop an equation set for estimating soil surface temperature. After implementing this equation set into an ecosystem model and evaluating the performance of the ecosystem model in simulating soil temperature at different depths in the soil profile, we applied the model to simulate interactions among vegetation cover, freeze-thaw cycles, and soil erosion to demonstrate potential applications made possible through the implementation of the methodology developed in this study. Results showed that (1) to properly estimate daily soil surface temperature, algorithms should use air temperature, downward solar radiation, and vegetation cover as independent variables; (2) the equation set developed in this study performed better than soil surface temperature algorithms used in other models; and (3) the ecosystem model performed well in simulating soil temperature throughout the soil profile using the equation set developed in this study. Our application of the model indicates that the representation in ecosystem models of the effects of vegetation cover on the simulation of soil thermal dynamics has the potential to substantially improve our understanding of the vulnerability of alpine grassland ecosystems to changes in climate and grazing regimes.

Alpine grassland ecosystems on the Qinghai-Tibetan Plateau (QTP) are vulnerable to climate change and anthropogenic disturbances, which may have significant effects on the QTP’s carbon budgets. In this study, vegetation and soil characteristics were compared among alpine grassland ecosystems in a semi-arid basin on the northeast ridge of the QTP (1) among alpine swamp meadow, meadow, steppe meadow and steppe soils, which represent the direction of succession under climate-warming conditions, and (2) among alpine, degraded and tilled meadow soils to investigate the effects of human disturbance. The results showed that (1) if the alpine grassland ecosystems succeed in this direction, climate warming will cause a loss of carbon, and (2) tilling activity also results in carbon loss. Therefore, these results indicate that anthropogenic disturbance regimes that change more rapidly than climate may exert a more profound influence on carbon dynamics and balance. However, the plots that were set in the present study represented only part of the basin due to road accessibility. Relationships between leaf area index (biomass and soil carbon) and fractional vegetation cover × vegetation height from this study are fairly good, which can be applied at regional scale to estimate carbon pools. In combination with detailed information of grassland types, climate and human activities, the effects of climate change and disturbances can be estimated using remote sensing datasets.

Estimating the impact of mountain landscape on hydrology or water balance is essential for the sustainable development strategies of water resources. Specifically, understanding how the change of each landscape influences hydrological components will greatly improve the predictability of hydrological responses to mountain landscape changes and thus can help the government make sounder decisions. In the paper, we used the VIC (Variable Infiltration Capacity) model to conduct hydrological modeling in the upper Heihe River watershed, along with a frozen-soil module and a glacier melting module to improve the simulation. The improved model performed satisfactorily. We concluded that there are differences in the runoff generation of mountain landscape both in space and time. About 50% of the total runoff at the catchment outlet were generated in mid-mountain zone (2,900–4,000 m asl), and water was mainly consumed in low mountain region (1,700–2,900 m asl) because of the higher requirements of trees and grasses. The runoff coefficient was 0.37 in the upper Heihe River watershed. Barren landscape produced the largest runoff yields (52.46% of the total runoff) in the upper Heihe River watershed, followed by grassland (34.15%), shrub (9.02%), glacier (3.57%), and forest (0.49%). In order to simulate the impact of landscape change on hydrological components, three landscape change scenarios were designed in the study. Scenario 1, 2 and 3 were to convert all shady slope landscapes at 2,000–3,300 m, 2,000–3,700 m, and 2,000–4,000 m asl respectively to forest lands, with forest coverage rate increased to 12.4%, 28.5% and 42.0%, respectively. The runoff at the catchment outlet correspondingly declined by 3.5%, 13.1% and 24.2% under the three scenarios. The forest landscape is very important in water conservation as it reduced the flood peak and increased the base flow. The mountains as “water towers” play important roles in water resources generation and the impact of mountain landscapes on hydrology is significant.

There is considerable controversy about the role of Plateau pika (Ochotona curzoniae) in alpine grassland on the Qinghai-Tibetan Plateau (QTP). It is on one hand considered as a keystone species, on the other hand poisoned. Although significant amount of efforts have been made to study the effects of Plateau pika at a quadrat scale (~ m2), our knowledge about its distribution and effects at a larger scale is very limited. In this study, we investigated the direct effects, i.e. burying and grazing, of pika by upscaling field sampling at a quadrat scale to a plot scale (~ 1,000 m2) by aerial photographing. Altogether, 168 plots were set on 4 different types of alpine grassland in a semi-arid basin on the QTP. Results showed that: 1) the effects of burying by pika piles on the reduction of vegetation cover, biomass and soil carbon/nitrogen were less than 10 %, which was much smaller than the effects of bald patches; and 2) pika consumed 8–21 % of annual net primary production of grassland. We concluded that the direct burying and grazing effects of pika on alpine grassland were minor in this region. Quadcopter is an efficient and economic tool for long-term repeated monitoring over large regions for further understanding the role of pika.

To investigate the expression level of large tumor suppressor (LATS)1, LATS2 mRNA and its prognostic value in mantle cell lymphoma (MCL).A total of 36 B-NHL cases (including MCL 16 cases, chronic lymphoblastic leukemia (CLL) 11 cases, splenic marginal zone cell lymphoma (SMZL) 9 cases) and 8 healthy donors were enrolled in this study from January 2008 to April 2011 in our Lymphoma Clinic Center. The mRNA level of Yap (effector of Hippo pathway) and LATS1, LATS2 mRNA were detected by using real-time quantitative PCR. Log expression values of real-time quantitative PCR data were used in this analysis.The YAP mRNA expression level in MCL, CLL and SMZL patient were significantly higher than that in health donor (lg: 1.97±0.79, 1.83±0.54, 2.12±0.42 vs 1.21±1.56, all P0.05). The expression level of LATS1, LATS2 mRNA in MCL was significantly correlated with molecular cytogenetic aberrations, progression free survival (PFS) and overall survival (OS). The LATS1 expression level was statistically lower in the group of MCL with delection P53 than the group of MCL without delection P53 (lg: 0.75±0.27 vs 1.10±0.19, P=0.035). And the LATS1 expression level was statistically lower in the death group than the survival group (lg: 0.76±0.27 vs 1.15±0.17, P=0.026). The PFS and OS were significantly longer in the MCL patients with high level of LATS1 than that of other MCL patients ((70.4±32.7) vs (5.6±2.2) months, P=0.044; (123.8±22.0) vs (7.7±2.2) months, P=0.017).Hippo pathway is dysfunctional in B-NHL, especially in MCL.The reduced expression of LATS1, LATS2 in MCL patients is associated with progressive disease, and might be an important prognostic factor in MCL.

For the sustainable utilization of rivers in the mid and downstream regions, it is essential that land surface hydrological processes are quantified in high cold mountains regions, as it is in these regions where most of the larger rivers in China acquire their headstreams. Glaciers are one of the most important water resources of north-west China. However, they are seldom explicitly considered within hydrological models, and climate-change effects on glaciers, permafrost and snow cover will have increasingly important consequences for runoff. In this study, an energy-balance ice-melt model was integrated within the Variable Infiltration Capacity (VIC) macroscale hydrological model. The extended VIC model was applied to simulate the hydrological processes in the Aksu River basin, a large mountainous and glaciered catchment in north-west China. The runoff components and their response to climate change were analyzed based on the simulated and observed data. The model showed an acceptable performance, and achieved an efficiency coefficient R2 ≈ 0.8 for the complete simulation period. The results indicate that a large proportion of the catchment runoff is derived from ice meltwater and snowmelt water. In addition, over the last 38 years, rising temperature caused an extension in the snow/ice melting period and a reduction in the seasonality signal of runoff. Due to teh increased precipitation runoff, the Aksu catchment annual runoff had a positive trend, increasing by about 40.00 × 106 m3 per year, or 25.7 %.

Against the background of global climate warming, the relationship between plant communities in high-cold ecosystems and environmental gradients has attracted much attention. We investigated the relationship between the distribution of plant communities and environmental factors in a semi-arid region of the Qinghai-Tibet Plateau. We analyzed the effects of environmental factors on the distribution of plant communities using two-way indicator species analysis and canonical correspondence analysis. The most important factor explaining the distribution of plant communities was the depth of the active layer of permafrost (denoted as PF), followed by soil water content at 40-cm soil depth. There was a strong correlation between these two factors. With changes in the PF, the dominant species in plant communities showed an obvious transition. The indices of species richness and species diversity decreased markedly with increasing PF, whereas biomass and vegetation coverage showed weaker responses to changes in the PF. The distribution structure for plant communities in this area mainly results from changes in the PF. Furthermore, the PF has remarkable and important effects on the characteristics of the plant community.

Recently, a gene named TOSO was identified as being overexpressed and associated with the anti-apoptotic characteristic of chronic lymphocytic leukemia (CLL). However, the association of TOSO expression with clinical features of CLL has not been fully described, especially in Chinese patients. TOSO expression was detected by quantitative RT-PCR in CD19+ sorted cells in a cohort of 81 untreated patients with CLL. The results showed that the expression of TOSO in CLL was significantly higher than that in healthy controls (p = 0.027) and other B-cell lymphoproliferative diseases (p = 0.033). The expression level of TOSO was significantly correlated with Binet staging, IGVH mutation status, age, and time to treatment in CLL. A negative correlation was observed between age and TOSO expression (Spearman's, p = 0.025). No correlation was observed between the expression of TOSO and CD38 or ZAP-70. Cox regression analysis indicated that high expression of TOSO (more than 8.4) was an independent indicator for shorter treatment-free survival in CLL. We conclude that TOSO is specifically overexpressed and associated with progressive disease, and might be an important prognostic factor in CLL.

Aboveground biomass is a key indicator of a grassland ecosystem. Accurate estimation from remote sensing is important for understanding the response of grasslands to climate change and disturbance at a large scale. However, the precision of remote sensing inversion is limited by a lack in the ground truth and scale mismatch with satellite data. In this study, we first tried to establish a grassland aboveground biomass estimation model at 1 m2 quadrat scale by conducting synchronous experiments of unmanned aerial vehicle (UAV) and field measurement in three different grassland ecosystems. Two flight modes (the new QUADRAT mode and the commonly used MOSAIC mode) were used to generate point clouds for further processing. Canopy height metrics of each quadrat were then calculated using the canopy height model (CHM). Correlation analysis showed that the mean of the canopy height model (CHM_mean) had a significant linear relationship with field height (R2 = 0.90, root mean square error (RMSE) = 19.79 cm, rRMSE = 16.5%, p < 0.001) and a logarithmic relationship with field aboveground biomass (R2 = 0.89, RMSE = 91.48 g/m2, rRMSE = 16.11%, p < 0.001). We concluded our study by conducting a preliminary application of estimation of the aboveground biomass at a plot scale by jointly using UAV and the constructed 1 m2 quadrat scale estimation model. Our results confirmed that UAV could be used to collect large quantities of ground truths and bridge the scales between ground truth and remote sensing pixels, which were helpful in improving the accuracy of remote sensing inversion of grassland aboveground biomass.

Mantle cell lymphoma (MCL) is an aggressive lymphoid malignancy characterized by cytogenetic aberration of t(11;14), although it is not the prerequisite. Until now, the pathogenesis of MCL has not been fully interpreted. Our current study showed that microRNA (miR)-223 was downregulated in purified CD19+ lymphocytes from MCL patients (n = 21) compared with that of healthy donors (n = 20). In addition, patients with a high-risk Mantle Cell Lymphoma International Prognostic Index (MIPI) score, elevated lactate dehydrogenase, and Eastern Cooperative Oncology Group performance status >2 were more likely to have much lower miR-223 expression. Furthermore, low miR-223 expression predicted inferior overall survival regardless of treatment in our cohort of 21. To explore the role of miR-223 in MCL, we constructed an ectopic miR-223 MCL cell line and revealed that miR-223 inhibited cell proliferation and promoted G0/G1 accumulation and cell apoptosis. A database search showed that SOX11, a crucial transcription factor in MCL, is the putative target of miR-223. In support of this, we observed a much lower level of SOX11 protein in miR-223-overexpressing cells than in parental cells. Further, the luciferase reporter assay confirmed that miR-223 at the posttranscriptional level suppressed the wild-type 3′-untranslated region of SOX11 but not the mutated one. Finally, miR-223 was found to be negatively correlated with the mRNA level of SOX11 in clinical samples. Our work demonstrates for the first time that miR-223 is repressed and correlated with high-risk clinical features in MCL, which provides a potential molecule to target to optimize MCL management.

Vegetation phenology in temperate grasslands is highly sensitive to climate change. However, it is still unclear how the timing of vegetation phenology events (especially for autumn phenology) is altered in response to climate change across different grassland types. In this study, we investigated variations of the growing season start (SOS) and end (EOS), derived from Moderate Resolution Imaging Spectroradiometer (MODIS) data (2000–2016), for meadow steppe, typical steppe, and desert steppe in the Inner Mongolian grassland of Northern China. Using gridded climate data (2000–2015), we further analyzed correlations between SOS/EOS and pre-season average air temperature and total precipitation (defined as 90-day period prior to SOS/EOS, i.e., pre-SOS/EOS) in each grid. The results showed that both SOS and EOS occurred later in desert steppe (day of year (doy) 114 and 312) than in meadow steppe (doy 109 and 305) and typical steppe (doy 111 and 307); namely, desert steppe has a relatively late growing season than meadow steppe and typical steppe. For all three grasslands, SOS was mainly controlled by pre-SOS precipitation with the sensitivity being largest in desert steppe. EOS was closely connected with pre-EOS air temperature in meadow steppe and typical steppe, but more closely related to pre-EOS precipitation in desert steppe. During 2000–2015, SOS in typical steppe and desert steppe has significantly advanced by 2.2 days and 10.6 days due to a significant increase of pre-SOS precipitation. In addition, EOS of desert steppe has also significantly advanced by 6.8 days, likely as a result from the combined effects of elevated preseason temperature and precipitation. Our study highlights the diverse responses in the timing of spring and autumn phenology to preceding temperature and precipitation in different grassland types. Results from this study can help to guide grazing systems and to develop policy frameworks for grasslands protection.

Assessing potential future changes in arctic and boreal plant species productivity, ecosystem composition, and canopy complexity is essential for understanding environmental responses under expected altered climate forcing. We examined potential changes in the dominant plant functional types (PFTs) of the sedge tundra, shrub tundra, and boreal forest ecosystems in ecotonal northern Alaska, USA, for the years 2003-2100. We compared energy feedbacks associated with increases in biomass to energy feedbacks associated with changes in the duration of the snow-free season. We based our simulations on nine input climate scenarios from the Intergovernmental Panel on Climate Change (IPCC) and a new version of the Terrestrial Ecosystem Model (TEM) that incorporates biogeochemistry, vegetation dynamics for multiple PFTs (e.g., trees, shrubs, grasses, sedges, mosses), multiple vegetation pools, and soil thermal regimes. We found mean increases in net primary productivity (NPP) in all PFTs. Most notably, birch (Betula spp.) in the shrub tundra showed increases that were at least three times larger than any other PFT. Increases in NPP were positively related to increases in growing-season length in the sedge tundra, but PFTs in boreal forest and shrub tundra showed a significant response to changes in light availability as well as growing-season length. Significant NPP responses to changes in vegetation uptake of nitrogen by PFT indicated that some PFTs were better competitors for nitrogen than other PFTs. While NPP increased, heterotrophic respiration (RH) also increased, resulting in decreases or no change in net ecosystem carbon uptake. Greater aboveground biomass from increased NPP produced a decrease in summer albedo, greater regional heat absorption (0.34 +/- 0.23 W x m(-2) x 10 yr(-1) [mean +/- SD]), and a positive feedback to climate warming. However, the decrease in albedo due to a shorter snow season (-5.1 +/- 1.6 d/10 yr) resulted in much greater regional heat absorption (3.3 +/- 1.24 W x m(-2) x 10 yr(-1)) than that associated with increases in vegetation. Through quantifying feedbacks associated with changes in vegetation and those associated with changes in the snow season length, we can reach a more integrated understanding of the manner in which climate change may impact interactions between high-latitude ecosystems and the climate system.

To investigate the efficacy and safety of Rituximab combined with second line regimen for treatment of relapsed and refractory Hodgkin lymphoma.Seven patients with relapsed and refractory Hodgkin lymphoma were treated with Rituximab combined with second line regimen. Among them, two patients were treated with R-GDP (E) [rituximab, gemcitabine, cisplatin, dexamethasone (etoposide)] regimen, another two patients with R-IGVP (rituximab, ifosfamide, gemcitabine, vinorelbine, prednisone)regimen, and the left three patients with R-BEACOPP (rituximab, bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone)regimen. The efficacy and safety were evaluated during and after chemotherapy.There're three male and four female patients, whose median age was 21 years (range 12-36 years) old. One patient was diagnosed as nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL), and the other six patients as classical HL (four nodular sclerosis HL, one lymphocyte-rich classical HL and one hmixed cellularity HL). The median cycles of salvage therapy were 4(1-4), and the median follow-up was 29 months (24-58 months). Among these 7 patients, the complete remission was observed in 4 patients, stable disease in 2 patients, but one patient died during salvage therapy. The two-year survival rates were 85.7% and the major toxic effects were bone marrow suppression.These results indicate that the Rituximab combined with second line regimen is an effective therapy for relapsed and refractory Hodgkin lymphoma.

To investigate the influence of renal function on the level of β₂-microglobulin (β₂-MG) as prognostic factor in newly diagnosed multiple myeloma (MM) patients, and to analyze the overall survival (OS) in different level of β₂-MG with relatively normal or abnormal renal function in MM patients.According to the level of β₂-MG, 666 newly diagnosed MM patients were divided into three groups as β₂-MG3.5, 3.5-5.5, ≥5.5 mg/L. According to the level of serum creatinine, these patients were divided into two groups:serum creatinine177 μmol/L as relatively normal group, serum creatinine ≥177 μmol/L as abnormal group.Among 666 patients, there were 416 male and 250 female, the median age was 58 (25-86) years old. Comparison of OS among β₂-MG3.5, 3.5-5.5, ≥5.5 mg/L groups indicated that the median OS of the three groups were 85.75 (95% CI 70.99-100.50), 47.25 (95% CI 40.98-53.53) and 35.05 (95% CI 30.75-39.35) months, respectively (P0.01). Comparison of OS between serum creatinine177 and ≥177 mmol/L groups, the median OS of the two groups were 64.67 (95% CI 56.57-72.77) and 32.74 (95% CI 27.74-37.73) months, respectively (P0.01). In β₂-MG≥5.5 mg/L, the median OS of relatively normal and abnormal groups were 37.25 (95% CI 31.45-43.06) and 32.55 (95% CI 26.26-38.83) months, respectively (P=0.142).High level of β₂-MG and renal function correlated with shorter survival of MM patients. Higher level of β₂-MG with abnormal renal function can't change the prognostic value of β₂-microglobulin on MM.

The incidence and prognostic role of MYC and BCL2 rearrangements in mature B-cell lymphomas have been extensively studied, except the infrequent mantle cell lymphoma (MCL). Here, we analyzed the MYC and BCL2 abnormalities and other cytogenetic aberrations by fluorescence in situ hybridization (FISH) in 50 MCL patients with bone marrow involvement. Eighteen patients (36.0%) had MYC gains and/or amplifications, and twelve patients (24.0%) had BCL2 gains and/or amplifications. Among the 18 patients with MYC abnormality, four had simultaneous MYC translocations, but no BCL2 translocation was detected among patients with BCL2 abnormality. Only two patients (4.0%) had both MYC and BCL2 abnormalities. The patients with a MYC abnormality had a significantly higher tumor burden, a higher percentage of medium/high risk MIPI group and genomic instability compared to those without this abnormality. However, no significant difference was observed between patients with or without a BCL2 abnormality in terms of clinical and cytogenetic factors. Patients with a MYC abnormality had poorer progress-free survival (PFS) (9.0 vs. 48.0 months, p = .000) and overall survival (OS) (12.0 vs. 94.5 months, p = .000), but the presence of a BCL2 abnormality did not significantly influence either PFS or OS. In multivariate analysis, the MYC abnormality was the independent adverse factor for both PFS and OS, and intensive chemotherapy did not improve the outcome of these patients. Thus, the presence of a MYC but not BCL2 abnormality predicted the poor survival of MCL patients, and a new treatment strategy should be developed for these patients.

Background Rituximab has been confirmed to improve the survival of patients with B cell indolent non-Hodgkin lymphomas (B-iNHLs) in Western world as previously reported, however, it is rarely reported in Chinese cohort. This study is to investigate the efficacy and safety of rituximab-based chemoimmunotherapy and select subpopulations most sensitive to the regimen in Chinese B-iNHL patients. Methods 334 B-iNHL patients from our center were retrospectively assessed. Results Patients received R-based chemoimmunotherapy showed significantly higher rates of overall response (OR) (93.0 % vs. 53.4 %, P

To report the diagnosis, differential diagnosis and treatment of three rare cases of primary bone marrow diffuse large B cell lymphoma (DLBCL), and to improve the recognition of this disease.The clinical characteristics, therapeutic course and the outcome of these patients were reviewed. Meanwhile, a series of examinations including morphology, flow cytometry, immunohistochemistry and molecular biology of bone marrow samples were also performed.These three patients who were old at the onset age (56, 60 and 70 years old), primarily revealed as abnormal blood count and experienced an aggressive course of disease. Physical and imaging examination showed no enlargement of lymph node, liver and spleen, the patients were finally diagnosed as primary bone marrow DLBCL by bone marrow morphology, flow cytometry and immunohistochemistry analyses. They were treated with rituximab combined chemotherapy, which achieved a complete response, but still need longer follow-up to further evaluate their survival.Primary bone marrow DLBCL was encountered rarely in clinical practice, and this is the first report in China. Further investigation of pathogenesis and therapeutic strategies of this rare disease was warranted.

Waldenström macroglobulinemia (WM) is an uncommon lymphoid malignancy. The characteristics and prognosis of WM have never been systematically studied in the East.We analyzed the clinical characteristics and the prognostic factors of 90 Chinese WM patients, and compared them with the Western reports.The 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, age62 years, thrombocytopenia, leucopenia, cytopenias ≥ 2, and high risk on the international prognostic scoring system for WM were the adverse risk factors, but only age62 years and ≥ 2 cytopenias were the independent prognostic factors in the multivariate analysis. Using age62 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% (P0.001).Distinct characteristics exist in WM in China compared to the West and we describe a new simple prognostic model for newly diagnosed WM patients.

The common features shared by primary plasma cell leukemia (pPCL) and multiple myeloma (MM) with circulating plasma cells (CPCs) are peripheral blood invasion and expansion of plasma cells independent of the protective bone marrow (BM) microenvironment niche. However, few studies have addressed the relationship between pPCL and MM with CPCs. Here, we quantitated the number CPCs by conventional morphology in 767 patients with newly diagnosed MM; their clinic features were compared with those of 33 pPCL cases. When the presence of CPCs was defined as more than 2 % plasma cells per 100 nucleated cells on Wright–Giemsa stained peripheral blood smears, the incidence of MM with CPCs was 14.1 % in newly diagnosed MM. Patients with CPCs shared many clinical features with pPCL, especially clinical parameters related to tumor burden. However, no commonalities were found in immunophenotyping and cytogenetics. The prognosis of pPCL was poor, with a median progression free survival (PFS) of 12 months and an overall survival (OS) of 15 months. MM patients with CPCs had a clearly inferior PFS and OS as compared with the control cohort. Most interestingly, although the CPCs were not high enough to meet the diagnostic criteria for pPCL, the survival of MM patients with CPCs was comparable with that of pPCL, with a median PFS of 17 months and an OS of 25 months.

To explore the immunophenotypic characteristics of CD5⁺ B cell lymphoproliferative disorders (B-LPD) of Chinese patients.Immunophenotyping 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.(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 (P0.01). 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 (P0.001). The difference of CD11c expression was also statistically significant between MCL and other B-LPD (P0.01). In comparison of MCL with other B-LPD, there was a significant difference in the expression of CD11c (P0.01). 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.The 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.

To explore the clinical and laboratory characteristics for large granular lymphocytic leukemia (LGL).A total of 35 LGL patients were retrospectively analyzed from March 2004 to May 2013 at our department.Their median age of diagnosis was 51 years. The anemia-related symptoms included splenomegaly (n = 11, 31.4%). And one patient (2.8%) with a history of rheumatoid arthritis. Anemia was the most frequent hematological abnormality (n = 27, 77.1%). The range of LGL count in peripheral blood was (0.82-23.7) ×10(9)/L. Among them, 19 patients (54.2%) showed the CD3(+)CD57(+) CD56(-)indolent LGL phenotype. Two patients showed complex karyotype. T cell receptor β chain variable region (TCRVβ) analysis was positive in 8 patients. The median overall survival of aggressive LGL patients was significant shorter than that of indolent patient(16 months vs not reached, P = 0.000). Univariate analysis showed the median overall survival of patients with B symptom was significant shorter than that without B symptom (19 vs 45 months, P = 0.039); the median overall survival of patients with thrombocytopenia was significant shorter than that with platelet normal (16 vs 42 months, P = 0.000). Multivariate analysis showed B symptom (P = 0.736) and thrombocytopenia (P = 0.977) at diagnosis were not prognostic factors.Chinese LGL patient with rheumatoid arthritis is infrequent compared with foreign reports. TCRVβ analysis is important for its diagnosis. The overall survival of aggressive LGL patients is significantly inferior to indolent patients, and need earlier intensive therapy in order to achieve longer survival.

Background: Splenic marginal zone lymphoma (SMZL) is a rare indolent B-cell neoplasm, which often involved with spleen, bone marrow (BM), and sometimes involved with the peripheral blood. However, the clinical characteristics of Chinese SMZL patients remain elusive.. This present study is undertaken to systematically analyze the clinical and biological characteristics of SMZL in Chinese patients, and draw out an appropriate hierarchical prognostic model of SMZL in the rituximab era. Method: A total of 172 patients with newly diagnosed SMZL in Institute of hematology and blood disease hospital were retrospectively analyzed. Clinical characteristics, including flow cytometry analysis of tumor cells, immunohistochemistry, cytogenetics and molecular detection data were collected and IgHV mutation status, fluorescence in situ hybridization (FISH) data were carried out on patients with available samples. Result: The median age at diagnosis of 172 patients with SMZL was 57 years (range 25-81) and male having little prominence (52.3%). Using a homology cut-off value of 98% to the nearest germline gene, we observed mutated IGHV in 29 (74.4%) and unmutated IGHV in 10 (25.6%) of the 39 SMZL patients. The most frequently used fragments of IGHV gene were IGHV1-2 (25.6%), IGHV4-34 (15.4%), IGHV2-27 and IGHV3-30 (10.3% and 7.8% respectively). The 49.0% patients had HBV infection currently or before SMZL diagnosis, and 14.6% with active HBV infection. Chromosomal aberration was noted in 21.2% patients and 14.4% patients have complex karyotype (more than three aberrations). The FISH detection indicated that the cytogenetic aberrant of 13q- (Rb1/ D13S25), trisomy 12, 17p-(TP53) and t(14q32) was 9.8% (8/82), 9.6% (8/83), 4.7% (6/126) and 20.4% (19/93), respectively. Among those patients, 64 patients (41.6%) received rituximab-based immunochemotherapy as the first line treatment and other 37 patients (24.0%) with conventional chemotherapy treatment alone. With a median follow-up of 50.5 months (range, 6-214 months), the estimated 5-year failure-free survival (FFS) and overall survival (OS) rates were 74.6% and 80.8%, respectively. The 5-year FFS for patients with rituximab-based treatment was significantly prolonged than those rituximab-free treatment patients (89.9% vs 60.9%, P = 0.005). Based on the univariate analysis, the significant predictive parameters for shorter OS included hemoglobin level Using above 3 independent variables, we identified a novel hierarchical prognostic model with three risk groups: low-risk group (39.2%) with no adverse factors, intermediate-risk group (38.6%) with one factor and high-risk group (22.1%) with 2 or 3 factors. The 5-year OS was 96.7%, 78% and 53.3%, respectively (p=0.000). The 5-year FFS was 95%, 67.5% and 39.4%, respectively (p=0.000). The novel hierarchical prognostic model showed an advanced c-index than the other risk models, including IPI, FLIPI and the tradition SMZL score significantly. Conclusion: Chinese patients with SMZL have distinct clinical characteristics. The novel prognostic index system composed of hemoglobin, HBVs-Ag and complex karyotype aberrant could effectively stratify the outcomes of patients with SMZL and appears to be a promising risk model for Chinese SMZL patients in the rituximab era. Disclosures No relevant conflicts of interest to declare.

Objective: To evaluate the efficacy and long-term outcome of the total treatment of induction therapy, ASCT and consolidation and maintenance therapy. Methods: A retrospective analysis was made on in multiple myeloma patients in our center between April 1, 2003 and February 1, 2016. The 157 patietns received autologous hematopoietic stem cell transplantation and review the autologous transplantation of long-term follow-up results. Analysis of the effect of transplantation efficacy, the impact on survival remission of different transplantation depth, transplantation in first line or not, salvage transplantation, prognosis of different staging system and other factors. Results: The baseline characteristics of the patients were shown in table 1. Overall patient ASCT before total effective rate (ORR) was 93.6%, in which the complete remission (CR) ratio was 33.1%. After ASCT, the best treatment response rate of PR was 80.3%, and the rate of CR was 58.6%. 91.69 months of median follow-up, patients with an overall survival (OS) and progression free survival (PFS) respectively 91.69 and 50.76 months; in 2005 before the median OS and PFS 39.0m and 23.0m. In 2005 after respectively and 56.41m 120.90m, P = 0.000. The median OS and PFS in the first line transplantation group and salvage transplantation group were vs 54.21m 39.0m and vs 7.09m 119.0m (P value was 0). 136 cases of patients with R-ISS stage, I, II, III of the patients with the median survival time were 120.90m (n=46), 86.43m (n=69), 35.65m (n=21), there were significant differences between groups, p=0.000. Each period of PFS were 72.11m, 51.84m, 28.09m, I and II, III,, p=0.001 and p=0.03, while there was no significant difference between II and III, p=0.122. The received autologous transplantation as first-line and salvage treatment of patients with subgroup survival analysis, median OS of the R-ISS stage III patients and different 15.84m 35.65m, P = 0.031; two groups of patients the median PFS (phase I: 91.69m vs18.92m; II: vs 16.69m 53.42m; phase III: vs 5.91m 28.52m) have difference (P = 0.000). In the first-line transplantation group, transplantation is more than or equal to PR and did not get effective PR group between OS were significantly different; before transplantation achieved CR, PR but did not obtain Cr and did not get effective PR group between PFS were significantly different; after transplantation and achieved CR CR did not get the patients had a median PFS were 65.57m 48.13m, P = 0.039 and median OS no difference. Accept any kind of noval agent- based chemotherapy were significantly longer OS and PFS than traditional chemotherapy (P = 0.001, P = 0.004) .There was no obvious difference on median OS between based regimen (bortezomib group median OS: NR; thalidomide group:120.90m); PFS in thalidomide group (median PFS : NR vs 54.21m) significantly prolonged (P = 0.010). By comparing the baseline characteristics of the two groups, it was found that the PFS was significantly shorter in the bortezomib group with an extra medullary lesion. Multivariate analysis showed that only R-ISS and the depth of remission before transplantation had effect on OS (p=0.003) and PFS (p=0.036) respectively. Conclusion: The total treatment of novel agent-based chemotherapy and ASCT for transplantation-eligible multiple myeloma patients is effective, further improve the remission rate and remission depth, prolong PFS and OS, the overall median survival up to 120.9m. First line transplantation can significantly prolong the OS and PFS compared with salvage transplantation. R-ISS and pre-transplant remission depth are prognostic factors influencing survival of patients. The total treatment to thalidomide based without extramedullary perhaps makes patients get long-term survival. Disclosures No relevant conflicts of interest to declare.