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Thrombopoietin (TPO) can activate hematopoietic cell proliferation by its receptor c-MPL mediated downstream pathways and induce the generation of megakaryocyte. In recent years, domestic and foreign researches have confirmed that TPO/ c-MPL pathway also plays an important role in the self-renewal and quiescence of leukemia stem cell, and its expression in acute myeloid leukemia (AML) also indicates the chemotherapy resistance and poor prognosis. In this article, the research progress of the roles of TPO/c-MPL pathway in chemotherapy resistance, prognosis of AML patients, and the application of TPO/ c-MPL receptor agonists in AML were summarized briefly.

Objective: To investigate the effects of recombinant human thrombopoietin (rhTPO) to proliferation and apoptosis of acute myeloid leukemia (AML) cell lines., Methods: After the treatment of different concentrations of rhTPO (0, 50, 100 ng/ml) for different time (24,48,72 h)，the cell proliferation rates of the AML cell lines (Kasumi-1, Skno-1, HEL, HL-60, THP-1) were determined by CCK-8 method. Apoptosis rate of each cell line cocultured with rhTPO was detected by Annexin V/PI method. The relative expression of TPO receptor c-MPL (myeloproliferative clonal antibody) mRNA in AML cell lines was detected by Q-PCR. The expression of c-MPL protein in each cell line was detected by Western blot. The expression of c-MPL antigen in HL-60 cells treated by different concentrations of rhTPO was detected by Flow cytometry., Results: RhTPO showed no promotion to the proliferation of Kasumi-1, Skno-1, HEL, HL-60, THP-1 cell lines，however，it showed inhibitory effect to cell proliferation (72 h 0 ng/ml vs 100 ng/ml, P= 0.029) and pro-apoptotic (48 h 0 ng/ml vs 50 ng/ml, P=0.0143) in HL-60 cells. In Kasumi-1, Skno-1, HEL and THP-1 cells, there showed no statistically significant differences in apoptosis rate among each groups treated by different concentrations of rhTPO. Each AML cell line showed different levels of c-MPL gene and c-MPL protein expression, but HEL cells showed the highest expression in both of them. After HL-60 cells were treated by different concentrations of rhTPO for 48 hours, there showed no statistical difference in c-MPL antigen expression among each groups., Conclusion: RhTPO can not promote the proliferation of Kasumi-1, Skno-1, HEL, HL-60 and THP-1 leukemia cell lines. On the contrary, rhTPO can inhibit HL-60 cell proliferation and promote its apoptosis, and this effect is not related to c-MPL gene expression or protein expression.

Objective: To observe the clinical and laboratory characteristics of adult Langerhans cell histiocytosis(LCH) patients and to analyze the influencing factors of its prognosis., Methods: The clinical and laboratory charac-teristics of 38 adult LCH patients treated in our hospital from January 2010 to August 2019 were retrospective analyzed, and the clinical prognosis of the patients was analyzed., Results: The median age of 38 patients was 41 (21-65) years old, and the ratio of male and female was about 2∶1. Among 38 patients, 44.7% (17/38) were involved in multiple systems, and 31.6% (12/38) were involved in high-risk organs (including liver, lung, hematopoietic system or spleen). The bone involvement was the most common (21/38, 55.3%), and the most common clinical symptom was pain (19/38, 50.0%). The result of laboratory showed that anemia (4/38，10.5%), thrombocytopenia (1/38，2.6%), neutropenia (2/38，5.3%), lymphopenia (6/38，15.8%), monocytosis (11/38，28.9%), C-reactive protein increasing (6/21，28.6%), erythrocyte sedimentation rate increasing (10/18, 55.3%), and ferritin protein increasing (9/17, 55.3%). The median follow-up time was 53 months, and a total of 5 patients were died. The 10-year overall survival rate of patients with single-system involvement was 100%, which was significantly higher than that of patients with multiple-system involvement (70.1%) (P=0.0078). The prognosis of patients without risk-organ involvement was better than that of patients with risk-organ involvement (10-year overall survival rate: 100% vs 60.6%) (P=0.0007). Further analysis showed that in addition to multiple-system involvement and risk-organ involvement, the increase of peripheral blood monocyte cells and the increase of ferritin protein were also associated with poorer prognosis of the patients., Conclusion: The multiple system involve-ment and risk-organ involvement, the increasing of monocyte cells and the increasing of ferritin protein were the independent risk factors of adult LCH patients.

Objective: To explore the appropriate procedures for preparing extracellular microvesicles (MV) derived from human mesenchymal stem cells (MSC)., Methods: Human MSCs from umbilical cords were cultured in a serum-free medium and maintained in a basal medium for 72 hours after the cell confluence reached to 80%. The supernatants of cultured cells were collected and MVs were enriched. MVs were identified by flow cytometry and electron microscopy. The total protein amount in MVs was used as a parameter for the content of MVs. The supernatants were adjusted to different pH values, and the output of MVs was detected. The supernatants were also collected for enriching the MV and detecting the protein content of MV after the cells were maintained in the basic medium for different time., Results: Flow cytometric analysis showed that the MVs expressed CD9, CD63 and CD81, morphologically presented round under an electron microscope and the diameter of MV was around 100 nm. After enrichment of MV, the protein content of MVs in the supernatants was 416.8±128.1, 255.4±77.9 and 142.8±46.4 μg per 10 7 MSC，respectively at pH of supernatant 3, 7 and 9 (P＜0.05). The protein content of the supernatants per 10 7 MSC was 173.6±44.5, 262.4±49.6 and 364.2±37.8 μg respectively after starvation culture for 48, 72 and 96 hrs (P＜0.05)., Conclusion: MVs can be readily collected after MSCs were starved for 96 hours, and the pH of the supernatants is adjusted at 3.0.

Objective: To investigate the prognosis prediction value of PET/CT in DLBCL patients treated with CAR-T therapy., Methods: The effects of PET/CT were retrospectively explored on 13 R/R DLBCL patients who were treated with CAR-T therapy. Parameters reflecting tumor metabolic burden, such as metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were measured before and after CAR-T treatment., Results: Patients with larger baseline MTV or longer sum of longest diameters showed shorter overall survival (OS) time than those with low tumor burden. Patients achieved complete remission (CR), partial remission (PR) and minor remission (MR) determined by response evaluation criteria in lymphoma (RECIL) in 12 weeks showed progression-free survival and OS time superior to those of patients with no remission. In addition, it was found that 2 patients with residual masses classified as PR by contrast-enhanced CT of patients were evaluated as complete metabolic response by PET/CT imaging., Conclusion: PET/CT shows a great value in the evaluation of prognosis and response in CAR-T-treated R/R DLBCL patients.

Objective: To analyze the incidence, clinical characteristics, treatment efficacy and prognosis of lymphoma patients with mediastinal masses., Methods: The clinical data of 56 lymphoma patients with mediastinal masses treated in our hospital from February 2007 to January 2018 were collected, and the clinical characteristics, typing, staging, treatment efficacy as well as prognosis analyzed retrospectively., Results: Among the 56 patients, male and female were 25 (45%) cases and 31(55%) cases, respectively. The median age was 31 (17-72) years old, out of them 48 (86%) patients aged below 40 years old. According to pathological classification, 9 (16.1%) cases were diffuse large B cell lymphoma, not otherwise specified (DLBCL-NOS), 26(46.4%) cases were primary mediastinal large B cell lymphoma (PMBCL), 17 (30.4%) cases were classical Hodgkin's lymphoma (cHL), and 4 (7.1%) cases were primary mediastinal grey zone lymphoma (MGZL). All the patients were treated with chemotherapy or immuno-chemotherapy.The median follow-up time was 54.5(11-149) months. In cHL group, 10 cases received involved field radiotherapy (IFRT), 10 (58.8%) cases achieved complete remission (CR), 2 (11.8%) cases achieved partial remisson (PR), and 5 (29.4%) patients experienced progressive disease (PD) , 6 patients with relapsed/refractory disease received autologous hematopoietic stem cell transplantation (auto-HSCT), the 1, 2, and 5 year overall survival (OS) rates of cHL group were 94.1%, 88.2%, and 67.2%, respectively. In MGZL group, 3 cases combined with IFRT, 1 case with auto-HSCT, 2 (50%) cases achieved CR, 2 (50%) cases experienced PD, the 1, 2, 5 year OS rates of MGZL group were 66.7%, 66.7%, and 33.3%, respectively. In PMBCL group, 8 cases combined with IFRT, 7 cases with auto-HSCT, 22 (84.0%) cases achieved CR, 2 (8.0%) cases achieved PR, 1 (4.0%) case was stable disease (SD) and 1 (4.0%) case experienced PD, the 1, 2 year OS rates of PMBCL group were both 100%, and 5 year OS rate was 95.7%. In DLBCL-NOS group, 3 cases combined with IFRT, 2 cases with auto-HSCT, 4 (44.5%) cases achieved CR, 2 (22.2%) cases achieved PR, 1 (11.1%) case was stable disease (SD) and 2 (22.2%) cases experienced PD, the 1 year OS rate of DLBCL-NOS cohort was 100%, 2, and 5 year OS rates were both 77.8%. There was a significant difference of OS rate among these 4 group (P＜0.05). In intra-group comparison, OS rate in PMBCL group were significantly longer than both MGZL group (P＜0.01) and cHL group(P＜0.05), and showed no significant difference from DLBCL-NOS group (P＞0.05)., Conclusion: Mediastinal masses are characterized by unique clinical features due to their unique anatomical location. Several B cell originated lymphomas including cHL,MGZL,PMBCL and DLBCL-NOS, manifested primary or secondary mediastina involvement, tend to occur in young adults and have similar clinical features. However, their therapeutic response was significantly different. The prognosis of PMBCL is prior to MGZL and cHL.

Objective: To investigate the clinical manifestation, immunophenotypes and prognostic factors of patients with primary tonsil afftive large B cell lymphoma ( PT-DLBCL )., Methods: The clinical data including clinical characterstics, typing, staging, treatment efficacy and prognostic factors of PT-DLBCL patients were collected and analyzed restrospectively., Results: Out of 36 cases with the detinite cell origin, 24 cases (66.7%) were detecmined as the type of germinal center B-cell (GCB) and 12 cases (33.3%) was non-germinal center B-cell (non-GCB), 15 (40.5%) out of 37 cases were in Ann Arbor stage Ⅰ, and 22 (59.5%) in stage Ⅱ. With the median follow-up of 44 (10-101) months, 2 cases (5.4%) failed to be followed-up, after treatment for 6 (3-8) cycles 35 patients were evaluated. Among them 26 cases (74.3%) reached to complete remission (CR), 8 cases (22.9%) to partial remission ( PR ), and 1 (2.8%) to stable disease (SD). Both the 3 years and 5 years progression-free survival ( PFS ) were 82.5%, and both 3 and 5 years overall survival (OS) were 95.5%. 5 cases (13.5%) received radiotherapy. The patients aged＞60 ( P＜0.05 ) or aged＞70 (P＜0.05) had shorter PFS than younger patients. The patients with increased lactic dehydrogenase ( LDH ) level (P＜0.01) and without rituximab (R) (P＜0.05) in the treatment regimen had relatively short OS., Conclusion: The patients sensitive to chemotherapy and/or radiotherapy have a good prognosis. Most of the patients can obtain long-term survival after treatment. The effect of combined immunotherapy are better than that of the simple chemotherapy.

Objective: To investigate the prognostic evaluation value of fluorodeoxyglucose (FDG) interim positron emission tomography/computed tomography (PET/CT) for diffuse large B cell lymphoma (DLBCL)., Methods: Two hundred and twenty-seven patients with pathologically diagnosed DLBCL underwent 18F-FDG scans at baseline and before 3 cycles of a rituximab-containing chemotherapy regimen. The Visual Deauville score (DS) and changes in maximum standard uptake values (ΔSUVmax) were calculated for tracer for the predominant lesion of each patient, for prediction of progression-free survival (PFS) and overall survival (OS) using Kaplan-Meier method and COX regression., Results: The median follow-up period was 71 months. Receiver operating characteristic analysis indicated that the best ΔSUV cut-off values for FDG (ΔSUVFDG) was 71%. The sensitivity, specificity and accuracy of DS and ΔSUVmax were 86.9%, 74.3%, 82.8% and 77.8%, 63.5%, 73.1%, respectively in response assessment. Kaplan-Meier analysis showed DS, ΔSUVmax and IPI had significance for prediction of PFS and OS (P = 0.001). The DS 4-5 and IPI 3-5 were independent risk factors of poor prognosis by COX regression analysis., Conclusion: Interim PET/CT is important predictor for evaluation therapeutic response and prognosis in DLBCL patients.

Objective: To evaluate the efficacy and safety of ruxolitinib in treatment of myeloproliferative neoplasm., Methods: Random clinical trials (~September 30, 2017) were identified from PubMed, Embase, Cochrane Library, Clinical Trials, CBM and Chinese Journal Full-text Database. The quality of RCT was assessed by Cochrane risk bias. Meta analysis was performed with Revman 5.3., Results: Ruxolitinib was efficacious in relieving splenomegaly (RR 49.12, 95% CI [15.81-152.59], P<0.001). The incidence of anemia significantly increased after ruxolitinib treatment (RR 1.71, 95% CI [1.05-2.77], P=0.16), while the thrombocytopenia (RR 1.04, 95% CI [0.50-2.16], P=0.92) and neutropenia (RR 2.46, 95% CI [0.91-6.61], P=0.07) had no statistical difference as compared with that in control group. Ischemia events had no significant difference as compared with control (RR 0.57, 95% CI [0.33-1.00], P=0.05). Infection events had no significant difference as compared with the control group (RR 1.18, 95% CI [0.79-1.78], P=0.24)., Conclusion: Ruxolitinib is an efficacious therapeutic strategy on MPD with controlling splenomegaly. However,anemia events and bleeding events may threat its clinical safety, so more high quality RCT are needed.

As an important noninvasive diagnostic tool, the positron emission tomography/computed tomography (PET/CT) plays a significant role in diagnosis and therapy of patients with diffuse large B-cell lymphoma (DLBCL). PET/CT, a standard imaging tool for initial accurate staging and response assessments, has replaced conventional CT in rituximab era. In this review, the definition, interpretation method, prognostic value and risk stratification of interim PET/CT are introduced to clarify the guiding significance of PET/CT in the diagnosis and theray of DLBCL, and the application of PET/CT scanning-guided prognostic factors and response-adapted therapy for DLBCL is summarized.

Cancer-testis antigens (CTA) are a class of tumor-associated antigens, which are mainly located in X chromosome. CTA restrictively expressed in normal testis, ovary, placenta and so on. Their expression in other normal tissues is much lower, even can not be detected. However, their expressions are aberrantly high in human cancers. Based on CTA encoding immunogenic proteins, they can be regulated by epigentics, CTA provides very attractive targets for cancer immunotherapy. Multiple myeloma (MM) is incurable and has a low cureative rate and a high relapse rate. CTA have been detected in many MM cell lines and primary MM cells, they may be relaled to clinical prognosis. This reviews briefly summarized the research advances of CTA in the immune therapy of multiple myeloma, so as to provide a valuable therapeutic idea for myeloma.

Outstanding progress has been achieved in the treatment of Hodgkin's lymphoma in recent years, most of patients can be cured by using modern therapy. However, more and more attentions have been paid on treatment-related complications, the current treatment strategies are focusing on further improving treatment efficacy, while reducing treatment-related toxicity. It is still to be determined whether interim PET imaging could directly judge the therapeutic response so as to make the individualized treatment programs for the patients, for instance through intensifying or abbreviating chemotherapy regimens and/or omitting radiotherapy. The emergence of some novel highly effective targeted drugs might offer hope for the relapsed and refractory patients. In this review, the recent advances on the treatment of Hodgkin's lymphoma are summaried.

Objective: To investigate the therapeutic efficacy of allogeneic peripheral blood hematopoietic stem cell transpdantation (allo-HSCT) for T lymphoblastic lymphoma (T-LBL)., Methods: The clinical data of 14 adult patients with T-LBL treated with allo-HSCT were collected, the hematopoietic reconstruction, survival and relapse, as well as overall survival (OS) rate, event-free survival (EFS) rate of 1, 3 and 5 years were analysed retrospectively., Results: All the patients were engrafted with neutrophil successfully, the median time of absolute neutrophil count >0.5 × 10(9)/L was 13 (10-19) d; 13 patients were engrafted with platelets successfully, the median time of Plt count >20 × 10(9)/L was 17 (12-62) days. The acute GVHD occurred in 6 patients, but among them only 1 case with 3 grade of aGVHD; out of 14 patients, 5 developed chronic GVHD. The transplant-related mortality at 100 days was 7.1% (1/14), mainly from coronary heart disease and pulmonary infection. The median follow-up time was 26.5 months, the estimated 1, 3 and 5 year OS rate was 85.7%, 47.6% and 38.1%, respectively, and estimated 1, 3 year EFS rate was 85.7%, 34.4% and 34.1%, respectively. The relapse rate was 42.8% (6/14) and the median relapse time was 22.5% months after transplantation. Up to now, 7 patients still survive, 1 patient out of them have survived for 103 months., Conclusion: The allo-HSCT is a safe and effective method for treatment of T-LBL.

Objective: To establish a new method for detection of red blood cell osmotic fragility by using flow cytometry., Methods: The hypotension salt solution of different concentrations (0.70 ml normal saline+0.3 ml deionized water, 0.60 ml normal saline+0.40 ml deionized water and 0.55 ml normal saline+0.45 ml deionized water) were prepared with normal saline and deionized water, in which the red blood cells were suspended, and the residual red blood cells were detected by flow cytometer., Results: There was no significant difference in percentage of residual red blood cells between different time points detected by flow cytometer in 3 different hypotonic salt solutions. The percentage of residual red blood cells in B+C+D+E+F+G detected time region was different among 3 NaCl dilution groups. The percentage of residual red blood cells in normal control was lower than that in hemoglobinopathy group. The percentage of residual red blood cells in hereditary spherocytosis (HS) group was obviously lower than that in hemoglobinopathy and normal control groups. The comparison of 3 different dilution concentrations found that the second concentration (0.60 ml normal saline+0.40 ml deionized water) is more suitable to screen HS by FC500 flow cytometer., Conclusion: The detection of red cell osmotic fragility by using flow cytometry is a simple, rapid, objective and economic way that can be an effective screening method for diagnose the HS.

Objective: To investigate the expression of BAG3 gene in acue myeloid leukemia (AML) and its prognostic value., Methods: Real-time quantitative RT-PCR was used to detect the expression of BAG3 mRNA in 88 previously untreated AML patients. The corelation of BAG3 expression level with clinical characteristics and known prognostic markers of AML was analyzed., Results: In 88 patients with AML, the expression of BAG3 mRNA in NPMI mutated AML patients was obviously lower than that in NPMI unmutated patients (P = 0.018). The expression level of BAG3 mRNA did not related to clinical parameters, such as age, sex, FAB subtype, WBC count, extra-modullary presentation, and to prognostic factors including cytogenetics, FLT3-ITD, c-kit and CEBPα mutation status (P > 0.05). The expression level of BAG3 had no obvious effect on complete remission (CR) of patients in first treatment. The expression level of BAG3 in non-M3 patients was higher than that in relapsed patients (P = 0.036). The expression level of BAG3 had no effect on overall survival (OS) of patients., Conclusion: The expression level of BAG3 does not correlated with known-prognostic markers of AML, only the expression level of BAG3 in NPM1 mutated patients is lower than that in NPM1 unmutated patients. The expression level of BAG3 has no effect on OS of AML patients, the BAG3 can not be difined as a prognostic marker in AML.

Diffuse large B cell lymphoma (DLBCL) is one of the most common pathological type of non Hodgkin's lymphoma in adult, with a high mortality and a variety of prognostic factors. (18)F-FDG PET/CT, a functional imaging modality used for staging and monitoring response of a variety of human neoplasia to treatment, has a higher sensitivity and specificity than conventional anatomical imaging. Patinets taking (18)F-FDG PET/CT scanning for DLBCL before treatment and after complete standard treatment of DLBCL patients not only contributes to the clinical accurate staging, but also has a certain value in evaluating the prognosis of DLBCL patients and monitoring of recurrence. However, the value of interim PET/CT for evaluation of prognosis remains controversial. Therefore, this review focuses on the research progress of (18)F-FDG PET/CT for evaluating prognosis of patient with DLBCL, including baseline, interim and post-treatment (18)F-FDG PET/CT.

Objective: This study was aimed to detect the change of T-lymphocyte functional subsets marked by CCR7 and CD45RA in the aGVHD within 100 days after allo-HSCT and to explore its clinical significance., Methods: The peripheral blood of 42 patients after allo-HSCT was collected every two weeks since hematopoietic reconstitution. The expression of CD3, CD4, CD8, CCR7 and CD45RA-marked T-lymphocytes was detected by flow cytometry, the relationship between their expression and the prognosis of aGVHD was analyzed., Results: The percentage and the absolute count of CCR7(+) T lymphocyte were significantly reduced in aGVHD. The percentage of T(naïve), T(CM), T(EM) and the absolute count of T(naïve), T(EM), TTD were sharply reduced in aGVHD, moreover has changed correspondingly with outcome of aGVHD. The percentage of CD3, CD4, CD8-marked T-lymphocyte subsets did not significantly changed., Conclusion: T-lymphocyte functional subsets marked by CCR7 and CD45RA are a valuable indicator to monitor early immune reconstruction for patients with the aGVHD after allo-HSCT.

Objective: This study was to investigate the therapeutic effectiveness and side effect of decitabine combined with modified CAG regimen for relapse or refractory patients with acute myeloid leukemia., Methods: Ten patients suffered from relapsed or refractory acute myeloid leukemia from January 2013 to July 2013 were analyzed retrospectively, and the clinical characteristics, therapeutic effectiveness, side effect were observed. Among 10 patients 7 patients were males and 3 patients were females, the ratio of male to female was 7:3, median age was 45 (17-61) years., Results: After treatment by using decitabine combined with modified CAG regimen, 7 patients achived complete remission, 1 patient achived partial remission, 2 patient did not achieve remission, the overall remission rate was 80% (8/10), the median time of white blood cell count recovery was 18.5 (5-28) days, median time of platelet level recovery was 19 (12-29) days. The main side effects of treatment were myelosuppression. There was no new lung infection in all cases, one case died of exacerbation of primary lung infection after therapy., Conclution: The treatment of decitabine combined with modified CAG regimen for relapsed and refractory AML shows high response rate, low side effects, so it worthy to further clinical study.

This study was aimed to investigate the clinical characteristics of relapsed-refractory acute myeloid leukemia (AML) with AML1-ETO⁺, and its therapeutic efficacy and side effects when decitabine combined with modified CAG regimen was used. Clinical data of 5 cases of AML with AML1-ETO⁺ from January 2013 to Agust 2013 were analyzed retrospectively. The analyzed data included age, sex, initial symptoms, peripheral blood and bone marrow characteristics. Meanwhile, the therapeutic effecacy and side effects of decitabine combined with modified CAG regimen were evaluated. The 5 patients were with median age of 35 (17-43) years. Among these 5 patients, 2 patients were relapsed and other 3 patients were relapsed-refractory patients, their median white blood cell count was 12.55 (7.8-66.55) × 10⁹/L, median platelets count was 44 (20-72) × 10⁹/L, median hemoglobin level was 110 (77-128) g/L, median lactate dehydrogenase level was 312.9 U/L (123.6-877.8) at the initial diagnosis. The results showed that after decitabine combined with modified CAG regimen was administered, 4 patients achieved complete remission, 1 patient did not achieve remission, the overall remission rate was 80% (4/5). The main side effects of this regimen was myelosuppression, these were no new lung infection and other serious complications, one case without complete remission treated with FLAG once again died of heart failure when being mobilized for transplantation. It is concluded that according to preliminary results of decitabine combined with modified CAG regimen for relapsed and refractory AML patients with AML1-ETO⁺ displays higher remission rate and lower side effects, which worthy to further explore for clinal application.

This study was aimed to investigate the morphological, biological ,clinical and therapy features in a special case of primary gastric non-Hodgkin's lymphoma (PG-NHL) through analysis of PG-NHL patient who developed fulminating hepatitis following chemotherapy and radiotherapy and thus received liver transplantation (LT). The morphological changes of cells were analyzed by bone marrow smear, the expression and mutation of abnormal genes were detected by nested multiplex PCR, and HBV-DNA copies were detected by real-time fluorescence quantitative PCR (FQ-PCR). The results showed that at onset of disease, patient was diagnosed as primary gastric non-Hodgkin's lymphoma (PG-NHL) with HBsAg(+) and HBVDNA(-). LUGANO stage was Ia. aaIPI score was 0.The patient was treated with R-CHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone), rituximab maintenance treatment and radiotherapy. During the treatment, the patient has taken entecavir, 1 week later after the radiotherapy (2 months later after the chemotherapy), then the entecavir was discontinued. Six months later HBV DNA(+), the progressive acute hepatic failure (AHF) happened to the patient, who thus received phylogenetic right liver transplantation (LT). He has survived for 3 years after LT so far. The liver function of patient was normal more than 3 years after LT. The patient was checked regularly by PET-CT, and his PG-NHL continue complete remission(CR). It is concluded that the patients receiving chemotherapy or immunosuppressive therapy should be screened for HBV DNA, liver function and HBV reactivation signs. HbsAg positive patients should receive preventive antiviral therapy. After chemotherapy or immunosuppressive therapy, the patients should be given antiviral maintenance therapy, and the liver damage should receive the hepatoprotective and effective support treatment, LT is necessary and feasible to obtain long-term survival.

This study was purposed to investigate the clinical features, diagnosis, treatment and prognosis of elderly patients with acute myeloid leukemia (AML) (non-APL). The clinical data of 76 elderly ( ≥ 60 old years) AML (non-APL) patients from January 2000 to January 2010 were analyzed retrospectively. According to treatment methods,the 76 patients were divided into 2 groups: induction chemotherapy group (51 cases) and best supportive treatment group (25 cases). The patients in induction chemotherapy group received the cytarabine-based induction chemotherapy regimens, including DA, MA, HA, IA and CAG; the patients in best supportive treatment group received supportive treatment including hydroxyurea, blood transfusion and so on. The clinical features, diagnosis, treatment and prognosis between 2 groups were compared. The results showed that the median survival times of patients in induction chemotherapy and best supportive treatment groups were 5 (0.2-89) and 3 (0.1-17) months respectively, there was significantly statistical difference in median survival time between 2 groups(P < 0.01) suggesting that the induction chemotherapy obviously prolonged the survival time of elderly CML patients. The 5 patients in induction chemotherapy group survived more than 60 months, one of them survived more than nine years. After the first cycle of chemotherapy, the complete remission (CR) rate of patients was 19.6% (10/51), partial remission (PR) rate was 19.6% (10/51), the overall response rate (ORR) was 39.2%, the mortality of patients in induction remission stage was 13.7% (7/51) in induction chemotherapy group; no 1 case in best supportive treatment group reached to CR. The CR rate of patients by using MA regimen was 44.4% and its ORR was 55.5%, which was higher than that by using DA, HA, IA and CAG regimens. The median chemotherapy cycles were 3 (1-14). The follow-up found that the 3 months-survival rate of patients was 65% and 42%, the 6 month-survival rate of patients was 43% and 21%, the 1 year-survival rate of patients was 29% and 13%, the 5 year-survival rate of patients was 13% and 0% in induction chemotherapy and best supportive treatment groups respectively, showing that the survival of patients in induction chemotherapy group was better than those in best supportive treatment group. A total of 31 of out 51 cases (60.8%) in induction chemotherapy group not response to the first cycle of chemotherapy, the survival time of these patients was not statistically significantly different from that of patients in best supportive treatment group. It is concluded that the induction chemotherapy can significantly improve the prognosis of elderly patients with AML, and prolong their median survival time. The induction remission rate in elderly patients with AML is lower than that of younger patients. The MA regimen is better than DA, HA, IA and CAG, there is individual difference in the elderly patients with AML, If the first cycle of chemotherapy has not reached to CR or PR, the best supportive treatment may be considered. The low toxicity, efficient and well-tolerated chemotherapy regimens may be chosen to prolong the survival time of the elderly patients with AML (non-APL).

Purpose of this study was to analyse the characteristics of clinical, iconographical, pathological and treatment methods of Langerhans cell histiocytosis (LCH), so as to improve the diagnosis and treatment level of this disease. The clinical data of 35 LCH patients were studied retrospectively. These patients were divided into 2 groups according to age <14 years old and ≥ 14 years old. The clinical symptoms were analysed and the signs, imageology and pathology manifestation and treatment results were evaluated. The results showed that LCH clinical manifestations were diverse and complex. Surgical treatment for patients with single system involvement of LCH was better than that of multi-system involvement of LCH (MS-LCH). For the latter, combined chemotherapy effects was better. After 3-year follow-up, 1-year OS was 94% ± 4%, 2-years OS was 91% ± 5%, 3-year OS was 86% ± 7%. 3 years OS of group <14 years old and ≥ 14 years old was 94% ± 6% and 81% ± 10% respectively. The OS of former was better than that of the later, but because a small number of cases, this difference was not statistically significant. It is concluded that LCH is easy to be misdiagnosed, the pathological biopsy is the gold standard of LCH diagnosis. The PET-CT can be of great help in identifying stages and finding lesion areas of the disease. Pulmonary Langerhans cell histiocytosis (PLCH) is more common in adult. Combined chemotherapy can improve the prognosis of the patients. The treatment methods should be choosed according to the stage and classification of disease.

This study was aimed to investigate the clinical characteristics of acute myeloid leukemia (AML) with t (8;21) (q22;q22) and loss of Y chromosomes. Clinical data of 267 cases of AML were collected from January 2010 to June 2013. Among 267 AML, there were 13 cases with t (8;21) (q22;q22) and loss of Y chromosomes. The clinical data including clinical indicators, treatment protocols, curative effect and prognosis were analyzed retrospectively. The results showed that after normalized chemotherapy, there were 4 patients with complete remission at the first cycle of treatment, 4 patients with complete remission at the second cycle, 4 patients with complete remission at the third cycle, but one patient without complete remission after 4 cycles. There were 6 patients who did not relapse during consolidation and intensive therapy. Among these 6 patients, 4 cases accepted chemotherapy combined with transplantation, other 2 cases accepted chemotherapy. In the remainder 6 patients, 4 cases relapsed once, one cases relapsed twice, 1 cases relapsed for three times. Moreover, 2 cases who accepted the chemotherapy and auto-hematopoietic stem cell trans-plantation, were diagnosed as relapse, after accepted allo-hematopoietic stem cell transplantation, currently are in disease-free status. In follow-up period, the relapse-free survival (RFS) time was 4.67 ± 3.45 months in chemotherapy group, the RFS time is 34.17 ± 21.37 months in chemotherapy and transplantation group. The chemotherapy combined with transplantation extended the RFS time (P < 0.05). It is concluded that the NCCN guide indicates that AML with t (8;21) ( q22;q22) showed a good prognosis. but the clinical course of treatment confirmed that the prognosis of AML patients with t (8;21) (q22;q22) and loss Y chromosomes is poor, including uneasy remission and easy relapse, for improving the prognosis of these patients, the hematopoietic stem cell transplantation should be recommended.

The purpose of study was to analysis the clinical manifestation and treatment protocol of acute promyelocytic leukemia (APL) accompanied by craniopharyngioma so as to promote the understanding of this disease. The APL was diagnosed by morphologic examination of bone marrow cells, the leukemia bone marrow cells were analyzed by immunophenotyping technique, the qualitative and quantitative changes of PML-PARα fusion gene before and after treatment were monitored by using molecular biological test; the cytogenetic features were analyzed by using conventional karyotype and FISH analysis. The results indicated that the clinical manifestation of this disease was diverse and disease status was complex. The good therapeutic efficacy could be achieved, the misdiagnosis and delayed treatment could be avoided through early detection, timely treatment and multidisciplinary cooperation. It is concluded that when other clinical symptoms reappear after APL achieves remission, the possibility of second tumor must be considered, the clinical presentation should be carefully monitored, the early detection and timely treatment should be performed to improve the survival of patients.

This study was aimed to investigate the pathology, MICM classification, PET/CT characteristics and therapeutical experience of subcutaneous soft tissue muscle gap lymphomatoid granulomatosis (LYG) through analysis of a cases of LYG. The pathologic changes of LYG were assayed by using immunohistochemistry method;the immuno-phenotypes were detected by flow cytometry. The nested multiplex PCR was used to detect the expression and mutation of abnormal genes; the real-time fluorescence quantitative PCR was used to detect the EBV-DNA copies. The clinical staging was performed by means of fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT). The results showed that at onset of disease the clinical manifestations of patient presented only a mass in right thigh and swelling of right submandibular lymph nodes. However, PET/CT revealed that the abnormal image in multiple soft tissue accompanied by increasing metabolic activity (SUVmax = 12.8), these pathologic changes were involved in lung, thyroid, lymphonodes and stomach. The right thigh mass biopsy confirmed the histological diagnosis of grade II LYG. The bone marrow smear showed no abnormal tumor cell infiltration, the immunophenotyping detection revealed that the proportion of NK cells increased with phenotypic abnormality, the karyotype was 46, XY[24], the expression and mutation of abnormal gene not could be detected, and the EBV-DNA level was <10(2) copies/ml. After 2 cycles of treatment with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone(R-CHOP), the images of increasing metabolic activity in subcutaneous soft tissue gap disappeared, but the partial increasing metabolism focus could be observed in soft tissue of left knee hollow. The patient achieved partial remission. It is concluded that LYG is an extremely rare hematopoietic malignancy, the incidence rate is very low. Subcutaneous soft tissue muscle gap LYG literature was not reported in domestic and foreign literatures.Its pathogenetic remains unclear. A standard treatment protocol for LYG has not yet been established. PET/CT can find more lesions that not could be found in the clinical examination. The (18)F-FDG PET/CT is an efficient tool for the LYG in diagnosis, staging and treatment. Therefore, increased SUV(max) in FDG-PET may be useful for diagnosis of LYG.

This study was aimed to explore the clinical characteristics and optimal therapeutic methods for newly diagnosed acute promyelocytic leukemia (APL) combined with disseminated intravascular coagulation (DIC) so as to guide the clinical therapy. The clinical date and therapeutic outcome of 25 cases of APL combined with DIC treated from January 2008 to March 2013 in our department were analysed retrospectively. The 25 patients were given ATRA 20 mg orally twice a day and arsenic trioxide (ATO) 10 mg intravenously once a day to induce differentiation therapy, the chemotherapy was added after degranulation of promyelocytes. At the same time the platelets, fresh frozen plasma, fibrinogen, cryoprecipitate,prothrombin complex and amino methylbenzoic acid, low molecular weight heparin were given to treat DIC. According to the laboratorial examination of coagulation and fibrinolysis, the medication was adjusted.The white blood cell count, platelet level, prothrombin time (PT), partial thromboplastin time of plasma (APTT), fibrinogen level were detected, and the relation of those factors and age with bleeding severity was analyzed by multivariate manner. The results showed that among 25 patients with APL (low-risk 5 cases, intermediate risk 13 cases and high risk 7 cases), 22 cases combined with DIC, incidence of DIC was 88%. Out of 22 patients with DIC 21 patients (95.5%) were corrected, except 1 case death. After the first course of treatment, 23 cases (92%) gained complete remission (CR) with average CR time 31.8 ± 7.2 days. During the induction of CR, the average platelet transfusion level was 75.68 ± 55.88 U, the RBC level was 8.90 ± 5.69 U, the average level of fresh frozen plasma transfusion of APL patients with DIC was 21.92 ± 19.32 U. The recovery time of platelet level to normal was 29.3 ± 9.3 days, the recovery time of PT, APTT, FDP and fibrinogen to normal were 12.7 ± 9.5 days, 11.6 ± 8.6 days, 16.0 ± 9.3 days and 125.3 ± 85.3 days respectively. The multivariate analysis showed that WBC count at onset was >10 × 10(9)/L and APTT was prolonged. These two factors were main reasons resulting in severe bleeding. It is concluded that the newly diagnosed APL always combined with DIC, therefore in the early phase of disease active transfusion of blood products, application of anti-coagulation and anti-fibrinolytic drugs as well as heparin should be performed; the coagulation function should be as soon as recovered to normal so as to early correct DIC. These measures can significantly decrease the mortality of APL patients resulting from DIC. The hyperleukocytosis and prolonged APTT are the main factors for severe bleeding.

This study was purposed to analyze the clinical feature,diagnosis and treatment efficacy of primary granulocytic sarcoma (PGS). A total of 15 patients with PGS from January 2008 to March 2013 was evaluated retrospectively, among 15 patients 8 patients were treated with chemotherapy (chemotherapy alone,chemotherapy combined with local irradiation,chemotherapy combined with surgical resection or bone marrow transplantation), 7 patients were treated without chemotherapy, but were treated with surgical resection or surgical resection plus local irradiation.The chemotherapy method for PGS patients was similar as treatment of acute myeloid leukemia. The results indicated that the proportion of disease progression into bone marrow abnormality in patients treated with chemotherapy and in patients treated without chemotherapy was 25% and 85.7% respectively, suggesting that the chemotherapy can reduce the incidence of progression into bone marrow abnormality (P < 0.05). The average survival time of PGS patients treated with chemotherapy or without chemotherapy was 26.063 ± 14.97 and 12.214 ± 6.83 months (P < 0.05),suggesting prolonging of survival time of patients treated with chemotherapy, moreover 2 patients who were treated using chemotherapy combined with bone marrow transplantation still alive now,and their living times were 39 months and 45 months respectively. It is concluded that intensive chemotherapy similar as treatment of AML can decrease the probability of disease progressing into bone marrow abnormality, and if chemotherapy combines with bone marrow transplantation, the survival time of PGS patients can be longer. In this aspect, the efficacy of treatment and survival time at home and abroad are similar.

The purpose of this study was to investigate the efficacy of autologous hematopoietic stem cell transplantation (auto-HSCT) for patients with diffuse large B-cell lymphoma (DLBCL), and analyse the factors influencing prognosis. The clinical data of 67 patients with DLBCL received auto-HSCT from 1996 to 2011 and cumulative overall survival (OS), progression-free survival (PFS), transplant-related mortality (TRM), and relapse rate were retrospectively analyzed. The results showed that the median follow-up time was 40 months after transplantation. Three-year cumulative OS and PFS were 70.6% and 66.4% respectively, 5-year cumulative OS and PFS were 70.6% and 63.8% respectively, and TRM was 7.2%. One-year and three-year cumulative relapse rate were 16.5% and 23.7% respectively. Univariate analysis revealed that the age and pre-transplant disease status were significantly associated with poor prognosis (P < 0.05). It is concluded that auto-HSCT is a safe and effective therapeutic option for patients with DLBCL, especially for the young patients or patients with better remission.

This study was purposed to investigate the clinical efficiencies and adverse reactions of treating the myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) by using decitabine. The clinical data of 12 MDS and AML patients treated with decitabine were analyzed retrospectively. Among 12 patients there were 1 case of MDS-RA, 2 cases of MDS-RAEB-I, 3 cases of MDS-RAEB-II, 2 cases of AML-M4, 2 cases of AML-M5, 1 case of AML-M6 and 1 case of AML-M0. In decitabine chemotherapy program for 5 days (n = 8), decitabine 20 mg/(m(2)·d) × 5 days was applied, 4 weeks for 1 cycle; in program for 3 days (n = 2), decitabine 15 mg/m(2), once 8 h for 3 days, 6 weeks for 1 cycle; another program (n = 2), decitabine 20 mg/(m(2)·d) every other day for 5 times. For 1 patient achieved complete remission (CR) after treatment with decitabine, ID4 gene methylated level was detected by MS-PCR and ML-PCR before and after treatment. The results showed that 2 cases achieved CR, 1 case partial remission, 5 cases stable disease, 1 case progress of disease and 3 cases died. Disease control rate was 66.67% (8/12), the effective rate 25% (3/12). The average survival time was (11.5 ± 2.1) months. 1-year OS rate was 40%, 2-year OS rate was 16.7%. MS-PCR detection showed that the decitabine could significantly reduce the ID4 gene methylation level. It is concluded that decitabine can stabilize disease status of MDS patients, reduce blood transfusion dependence and improve the life quality of patients, and even some patients who transformed from MDS to leukemia achieved CR after treatment with decitabine. Decitabine can reduce the ID4 gene methylation level. The main adverse reaction of decitabine was myelosuppression, infection and so on. So the blood transfusions, antibiotics and other supportive treatments for these patients are needed. Most of patients well tolerate the adverse effects of decitabine after active symptomatic and supportive treatment. The efficacy and survival rate of patients in this study were similar to that of application of decitabine to treat MDS in other domestic studies.

This study was aimed to investigate the factors influencing mobilization efficiency of peripheral hematopoietic stem cells with granulocyte colony stimulating factor (G-CSF) and their impact on healthy donors. 181 donors were mobilized subcutaneously with G-CSF at 5 - 10 µg/(kg·d), and 10 donors were mobilized with G-CSF at 3.3 - 4.9 µg/(kg·d), once 12 h, for 4 - 5 d. Peripheral blood mononuclear cell (MNC) and CD34(+) cell counts were analyzed by flow cytometry. Mobilization-related side effects were also monitored. The results showed that white blood cell counts increased by 6 times averaged after mobilization (P < 0.01). The platelet count obviously decreased (P < 0.01), while the hemoglobin level did not show significant difference. No significant differences were observed in MNC and CD34(+) cell counts between those subjects harvested on the 4th and 5th day after mobilization. Male donors were superior to female ones in cell harvest (P < 0.01). Donor body weight played positive role in cell yield, while impact of age on harvest was not remarkable. Neither MNC nor CD34(+) cell count showed a linear relationship with G-CSF dose. Only slight side effects were observed on the donors in this study. It is concluded that mobilization with G-CSF is sufficient in healthy donors without remarkable side effects.

The aim of this study was to evaluate the role of (18)F-FLT positron emission tomography/computed tomography (PET/CT) in diagnosis and staging of diffuse large B-cell lymphoma (DLBCL) patients and compare with CT. Thirty-six patients with DLBCL in our hospital from September 2008 to December 2009 were prospectively evaluated. All 36 patients underwent whole body and head (18)F-FLT PET/CT and CT (chest, abdomen cavity and pelvis) were studied before therapy. The maximal standardized uptake value (SUV(max)) of every single focus and the SUV(max) of aortic arch blood pool were measured and used to calculate the median T/MB value (tumor SUV(max)/mediastinal SUV(max)) of every patient. The results showed that the consistency of (18)F-FLT PET/CT and CT examinations in focus of DLBCL was 79.10%, the sensitivity, specificity, positive predictive value, negative predictive value and accurate rate of (18)F-FLT PET/CT were 96.65%, 100%, 100%, 61.11% and 96.82%, respectively, which were much higher than that of CT (85.44%, 57.14%, 96.70%, 21.05% and 83.64%). It is concluded that the (18)F-FLT PET/CT is a good means for DLBCL diagnosis and staging, which is more sensitive and specific than CT.

Myeloid neoplasms with eosinophilia and abnormalities of PDGFRB gene are a new kind of myeloid disorders in the revised 2008 WHO classification. Out of detected 2000 cases of myeloid cell abnormalities in our hospital, 12 cases of myeloid neoplasms with eosinophilia and abnormalities of PDGFRB were found. This study was purposed to summarize and analyze the clinical and laboratorial characteristics of the 12 cases with PDGFRB gene abnormalities. The results indicated that among 12 cases of myeloid neoplasms with PDGFRB abnormalities, 5 cases with TEL/PDGFRB fusion gene, 2 cases with HEPI/PDGFRB, 1 case with PDGFRB mutation, 1 case with RABAPTIN-5/PDGFRB, 1 case with GIT2/PDGFRB, 1 case with TP53/PDGFRB, 1 case with WDR43/PDGFRB fusion gene were detected, showing the polymorphism of PDGFRB gene abnormalities. Among this kind of myeloid neoplasm patients, almost all patients manifested monocytosis and eosinophilia in different degree, the thrombocytosis mainly was observed in atypical myeloid neoplasms, acute leukemia, chromic myelo-monocytic leukemia patients. The treatment with imatinib mesylate for this kind of patients was effective in some cases. It is concluded that the myeloid neoplasms with PDGFRB gene abnormalities are a kind of heterogenetic myeloid neoplasms, their gene abnormal types and clinical manifestations show polymorphism too. The monocytosis and eosinophilia appear in this kind myeloid neoplasms which may be treated with tyrosine kinase inhibitors such as imatinib mesylate.

Imaging examination was already used for an overall assessment of disease sites in patient with malignant lymphoma, it is very important for the disease staging and evaluation of therapeutic effect. Staging is necessary to prevent hyper-or hypo-therapy as well as to minimize morbidity related to the radio-chemotherapy regimens given. (18)F-FDG-PET/CT, a functional imaging modality used for staging and monitoring response to treatment of a variety of human neoplasias, has higher sensitivity and specificity than conventional anatomical imaging. Baseline (18)F-FDG-PET/CT is used for the accurate staging, and helps to interpret the results of the middle therapy and post-therapy; middle therapy (18)F-FDG-PET/CT will be usually performed after 2-3 cycles of treatment, which can be used for risk assessment and judgement of therapeutic effect after treatment; posttherapy (18)F-FDG-PET/CT is used to evaluate the efficacy and monitoring of residual tumor, and to provide the basis for selecting treatment with or without high-intensity chemotherapy and transplantation. In this review, the significance of baseline, middle-therapy and post-therapy (18)F-FDG-PET/CT scanning for the diagnostic staging and evaluating therapeutic effect of malignant lymphoma as well as the characteristics of (18)F-FDG-PET/CT scanning for different pathologic types of lymphoma are summarized.

This study was purposed to investigate the mutational status of DNA methyltransferase (DNMT3a) gene and the clinical features of AML patients with DNMT3a mutations. Using PCR combined with directly sequencing, the somatic mutations of DNMT3a involving residue of amino acid 882 were detected in 77 AML patients. Furthermore, the clinical features of these patients were also studied. The results showed that the DNMT3a mutation were detected in 7 out of 59 patients with de novo AML (11.9%), which included 4 patients with DNMT3a R882C, 2 patients with DNMT3a R882H and 1 patient with DNMT3a Y874C. Morphology examination indicated that 2 patients were M(2), 1 patient was M(4) and 4 patients were M(5). Cytogenetic analysis revealed that karyotype in 5 out of 7 patients with DNMT3a mutation were normal. In total of 27 patients with normal karyotype 5 patients (22.7%) were found harboring DNMT3a mutation, while no DNMT3a mutation was found in 21 patients with abnormal karyotype. The mutation rate in patients with positive CEBPA was obviously higher than that in patients with negative CEBPA (p = 0.002). Immunophenotype analysis showed that 4 patients (4/7, 57.1%) with DNMT3a mutation expressed lymphoid antigens including CD4 or/and CD7. There were no statistical significance in age, gender, blast cells of bone marrow, white blood cell and platelet counts, hemoglobin level, ratio of CR, mutations of FLT3-ITD, NPM1 and c-kit between patients with DNMT3a mutation and patients with wild DNMT3a (p > 0.05). It is concluded that the DNMT3a mutations are more prevalent in AML patients with normal karyotype accompanying with positive NPM1 and/or CEBPA mutation, the role of DNMT3a mutation in AML prognosis needs to be further studied.

In order to evaluate the clinical, biological features and prognostic factors of Richter's syndrome (RS), 8 RS patients were analyzed retrospectively. The serological test, multiplex parameter flow cytometry, conventional cytogenetic analysis, FISH technique and PCR combined with sequence detection were used to detect the LDH, β(2)-MG, TK1, SF, CA125, ZAP-70, chromosome karyotype, ATM and p53 gene deletion, as well as +12 abnormality and IgVH mutation. The results indicated that 7 out of 8 patients transformed to diffuse large B cell lymphoma (DLBCL) and 1 patient transformed to Hodgkin lymphoma (HL). Among 8 patients, LDH level in 7 patients, β(2)-MG level in 4 patients, SF level in 7 patients, CA-125 level in 4 patients and TK1 level in 1 patient exceeded the normal range. Meanwhile, ZAP-70 and CD38 were expressed positively in 4 and 7 out of 8 patients respectively. Unmutated IgVH was found in 5 patients, and 4 patients had the complex chromosome abnormalities. +12 and p53 deletion was found in 1 patient. 8 patients were divided into two groups (Binet A + B and Binet C), the mean time from diagnosis to progression was 98.5 months in Binet A + B group, compared with 38.3 months in Binet C group, there was significant difference between two groups (p = 0.021). Mean overall survival was 123.8 months and 49.8 months in two groups, respectively (p = 0.049). The mean survival after transformation was 34.5 months in Binet A + B group and 10.3 months in Binet C group. In conclusion, the level of LDH, β(2)-MG and SF are higher in RS patients in Binet C group, and so are the incidence of high expressed ZAP-70 and CD 38, unmutated IgVH. The clinical stage may be the risk and prognostic factors for RS transformation.

This study was to explore the stimulating effect of CpG-oligodeoxynucleotides (CpG-ODN) in combination with interleukin-2 (IL-2) on cytogenetic features of chronic lymphocytic leukemia (CLL) cells. Peripheral blood or bone marrow cells of 115 patients with CLL were cultured for 72 hours with CpG-ODN plus interleukin-2 (IL-2), and routine karyotype analysis was performed with R-banding technique. The metaphase number≥20 was considered as successful stimulation. The results showed that among the 115 CLL patients, successful stimulation rate was 74.8%. The rate of chromosome aberrations was 58.1%. One kind of aberration was detected in 21 cases (24.4%), two kinds of aberration in 6 cases (7.0%), complex aberrant karyotype in 23 cases (26.7%), included highly complex aberrant karyotype in 9 cases (10.5%), respectively. A total of 163 abnormalities of 102 kinds were detected in 86 patients. Number aberrations were 116 (71.2%), and structural abnormalities were 47 (28.8%). The most frequent number aberration was trisomy 12 (14.0%), and structural aberration was 15q+ (5.8%). It is concluded that most of CLL patients have chromosome abnormality, and the number abnormality are more frequent than the structural aberrations. CpG-ODN plus IL-2 can effectively raise the number of cells at metaphase and the detection rate of chromosome aberrations in CLL patients.

The study was aimed to evaluate the adverse effects of PAD (bortezomib + adriamycin + dexamethasone) and VAD (vincristine + adriamycin + dexamethasone) as chemotherapy regimens in multiple myeloma patients. 27 and 30 patients with multiple myeloma (MM) were enrolled in PAD and VAD groups respectively. MM patients accepted 3 - 5 cycles of VAD or PAD regimens. The type, degree and occurrence time of adverse reactions during the treatment were observed. The results showed that the rash was found in two patients only in PAD group, leucocytopenia, thrombocytopenia, peripheral neuropathy, infection, fatigue, nausea, constipation, and adverse effects of cortex hormone (hypertension, glycemia, hypokalemia, hyponatremia and acne) were found in the both two groups. The thrombosis was not observed in both two groups during treatment. Although statistical analysis indicated that only the incidence of thrombocytopenia was higher in PAD group than in VAD group with statistical difference but the incidence of leucocytopenia, peripheral neuropathy and infection in PAD group were higher than those in VAD group. Rash, constipation, peripheral neuropathy could be found in the first course of chemotherapy, while the others mostly emerged after 3 courses of treatment. The main reasons for the patients who's treatment was stopped include infection and intolerable peripheral neuropathy. Although peripheral neuropathy could be found in the two groups, but the chemotherapy was stopped only in 2 patients of PAD group after 3 cycles of treatment. It is concluded that compared with conventional VAD chemotherapy, PAD may improve therapeutic effect, but it may bring more severe toxicities to the patients with multiple myeloma.

The aim of this study was to investigate bag3 gene expression in chronic lymphocytic leukemia (CLL)patients and its association with clinical prognosis. A total of 46 blood samples from untreated CLL patients were collected, SYBR Green-based real-time PCR was used to detect the bag3 mRNA expression, and its association with prognostic index was analyzed by statistical software. The results showed that the median values of bag3 level detected by real-time PCR in 46 CLL patients and normal controls were 0.021 (0.0007 - 1.124) and 0.0025 (0.0005 - 0.014) respectively, the former was significantly higher than the latter. The bag3 level in drug-resistant group was obviously higher as compared with the drug-responsive group. No association was found between bag3 expression and patient clinical baseline information (gender and age) as well as established prognostic factors (lymphocyte count, disease stage, IgVH mutation status, cytogenetics analysis and CD38, ZAP 70 expression). It is concluded that the bag3 expression in CLL patients is markedly higher than that in normal controls, while the high bag3 level in CML patients is probably related with drug resistance, but is not related with clinically established prognostic factors.

This study was aimed to explore the prognostic significance of telomere length in patients with chronic lymphocytic leukemia (CLL) and to analyze relation of telomere length with Binet stage, IgVH mutation status, CD38, ZAP-70 expression as well as other clinical features. 35 CLL patients who contained 80% or more tumor cells in the peripheral blood or bone marrow samples were selected as objects studied, while 13 healthy donors were served as normal controls. The telomere relative length was detected by using a real-time fluorescent quantitative polymerase chain reaction method (qPCR); the expression of CD38 and ZAP-70 protein were detected by flow cytometry, the IgVH mutation was detected by multiplex PCR. The results showed that the mean telomere relative length in CLL patients and normal controls were 0.384 and 0.443 respectively, but the difference between them was not significant (p > 0.05). The telomere length was significantly correlated with Binet stages and IgVH mutation status. Patients in Binet stage B and C showed significantly shorter telomeres than those in Binet stage A (p = 0.001). Mean telomere relative lengths in patients without IgVH mutation were shorter than those in patients with IgVH mutation (p = 0.015). No relation of telomere length with sex, age, ZAP-70 protein and CD38 were found (p > 0.05). It is concluded that telomere length may have a prognostic significance for CLL patients. Combining telomere length and IgVH mutation status may achieve a better prognostic subclassification for CLL patients.

This study was purposed to establish a method for detecting miRNA expression by using fluorescent quantitative polymerase chain reaction (RQ-PCR), and to investigate the application value of this method in quantitative detection of miRNA. Total RNA was extracted from the peripheral blood or bone marrow of 82 patients with chronic lymphocytic leukemia (CLL) and 70 patients with acute leukemias (AL). Standard curves of U6 and miRNA were constructed from 10-fold serial dilutions of the cDNA, the quantitative detection was performed by using real-time quantitative PCR with SYBR Green by Roche Light Cycler. U6 RNA was used as the reference, the relative expression levels of miR-15a, miR-16-1, miR-29b, miR-181a and miR-181b in patients with CLL, while miR-128-1, miR-223, let-7b, miR-155 and miR-181a in patients with AL were analyzed by 2((-DeltaDeltaCT)) method. The relative parameters including specificity, linearity range, sensitivity and repeatability were evaluated. The results showed that the RQ-PCR assay could precisely detect the mature miRNA in as few as 10-50 ng of total RNA with the sensitivity of 0.05 ng RNA. Ct values of miRNA and U6 were all within 15 to 30. A good linear relationship (R(2) > 0.980) was obtained from the standard curves, also the efficiency of amplification was above 90%. Only a specific peak was shown on the melting curve diagram. The coefficients of variation (CV) of interrun and intrarun assay was < 4.8% and 6.3% respectively. It is concluded that the RQ-PCR is a sensitive and fast method for the detection of miRNA with its high-flux and low cost, this method will facilitate the research with detection of miRNA.

This study was aimed to compare the efficacy and adverse effects of PD (bortezomib + dexamethasone) and VAD (vincristine + adriamycin + dexamethasone) as regimens for treatment of multiple myeloma patients. 21 and 31 multiple myeloma patients were enrolled in the PD and VAD groups respectively which received 2 to 5 courses of treatments, and both clinical effects and adverse reactions were observed. In the all 52 patients, 48 were newly diagnosed and the other 4 patients had accepted 1 to 2 courses of M2 or MP treatment, but didn't get PR. In 52 patients, 4, 4, 8 and 5 patients accepted 2, 3, 4 and 5 courses of PD regimen respectively, while 6, 11, 12 and 2 patients accepted 2, 3, 4 and 5 courses of VAD regimen respectively. The results indicated that the rate of good efficacy (both CR and VGPR) in PD group was 57.1%, while the rate of good efficacy in VAD group was 16.1%, there was significant difference (p = 0.0052). The percentage of patients who got CR, VGPR and PR in PD and VAD groups were 95.2% and 74.2% respectively, there was no significant difference (p = 0.1108). The incidences of adverse effects in 2 groups were similar, which included hematological toxicity, liver and kidney functional lesion, peripheral neuropathy, infection, interstitial pneumonia. It is concluded that compared with conventional VAD chemotherapy, PD may improve CR and VGPR rate in newly diagnosed patients with multiple myeloma, meanwhile it does not bring about more and worse toxicity.

CD4+ T cells mainly interact with Sphingosine 1-phosphate (S1P) to regulate immune function through Sphingosine 1-phosphate receptor 1 (S1P1). This study was aimed to investigate the effects of recombinant human granulocyte-colony-stimulating factor (rhG-CSF) mobilization on S1P1 expression in CD4+ T cells of donor's peripheral blood. The CD4+T cells of peripheral blood were isolated by magnetic beads from 17 allo-hematopoietic stem cell transplantation (allo-HSCT) donors before and at fourth day of mobilization with rhG-CSF. The S1P1 expression was detected by real time quantitative PCR in the RNA extracted from CD4+ T cells collected before and after rhG-CSF mobilization. The results showed that the expression of S1P1 was found in CD4+ cells before and after rhG-CSF mobilization, but the expression level of SIP1 in CD4+ cells after rhG-CSF mobilization was significantly lower than that before rhG-CSF mobilization (p<0.01). It is concluded that the mobilization with rhG-CSF obviously down-regulates the expression of S1P1 in CD4+ T cells of donor's peripheral blood.

The study was purposed to explore the relationship between the expression of deoxycytidine kinase (dCK) gene and fludarabine (Flud) resistance in patients with chronic lymphocytic leukemia (CLL). The real time quantitative polymerase chain reaction (RQ-PCR) technique was used to detect the mRNA expression of dCK gene in the bone marrow or peripheral blood mononuclear cells from 30 CLL patients, the difference of dCK expression levels between CLL patients sensitive to Flud and patients resistant to Flud was analyzed. The results showed that dCK expression level in the Flud-sensitive patients was much higher than that in the Flud-resistant ones (p = 0.001); dCK expression level had no relationship with sex, age, Binet stage, IgVH mutations, CD38, ZAP-70 or p53 gene mutation (p > 0.05). It is concluded that low expression or deficiency of dCK in patients may contribute to resistance against Flud- and the prognostic significance of dCK expression remains to be further studied.

This study was aimed to explore the efficacy and associated complications of haploidentical peripheral blood stem cell transplantation (hi-PBSCT) without ex vivo T-cell depletion in treatment of hematological malignancies. 15 high-risk patients received HLA 1-3 loci (A, B, or DRB1) mismatched hi-PBSCT. The modified Bu/Cy or TBI/Cy regimen was used for preconditioning of patients. The anti-thymocyte globulin, cyclosporin A, methotrexate and mycophenolate mofetil were used for GVHD prophylaxis. 4 cases were administrated with anti-CD25 monoclonal antibody. G-CSF-mobilized peripheral blood stem cells were infused, with the median number of infused nucleated cells was 8.16 (3.92-10.86)x10(8)/kg and that of CD34+ cells was 4.51 (1.27-5.95)x10(6)/kg. The results showed that the rapid engraftment was observed in all cases. The median times of neutrophil recovery>or=0.5x10(9)/L and platelet recovery>or=20x10(9)/L were 14 (11-19) and 22 (11-52) days after transplantation respectively. 6 cases developed acute GVHD of grade I-II, and 2 cases experienced chronic extensive GVHD. Infection within 100 days after hi-PBSCT was documented in all cases. 8 cases were subjected to bacterial infection, and six got cytomegalovirus infection. Relapse occurred in five cases. Overall survival of patients was 46.7% (7/15), with a median follow-up of 213 (42-589) days. In conclusion, hi-PBSCT provides an effective alternative treatment for high-risk patients in lack of matched donors, and to reduce the high transplantation-related mortality.

This study was aimed to evaluate the effects of recombinant human interleukin 11 (rhIL-11) and recombinant human granulocyte colony stimulating factor (rhG-CSF) in mobilization for autologous peripheral blood stem cell transplantation (APBSCT). 16 patients with non-Hodgkin's lymphoma or acute myeloblastic leukemia were given myelosuppressive chemotherapy, then were mobilized by using rhG-CSF 5 microg/(kg.d) for median 5.5 days and rhIL-11 50 microg/(kg.d) for median 4 days (experimental group) or rhG-CSF 5 microg/(kg.d) alone for median 5.5 days (control group). After mobilizing, the peripheral blood leucocyte and platelet counts, total mononuclear cells, CD34+ cells and CFU-GM counts in PBSC collection, and amount of apheresed platelet transfusion were assayed. The results showed that the peripheral blood leucocyte and platelet counts, total mononuclear cell, CD34+ cell and CFU-GM counts in PBSC collection were no significant difference between two groups (p>0.05). After APBSCT, the median time for neutrophil count>or=0.5x10(9)/L and the median time for platelet count>or=20x10(9)/L were 10.5 and 11.5 days in experimental group, while were 13 and 13 days in control group, respectively. The median amount of apheresed platelet transfusion was 3.5 unit in experimental group and 5 unit in control group. Data were significantly different between two groups (p<0.05). The adverse reactions of mobilization were mild fever, fatigue, symptoms like as common cold, poor appetite, dizziness, muscular soreness in experimental group, but only mild fever in control. These symptoms were well tolerated and overcome with drug withdrawal. It is concluded that the regimen of rhIL-11 in combination with rhG-CSF after myelosuppressive chemotherapy to mobilize PBSC is efficient and safe with rapid hematologic reconstitution and less platelet transfusions after APBSCT were used.

The aim of this study was to evaluate the safety and efficacy of allogeneic hematopoietic peripheral blood stem cell transplantation (allo-PBHSCT) for post-operative therapy of acute non-lymphocytic leukemia (ANLL) patient complicated with renal cell carcinoma (RCC). One ANLL patient complicated with RCC underwent an myeloablative HLA-identical relative allo-PBHSCT after RCC operation. The conditioning regimen consisted of total body irradiation, cyclophosphamide and cytarabine. Graft versus host disease (GVHD) prophylaxis regimen composed of cyclosporine A, myco-phenolate mofetil and short course of methotrexate. The results indicated that the patient achieved engraftment 16 days after transplantation with full donor-type chimerism detected by STR-PCR at 30 and 100 days after transplantation. No acute or chronic GVHD and any severe complication developed. As of March 2007, the patient remains without disease at follow-up of 44 months. In conclusion, allo-HSCT procedure is feasible and effective for post-operative therapy of ANLL patient complicated with RCC without severe toxicity.

Sphingosine 1-phosphate (S1P) is an important biologically active lysophospholipid that transmits signals through a family of G-protein-coupled receptors (GPCRs) to regulate the vital functions of several types of immune cells. The S1P GPCRs suppress both generation of specialized functional cytokines, such as IFN-gamma and IL-4, and proliferation of T-cells. Although S1P is chemotactic to T cells, B cells, dendritic cells, and natural killer cells, the major effect of S1P on the immune system is the regulation of lymphocyte recirculation and tissue distribution by S1P and S1P1. Chemotactic response of CD4+CD25+ regulatory T cells to S1P is reduced, but its optimal suppressive activities require S1P. FTY720, a new class of immunomodulator, is rapidly phosphorylated by sphingosine kinase 2 in vivo to form the biologically active phosphorylated-FTY720 (FTY720-P), which closely resembles S1P. The FTY720-P is a true agonist for S1P1, S1P3, S1P4, and S1P5, it affects the tissue distribution and functional activity of T cells, B cells, dendritic cells and regulatory T cells. FTY720 were demonstrated to be a hypotoxic, great effective and reversible immunosuppressive efficacy to prevent allograft rejection and treat some autoimmune diseases. In this article, the synthesis and metabolism of S1P, the expression of S1P GPCRs in immune cells, the effect of S1P on immune cells, the drugs targeted to S1P GPCRs and their clinical implications are reviewed.

The aim of study was to explore the incidence, risk factors, outcome and efficacious treatment of late-onset noninfectious pulmonary complications (LNIPC) after allogeneic peripheral blood stem cell transplantation (allo-PBSCT). Seventy patients received allo-PBSCT were analyzed retrospectively. The results showed that 9 out of 63 patients surviving more than 3 months occurred late-onset noninfectious pulmonary complications (14.3%). Five out of the 9 patients developed secondary pulmonary infections. In 4 patients, LNIPC caused death directly. Advanced stage of disease at transplantation and extensive chronic graft-versus-host disease (GVHD) happened in association with LNIPC. However, other transplantation-related factors including age at transplantation, gender of patient, conditioning regimen, HLA matching and GVHD prophylaxis were not significantly correlated with the incidence of LNIPC. It is concluded that performing pulmonary function test (PFT) and thoracic computer tomography should be taken routinely after transplantation. Most patients who get correct and early diagnosis for LNIPC will show a positive response to prednisone with or without CsA.

This study was aimed to explore feasibility and efficacy of unrelated donor peripheral blood stem cell transplantation (UD-PBSCT) in treatment of hematologic malignancies. Ten patients with hematologic malignancies underwent high resolution DNA based typing HLA-matched or 1 locus mismatched UD-PBSCT. Busulfan, cyclophosphamide, Ara-C, MeCCNU and antithymocyte globulin (ATG) were used for preconditioning regimen in all cases. All patients received mycophenolate mofetile, cyclosporin A and short-term methotrexate with CD25 antibody as the graft-versus-host disease (GVHD) prophylaxis. The results showed that rapid engraftment was observed in all cases who presented full donor chimerism at 28 days post transplantation by STR-PCR. The median time of neutrophil recovery > 0.5 x 10(9)/L, platelet recovery > 20 x 10(9)/L was 13, 17.5 days respectively after transplantation. The incidence of acute GVHD was 3 cases (one case with grade I was recovered from GVHD by himself, one case with grade III was cured, one case with grade VI was died). It is concluded that above-mentioned preconditioning regimen and GVHD prophylaxis are effective approaches for unrelated donor peripheral blood stem cell transplantation in hematopoietic malignancies.

To investigate the changes of donor's peripheral blood immunocytes after mobilization with medium-dose recombinant human granulocyte-colony stimulating factor (rhG-CSF), the amounts of immunocytes in peripheral blood cells and the immunocyte components of donor peripheral blood mononuclear cells (PBMNC) in 12 healthy donors were detected by flow cytometry before and after mobilization with rhG-CSF 10 microg/(kg.day). The results showed that the median amounts of peripheral blood leukocytes before mobilization was 6.25 (4.7-7.8) x 10(9)/L, for lymphocytes it was 2.07 (1.63-3.10) x 10(9)/L, and for monocytes it was 0.163 (0.078-0.414) x 10(9)/L. In the fifth day after mobilization, the median amounts of peripheral blood leukocytes was 37.47 (24-72.57) x 10(9)/L, and for lymphocytes it was 3.22 (1.46-5.31) x 10(9)/L, and for monocytes, it was 1.2 (0.706-3.627) x 10(9)/L. The average amount of leukocytes after mobilization was 6.26 +/- 2.14 multiple of that before mobilization (P < 0.01), and the median amounts of lymphocytes after mobilization was 1.45 +/- 0.76 multiple of that before mobilization (P < 0.05), and the amount of monocytes after mobilization was 7.48 +/- 4.41 multiple of that before mobilization (P < 0.01). The median percentage of CD3(+) T lymphocytes before mobilization was 46.96% [(32.36-57.45)%], but 40.94% [(25.31-48.9)%] after mobilization. The ratio of CD4(+)/CD8(+) before mobilization was 1.27 +/- 0.46, while 1.36 +/- 0.51 after mobilization. The median percentage of CD4(+)CD8(+) T lymphocytes was 0.41% [(0.16-1.51)%], and 0.49% [(0.09-2.0)%] after mobilization. The median percentage of CD16(+)CD56(+) NK cells was 13.98% [(4.08-25.08)%] versus 16.65% [(12.06-33.05)%] after mobilization. The median percentage of CD3(+)CD16(+)CD56(+) NK-T cells was 2.75% [(0.37-6.38)%], but 3.13% [(0.46-5.95)%] after mobilization. The median percentage of CD20(+) B cells was 9.28% [(5.97-16.33)%], while 9.94% [(7.36-20.41)%] after mobilization. The median percentage of CD14(+) monocytes was 12.48% [(3.54-19.35)%] versus 29.52% [(16.51-36.76)%] after mobilization. The percentage of CD3(+) T lymphocytes, CD4(+)CD8(+) T lymphocytes, NK cells, NK-T cells and B lymphocytes in PBMNC did not change markedly before and after mobilization with middle-dose rhG-CSF. The ratio of CD4(+)/CD8(+) did not change significantly (P > 0.10). The percentages of CD14(+) monocytes in PBMNC after mobilization increased up to 2.87 +/- 1.51 higher than that before mobilization (P < 0.05). It is concluded that the changes of the CD14(+) monocytes after mobilization with rhG-CSF may be involved in graft rejection and graft versus host disease after allo-PBSCT.