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

To investigate the effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on chemokine receptors and explore the potential mechanism of rhG-CSF inducing immune tolerance, ninety-seven donor and recipient pairs undergoing family-donor allogeneic hematopoietic stem cell transplantation were studied. The results indicated that different donors showed great disparities in expression changes after mobilization. Multivariate analysis revealed that both HLA mismatching and CCR7 downregulation on donors' CD4+ T cells after mobilization were independent risk factors for acute graft-versus-host disease (GVHD). In contrast, CCR5 downregulation on CD4+ T cells was associated with reduced incidence of acute GVHD. In conclusion, rhG-CSF mobilization could lead to differential regulation of chemokine receptors expression on T cell subsets in different donors. Downregulation of CCR5 and upregulation of CCR7 expression on donor CD4+ T cells might protect recipients from acute GVHD. This finding may provide a promising new strategy for the prevention and treatment of acute GVHD.

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

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

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

To investigate the expression level of HB-1 gene in patients with acute lymphoblastic leukemia (ALL) and the significance of HB-1 gene in monitoring of minimal residual disease (MRD).The method of real-time fluorescence quantitative RT-PCR (Taqman probe) was established to detect the expression levels of HB-1 gene; then the sensitivity, specificity and repeatability of this assay were evaluated and verified. The HB-1 gene expression levels in bone marrow of 183 cases of ALL, 70 cases of acute myeloid leukemias (AML), 52 cases of non-malignant hematologic diseases and 24 healthy hematopoietic stem cell donors were detected. The correlation of HB-1 level with diagnosis and relapse was analyzed by detecting bone marrow samples of 33 B-ALL.The sensitivity of this assay reached the 10HB-1 gene specifically expressed in acute B lymphoblastic leukemia cells. The established real-time fluorescence quantitative RT-PCR assay shows good sensitivity, specificity and repeatability, thus, can be used as a biological marker in the clinical detection, monitoring MRD and predicting of early relapse for B-ALL patients.

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

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

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

To summarize the clinical experience and evaluate the efficacy of haploidentical HSCT.The survival rates of 156 patients receiving either haploidentical (83 cases) or HLA-identical (73 cases) transplantation for hematologic diseases were compared and risk factors related to overall survival (OS) were analyzed.HLA-identical and haploidentical cohorts were not statistically different in the hematopoietic reconstitution, incidence of acute and chronic graft-versus-host disease (GVHD), OS, disease-free survival (DFS), relapse and treatment-related mortality (TRM) after transplantation. Multivariate analysis showed that advanced disease status, relapse and grade III-IV acute GVHD were independent prognostic indictors for OS with relative risk (RR) of 4.8 (95% CI 2.2-10.1), 4.3 (95% CI 2.6-8.0) and 3.3 (95% CI 1.6-7.0), respectively (P0.05).Haploidentical transplantation with the present conditioning can achieve the therapeutic effects comparable to HLA-identical sibling transplantation. Disease status before transplantation and the presence or not of severe GVHD after transplantation have important significance for the long-term survival after transplantation.

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

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

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

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

This study was to investigate the differential regulation of CCR5 expression on T cells in healthy donors after mobilization with recombinant human granulocyte colony-stimulating factor (rhG-CSF) and analyze its correlation with acute graft-versus-host disease (aGVHD) so as to understand the possible mechanisms underlying rhG-CSF-induced immune tolerance. Sixty-eight related healthy donor and their corresponding recipient for allogeneic hematopoietic stem cell transplantation (allo-HSCT) were enrolled in this study. The expression of CCR5 on CD4(+) and CD8(+) T cells in the peripheral blood (PB) before and after mobilization were detected by using flow cytometry (FCM) respectively. According to the changes of CCR5 expression on CD4(+) and CD8(+) T cells, the Sixty-two evaluable donors were divided into the downregulated and unchanged/upregulated (non-downregulated) groups, and the incidence of grades II to IV aGVHD in two groups were compared. The results showed that the mean value of CCR5 expression on CD4(+) and CD8(+) T cells in PB was not different significantly after mobilization (P0.05). Apparent inconsistency was showed among different individuals. Thirty-four (50%) donors displayed downregulation of CCR5 expression, while 34 (50%) donors manifested unchanged or upregulated CCR5 expression on CD4(+) T cells. CCR5 expression on CD8(+) T cells was downregulated in 42 (61.8%), unchanged or upregulated in 26 (38.3%) donors. The cumulative incidence of grades II to IV aGVHD in the downregulated and non-downregulated groups for CD4(+) T cells were 16.1% and 41.9% (P = 0.032), and recipients with CCR5 downregulation on CD8(+) T cells showed an increased tendency of developing aGVHD (37.8% vs 16.0%, P = 0.065). In conclusion, rhG-CSF mobilization could lead to differential regulation of CCR5 expression on T cells, which might influence the migration of T cells in vivo, decrease T cell trafficking towards GVHD target organs, and thus reduce the incidence of aGVHD after transplantation.

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

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

To investigate the clinical manifestation, diagnosis and treatment of respiratory amyloidosis.Data of 11 patients with respiratory amyloidosis diagnosed by biopsy in Peking University First Hospital from January 2002 to January 2012 were analyzed, and the related literatures were reviewed.In the last decade, 250 of 389 402 hospitalized patients were pathologically diagnosed as having amyloidosis, and 11 cases were pathologically confirmed to be respiratory amyloidosis. In these 11 patients, 4 cases were with serum amyloid A (AA) amyloidosis and 7 with light-chain (AL) amyloidosis. The main clinical manifestations included hoarseness, cough and dyspnea. In 4 cases with AA type unilateral larynx was involved and there was no recurrence after surgical resection. Of 7 cases with AL type, 2 cases had involvement of bilateral larynxes and both relapsed after surgery. Diffuse involvement of trachea and bronchi was found in 4 cases, and the chest CT scans showed diffuse thickening and local calcification of the airway wall, bronchial stenosis and nodules protruding into the lumen. Bronchoscopy showed airway mucosal hypertrophy, hyperemia, edema and bronchial stenosis. Lung involvement was found in 3 cases, 2 of which presented with diffuse pulmonary interstitial infiltrates, and another case presented with solitary pulmonary mass and extrapulmonary lesions. Of the 7 cases with AL type, 3 cases were treated by chemotherapy and/or radiotherapy, 3 received surgery, 2 underwent autologous hematopoietic stem cell transplantation, and 2 underwent bronchoscopic interventional therapy. Within 3 years of follow-up, 4 patients were alive, 2 dead and 1 lost to follow up.Respiratory amyloidosis, which can be divided into AA and AL types, is clinically rare. Patients with AA type usually present with local lesions, which can be cured by surgery, while patients with AL type often present with diffuse lesions and require integrated therapies including surgery, interventional treatment, chemotherapy, radiotherapy, and autologous hematopoietic stem cell transplantation.

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

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

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

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

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

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

Wide application of umbilical cord blood transplantation (UCBT) in adult patients is limited by low cell-dose available in one umbilical cord blood (UCB) unit. The aim of this study was to investigate the safety and long-term outcomes of UCBT from unrelated donors in adult and adolescent patients with leukemia.Thirteen patients with leukemia received double-unit UCBT with human leukocyte antigen (HLA) mismatched at 0 - 2 loci. We analyzed the engraftment, graft-versus-host disease (GVHD) and survival.Twelve evaluable patients (92.3%) had neutrophil and platelet engraftment at a median of 21 days (range, 16-38 days) and 34 days (range, 25 - 51 days), respectively. At day 30, engraftment was derived from one donor in 8 patients (66.7%, 95%CI 40.0% - 93.4%), and from both donors in 4 patients (33.3%, 95%CI 6.7% - 60.0%) with 1 unit predominated. Unit with larger nucleated cell (NC) dose would predominate in engraftment (P = 0.039), whereas CD34(+) cell dose or HLA-match failed to demonstrate any relationship with unit predominance. Only one patient developed grade II acute graft-versus-host disease (aGVHD). Chronic GVHD (cGVHD) was observed in 2 of 11 patients who survived more than 100 days, and both were limited. The median follow-up after transplantation for the 13 patients was 45 months (range 1.5 - 121.0 months) and 72 months (range 41.0 - 121.0 months) for the 8 alive and with full donor chimerism. The 5-year cumulative disease free survival (DFS) was (61.5 ± 13.5)%. Of the 13 patients, 5 patients died in 1 year and 1-year transplantation related mortality (TRM) was 23.1% (95%CI 0.2% - 46.0%).Double-unit UCBT from unrelated donors with HLA-mismatched at 0-2 loci may overcome the cell-dose barrier and be feasible for adults and adolescents with leukemia.

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

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

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

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

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

The objective of this study was to analyze the relationship between some chemokines and the pathogenesis of GVHD and to find some biomarkers with diagnostic significance through observing and comparing the changes of some chemokine levels in samples from patients with or without aGVHD after allogeneic hematopoietic stem cell transplantation (allo-HSCT). 26 plasma samples were obtained from 26 patients undergoing allo-HSCT at various time points after transplantation, of which 13 samples from patients with aGVHD were served as investigating group and 13 samples from patients without GVHD after Allo-HSCT were used as control group. The patient characteristics between the two groups were compared, the levels of 40 chemokines in these samples were detected by ELISA, the changes of chemokine levels in samples of 2 groups were analyzed by means of significance analysis microarray (SAM), clustering method and c-test. The results showed that there were significant differences in levels of 6 chemokines including HCC-1, MIF, IP-10, ITAC, TARC and NAP-2 between 2 groups, in which the level of MIF in plasma samples after HSCT was the highest, the difference of TARC level between 2 groups was over 10-fold. It is concluded that the level changes of chemokines mentioned above can be used as a indicator of GVHD presence, but their pathogenetic role in occurrence of aGVHD remains to be determined.

The aim of this study was to investigate the incidence, risk factors of acute renal failure (ARF) after allogeneic hematopoietic stem cell transplantation (allo-HSCT), and evaluate its effect on the prognosis of patients after allo-HSCT. A retrospective analysis was performed in 86 patients undergoing allo-HSCT at Peking University First Hospital from June 2003 to April 2007. ARF is defined as a doubling of baseline serum creatinine at any time during the first 100 days post-transplant. The risks of ARF and mortality after ARF were examined using univariate analysis and multivariate unconditional logistic regression. The correlation of ARF and survival was examined using Cox regression. The results indicated that 27 patients (31.40%) developed ARF at a median of 59.5 days after transplant (range 1 to 93 days). The univariate analysis showed that elevated risks were severe acute GVHD (OR 6.196; 95% CI 1.121 - 34.249, p = 0.033), sepsis or septic shock (OR 4.184; 95% CI 1.314 - 13.325, p = 0.018) and hyperbilirubinemia (OR 3.709; 95% CI 1.428 - 9.635, p = 0.006). Renal disease before transplant (OR 6.711; 95% CI 1.199 - 37.564, p = 0.027), hypertension (OR 2.067; 95% CI 0.739 - 5.782, p = 0.165), the use of vancomycin (OR 2.133; 95% CI 0.844 - 5.392, p = 0.106) or foscarnet sodium (OR 2.133; 95% CI 0.844 - 5.392, p = 0.106) may be potential risks. Multivariate logistic regression analysis showed that renal disease before transplant (OR 6.288; 95% CI 1.218 - 32.455, p = 0.028), sepsis or septic shock (OR 3.614; 95% CI 1.040 - 12.544, p = 0.043) and hyperbilirubinemia (OR 4.448; 95% CI 1.563 - 12.665, p = 0.005) appear to be independently associated with an increased risk of ARF. Age, gender, baseline serum creatinine level, advanced malignant disease, unrelated-donor, total body irradiation (TBI) and cyclosporine levels were not associated with the development of ARF. Cox regression showed that ARF (RR 2.124; 95% CI 1.016 - 4.441, p = 0.045) was independently associated with survival of patients after allo-HSCT. The mortality of patients with ARF within 6 months post-transplant was significantly higher than that of those without ARF (44.4% vs 8.47%, p0.001). It is concluded that the cumulative incidence of ARF after allo-HSCT remains high. Renal disease before transplant, hyperbilirubinemia and sepsis or septic shock are all related factors which can increase the risk of ARF. ARF appears to be independent factor influencing survival of patients after allo-HSCT.

To explore the therapeutic feasibility of allogeneic hematopoietic stem cell transplantation (allo-HSCT) from partially HLA-mismatched related donors for hematologic diseases.Thirty patients with hematologic diseases received allo-HSCT from 1 - 3 loci mismatched related donors conditioning regimen consisting of ATG (thymoglobulin, total dose of 10 mg/kg, intravenously on - 4 d to - 1 d), and only 5 (18%) of 28 recipients from HLA-identical sibling donors were treated with regimen containing ATG. Donors were given G-CSF prior to hematopoietic stem cell harvest and CsA, short-term MTX and mycophenolate mofetil (MMF) were used for GVHD prophylaxis in both group.All patients were successfully engrafted. There was no significant difference in the incidence of grade II to IV acute graft-versus-host disease (aGVHD) and grade III to IV aGVHD between the mismatched and matched groups (34% vs 32%, and 13% vs 11%, respectively). 3-year overall survival (OS) and disease-free survival (DFS) in mismatched and matched groups were 57% vs 77% (P = 0.14) and 57% vs 69% (P = 0.28), respectively. Multivariate analysis showed that advanced disease pre-transplant (P = 0.006) and CMV infection (P = 0.04) were risk factors for OS. OS for patients with stable disease in mismatched and matched groups were 87% vs 81% (P = 0.65) respectively, and for those with advanced disease were 21% vs 71% (P = 0.02).It is feasible to perform allo-HSCT from 1 -3 loci HLA-mismatched related donors for patients with stable disease who lack HLA-identical sibling donors. Nevertheless, for patients with advanced disease optimized conditioning regimen and intensive supporting therapy should be administered to obtain better clinical outcomes.

The aim of this study was to investigate the relationship between the plasma levels of chemokine CCL-2/MCP-1 and acute graft-versus-host disease (aGVHD) and/or idiopathic pneumonia syndrome (IPS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). ELISA assays were used to detect the plasma level of CCL-2/MCP-1 of 22 patients who received allo-HSCT, including 14 patients without or with grade I, 8 patients with grade II - IV aGVHD, respectively. 8 out of 22 patients were also diagnosed with IPS clinically. The dynamic changes of the plasma levels of CCL-2/MCP-1 chemokine and its correlation with aGVHD and/or IPS were analysized retrospectively. The results showed that the plasma levels of CCL-2/MCP-1 in the patients with moderate and serious aGVHD (grade II - IV) significantly increased, as compared with that prior to allo-HSCT (p0.05). The plasma levels of CCL-2/MCP-1 in the patients with aGVHD and/or IPS were higher significantly than those without any of these complications (p = 0.001). The retrospective analysis indicated that the plasma levels of CCL-2/MCP-1 in the patients with IPS significantly increased (p = 0.006). It is concluded that plasma level of CCL-2/MCP-1 correlates with aGVHD and/or IPS, and plays a role in the pathogenesis of these complications.

To observe the engraftment, survival and graft-versus-host disease (GVHD) after 2 units unrelated cord blood (UCB) transplantation for treatment of adult hematological malignancies.Among twelve patients with hematological malignancies, ten were in stable stage and 2 in advanced stage. Conditioning regimen was Bu/Cy or Cy/TBI in 11 cases, and 1 received nonmyeloablative regimen. Antithymocyte globulin (ATG) was administered in all patients. GVHD prophylaxis consisted of cyclosporine A (CsA), mycophenolate mofetil (MMF) and short course methotrexate (MTX). Each patient received 2 units UCB of HLA mismatched at 0 -2 loci. Median total nucleated cells (TNC) infused was 5.55 x 10(7)/kg [range (2.99 -8.18) x 10(7)/kg].One patient showed primary graft failure. The other 11 patients showed neutrophil engraftment at a mean time of (21.6 +/- 5.1) days and platelet engraftment at (34.9 +/- 9.5) days. One patient showed secondary graft failure and died of leukemia relapse at 3 months after transplantation. Ten patients (83.3%) gained sustained engraftment. In 9 patients the UBC unit with larger TNC dose predominated engraftment, and only 1 patient showed the unit with smaller TNC predominated (P = 0.011). Acute GVHD was observed in 6 patients, including grade I in 5 and grade II in 1. Limited chronic GVHD was observed in 2 of 10 patients survived more than 100 days. Of the total 12 patients, eight were still alive in event-free status and 3-year event-free survival(EFS) was (66.7 +/- 13.6)%. Of the 10 patients in stable stage at the time of transplantation, the probability of EFS was (70.0 +/- 14.5 )%.Two UBC units transplantation with HLA mismatched at 0 - 2 loci is feasible as a treatment modality for adult hematological malignancies, and the unit with larger TNC dose would predominate the engraftment.

To observe whether rhIL-11 could accelerate the engraftment of platelets after unrelated cord blood transplantation (CBT).Nine patients (3 children and 6 adults) were enrolled in this study. The degree of HLA disparity was 0-2 loci. Cord blood was given two units for adults and one unit for children. Conditioning regimens were CY/TBI in 1 and BU/CY in 8 cases, both with antithymocyte globulin. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and short-term methotrexate. On day +1, rhIL-11 was used at 50 microg x kg(-1) x d(-1) and G-CSF at 5 microg x kg(-1) x d(-1) to accelerate hematopoiesis recovery.The median age of the patients was 22.3 years and the median weight 52.3 kg. Among the 9 patients, 8 (88.9%) experienced engraftment. The median time to neutrophil0.5 x 10(9)/L was 21.3 (14-37) days and to platelet20 x 10(9)/L was 25 (18-36) days. 42.9% of the patients developed grade I aGVHD and 33.3% developed localized chronic GVHD. Six patients were alive and disease-free at a median follow-up of 7 months. Infection was the primary cause of death. The expected 1-year survival was 77.8%, 2-year survival was 52.2%. Five of 8 patients (62.5%) who received IL-11 presented leakage syndrome. On prophylaxis with drugs containing Arnebia root extract, all patients could tolerate the treatment.rhIL-11 maybe helpful for accelerating the platelet recovery and reducing aGVHD severity in unrelated CBT. The major side effect is leakage syndrome. It is well tolerated on prophylaxis with drugs containing Arnebia root.

To investigate the relationship between the plasma levels of chemokine CXCL9/Mig and acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The plasma levels of CXCL9/Mig of 35 patients who received all-HSCT were detected by using ELISA assay, these patients included 13 patients with grade 0-I, 12 patients with grade II and 10 patients with grade III - IV aGVHD, respectively. The four different time points including prior to allo-HSCT, one week before aGVHD onset, the plateau of aGVHD and time after completely controlled, were studied. The results showed that the plasma levels of CXCL9/Mig in the patients with serious aGVHD (grade II - IV) were significantly increased during aGVHD than those in the patients without aGVHD or with slight aGVHD (P0.001). It was found that CXCL9/Mig levels were significantly correlated with the severity of grade aGVHD (P0.001). Another important finding was that CXCL9/Mig levels obviously increased at one week before aGVHD was diagnosed. CXCL9/Mig level was not obviously correlated with CMV infection or other infectious complication (P0.05). It is concluded that the plasma level of CXC19/Mig significantly correlated with the severity of aGVHD and plays a critical role in pathogenesis of aGVHD, the changes in plasma level of CXCL9/Mig after allo-HSCT may be used as a valuable indicator for early diagnosis of aGVHD, finally, provide a early therapeutic approach to reduce aGVHD severity and improve the outcome for patients after allo-HSCT.

Introduction To study the correlation of chemokine receptors expression on T lymphocyte subsets in recipients after allogeneic hematopoietic stem cell transplantation (allo-HSCT) with acute graft-versus-host disease (acute GVHD). Methods Forty-four recipients of family donor allogeneic hematopoietic stem cell transplantation were included in this study. According to the severity of acute GVHD, the recipients were divided into Grade II-IV acute GVHD group (n=16) and Grade 0-I acute GVHD group (n=28). Additionally,fifty healthy donors were also included in this study as the control group (n=50). The expression of chemokine receptors (CCR2,CCR5,CCR6,CCR7,CCR9 and CXCR3) on CD4+ and CD8+T cells in the peripheral blood after transplantation were detected using flow cytometry (FCM) respectively. The differences of the chemokine receptors expression between each group were compared. Results In both Grade 0-I acute GVHD group (on the 30th day after transplantation) and Grade II-IV acute GVHD group (at the peak of GVHD), CCR5 expression was significantly higher than that in the control group (p Conclusions Chemokine receptors on T cell subsets are involved in the pathogenesis of acute GVHD. Expression of chemokine receptors can be used as a powerful marker for early diagnosis and differential diagnosis of acute GVHD. And targeting chemokine receptors might be the new direction of prevention and treatment of acute GVHD. Disclosures: No relevant conflicts of interest to declare.

Introduction This study is aimed to investigate chemokine receptors (CCR5, CCR6, CCR7, CCR9, CXCR3 and CCR2) expression on T cell subsets in healthy donors after mobilization with recombinant human granulocyte colony-stimulating factor (rhG-CSF) and analyze its correlation with acute graft-versus-host disease (aGVHD) and to understand the possible mechanisms underlying rhG-CSF-induced immune tolerance. Methods Sixty-eight healthy donor and their recipient pairs of family donor allogeneic hematopoietic stem cell transplantation (allo-HSCT) were included in this study. The expressions of chemokine receptors on CD4+ and CD8+ T cells in the peripheral blood (PB) before and after mobilization was detected using flow cytometry (FCM) respectively. Six chemokine receptors (CCR2, CCR5, CCR6, CCR7, CCR9 and CXCR3) were detected on T cell subsets in all the donors, and CCR5 and CCR7 were detected only in eighteen of all the donors. The expressions of chemokine receptor before and after mobilization was compared and its correlation with II-IV aGVHD were analyzed. Results After rhG-CSF mobilization, the expression of CCR9 on CD4+ T cells and CCR7 on CD8+ T cells were significantly upregulated compared with that before mobilization (p0.10). However, different individuals showed apparent inconsistencies. According to the changes of chemokine receptor expression on CD4+ and CD8+ T cell subsets, the evaluable donors and their relevant recipients were divided into the down-regulated group and the non-down-regulated (unchanged or up-regulated ) group. The incidence of grade II to IV aGVHD in the two groups were compared in their corresponding recipients. In the univariate analysis, mismatched HLA (p=0.046), down-regulation of CCR7 expression on donor CD4+ T cell subsets (p=0.010), unchangeableness or up-regulation of CCR5 expression on donor CD4+ T cell subsets (p=0.032) and CCR6 down-regulation on donor CD8+ T cells (p=0.045) were risk factors for recipients to develop II-IV aGVHD. In the multivariate analysis, down-regulation of CCR7 expression on donor CD4+ T cells after rhG-CSF was independent risk factor for II-IV aGVHD [RR=3.5, 95% CI (1.3-9.4), p=0.012], while CCR5 down-regulation on CD4+ T cells could reduce the incidence of II-IV aGVHD [RR=0.3, 95% CI (0.1-0.8), p=0.031]. Conclusions rhG-CSF mobilization could lead to differential regulation of chemokine receptors expression on T cell subsets, which might cause different effects on the migration of T cells in vivo, and decrease T cells trafficking towards GVHD target organs, and thus reduce the incidence of aGVHD after transplantation. Disclosures: No relevant conflicts of interest to declare.

The aim of this study was to investigate the expression of chemokine receptors on T cells and functional changes of T helper (Th) cells in peripheral blood stem cell (PBSC) harvests after treating healthy donors with recombinant human granulocyte colony-stimulating factor (rhG-CSF). Using multiparameter flow cytometry, we analyzed the expression of CXCR3 and CCR6 on T cells and the production of interferon-gamma (IFN-gamma), interleukin-4 (IL-4), and IL-17 by CD4(+) Th cells in PBSC grafts of healthy donors after in vivo rhG-CSF application. Alterations in the relative expression levels of T cell receptor beta variable (TCRBV) family members were determined using real-time polymerase chain reaction (PCR). rhG-CSF mobilization significantly decreased the expression of CXCR3 and CCR6 on T cells. Treating donors with rhG-CSF resulted in decreased IFN-gamma production and dramatically increased IL-4 and IL-17 secretion by CD4(+) Th cells, leading to T cell polarization from the Th1 to the Th2 phenotype and a preferential increase in IL-17-producing CD4(+) Th cells. We did not observe any differences in the relative expression levels of TCRBV family members before and after in vivo rhG-CSF application. Our results suggest that the expression of CXCR3 and CCR6 on donor T cells was dramatically downregulated and an IL-17 phenotype of CD4(+) Th cells was preferentially induced in PBSC grafts after treating healthy donors with rhG-CSF. The observed effects of rhG-CSF on T cells may be independent of the relative expression levels of TCRBV family members.