Wang Sh

Unmanipulated HLA-mismatched/haploidentical peripheral blood stem cell transplantation for high-risk hematologic malignancies.

BACKGROUND: Haploidentical hematopoietic stem cell transplantation (HSCT) has been increasingly applied in high‐risk hematologic patients due to the absence of HLA‐matched donors. The aim of this study was to investigate the efficacy and safety of unmanipulated haploidentical allogeneic peripheral blood stem cells transplantation (PBSCT) for hematologic malignancies.

The efficacy and safety of rabbit anti-thymocyte globulin vs rabbit anti-T-lymphocyte globulin in peripheral blood stem cell transplantation from unrelated donors

The comparative efficacy and safety of antithymocyte globulin (ATG) at fixed doses in patients undergoing allogeneic peripheral blood stem cell transplantation from unrelated donors (UR-PBSCT) has not been evaluated. In this study, the records of 56 patients and 54 patients who received pre-transplant ATG-Thymoglobulin (ATG-T) at a total dose of 10 mg/kg and ATG- Fresenius (ATG-F) at a total dose of 20 mg/kg, respectively, were retrospectively analyzed. ATG-F patients had a significantly lower probability of developing chronic graft-vs-host disease (cGVHD) than those treated with ATG-T (p = 0.04). ATG-F was associated with a non-significant trend towards lower relapse rates and higher survival at 3- and 5-years of follow-up compared with ATG-T. A significantly greater proportion of ATG-T patients experienced chills and high fever than ATG-F patients (p < 0.01). The current findings suggest that ATG-F may more effectively and safely prevent cGVHD without increasing relapse rates in patients undergoing UR-PBSCT.

Long-term outcomes of peripheral blood stem cell transplantation for 38 patients with peripheral T-cell lymphoma.

OBJECTIVE In this study, to investigate clinical characteristics, response, outcome, and prognosis of peripheral blood stem cell transplantation (PBSCT) for patients with peripheral T-cell lymphoma (PTCL). METHODS This study retrospectively analyzed the efficacy of PBSCT in 38 patients with PTCL. Kaplan-Meier methods were used in survival analysis, and the Cox regression model was applied in multivariate analysis. There were ten clinical parameters were analyzed. RESULTS The 2-year overall survival (OS) was 46%, and the 5-year OS was 34% after a median follow-up of 40 months. The patients who received allogeneic PBSCT (allo-PBSCT) had a higher nonrelapse mortality than autologous PBSCT (auto-PBSCT), but they could achieve a longer-term disease-free survival in the former, which OS could achieve 40%. Survival analysis with Kaplan-Meier method showed the pretransplant disease status, B symptoms, serum lactate dehydrogenase (LDH) in early (>275 U/L), Eastern Cooperative Oncology Group (ECOG) score (>1), prognostic index for PTCL score (>2) were all prognostic factors for posttransplant OS. Pretransplant disease status is the only prognostic factor for allo-PBSCT. CONCLUSION The key was to reducing transplant-related mortality of allo-PBSCT by reduced-intensity conditioning. Factors such as level of early serum LDH, extranodal involvement, B symptoms, ECOG score, Ann Arbor stage, and pretransplant disease status were all related to the prognosis of patients treated with PBSCT. Allo-PBSCT maybe suggested as the first line therapy for late-stage PTCL patients who could reach treatment remission before transplantation.

Primary antifungal prophylaxis: decrease of invasive fungal disease incidence and reduction of risk factors in haematological patients in a 5-year retrospective study: PAP in haematological patients

Invasive fungal disease (IFD) is a major cause of morbidity and mortality in patients with haematological malignancies.

Sorafenib as a Salvage Therapy in FLT3-ITD Negative Relapse/Refractory Acute Myeloid Leukemia

BACKGROUND Multi-kinase inhibitor sorafenib showed dramatic effects in acute myeloid leukemia (AML) cells harboring fms-related tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutation. However, FLT3-ITD mutation only occurs in 25% of AML cases. The therapeutic effects of sorafenib in AML patients without FLT3-ITD are still in need of further investigation. METHODS A young AML patient with central nervous system (CNS) relapse was treated with sorafenib combined with chemotherapy. Another patient with refractory AML arising form chronic myelomonocytic leukemia (CMML) was treated with sorafenib monotherapy. Spinal and cranial magnetic resonance imaging (MRI), minimal residual disease (MRD) and peripheral blood cell count were monitored to evaluate disease status. RESULTS The patient with CNS relapse exhibited significant shrink of tumor volume. The other patient with refractory AML achieved hematological improvements. CONCLUSION These two cases suggested that sorafenib might be utilized as a potent salvage therapy for some refractory/relapsed AML patients without the FLT3-ITD mutation.

[Clinical characteristics and prognostic analysis of 90 patients with primary gastro-intestinal marginal zone lymphoma].

目的 了解原发胃肠道黏膜相关淋巴组织结外边缘区B细胞淋巴瘤（MALT淋巴瘤）患者临床特征及预后情况。 方法 回顾性分析90例原发胃肠道MALT淋巴瘤患者资料，对患者临床特征和相关预后因素进行分析。 结果 90例患者中胃内起病者78例，非胃内起病者12例。国际预后指数（IPI）评分0~2分者80例，3~5分者10例。与胃内起病者比较，非胃内起病者多为IPI 3~5分的高危患者（7.7%对33.3%，P=0.025）、幽门螺旋杆菌（Hp）感染率显著降低（50.0%对87.2%，P<0.01）。IPI评分0~2分的低危患者可选择抗Hp治疗、手术、放疗及化疗等治疗，其中化疗可提高患者无进展生存（PFS）率。接受化疗的高危患者3年总生存（OS）率达100.0%。单因素分析结果显示，ECOG评分（P=0.006）、Musshoff分期（P=0.008）、IPI评分（P=0.000）、LDH水平（P=0.019）和是否接受化疗（P=0.026）是影响患者PFS率的相关因素。多因素分析结果显示IPI评分（3~5分）（OR=8.325，95%CI 3.171~21.853，P= 0.000）和是否接受化疗（OR=0.319，95% CI 0.121~0.838，P=0.020）是影响患者PFS率的独立预后因素，ECOG评分（≥2分）是影响患者OS率的独立预后因素（OR=5.092，95% CI1.005~25.788，P=0.049）。 结论 原发胃肠道MALT淋巴瘤是一种低度恶性的淋巴瘤，以低危患者多见，多数患者可获得长期生存。低危患者可选择放疗或抗Hp治疗作为起始治疗方案，高危患者应选择化疗。OBJECTIVE To evaluate the clinical characteristics and prognostic factors of patients with primary gastro-intestinal marginal zone lymphoma (MALT). METHODS Retrospective analysis was performed in 90 patients diagnosed with primary gastro-intestinal MALT lymphoma clinical characteristics and survival analyses. RESULTS Among 90 patients, 78 cases were originated from the stomach and 12 cases with extra-gastric origin. Eighty patients were classified as low-risk (IPI score 0-2), and 10 patients high-risk (IPI score 3-5). Compared to gastric MALT patients, extra-gastric cases presented with higher IPI score (7.7% vs 33.3%, P=0.025) and higher Hp infection rate (50.0% vs 87.2%, P<0.01). Treatment options for low risk patients (IPI score 0-2) included Hp eradication, surgery, radiotherapy and chemotherapy. Chemotherapy could improve progression-free survival (PFS) in low-risk patients. For high-risk patients, those receiving chemotherapy had 100% 3-year overall survival (OS). Univariate analysis revealed that ECOG (P=0.006), Mussh-off staging (P=0.008), IPI score (P=0.000), elevated LDH (P=0.019) and chemotherapy (P=0.026) were correlated with PFS. Multivariate analysis showed that higher IPI score (IPI 3-5) (OR=8.325, 95% CI 3.171-21.853, P=0.000) and chemotherapy (OR=0.319, 95% CI 0.121-0.838, P=0.020) were independent prognostic factors for PFS. ECOG (≥ 2) was independent prognostic factor for OS (OR=5.092, 95%CI 1.005-25.788, P=0.049). CONCLUSION Primary gastro-intestinal MALT lymphoma was an indolent subtype of non-Hodgkins lymphoma. Patients usually had low risk IPI and achieved long-term survival. Frontline therapy for low-risk patients was radiotherapy or Hp eradication, and chemotherapy for high-risk ones.

[Inhibitory effect of von Willebrand factor-cleaving protease on angiogenesis].

OBJECTIVE To investigate the inhibitory effect of von Willebrand factor-cleaving protease, a disintegrin-like and metalloprotease with thrombospondin-1 repeats (ADAMTS13)on angiogenesis induced by vascular endothelial growth factor (VEGF)in vitro and in vivo. METHODS Cell proliferation assay, differentiation (tube formation)assay and wound migration assay were performed by using human umbilical vein endothelial cells (HUVECs)to explore the effect of ADAMTS13 on angiogenesis in vitro. Cells were treated with different concentrations of ADAMTS13 (1, 5, 25, 50 and 100 nmol/L)and the number of cells was counted via MTT assay. In addition, effect of ADAMTS13 on differentiation was assessed by measuring the length of capillary-like tube structures formed by HUVECS in matrigel. Effect of ADAMTS13 on HUVEC migration was assessed via calculation of wound healing distance after 8 hrs culture with VEGF or ADAMTS13. Chick embryo chorioallantoic membrane (CAM) assay and Matrigel plug assay were performed to investigate the effect of ADAMTS13 on angiogenesis in vivo. RESULTS ADAMTS13 significantly inhibited the proliferation of HUVECs induced by VEGF in a dose-dependent manner. Migration distance of HUVECs was (79 ± 22) μm in control group, (250 ± 8)μm in VEGF-treated group and (170 ± 23)μm in VEGF and ADAMTS13 cotreated-group after 8 hrs, respectively. The tube length is (450.6 ± 16.6)% in VEGF-treated group and (235.3 ± 19.0)% in VEGF and ADAMTS13 cotreated-group of that of control group after HUVECs cultured in matrigel for 16 hrs. The number of blood vessels decreased after treatment with ADAMTS13 in CAM assay. The number of blood vessels was (228.2 ± 10.8)%, (69.2 ± 21.1)%, (184.6 ± 15.2)% in VEGF treated-group, ADAMTS13 treated-group and VEGF and ADAMTS13 cotreated-group of that of control group, respectively. Formation of capillary-like network in matrigel plugs containing VEGF was reduced to 43.5% by ADAMTS13 in matrigel plug assay in mouse model. CONCLUSION ADAMTS13 inhibits the HUVECs proliferation, differentiation and migration in vitro. ADAMTS13 inhibits chick embryos vascularization and formation of capillary-like network in vivo.目的 观察血管性血友病因子裂解酶（ADAMTS13）对血管内皮细胞生长因子（VEGF）介导的血管新生的抑制作用。 方法 以不同浓度的ADAMTS13（1、5、25、50、100 nmol/L）处理脐带静脉内皮细胞（HUVEC），采用MTT法检测ADAMTS13对HUVEC增殖的影响，通过管腔形成实验观察ADAMTS13对HUVEC分化的影响，通过刮伤愈合实验观察ADAMTS13对HUVEC迁移的影响，利用鸡胚绒毛尿囊膜实验和基质胶塞实验观察ADAMTS13在体内对血管新生的影响。 结果 与对照组相比，25、50、100 nmol/L ADAMTS13对HUVEC增殖均有明显的抑制作用（P值均<0.01）。在刮伤愈合实验中，制造损伤8 h后，对照组HUVEC的迁移距离为（79±22）µm, VEGF处理组为（250±8）µm，VEGF+ADAMTS13处理组为（170±23）µm，组间差异均有统计学意义（P值均<0.05）。在管腔形成试验中，VEGF处理组、VEGF+ADAMTS13处理组HUVEC培养16 h后形成的管状结构长度分别是对照组的（450.6±16.6）%、（235.3±19.0）%，VEGF+ADAMTS13处理组管状结构少于VEGF处理组（P< 0.001）。鸡胚绒毛尿囊膜实验中，VEGF（20 ng/ml）、ADAMTS13（100 nmol/L）、ADAMTS13（100 nmol/L）+VEGF(20 ng/ml)处理组的血管形成数量分别为对照组的（228.2±10.8）%、（69.2±21.1）%、（184.6±15.2）%。基质胶塞实验结果显示VEGF+ADAMTS13处理组小鼠体内的血管数量为VEGF组的43.5%。 结论 体外实验结果表明ADAMTS13对HUVEC增殖、分化、迁移能力均有抑制作用；体内实验结果提示ADAMTS13对血管新生有抑制作用。