| Objective: Fluorescence resonance energy transfer substrate VWF73(FRETS-VWF73) assay was used to observe the changes of ADAMTS13activity andinhibitor in patients following hematopoietic stem cell transplantation (HSCT) in twoperiods(before the transplantation pretreatment, after pretreatment). Then to analyze therelationship between ADAMTS13active and inhibitor in two periods, and to investigatethe clinical significance of ADAMTS13inhibitor in patients following HSCT.Methods:（1） Patients：A total of113patients (66males,47females) receiving HSCTwere investigated from Sep2010to Sep2011in our hospital. Median age is32(4-57)years old, including39cases with acute myeloid leukemia (AML),24cases with acutelymphoid leukemia (ALL),16cases with chronic myelogenous leukemia (CML),4caseswith acute heterozygous cell leukemia (AHL),13cases with lymphoma,17cases withother diseases. According to the donor type,16cases received autologous transplantation,97cases received allogeneic transplantation (49cases from sibling matched donors,30cases from unrelated donor,10cases from partially matched family donors,9cases fromumbilical cord blood stem cell transplantation). The modified BU/CY or TBI/CY was usedfor conditioning regimen in most patients, the BEAM or nonmyeloablative regimen wasused in the rest cases. (2)Using FRETS-VWF73assay,we detect the ADAMTS13activity of113patients at twoperiod (before the transplantation pretreatment, after pretreatment).(3)We detect the ADAMTS13inhibitor in83patients: Anti-ADAMTS13neutralizing antibodywas titrated measuring ADAMTS13residual activity in a1:1mixture of heat-inactivated(incubation for1h at56℃) patient plasma and NHP. FRETS-VWF73was performedafter2h of incubation of NHP and heat-inactivated patient plasma mixture25℃.(4)Statistical analysis:data was expressed as mean±standard deviation. Data differentwas analyzed using analysis of variance and t test. Rates were compared using chi-squaretest (X2). P<0.05was considered as significant difference. Logistic regression model wasused for analysis of correlation. Statistical software is SPSS17.0.Results:The average values of ADAMTS13activity in113cases following HSCT at eachperiod (before the transplantation pretreatment, after pretreatment,) were (45.1±30.6)%,and(38.3±26.3)%. The ADAMTS13activity in each period were less than the normalcontrols (P<0.05). Moreover, compared with the stage before, the ADAMTS13activity inpatients after transplantation conditioning was decreased (F=13.08，P=0.0004). Thedegree of ADAMTS13activity decreasing is different in the patients(less than30%in31cases(27.4%),30-60%in27cases(23.9%), over60%in9cases(8.0%)). Thrombosiscomplications occurred in8patients, including veno-occlusive disease (VOD), thromboticmicroangiopathies (TMA), pulmonary embolism(PE). The ADAMTS13activity afterpretreatment (41.6±39.5)%were much less than pretreatment before(77.6±71.1)%(F=6.07,P=0.0432).The ADAMTS13activity in3patients (37.5%) reduced more than60%in the stage after pretreatment while in patients without thrombosis reduced more than60%(9.0%)(X2=10.2458,P=0.0014). Logistic regression analysis showed that theADAMTS13activity declined by more than60%is the risk of thrombosis (P=0.0065,OR=9.903,95%CI:1.899～51.644),Logistic regression analysis showed that thepretreatment BUCY scheme can increase the risk of ADAMTS13activity decline (P=0.001, OR=6.516,95%CI:2.054~20.673),.(2)The ADAMTS13inhibitor of83patients were detected with FRETS-VWF73. TheADAMTS13activity of45patients was decline. The degree of ADAMTS13activitydecreasing is different in the patients:less than20%in15cases, among them,9patients（9/15，60%） can be detected ADAMTS13inhibitor;20-40%in16cases, the ADAMTS13inhibitor can be tested in11patients (11/16，68.8%),over40%in14cases,.11patients（11/14，78.6%） can be detected ADAMTS13inhibitor;The ADAMTS13inhibitor oftwo groups were no statistic differences (the ADAMTS13activity decline between20%-40%vsmore than40%,P=0.55). Logistic regression analysis showed there is no significant correlationbetween ADAMTS13activity decline and inhibitor (P=0.530).Conclusions:(1)The FRETS-VWF73assay shows that the ADAMTS13averageactivity level is lower than normal in the early stage of HSCT. The levels of ADAMTS13activity before pretreatment is lower than the level after pretreatment. Most of themreduced less than60%. Logistic regression analysis showed that the BUCY regimen is therisk of ADAMTS13activity declined.(2)The ADAMTS13activity of the patients with thrombosis reduced more thannon-thrombotic group. The ADAMTS13activity more than60%is the risk factor ofthrombotic complications.(3)The ADAMTS13activity of some patients was reduced after pretreatment, amongthem,we can detect the low titer ADAMTS13inhibitor,There is no significant correlationbetween ADAMTS13activity decline and inhibitor. Background: Peripheral T-cell lymphoma (PTCL) is a heterogeneous group ofaggressive lymphomas with poor clinical outcomes. The aim of this retrospective studywas to explore the clinical features and prognostic factors of Chinese patients with PTCL.Patients and Methods: A total of75patients were newly diagnosed and treated at ourcenter from April2004to November2011. Histologic subtypes includedPTCL-not-otherwise specified (PTCL-NOS)(n=37,49.3%), natural killer/T-celllymphoma (NK/TCL)(n=25,33.3%), anaplastic large cell lymphoma (ALCL)(n=11,14.7%), and angioimmunoblastic T-cell lymphomas (AITL)(n=2,2.7%). According toAnn Arbor staging (AASS), PTCL patients were divided into4period: stage I~II22cases, III~IV53patients,55patients with B symptoms, there are some clinicalpathological indicators, mainly including lactate dehydrogenase levels, bone marrowinvasion, β2-microglobulin and Ki-67levels. IPI scoring system was performed before treatment, IPI index mainly includes five risk factors: age, staging, serum LDH, physicalcondition Moreover，PIT is used on the new evaluation index of prognosis, mainly include:age, staging, serum LDH level, physical condition and bone marrow infringement case,0to2points：68cases.3~4points：7cases. The induction chemotherapy consistedprimarily of CHOP (cyclophosphamide, doxorubicin hydrochloride, vincristine andprednisone), hyper CVAD (fractionated cyclophosphamide,vincristine,adriamycin, anddexamethasone alternating with methotrexate and cytarabine), DHAP (Cisplatin, adriamycin,and dexamethasone), SMILE (dexamethasone,methotrexate, ifosfamide, etoposide, andL-asparaginase) or other second-line regimes. There are16patients received autologoushematopoietic stem cell transplantation after induction chemotherapy.Results: Of all the patients,3-year OS was49%. Based on univariate analysis,patients with older age (P<0.001), bone marrow involvement (P=0.019), higher level ofLDH (P=0.024) and higher level of β2-microglobulin (P=0.023) had inferior survival. Inaddition, ALK+ALCL patients exhibited better survival than other types, with the3-yearOS of100%. Multivariate analysis identified age and bone marrow involvement as theindependent prognostic factors for PTCL. Compared with46patients who received CHOPor CHOP-like regimens, the other29patients who received non-CHOP regimens achievedfavorable outcome. In addition, autologous stem-cell transplantation (ASCT) followed bychemotherapy may improve the survival of patients with PTCL.Conclusion: IPI and PIT were useful prognostic models for predicting survival inChinese patients with PTCL. Age and bone marrow involvement were two independentfactors that affected the OS in our study. CHOP or CHOP like regime did not showfavorable outcome than non-CHOP regime. In addition, intensive chemotherapy followedby ASCT may improve the survival of patients with PTCL. |
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