Prevention of hepatitis B reactivation in patients with hematologic malignancies treated with novel systemic therapies:Who and Why?

The risk of reactivation in patients with chronic or past/resolved hepatitis B virus(HBV)infection receiving chemotherapy or immunosuppressive drugs is a wellknown possibility.The indication of antiviral prophylaxis with nucleo(t)side analogue is given according to the risk of HBV reactivation of the prescribed therapy.Though the advent of new drugs is occurring in all the field of medicine,in the setting of hematologic malignancies the last few years have been characterized by several drug classes and innovative cellular treatment.As novel therapies,there are few data about the rate of HBV reactivation and the decision of starting or not an antiviral prophylaxis could be challenging.Moreover,patients are often treated with a combination of different drugs,so evaluating the actual role of these new therapies in increasing the risk of HBV reactivation is difficult.First results are now available,but further studies are still needed.Patients with chronic HBV infection[hepatitis B surface antigen(HBsAg)positive]are reasonably all treated.Past/resolved HBV patients(HBsAg negative)are the actual area of uncertainty where it could be difficult choosing between prophylaxis and pre-emptive strategy.

Combination of CRISPR/Cas9 System and CAR-T Cell Therapy:A New Era for Refractory and Relapsed Hematological Malignancies

Chimeric antigen receptor T(CAR-T)cell therapy is the novel treatment strategy for hematological malignancies such as acute lymphoblastic leukemia(ALL),lymphoma and multiple myeloma.However,treatment-related toxicities such as cytokine release syndrome(CRS)and immune effector cell-associated neurotoxicity syndrome(ICANS)have become significant hurdles to CAR-T treatment.Multiple strategies were established to alter the CAR structure on the genomic level to improve efficacy and reduce toxicities.Recently,the innovative gene-editing technology-clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated nuclease9(Cas9)system,which particularly exhibits preponderance in knock-in and knockout at specific sites,is widely utilized to manufacture CAR-T products.The application of CRISPR/Cas9 to CAR-T cell therapy has shown promising clinical results with minimal toxicity.In this review,we summarized the past achievements of CRISPR/Cas9 in CAR-T therapy and focused on the potential CAR-T targets.

Blockade of CD300A enhances the ability of human NK cells to lyse hematologic malignancies

Objective: The human cluster of differentiation(CD)300A, a type-I transmembrane protein with immunoreceptor tyrosine-based inhibitory motifs, was investigated as a potential immune checkpoint for human natural killer(NK) cells targeting hematologic malignancies(HMs).Methods: We implemented a stimulation system involving the CD300A ligand, phosphatidylserine(PS), exposed to the outer surface of malignant cells. Additionally, we utilized CD300A overexpression, a CD300A blocking system, and a xenotransplantation model to evaluate the impact of CD300A on NK cell efficacy against HMs in in vitro and in vivo settings. Furthermore, we explored the association between CD300A and HM progression in patients.Results: Our findings indicated that PS hampers the function of NK cells. Increased CD300A expression inhibited HM lysis by NK cells. CD300A overexpression shortened the survival of HM-xenografted mice by impairing transplanted NK cells. Blocking PS–CD300A signals with antibodies significantly amplified the expression of lysis function-related proteins and effector cytokines in NK cells, thereby augmenting the ability to lyse HMs. Clinically, heightened CD300A expression correlated with shorter survival and an “exhausted” phenotype of intratumoral NK cells in patients with HMs or solid tumors.Conclusions: These results propose CD300A as a potential target for invigorating NK cell-based treatments against HMs.

Laboratory hematologic features of COVID-19 associated liver injury:A systematic review

BACKGROUND Liver injury is a common complication of infection by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)virus.The utility of laboratory hematology data in the diagnosis and risk stratification of patients with coronavirus disease 2019(COVID-19)has not been comprehensively examined.AIM To address the following.(1)Are the abnormalities in hematologic parameters seen in the general population of patients with COVID-19 also seen in those patients with associated liver injury?(2)Is liver injury in COVID-19 a sign of severe disease and does liver injury correlate with hematologic markers of severe disease?And(3)What is the quality of this evidence?METHODS To address these questions,a comprehensive systematic review was performed.We searched the peer reviewed medical literature using MEDLINE(PubMed interface),Web of Science,and EMBASE for cohort studies that specifically addressed liver injury and COVID-19 without limitation of date of publication or language.A quality assessment of the studies was performed using the Newcastle-Ottawa Scale.RESULTS Thirty-two articles were suitable for inclusion in our systematic review.These included 22 articles with a cohort of COVID-19 patients with liver injury,5 comparing non-severe vs severe COVID-19 populations in which liver injury was addressed,and 5 other cohort studies with a focus on liver injury.White blood cell count,absolute neutrophil count,absolute lymphocyte count(ALC),and hemoglobin were the parameters most helpful in distinguishing COVID-19 with liver injury from COVID-19 without liver injury.ALC and d-dimer were identified as being potentially useful in distinguishing non-severe from severe COVID-19. Liver injury was more frequently seen in cohorts with severe disease.Most studies were of high quality (24/48, 86%) with 4/28 (14%) of moderatequality and 0 of low quality.CONCLUSIONOur study supports the use of select hematologic parameters in diagnosis and riskstratification of liver injury in COVID-19 patients. Although of overall highquality, the current medical literature is limited by the small number of studieswith high statistical power and the variable definition of COVID-19 liver injury inthe literature.

Preclinical evaluation of cyclophosphamide and fludarabine combined with CD19 CAR-T in the treatment of B-cell hematologic malignancies in vivo

Background:Chimeric antigen receptor T(CAR-T)cell therapy has achieved marked therapeutic success in ameliorating hematological malignancies.However,there is an extant void in the clinical guidelines concerning the most effective chemotherapy regimen prior to chimeric antigen receptor T(CAR-T)cell therapy,as well as the optimal timing for CAR-T cell infusion post-chemotherapy.Materials and Methods:We employed cell-derived tumor xenograft(CDX)murine models to delineate the optimal pre-conditioning chemotherapy regimen and timing for CAR-T cell treatment.Furthermore,transcriptome sequencing was implemented to identify the therapeutic targets and elucidate the underlying mechanisms governing the treatment regimen.Results:Our preclinical in vivo evaluation determined that a combination of cyclophosphamide and fludarabine,followed by the infusion of CD19 CAR-T cells five days subsequent to the chemotherapy,exerts the most efficacious therapeutic effect in B-cell hematological malignancies.Concurrently,RNA-seq data indicated that the therapeutic efficacy predominantly perturbs tumor cell metabolism,primarily through the inhibition of key mitochondrial targets,such as C-Jun Kinase enzyme(C-JUN).Conclusion:In summary,the present study offers critical clinical guidance and serves as an authoritative reference for the deployment of CD19 CAR-T cell therapy in the treatment of B-cell hematological malignancies.

Textile dyeing wastewater negatively influences the hematological profile and reproductive health of male Swiss albino mice

Objective:To determine the effects of textile dyeing industrial wastewater on the hematological parameters and reproductive health including histoarchitecture of male gonad(testes)of mice.Methods:Twenty-four Swiss albino mice at 4-weeks old were divided into four groups(n=6 per group).Mice of group 1 supplied with normal drinking water were served as the control group.Mice of group 2,3 and 4 were supplied normal drinking water mixed with textile dyeing wastewater at 5%,10% and 20% concentration,respectively.After completing 24 weeks of treatment,different hematological profile,weight of testes,gonadosomatic index(GSI),sperm concentration and morphology were measured.Moreover,histopathological changes in testes were examined.Results:Hematocrit value and hemoglobin concentrations were decreased in all groups of wastewater-treated mice compared to the control group.Likewise,weight of testes,GSI and sperm concentration were decreased significantly in wastewater-treated mice in comparison to the control group.The percentage of morphologically healthy epididymal sperm was significantly reduced in wastewater-treated mice.Histopathological examination revealed degenerative changes in seminiferous tubules,a smaller number of spermatogenic cells,elongation of seminiferous tubules and degenerative changes of seminiferous tubules in wastewater-treated mice.Conclusions:Textile dyeing wastewater has harmful effects on hematological profile and reproductive health of male mice.

Risk of hepatic decompensation from hepatitis B virus reactivation in hematological malignancy treatments

In this editorial,we discussed the apparent discrepancy between the findings described by Colapietro et al,in their case report and data found in the literature.Colapietro et al reported a case of hepatitis B virus(HBV)-related hepatic decompensation in a patient with chronic myeloid leukemia and a previously resolved HBV infection who was receiving Bruton’s tyrosine kinase(BTK)inhibitor therapy.First of all,we recapitulated the main aspects of the immune system involved in the response to HBV infection in order to underline the role of the innate and adaptive response,focusing our attention on the protective role of anti-HBs.We then carefully analyzed literature data on the risk of HBV reactivation(HBVr)in patients with previous HBV infection who were treated with either tyrosine kinase inhibitors or BTK inhibitors for their hematologic malignancies.Based on literature data,we suggested that several factors may contribute to the different risks of HBVr:The type of hematologic malignancy;the type of therapy(BTK inhibitors,especially second-generation,seem to be at a higher risk of HBVr than those with tyrosine kinase inhibitors);previous exposure to an anti-CD20 as first-line therapy;and ethnicity and HBV genotype.Therefore,the warning regarding HBVr in the specific setting of patients with hematologic malignancies requires further investigation.

Hematological picture of pediatric Sudanese patients with visceral leishmaniasis and prediction of leishmania donovani parasite load

BACKGROUND Visceral leishmaniasis(VL)is a systemic protozoan infection caused by Leishmania donovani(L.donovani)and transmitted by sand flies,causing macrophage invasion in the liver,spleen,and bone marrow.Diagnosis of VL is currently based on clinical signs,symptoms,and specific in-vitro markers and bone marrow investigations.However,VL's specific hematological and bone marrow manifestation in Sudanese pediatric patients is not well studied.AIM To examine the blood and bone marrow characteristics in pediatric patients from Sudan who have VL.METHODS This is a retrospective hospital-based study with a sample of 107 consecutive Sudanese pediatric patients.The data focused on hematological and bone marrow results.We included only the completed records of the pediatric patients with VL in the Tropical Disease Teaching Hospital in Khartoum,Sudan from the period of 2016 to 2020.RESULTS The majority of pediatric patients included in this study are below 5-years-old(n=59,55.2%).Moreover,anemia,thrombocytopenia,and leukopenia were among the prevalent characteristics in the population under study.To further analyze the data,we developed a machine learning model using boosted forest algorithms to predict L.donovani parasites load,with a mean accuracy of 0.88 for the training dataset and an accuracy of 0.46,0.50,and 0.74 for mild,moderate,and severe L.donovani parasite load in the validation dataset.CONCLUSION This study shows that the most common bone marrow change among Sudanese VL children was increased chronic inflammatory cells(n=88,82.2%)with present macrophage hemophagocytes(n=103,96.3%).While anemia and thrombocytopenia were the most common hematological changes.These results will hopefully lead to an early diagnosis and hence better management for Sudanese pediatric patients with suspected VL.

Review of Baduanjin and resistance exercise for the mental health of patients with hematologic malignancies

Patients with hematological tumors experience physical and psychological stress,and negative psychological states.Baduanjin,an emerging psychological rehabil-itation method combined with resistance exercise,has received widespread attention.This study reviews the current status of the application of Baduanjin combined with resistance exercise in improving the negative psychological state of patients with hematological tumors and discusses its problems and prospects.Through a literature review and comprehensive analysis,the application of Baduanjin and resistance exercise in the psychological rehabilitation of patients with hematological tumors was identified and evaluated.The results showed that Baduanjin with resistance exercise had a positive effect on improving negative psychological states of patients with hematological tumors,which can alleviate anxiety,depression,and other adverse emotions,and improve quality of life.However,there is a lack of unified and standardized exercise intervention programs for practical application,and patient participation and compliance must be improved.Baduanjin combined with resistance exercise can potentially improve the negative psychological status of patients with hematological tumors;however,it is still necessary to further standardize and improve the exercise program improving patient participation and compliance.Future studies should strengthen theoretical exploration and empirical research,providing more effective psychological rehabilitation strategies for patients with hematological tumors.

Hematological Malignancies in Sickle Cell Disease Patients: Report of Four Cases in Togo and Literature Review

Background: Hemopathies were rarely observed in major sickle cell disease patients some thirty years ago, probably due to the high mortality rate among the latter as a result of progressive complications. Thanks to advances in the management of sickle cell disease, patients' life expectancy has increased considerably, exposing them more frequently to neoplasia, including hematological malignancies. The increased risk of leukemogenesis is multifactorial and linked to the pathophysiological mechanisms of the clinical manifestations of sickle cell disease. Study Setting: The clinical haematology department of campus teaching hospital and the paediatric onco-haematology unit of Sylvanus Olympio teaching hospital in Lomé were used as study settings. Observations: Four hematologic malignancies were collected in a cohort of 5847 major sickle cell syndromes. The median age of the patients was 31.25 years (extremes: 14 and 58 years) and they were predominantly female (sex ratio M/F = 0.25). Two were on background therapy with hydroxyurea. Among the four patients, there were two cases of acute lymphocytic leukemia, including ALL3 in a 58-year-old SS woman and T-ALL2 in a 12-year-old SC. Then, a case of lymphocytic lymphoma in a 20-year-old SS man was reported and finally a case of chronic myelocytic leukemia in a 33-year-old woman of Sβ+ thalassaemia phenotype. Conclusion: To further report this coexistence, it is therefore essential to systematically consider hematological malignancies during major sickle cell syndromes even if there are similarities in the symptomatology of these two serious pathological situations.

Hematological Alterations in an Eastern Sudanese Chronic Kidney Disease Patient Population

Background: Chronic Kidney Disease (CKD), associated with a slow and progressive loss of kidney function over a period of several years, is an important clinical disaster with an increasing rate of morbidity and mortality especially in the least developed countries. Many hematological parameters are thought to alter dramatically during the course of the disease. These include white blood cells, red blood cells, and platelets. Methods: We tried, retrospectively, to evaluate the peripheral blood hematological alterations in a group of patients undergoing hemodialysis in an eastern Sudan dialysis center to add local medical information. Results: Anemia (Low hemoglobin and hematocrit) was detected in 94% of the patients’ group. Mean Erythrocyte count (3.32vs.4.76 (×109/L)), Hemoglobin concentration (9.4vs.13 (g/dl)), Hematocrit (28.7vs.38.7 (L/L)) and platelet count (296 vs. 238 (×109/L)) were significantly lower in the patients’ group than in the control group (P-values Conclusion: Five out of eight studied parameters (Red cell count, hemoglobin, hematocrit, mean cell hemoglobin concentration, and platelets count) have shown a significant alteration in CKD patients. As the complete blood count (CBC) test is the most utilized test in clinical laboratory practice, these alterations may be considered as early indicators for CKD. Furthermore, all patients with CKD must be routinely checked for these alterations.

Prevention and management of hepatitis B virus reactivation in patients with hematological malignancies treated with anticancer therapy

Hepatitis due to hepatitis B virus(HBV) reactivation can be severe and potentially fatal, but is preventable. HBV reactivation is most commonly reported in patients receiving cancer chemotherapy, especially rituximabcontaining therapy for hematological malignancies and those receiving stem cell transplantation. All patients with hematological malignancies receiving anticancer therapy should be screened for active or resolved HBV infection by blood tests for hepatitis B surface antigen(HBs Ag) and antibody to hepatitis B core antigen(antiHBc). Patients found to be positive for HBs Ag should be given prophylactic antiviral therapy to prevent HBV reactivation. For patients with resolved HBV infection, no standard strategy has yet been established to prevent HBV reactivation. There are usually two options. One is pre-emptive therapy guided by serial HBV DNA monitoring, whereby antiviral therapy is given as soon as HBV DNA becomes detectable. However, there is little evidence regarding the optimal interval and period of monitoring. An alternative approach is prophylactic antiviral therapy, especially for patients receiving highrisk therapy such as rituximab, newer generation of anti-CD20 monoclonal antibody, obinutuzumab or hematopoietic stem cell transplantation. This strategy may effectively prevent HBV reactivation and avoid the inconvenience of repeated HBV DNA monitoring. Entecavir or tenofovir are preferred over lamivudine as prophylactic therapy. Although there is no well-defined guideline on the optimal duration of prophylactic therapy, there is growing evidence to recommend continuing prophylactic antiviral therapy for at least 12 mo after cessation of chemotherapy, and even longer for those who receive rituximab or who had high serum HBV DNA levels before the start of immunosuppressive therapy. Many novel agents have recently become available for the treatment of hematological malignancies, and these agents may be associated with HBV reactivation. Although there is currently limited evidence to guide the optimal preventive measures, we recommend antiviral prophylaxis in HBs Ag-positive patients receiving novel treatments, especially the Bruton tyrosine kinase inhibitors and the phosphatidylinositol 3-kinase inhibitors, which are B-cell receptor signaling modulators and reduce proliferation of malignant B-cells. Further studies are needed to clarify the risk of HBV reactivation with these agents and the best prophylactic strategy in the era of targeted therapy for hematological malignancies.

Cellular immunotherapy for hematological malignancy: recent progress and future perspectives

Advancements in the field of cellular immunotherapy have accelerated in recent years and have changed the treatment landscape for a variety of hematologic malignancies.Cellular immunotherapy strategies exploit the patient’s immune system to kill cancer cells.The successful use of CD19 chimeric antigen receptor(CAR)T-cells in treating B-cell malignancies is the paradigm of this revolution,and numerous ongoing studies are investigating and extending this approach to other malignancies.However,resistance to CAR-Tcell therapy and non-durable efficacy have prevented CAR-T-cells from becoming the ultimate therapy.Because natural killer(NK)cells play an essential role in antitumor immunity,adoptively transferred allogeneic NK and CAR-modified NK cell therapy has been attempted in certain disease subgroups.Allogenic hematopoietic stem cell transplantation(allo-HSCT)is the oldest form of cellular immunotherapy and the only curative option for hematologic malignancies.Historically,the breadth of application of allo-HSCT has been limited by a lack of identical sibling donors(ISDs).However,great strides have recently been made in the success of haploidentical allografts worldwide,which enable everyone to have a donor.Haploidentical donors can achieve comparable outcomes to those of ISDs and even better outcomes in certain circumstances because of a stronger graft vs.tumor effect.Currently,novel strategies such as CAR-T or NK-based immunotherapy can be applied as a complement to allo-HSCT for curative effects,particularly in refractory cases.Here,we introduce the developments in cellular immunotherapy in hematology.

Liquid biopsies for liquid tumors: emerging potential of circulating free nucleic acid evaluation for the management of hematologic malignancies

Circulating free nucleic acids; cell free DNA and circulating micro-RNA, are found in the plasma of patients with hematologic and solid malignancies at levels higher than that of healthy individuals. In patients with hematologic malignancy cell free DNA reflects the underlying tumor mutational profile, whilst micro-RNAs reflect genetic interference mechanisms within a tumor and potentially the surrounding microenvironment and immune effector cells. These circulating nucleic acids offer a potentially simple, non-invasive, repeatable analysis that can aid in diagnosis, prognosis and therapeutic decisions in cancer treatment.

Prevention and management of hepatitis B virus reactivation in patients with hematological malignancies in the targeted therapy era

Hepatitis due to hepatitis B virus(HBV)reactivation can be serious and potentially fatal,but is preventable.HBV reactivation is most commonly reported in patients receiving chemotherapy,especially rituximab-containing therapy for hematological malignancies and those receiving stem cell transplantation.Patients with inactive and even resolved HBV infection still have persistence of HBV genomes in the liver.The expression of these silent genomes is controlled by the immune system.Suppression or ablation of immune cells,most importantly B cells,may lead to reactivation of seemingly resolved HBV infection.Thus,all patients with hematological malignancies receiving anticancer therapy should be screened for active or resolved HBV infection by blood tests for hepatitis B surface antigen(HBsAg)and antibody to hepatitis B core antigen.Patients found to be positive for HBsAg should be given prophylactic antiviral therapy.For patients with resolved HBV infection,there are two approaches.The first is pre-emptive therapy guided by serial HBV DNA monitoring,and treatment with antiviral therapy as soon as HBV DNA becomes detectable.The second approach is prophy-lactic antiviral therapy,particularly for patients receiving high-risk therapy,especially anti-CD20 monoclonal antibody or hematopoietic stem cell transplantation.Entecavir and tenofovir are the preferred antiviral choices.Many new effective therapies for hematological malignancies have been introduced in the past decade,for example,chimeric antigen receptor(CAR)-T cell therapy,novel monoclonal antibodies,bispecific antibody drug conjugates,and small molecule inhibitors,which may be associated with HBV reactivation.Although there is limited evidence to guide the optimal preventive measures,we recommend antivi-ral prophylaxis in HBsAg-positive patients receiving novel treatments,including Bruton’s tyrosine kinase inhibitors,B-cell lymphoma 2 inhibitors,and CAR-T cell therapy.Further studies are needed to determine the risk of HBV reactivation with these agents and the best prophylactic strategy.

Comprehensive evaluation of nutritional status before and after hematopoietic stem cell transplantation in 170 patients with hematological diseases

Objective： To investigate the nutritional status of patients before and after hematopoietic stem cell transplantation（HSCT）, and explore optimal methods for assessing nutritional status in patients with hematological diseases.Methods： This cohort study enrolled 170 patients who were diagnosed with hematological diseases and underwent allogeneic HSCT in the Department of Hematology, Peking University People＇s Hospital between May2011 and April 2013. We used fixed-point continuous sampling and four nutritional screening tools, Nutritional Risk Screening 2002（NRS-2002）, Mini Nutritional Assessment（MNA）, Subjective Global Assessment（SGA） and Malnutrition Universal Screening Tools（MUST）, in combination with body measurements, to extensively screen and evaluate nutritional risks and status in patients receiving HSCT before entering and after leaving laminar air flow rooms.Results： After HSCT, patients had significant reduction in weight, hip circumference, waist-hip ratio, calf circumference, mid-upper arm circumference, and suprailiac skinfold thickness compared with pre-HSCT measurements. Before HSCT, NRS-2002 identified that 21.2% of patients were at nutritional risks, compared with100% after HSCT. MUST indicated that before HSCT, 11.77% of patients were at high nutritional risk,compared with 59.63% after HSCT. MNA assessed that 0.06% of patients were malnourished before HSCT,compared with 19.27% after HSCT. SGA identified that before HSCT, 1.76% of patients had mild to severe malnutrition, which increased to 83.3% after HSCT. There is a significant increase in the nutritional risk and malnutrition in patients who received HSCT.Conclusions： Before HSCT, some patients already had nutritional risk or nutritional deficiencies, and prompt and close nutritional screening or assessment should be performed. The nutritional status of patients after HSCT was generally deteriorated compared with that before transplantation. Body measurements should be taken more frequently during the subsequent treatment window in the laminar air flow rooms. After HSCT, it is recommended to combine MNA and SGA to fully evaluate the nutritional status, and thus provide timely and reasonable nutritional support.

Low temperature stress on the hematological parameters and HSP gene expression in the turbot Scophthalmus maximus

To study the effect of low temperature stress on hematological parameters and HSP gene expression in the turbot （Seophthalmus maximus）, water temperature was lowered rapidly from 18 to 1℃. During the cooling process, three individuals were removed from culture tanks at 18, 13, 8, 5, 3, and 1℃. Blood samples and tissues were taken from each individual, hematological indices and HSP gene expression in tissues were measured. The red blood cell count, white blood cell count, and hemoglobin concentration decreased significantly （P〈0.05） as temperature decreased. Enzyme activities of plasma alanine transaminase and creatine kinase increased as temperature decreased, whereas aspartic transaminase and γ-glutamyl transpeptidase activities displayed no obvious changes above 1℃ and lactate dehydrogenase activity increased first and then decreased. Blood urea nitrogen and uric acid levels were highest at 8℃, and creatinine concentration was highest at 3℃. The concentrations of plasma cortisol, cholesterol, and triglyceride all increased significantly （P〈0.05） as temperature decreased. The serum glucose concentration increased first and then decreased to the initial level. The HSP70 mRNA expression showed various patterns in different tissues, whereas HSP90 mRNA expression showed the same tendency in all tissues. Overall, these results indicate that temperature decreases in the range of 8 to 5℃ may induce a stress response in S. maximus and that temperature should be kept above 8℃ in the aquaculture setting to avoid damage to the fish.

Diagnostic and Prognostic Value of Plasma Factor V Activity and Parameters in Thrombin Generation for Disseminated Intravascular Coagulation in Patients with Hematological Malignancies

In this study,we used plasma factor V activity and parameters of the thrombin generation test to discuss their diagnostic and prognostic value for disseminated intravascular coagulation (DIC) in patients with hematological malignancies.A total of 164 patients who were diagnosed with hematological malignancies in the Department of Hematology,Union Hospital,between Apr 2014 and Dec.2014 were enrolled in this study.There were 131 patients in the study group and 33 patients in the control group in terms of the laboratory results for DIC.The patients in the study group were divided into a DIC subgroup (n=59) and a non-DIC subgroup (n=72) based on the International Society of Thrombosis and Hemostasis (ISTH) Integral System,and they were divided into four subgroups [score ≤3 (n=35),score=4 (n=37),score=5 (n=47),and score >6 (n=12)] according to ISTH scores.Using 28-day mortality as the endpoint,the patients in the study group were divided into a survival subgroup (n=111) and a non-survival subgroup (n=20).The results showed that the plasma factor V activity was significantly weaker,and lag time and time to peak were significantly shorter in the study group than in the control group (P<0.01).The factor V activity,peak and endogenous thrombin potential (ETP) were significantly decreased in the DIC subgroup as compared with those in the non-DIC subgroup (P<0.01).Among factor V activity,lag time,peak,ETP,and ttPeak,only the factor V activity was significantly decreased in the nonsurvival subgroup compared with the survival subgroup (P<0.01).With the increase in ISTH score,the ETP and peak decreased gradually.The binary logistic regression analysis revealed that PLT,D-dimer,factor V activity and ETP had linear relationship with DIC diagnosed by ISTH Integral System.Using DIC diagnosed by ISTH Integral System as the endpoint,the area under curve (AUC) of factor V activity was found to be similar to that of blood platelet count (PLT) and prothrombin time (PT).In conclusion,factor V activity,ETP and peak had diagnostic value for DIC in patients with hematological malignancies,and only factor V activity had limited prognostic value.

Towards an evaluation of alcoholic liver cirrhosis and nonalcoholic fatty liver disease patients with hematological scales

BACKGROUND Seeking potentially novel blood markers of liver fibrosis and steatosis is constantly of crucial importance.Despite a growing number of studies in this field of hepatology,a certain role of hematological indices in the course of liver disorders has not been fully elucidated,yet.AIM To evaluate a diagnostic accuracy of neutrophil-to-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio(PLR)and mean platelet volume-to-platelet-ratio(MPR)in the course of alcoholic liver cirrhosis(ALC)and nonalcoholic fatty liver disease(NAFLD).METHODS One hundred forty-two patients with ALC,92 with NAFLD and 68 persons in control group were enrolled in the study.Hematological indices(NLR,PLR and MPR),indirect and direct markers of liver fibrosis(aspartate transaminase to alkaline transaminase ratio,aspartate transaminase to platelet ratio index,fibrosis-4,gamma-glutamyl transpeptidase to platelet ratio,procollagen Ⅰ carboxyterminal propeptide,procollagen Ⅲ aminoterminal propeptide,transforming growth factor-α,platelet-derived growth factor AB,laminin)were measured in each person.Model for end-stage liver disease(MELD)score in ALC group and NAFLD fibrosis score together with BARD score were calculated in NAFLD patients.Receiver operating characteristic(ROC)curves and area under the curve(AUC)values were applied to assess the sensitivity and specificity of examined markers and to evaluate proposed cut-offs of measured indices in the course of ALC and NAFLD.RESULTS MPR and NLR values in ALC patients were significantly higher in comparison to control group;PLR level was significantly lower.MPR and PLR correlated with assessed indirect and direct markers of liver fibrosis.MPR,NLR and PLR correlated with MELD score.NLR level in NAFLD patients was significantly higher in comparison to controls.MPR correlated with indirect markers of liver fibrosis and NAFLD fibrosis score.AUC values and proposed cut-offs for NLR,PLR and MPR in ALC patients were:0.821(>2.227),0.675(<70.445)and 0.929(>0.048),respectively.AUC values and proposed cut-offs for NLR,PLR and MPR in NAFLD group were:0.725(>2.034),0.528(>97.101)and 0.547(>0.038),respectively.CONCLUSION Hematological markers are inseparably connected with serological indices of liver fibrosis in ALC and NAFLD patients.MPR and NLR turned out to be the most powerful parameters in ALC patients.

TMTP1, a Novel Tumor-homing Peptide, Specifically Targets Hematological Malignancies and Their Metastases

TMTP1, a 5-amino acid peptide NVVRQ, obtained by using the flagella peptide library screening in our previous studies, can be used for the labeling of malignant in situ and metastatic lesions, and even micro-metastases. In this study, TMTP1 was assessed for its ability to specifically target the malignant hematopoietic cells and metastatic lesions of hematological malignancies. FITC-TMTP1 was chemically synthesized. Immunofluorescence assay and competitive test were carried out to determine the specific binding capacity of TMTPl to hematological malignant cell lines, including HL60, k562, SHI-1, Jurkat, Raji, El-4 and umbilical cord blood mononuclear cells. Mononuclear cells were isolated from the bone marrow of healthy subjects and patients with chronic myeloid leukemia. Then the cells were co-clutured with TMTP1 or scrambled peptides and the binding and affinity of TMTP1 peptide to the primary cells of hematological malignancies were flow cytometrically analyzed. The binding speci-ficity of TMTP1 to target hematological malignancies was measured in vivo by intravenous injection of FITC-conjugated TMTP1 into El-4 lymphoma-bearing mice. The results showed that TMTP1 specifi-cally bound to the cells of a series of hematological malignancies, including HL60, k562, Jurkat, Raji , El-4 and chronic myeloid leukemia primary cells but not to bone marrow mononuclear cells from healthy subjects. By contrast, TMTP1 could bind to the metastatic foci of lymphoma originating from the EL-4 cell line while the scrambled peptide failed to do so. Moreover, the occult metastases could be identified, with high specificity, by detecting FITC-TMTP1. We are led to conclude that TMTP1, as a novel tumor-homing peptide, can serve as a marker for primary malignant and metastatic lesions for the early diagnosis of hematological malignances and a carrier of anticancer drugs for cancer treatment.