The Effect of Immunized Platelet Transfusion Refractoriness on Allo-HSCT Patients with Malignant Hematological Diseases / 中国实验血液学杂志

OBJECTIVE@#To investigate the characteristics of platelet antibody in patients with hematological diseases, so as to research the effect of immunized platelet transfusion refractoriness (PTR) on the prognosis of allogeneic hematopoietic stem cell transplantation (allo-HSCT) recepients with malignant hematological diseases patients.@*METHODS@#The clinical data of platelet antibody positive patients tested by Capture-P in the First Affiliated Hospital of Soochow University from July 1, 2014 to July 1, 2019 were retrospectively analyzed, including sex, age, disease, platelet transfusion assessments, CD34@*RESULTS@#In 5 years, 913 (7.28%) hematologic patients with platelet antibody positive were identified, the detection rate of females (513 cases) were higher than males (400 cases). Among the 913 patients, the antibody positive rates of 520 patients with malignant hematological diseases (acute myeloid leukemia, acute lymphoblastic leukemia and myelodysplastic syndrome) showed significantly statistical different (10.27%, 8.01%, and 7.20%) (P<0.01), and the positive rate of the acute myeloid leukemia of those patients was higher than myelodysplastic syndrome patients(α<0.0125). There were 35 cases diagnosed as immunized PTR before allo-HSCT, the platelet increments, 14 h correct count increment, progression-free survival rate and overall survival rate of those patients were significantly lower than those in negative transfusion effective patients (P<0.01), while the percentage of ABO matching was significantly higher (α<0.0125).@*CONCLUSION@#The positive rate of platelet antibody identification is high in females and acute myeloid leukemia patients, and immunized PTR caused by antibody is a risk factor for poor prognosis of allo-HSCT in malignant hematological disease patients.

Combined laser peripheral iridectomy for primary angle-closure glaucoma / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To investigate the clinical effect of combined laser peripheral iridectomy for primary angle-closure glaucoma.<p>METHODS: A total of 82 eyes were included in 82 patients with primary angle-closure glaucoma who visited our hospital from August 2015 to October 2017. They were randomly divided into two groups. Patients in the simple laser group were performed Nd:YAG laser only. In the combined laser group, 532 semiconductor laser combined with Nd: YAG laser were used for laser peripheral iridectomy. Intraocular pressure(IOP)was measured preoperative and postoperative. Laser energy was recorded. Iridemia were observed.<p>RESULTS: Postoperative IOP increased significantly in the simple laser group compared with the combined laser group, and the differences between the two groups 1h, 1d and 1wk after operation were statistical significances(<i>P</i><0.01). The IOP of the two groups was basically restored to the preoperative level at 1mo postoperatively. The success rate of single laser surgery was significantly lower than that of combined laser surgery(73% <i>vs </i>100%, <i>P</i><0.05). The total energy of Nd:YAG laser was significantly higher than that of the combined laser group(40.16±13.43mJ <i>vs</i> 23.23±6.70mJ, <i>P</i><0.05). There was no significant difference in intraoperative iris bleeding rate between the two groups(33% <i>vs</i> 26%, <i>P</i>>0.05).<p>CONCLUSION: Totally 532 semiconductor laser combined with Nd: YAG laser for peripheral iridectomy has a high rate of penetration, especially for patients without iris recess. It can significantly decreases laser energy, reduces the difficulty of laser operation and relieves intraocular inflammation.

Establishment of Flow Cytometric Immunobead Array Assay for Quantitation of Platelet-Specific Antibodies and Its Application / 中国实验血液学杂志

OBJECTIVE@#To establish a flow cytometric immunobead array assay (FCIA) to quantify platelet antibodies and to explore its application in the diagnosis and treatment of ITP.@*METHODS@#The guantitative standard curve was established by binding the human IgG of known concentration on antibody-coated microbeads; at the same time, the platelet-specific antigen and antibody complex was captured and levels of platelet antibodies were detected using the microbeads coated by 5 kinds of antibodies against platelets suca as GPIX (SZ1), GPⅠb (SZ2), GpⅢa (SZ21), GPⅡb (SZ22) and p-selection (SZ51). The fluorescence signal detected by flow cytometry were transformed into the conentration of platelet antibodies in samples through the quantitative standard curve, thereby establishing the method for quantititive detection of platelet-specific antibodies in plasm samples (FCIA), moreover the property, efficiency and clinical application of establishod FCIA method were evaluated.@*RESULTS@#The FCIA could detect 5 kinds of antibodies against GPIX, GPⅠb, GpⅢa, GPⅡb and β-selection within a broad range of 33.29-1280 ng/ml, 45.17-1280 ng/ml, 42.07-1280 ng/ml, 46.40-1280 ng/ml, 42.48-1280 ng/ml and 42.48-1280 ng/ml respectively, and their recovery rates were 115.23%, 112.58%, 117.47%, 107.64% and 112.67% respectively. The intra-assay coefficient of variation (CV) for anti- GPIX, -GPⅠb, -GpⅢa, -GPⅡb and p-selection antibodies was 3.54%, 3.63%, 4.66%, 6.43% and 6.67% respectively, and the inter-assay CV for above mentioned antibodies were 10.89%, 7.57%, 10.34%, 6.95% and 10.72% respectively. The detection showed that the levels of 5 kinds of platelet-specific antibodies in ITP group all were higher than those in non-ITP and healthy control groups (P＜0.01). The sensitivity, specificity and accuracy of quantitatively detecting 5 kinds of antibodies for diagnosis of ITP by FCIA were 68.29%, 84.98% and 78.95% respectively, while the sensitivity, specificity and accuracy of detecting 5 kinds of antibodies by modified indirect MAIPA were 41.46%, 90.41% and 72.81% respectively.@*CONCLUSION@#The established quantitative FCIA for detection of antibodies provides a powerful tool for diaghosis and evaluation of therapeutic efficacy and prognosis of ITP patients.

Correlation of IgG Levels at Initial Diagnosis with Clinical Efficacy and Prognosis in 66 Patients with IgG Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To explore the IgG levels of newly diagnosed IgG-type multiple myeloma (MM) patients and analyze the relationship between the IgG levels and clinical efficacy and prognosis.@*METHODS@#The clinical data of 66 newly diagnosed IgG-type MM patients in our hospital from September 2012 to October 2018 were collected. These 66 patients were divided into group A (IgG≤64 g/L, n=41), and group B (IgG ＞64 g/L, n=25), then the MM patients in 2 groups were divided into 2 subgroups thalidomide (TM)-treated group (n=35) and bortezomib (BTZ)-treated group (n=25) according to therapeutic regimens. The climical efficacy, PFS and OS time as well as the factors affecting prognosis of patients were compared and analyzed.@*RESULTS@#The overall response rate (ORR) and CR+VGPR rate in group A were better than those in group B (P=0.008, P=0.036), the ORR of BTZ-treated group in group B was significantly better than that of TM-treated group (P=0.028), while the ORR of TM-treated group in group A was better than that of TM-treated group in group B (P=0.048), the CR+VGPR rate was better than that of TM-treated group in group B (P＜0.05). The number of patients with high risk cytogenetics (HRC) in group B was much more than that in group A (P=0.022). Spearman correlation analysis showed that serum IgG levels negatively correlated with albumin (r=-0.449，P=0.000) and hemoglobin (r=-0.608，P=0.000), and positively correlated with bone marrow plasma cells (r=0.328，P=0.007). Survival analysis showed that the PFS in group A was significantly better than that in group B (P=0.015), and the OS in group A was better than that in group B (P=0.049), but there was no significant difference in PFS and OS between TM group and BTZ group (PFS: P=0.695, OS: P=0.3250). Cox multivariate regression analysis showed that the ≥VGPR and standard-risk cytogenetics were independent prognostic factors for PFS and OS.@*CONCLUSION@#IgG＞64g/L in patients with newly diagnosed IgG-type MM is a poor prognostic factor affecting PFS and OS. The higher level of serum IgG at the initial diagnosis, the higher the risk of HRCs, and the worse clinical efficacy and prognosis of patients.

Related risk factor analysis of high intraocular pressure after vitrectomy / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To explore the risk factors of high intraocular pressure after vitrectomy.<p>METHODS: Patients who underwent vitrectomy in our hospital from June 2016 to December 2018 were retrospectively analyzed, general information of patients, intraocular pressure before and after operation and relevant information of operation were recorded, Univariate and Logistic multivariate regression analysis were performed to analyze the risk factors of high intraocular pressure after vitrectomy.<p>RESULTS: Early high intraocular pressure occurred in 49 of 159 eyes(30.8%). Gender and age had no significant effect on the occurrence of high intraocular pressure after vitrectomy(<i>P</i>=0.699; <i>P</i>=0.416). Early high intraocular pressure after vitrectomy was closely correlated with silicone oil filling, combined cataract surgery, total retinal laser photocoagulation and vitreous hemorrhage after vitrectomy, with statistically significant differences(<i>P</i><0.05). Logistic regression analysis showed that silicone oil filling, combined cataract surgery, total retinal photocoagulation and postoperative vitreous hemorrhage were independent risk factors affecting the occurrence of early postoperative high intraocular pressure(<i>P</i><0.05).<p>CONCLUSION: Early high intraocular pressure after vitrectomy is the result of multiple factors, which is closely related to silicone oil filling, combined cataract surgery, total retinal photocoagulation and vitreous hemorrhage after vitrectomy.

Cost-Effectiveness Analysis of Different Chemotherapy Regimens in the Treatment of Patients with Multiple Myeloma / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To compare the pharmaco-economic effect of 3 chemotherapeutic regimens in the treatment of patients with multiple myeloma(MM).</p><p><b>METHODS</b>One hundred and thirty-eight newly diagnosed cases of MM in our hospital were analyzed retrospectively, and then MM patients were divided into group A, B and C group according to therapeutic regimen. Group A was treated with VCD therapeutic regimen (bortezomib + cyclophosphamide + dexamethasone, 63 cases), The patients in group B was treated with BiCTD therapeutic regimen (clarithromycin+cyclophosphamide+thalidomide+dexamethasone, 44 cases), The patients in group C was treated with CTD therapeutic regimen (cyclophosphamide+ thalidomide+dexamethasone, 33 cases). The clinical efficacy, adverse reaction, cost-effectiveness were observed and analysed after 4 courses of treatment among 3 groups.</p><p><b>RESULTS</b>The overall response rates of group A, B and C were 96.83%, 81.82% and 64.52% with statistical significant difference (P<0.01). The high efficiency response rates of 3 groups were 82.5%, 59.09%, 32.26% with very significant statistical difference (P<0.01). The infection rate of group A was statistically and significantly higher than other 2 groups (P=0.048), and the constipation rate in group A was statistically and significantly higer than that in group B and C (P<0.05). The cost-effectiveness ratios of 3 groups were 69567.44, 20765.12 and 21475.48, respectively. The incremental cost-effectiveness ratio of group A and B were 183933.21 and 22259.09, as compared with group C. The result was in accordance with sensitivity test.</p><p><b>CONCLUSION</b>Clinicial efficacy of group A is the best,but group B has advantages on cost-effectiveness ratio as compared with other groups, otherwise, group B has low incidence of adverse reaction. In the view of safety, therapeutic efficacy and pharmacoeconomics for treatment of patients with MM, the BiCTD regimen has been confirmed to be superior to the other 2 groups.</p>

Effect and Clinical Significance of Bortezomib and Thalidomide on the Memory T Cells Subsets and Regulatory T Cells in Peripheral Blood of Patients with Multiple Myeloma / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the effects of bortezomib(BTZ) and thalidomide(TM) on peripheral blood memory T-cells (T) and regulatory T cells(Tregs) in patients with multiple myeloma(MM).</p><p><b>METHODS</b>Eighty-six MM patients received 2 courses of chemotherapy were divided into effective (partial response at least) group (63 cases) and ineffective (no partial response) group (17 cases) according to therapeutic efficacy; these 80 patients were divided into BTZ group (38 cases) and TM group (42 cases) yet according to therapeutic regimens, 20 newly diagnosed MM patients were used as baseline group, 30 healthy volunteers were used as healthy control group. The T subsets and Treg in peripheral blood of each groups were detected by flow cytometry.</p><p><b>RESULTS</b>The CD4 central memory T cells (CD4 T) percentage of CD4 T, the CD18 T percentage of CD18T and ratio of CD8 T and CD8 effector memory T cells (T) (CD8 T/T) in baseline group were all significantly lower than those in healthy control group (P<0.05). After treatment with BTZ regimen or TM regimen, the CD8T percentage of CD8 T in effective group significantly increased to level of healthy control group (P<0.05); the Treg cell level in effective and in effective groups was not significantly different from that in baseline group(P>0.05), but the Treg percentage of CD4 cells ineffective group was significantly higher than that in baseline group and ineffective group (P<0.05). According to ROC curve, the critical value of CD8T/T for predicting chemotherapeutic response was 0.27 with sensitivity of 57.1% and specificity of 94.1%.</p><p><b>CONCLUSION</b>When MM patients are in an immuno-exhanstive status, the treatment with BTZ or TM both can reverse the immuno-inhibitory status of MM patients, moreover, does not affect the Treg cell count; the Treg percentage in BTZ and TM effective groups both are significantly higher than that in baseline group and ineffective group. The ratio of CD8T/T contributes to evaluating the chemotherapeutic efficacy.</p>

Research Progress on Molecular Mechanisms of Resistance to Bortezomib in Multiple Myeloma- Review / 中国实验血液学杂志

Over the last decade, bortezomib(BTZ) has been extensively applied in the treatment of hematological malignancies, particularly in multiple myeloma and mantle cell lymphoma, however, the appearence of secondary resistance to BTZ has brought a huge challenge in MM treatment. In the present review, the mechanisms of resistance to bortezomib in MM are summarized, focusing on the action of ubiquitin-proteasome system(UPS), endoplasmin reticulum stress, antophagy, inducible pro-survival signalling and bone marrow microenvironment as well as exploration of the potential therapeutic strategies in the clinical perspective. With the understanding of the molecular mechanisms for resistance to BTZ, the novel histone deacetylase inhibitors(HDACi) have been approved for the treatment of replased/refractory MM and AKT inhibitor in the clinical trials. These novel combined therapies can enhance BTZ efficiency and improve the outcome of the patients.

Clinical and Immunophenotypic Properties of Small Cell Variant of T-cell Prolymphocytic Leukemia / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the clinical, morphologic and immunophenotypic properties of the patients with small cell variant of T-cell prolymphocytic leukaemia(T-PLL).</p><p><b>METHODS</b>Peripheral blood and bone marrow cytomorphologic and immunophenotypic examination, and T-cell receptor(TCR) gene rearrangement detection were used to verify the diagnosis for 2 patients with lymphocytosis. Two patients were treated with combined chemotherapeutic protocol based on fludarabine.</p><p><b>RESULTS</b>At diagnosis of case 1, the main lymphocytes of peripheral blood smear were the small mature lymphocytes without nucleoli. The immunophenotype of the cells was CD3CD5CD7CD4CD8TCRα/β. The patient achieved complete remission after treatment with combined with CTX of fludarabine. The disease relapsed at 32 months after diagnosis. The abnormal lymphocytes were medium-sized ones with a visible nucleolus. Immunophenotyping showed that the leukemic cells were predominantly CD8 positive(CD3CD5CD7CD4CD8TCRα/β). Both the peripheral blood and bone marrow cells of case 2 were predominanthy the mature lymphocytes, and their immunophenotype was HLA-DRCD7CD5CD4CD3CD2CD56cCD3TCRα/β. The combined fludarabine therapy was ineffective.</p><p><b>CONCLUSION</b>Immunophenotypical switch from CD4CD8to CD4CD8may be associated with a poor response to chemotherapy. CD56 expression is an independent poor prognostic factor for primary refractory disease in T-PLL and may be considered for implementing risked-adapted therapeutic strategies.</p>

Acute Promyelocytic Leukemia Developed during Imatinib Therapy for Gastrointestinal Stromal Tumors / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the clinicopathologic and molecular characteristics of acute promyelocytic leukemia(APL) developed during imatinib therapy for gastrointestinal stromal tumors(GIST).</p><p><b>METHODS</b>A 49-year-old woman was hospitalized for abdominal pain. The abdominal CT revealed a gastric mass. Laparoscopic resection of the tumor was performed. The histopathologic analysis showed poorly differentiated malignant cell infiltration with epithelioid features. Immunohistochemistry staining of these cells was positive for CD117 and CD34. GIST was confirmed and imatinib treatment was given.</p><p><b>RESULTS</b>After 1 year,the patient developed progressive pancytopenia. Bone marrow aspirate showed marked hyperplasia of bone marrow cells with 92.5% promyelocyte, consistent with APL. Cytogenetic analysis demonstrated t(15;17)(q22;q21) as the sole abnormality. PML/RARα fusion gene was positive and Kit mutation was negative. After combined treatment with ATRA, arsenic trioxide and idarubicin, patient achieved cytogenetic and molecular remission.</p><p><b>CONCLUSION</b>The metachronous coexistence of GIST with APL is uncommon. The potential nonrandom association and causal relationship between these malignancies remained to be investigated. Further studies would be necessary to clarify the relationship between imatinib and secondary malignancies in GIST patients.</p>

Establishment and Management of Multiple Myeloma Specimen Bank Applied for Molecular Biological Researches / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To establish a multiple myeloma specimen bank applied for molecular biological researches and to explore the methods of specimen collection, transportation, storage, quality control and the management of specimen bank.</p><p><b>METHODS</b>Bone marrow and blood samples were collected from multiple myeloma patients, plasma cell sorting were operated after the separation of mononuclear cells from bone marrow specimens. The plasma cells were divided into 2 parts, one was added with proper amount of TRIzol and then kept in -80 °C refrigerator for subsequent RNA extraction, the other was added with proper amount of calf serum cell frozen liquid and then kept in -80 °C refrigerator for subsequent cryopreservation of DNA extraction after numbered respectively. Serum and plasma were separated from peripheral blood, specimens of serum and plasma were then stored at -80 °C refrigerator after registration. Meantime, the myeloma specimen information management system was established, managed and maintained by specially-assigned persons and continuous modification and improvement in the process of use as to facilitate the rapid collection, management, query of the effective samples and clinical data.</p><p><b>RESULTS</b>A total of 244 portions plasma cells, 564 portions of serum, and 1005 portions of plasma were collected, clinical characters were documented.</p><p><b>CONCLUSION</b>A multiple myeloma specimen bank have been established initially, which can provide quality samples and related clinical information for molecular biological research on multiple myeloma.</p>

Effects of Mongolia Astragali Radix in protecting early cardiac and nephritic functions of patients of hypertension with metabolic syndrome / 中国中药杂志

To explore the effect of Mongolia Astragali Radix produced in Longxi of Gansu province in protecting cardiac and nephritic functions of patients of essential hypertension(EH) with metabolic syndrome(MetS). A total of two hundred and twenty-six EH patients with MetS aged above 18 were selected. Patients were randomly divided to control group(adopted conventional medical treatment), Astragali Radix group 1(added Astragali Radix capsules 10 g•d⁻¹ besides conventional medical treatment) and Astragali Radix group 2(added Astragali Radix capsules 5 g•d⁻¹ besides conventional medical treatment). Cardiac anatomy structure, cardiac systolic function and diastolic function were measured by M-mode echocardiography, two-dimensional echocardiography, Doppler echocardiographic determination and tissue Doppler imaging. The level of microalbuminuria(MAU) was evaluated by radioimmunoassay. In addition, the estimated glomerular filtration rate(eGFR) was calculated by modification of diet in renal disease (MDRD) formulas. The changes of relevant indicators for cardiac and nephritic functions before and after treatment were compared during the 12-month follow-up. The study protocol was registered at the website of Chinese clinical trial register and approved by the ethics committee of second hospital of Lanzhou university. Each patient was required to sign an informed consent. SPSS software was used for statistical analysis. According to the result, compare with before treatment, the three groups show no difference in efficacy of metablic indicators. Left ventricular end-systolic volume (ESV) and left ventricular end-systolic dimension (LVESd) of all patients were improved after treatment. However, there was no significant difference among the three groups. After the addition of Astragali Radix, the mitral flow velocity(Vp) of patients was improved to some extent(P<0.05). However, there was no significant difference among the three groups. Astragali Radix had a significant effect in reducing the MAU(P<0.05). Moreover, the MAU level of patients in Astragali Radix group 1 decreased more significantly than the other groups(P<0.05). Compared with conventional therapy, Astragali Radix combined with conventional therapy could improve cardiac structure, left ventricular systolic function, left ventricular diastolic function, and reduce the MAU to a certain extent in EH patients with MetS. Moreover, the effects of high-dose Astragali Radix are better than that of the low-dose Astragali Radix. However, the effect of Astragali Radix on EH patients with MetS shall be further observed to confirm its efficacy.

Clinico-pathologic Characteristics of Adult Patients with Atypical Infectious Mononucleosis / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the clinicopathologic characteristics of adult patients with atypical infectious mononucleosis(IM).</p><p><b>METHODS</b>From January 2003 to December 2013, a total of 5 cases of atypical IM misdiagnosed as lymphoma were selected, and the clinico-pathological characteristics and efficacy of treatment were analyzed. Biopsy of lymph node or tonsil was performed to evaluate the possibility of lymphoma. Peripheral blood EBV antibody and EBV-DNA were examined by ELISA and real-time fluorescence quantitative PCR, respectively.</p><p><b>RESULTS</b>All the cases were considered as lymphoma on the basis of morphological features in initial evaluation before relapse. These features included a florid immunoblastic proliferation, distortion of the underlying nodal or tonsillar architecture and the presence of necrosis. The immunophenotypic features, EBV encoded RNA (EBER) in situ hybridization and the gene rearrangement of immunoglobulin or T cell receptor may be helpful for the distinction of atypical IM from lymphoma.</p><p><b>CONCLUSION</b>IM as EBV-related lymphoproliferative process shows marked clinical and histological diversity. Atypical case of IM may mimic many different type of lymphoma in clinical and pathologic features, and the misdiagnosis should be avoided by using molecular and pathological examination.</p>

Clinicopathologic Characteristics and Outcome of Isolated Ovarian Relapse in Adolescent with Acute Lymphoblastic Leukemia / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the clinicopathologic characteristics,diagnosis and treatment of isolated ovarian relapse of acute lymphoblastic leukemia(ALL).</p><p><b>METHODS</b>A 16-year-old girl presented with complaints of bone and joint pain. The peripheral blood and bone marrow(BM) smears showed 32% and 72% blasts, respectively, which were myeloperoxidase-negative. The blasts were positive for HLA-DR, TdT, CD10, CD19, CD22 and cCD79a and negative for CD34, CD5, CD7, CD13, CD33, CD56 and MPO detected by flow cytometry. BM cytogenetic analysis and fusion gene screening revealed t(1;19)(q23;p13) and E2A/PBX1. She was diagnosed as B-cell acute lymphoblastic leukemia (B-ALL) and was treated with CALGB8811 protocol. She presented lower abdominal pain with intermittent colick at 7 months after complete remission. The pelvic ultrasound showed a lobulated mixed echogenic mass in the right ovary, and an exploratory laparotomy was performed.</p><p><b>RESULTS</b>Pathologic examination and immunohistochemistry of resected ovarian tumor revealed extensive infiltration by lymphoblasts with positive for TdT, CD20, CD43 and CD79a. Further investigations failed to reveal any other extramedullary involvement. Hemogram, peripheral blood and bone marrow smear examination were unremarkable at the same time. The isolated extramedullary ovarian relapse of ALL was confirmed. Simultaneous, the detection of minimal residual disease by multiparametric flow cytometry showed positive with 5.0×10. The reinduction chemotherapy including a high-dose methotrexate and cytarabine was given to the patients. She experienced the second ovarian relapse after 1 year and refused further treatment.</p><p><b>CONCLUSION</b>Although uncommon, ovarian recurrence after chemotherapy for ALL should be considered in the patients with suggestive symptoms. Screening by pelvic ultrasonography may be valuble for early detection of pelvic disease in ALL.</p>

Application Value of CD138 MACS-FISH in the Genetic Diagnosis of Plasma Cell Dyscrasia / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the cytogenetic characteristics of the various plasma cell dyscrasia using the CD138 MACS-FISH, to elucidate the application value of MACS-FISH in the genetic diagnosis of plasma cell dyscrasia, and to explore the standardization of FISH detection for plasma cell dyscrasia.</p><p><b>METHODS</b>A total of 232 patients with newly diagnosed plasma cell dyscrasia were collected, including 203 cases of MM, 24 cases of AL amyloidosis and 5 cases of MGUS, whose cytogenetic abnormalities were detected by MACS-FISH, and the differences of the positive detection rates of chromosome karyotype analysis, C-FISH and MACS-FISH in MM cytogenetic abnormality were compared. The sensitivity of C-FISH and MACS-FISH were analyzed and compared according to the proportion of bone marrow plasma cells. The correlation between the positive cell rates of C-FISH and MACS-FISH and the proportion of plasma cells were analyzed respectively. The differences in the clone size detected by C-FISH and MACS-FISH were compared.</p><p><b>RESULTS</b>The incidence of cytogenetic abnormality of MM, AL amyloidosis and MGUS detected by MACS-FISH were 85.9%, 62.5%, 60%, respectively. The incidence rate of MM cytogenetic abnormality detected by Chromosome karyotype analysis and C-FISH were 20.0% and 64.7%, respectively, which were significantly lower than that of MACS-FISH(P<0.001). The positive rate of 14q32 translocation, del(14q32), t(11;14), +17p13 and the coexistence of 2 and ≥3 kinds of cytogenetic abnormalities detected by MACS-FISH were significantly higher than that detected by C-FISH(P<0.05). When the plasma cell ratio was less than or equal to 5%, the positive detection rate of MACS-FISH was significantly higher than that of C-FISH (P=0.001), and there was no significant difference in different plasma cell proportion group of MACS-FISH. However, when the plasma cell ratio was less than or equal to 5%, the positive detection rate of C-FISH detection was significantly lower than that of the other 3 groups (P=0.013,P=0.001,P<0.001). The positive cell rates of all cytogenetic abnormalities in C-FISH group and +1q21 and 14q32 translocation in MACS-FISH group were significantly positively correlated with the proportion of plasma cells(P<0.05). The clone size of various cytogenetic abnormalities in MACS-FISH group were significantly higher than that in C-FISH group(P<0.001).</p><p><b>CONCLUSION</b>MACS-FISH may significantly enhance the detection rate of cytogenetic abnormalities in various plasma cell dyscrasia, and it can better reflect the cytogenetic abnormality of plasma cell dyscrasia and its clone size. MACS-FISH may be recommended as a standard method for the genetic diagnosis of plasma cell dyscrasia, the risk stratification of MM and SMM, as well as the genetic diagnosis and research of MGUS and AL amyloidosis.</p>

Older age is not related to hemorrhagic transformation and favorable outcomes in patients with wake-up ischemic stroke undergoing intravenous thrombolytic therapy / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate factors related to hemorrhagic transformation and favorable outcomes in wake-up ischemic stroke (WUIS) patients undergoing intravenous thrombolytic therapy.</p><p><b>METHODS</b>Clinical data of 600 patients undergoing multimodal image-guided intravenous recombinant tissue plasminogen activator (rt-PA) therapy in Department of Neurology, the Second Affiliated Hospital, Zhejiang University School of Medicine center from May 2009 to May 2015 were retrospectively analyzed. Among 600 patients, 68 were diagnosed as WUIS including 17 cases aged 80 or older. Hemorrhagic transformation within the first 24 h after thrombolysis was assessed according to ECASS II criteria. Favorable outcome was defined as three-month modified Rankin Scale (mRS) 0-3. Univariate and binary logistic regression were used to analyze the risk factors of hemorrhagic transformation and poor clinical outcomes in WUIS patients.</p><p><b>RESULTS</b>Univariate analysis showed that WUIS patients aged ≥ 80 years had a lower rate in males (41.2% vs 76.5%, P=0.007), smokers (11.8% vs 43.1%, P=0.019) and favorable outcome (52.9% vs 78.4%, P=0.043); and a higher rate of cardiac embolism (64.7% vs 35.3%, P=0.034) compared with those aged <80 years. Binary logistic regression showed that age was not an independent risk factor for favorable outcome (OR=0.524, 95% CI:0.141-1.953, P=0.336) or hemorrhagic transformation (OR=1.039, 95% CI: 0.972-1.111, P=0.262).</p><p><b>CONCLUSION</b>Older age is not related to the favorable outcome or hemorrhagic transformation in WUIS patients undergoing multimodal image-guided intravenous thrombolytic therapy.</p>

Research progress on multiple myeloma immunophenotyping and minimal residual disease detected by flow cytometry / 中国实验血液学杂志

Multiple myeloma (MM) is a haematological malignancy characterized by the accumulation of monoclonal plasma cells in the bone marrow and remained incurable. Flow cytometry has been widely used in the detection of immunophenotype and minimal residual disease, diagnosis, monitoring and prognosis of MM. Normal plasma cells and malignant plasma cells can be distinguished according to different cell surface antigen expression. The clinical significane of many immune markes has been elucidated. However, the clinical significance of some phenotype remains controversial, the detection scheme and gating strategy are not unified. This review discusses the recent research progress on detection of MM immunophenotype and minimal residual disease by flow cytovetry.

Progress of research on clarithromycin for treatment of multiple myeloma / 中国实验血液学杂志

Clarithromycin is a 14-membered ring macrolide antibiotics that is widely used in the treatment of infectious disease. Several clinical investigations showed that clarithromycin was highly efficient for multiple myeloma in improving response rate and survival when used in combination with the conventional chemotherapy since 1997. This finding highlights the importance of clarithromycin on the treatment of multiple myeloma. It offers a new regimen for the relapsed/refractory multiple myeloma patients, and provids a new thought for the treatment of multiple myeloma. However, its related mechanism is still unclear, and more investigations are needed. This review summerizes the recent research progress of clarithromycin for treatment of multiple myeloma and its potential mechanisms.

Test of Serum Free Light Chain and Its Clinical Significance in Light Chain Multiple Myeloma / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the clinical significance of serum free light chain (sFLC) detection in light chain multiple myeloma (LCMM).</p><p><b>METHODS</b>A total of 37 newly diagnosed LCMM patients were enrolled in this study, including 17 patients with k light chain type and 20 patients with λ light chain type, the sFLC and 24 hours urine light chain (ULC) were measured before and after chemotherapy. The correlation of sFLC level with ULC and renal impairment was analyzed.</p><p><b>RESULTS</b>All the patients displayed an abnormally increased level of sFLC at diagnosis wtih median value of 105.44 mg/L and 146.39 mg/L for k and λ light chain types, respectively. The sFLC did not correlate with ULC before and after chemotherapy. Among the 12 patients with very good partial remission and normal ULC level, the sFLC still was abnormally increased in 8 patients. Renal impairment was associated with the urine λ-type light chain, and the area under the ROC curve of urine λ light chain at diagnosis is 0.792 (P = 0.031).</p><p><b>CONCLUSION</b>All patients with LCMM show an abnormally increased level of sFLC at diagnosis. sFLC can be used to monitor the response to chemotherapy because it is more sensitive for analysis of therapeutic effect than urine λ light chain.</p>

Long-term follow-up for 39 newly diagnosed diffused large B-cell lymphoma patients treated by (R)-EPOCH / 中国实验血液学杂志

The purpose of this study was to evaluate the efficacy and safety of (R)-EPOCH protocol on patients with diffuse large B-cell lymphoma(DLBCL). From February 2004 to April 2009, a total of 39 patients who suffered from DLBCL and received (R)-EPOCH protocol were enrolled in the study. The median age of patients was 52 years old. 24 patients were on stage I/II, and 15 cases were on stage III/IV. Patients with stage I/II were administered with 4-6 cycles of (R)-EPOCH, while other patients with stage III/IV received 6-8 cycles of (R)-EPOCH. DLBCL patients with bulky disease received radiotherapy after completion of chemotherapy. 39 patients received a total of 209 cycles of chemotherapy and the median chemotherapy cycles was 6 (range, 2-8 cycles). The results showed that the overall response rate of 39 assessable patients was 87.2%, including 28 patients (71.8%) in complete remission (CR) and 6 patients (15.4%) in partial remission(PR). With a median follow-up of 57.7 months, the 1-year overall survival rate was 81.8%, while 70.9% for 3-year and 58.8% for 5-year. The major toxicity of (R)-EPOCH protocol was hematologic toxicity and the incidence of grade III-IV neutropenia and anemia were 29.2% and 14.4%, respectively. Other toxicities were mild, no treatment-related deaths occurred. At the end of follow-up,no secondary tumors occurred. It is concluded that (R)-EPOCH protocol is a effective and safe protocol for the patients with DLBCL.