Clinical Analysis of B-Cell Non-Hodgkin Lymphoma Treated with Modified Conditioning Regimen / 中国实验血液学杂志

OBJECTIVE@#To investigate the efficacy, safety and prognosis of auto-HSCT between classical and modified conditioning regimen in patients with B-cell non-Hodgkin lymphoma.@*METHODS@#36 patients diagnosed as B-cell non-Hodgkin lymphoma treated with autologous hematopoietic stem cell transplantation from January 2015 to June 2018 in Tianjin Cancer Hospital were retrospectively analyzed. The patients were divided into two groups: Idarubicin group and non-Idarubicin group. The overall survival (OS), progression-free survival (PFS), adverse reactions and hematopoietic reconstitution time between the two groups were compared. Survival analysis was performed by using the Kaplan-Meier method. Log-rank test was used for comparison between groups, and Cox regression was used for multivariate analysis.@*RESULTS@#The median follow-up time was 29 months. Among these 36 patients with B-cell non-Hodgkin lymphoma before transplantation, 21 patients achieved CR and 15 patients achieved PR. The reconstitution time of neutrophil (P>0.05) and platelet (P>0.05) was not significantly different between Idarubicin and non-Idarubicin group. Also, the adverse reactions were not significantly different between two groups. The addition of idarubicin showed not aggravate the adverse reactions of patients. The OS and PFS of patients with idarubicin was longer than that of patients without idarubicin. The multivariate analysis showed that, the modified conditioning regimen and the remission state before transplantation were closely associated with prognosis.@*CONCLUSION@#The above-mentioned results indicated that the combination of modified conditioning regimen with idarubicin can lengthen the OS and PFS of the patients significantly, and show not aggravate of bone marrow inhibition, moreover, the hematopoietic reconsititution time show not lengthen, which means that it can be a safe and effective choice for autologous HSCT in the patients with B cell non-Hodgkin lymphoma.

Clinical Significance of EBV-DNA Copy Number in EBV Positive Lymphoma Patients / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of EBV-DNA copy number on the prognosis of patients with EBV positive lymphoma.@*METHODS@#Clinical data of 109 patients diagnosed as EBV positive lymphoma in Tianjin Medical University Cancer Institute and Hospital from January 2010 to January 2020 were enrolled and analyzed retrospectively. Kaplan-Meier analysis was used for survival analysis, Log-rank was used to compare the clinical characteristics between the patients in different groups, and Cox regression was used for multivariate analysis.@*RESULTS@#Among the 109 patients with EBV-positive lymphoma, the medium age were 56 (range 15 to 83) years old. 29 patients at Ann Arbor stage I-II while 80 patients at stage III-IV. The average value of EBV-DNA was 1 023 510 IU/ml, 7 patients were higher than the average value, while 102 patients were lower. KM survival analysis showed that OS and PFS in patients with EBV-DNA above average level were shorter than those in patients with EBV-DNA below average level (OS: P=0.048, PFS: P=0.001), EBV-DNA copy number was a factor affecting the prognosis of patients. In addition, LDH level showed positive correlation with EBV-DNA copy number (r=0.650), which was also one of the factors affecting OS (P=0.053).@*CONCLUSION@#EBV-DNA copy number and LDH level can influence the prognosis of EBV positive lymphoma patients. Therefore, detection of EBV-DNA copy number in peripheral blood is important for evaluate the prognosis the patients.

Reaserch Advances in Immunotherapy for Acute Myeloid Leukemia--Review / 中国实验血液学杂志

Acute myeloid leukemia (AML) is a malignant tumor with abnormal myelocyte differentiation. With the development of immunological technology, great importance has been attached to the immunotherapy of AML patients, which may become an effective treatment strategy for AML, and providing a new means for the prognosis and survival. In this review, the advanced research of immunotherapy for AML, such as antibody-dependent drugs, chimeric antigen receptor T cell therapy, and checkpoint inhibitors, the bastest reaserch advanves of clinical experiment for immunotherapy was summarized briefly.

Clinical Characteristics of 219 Patients with Primary Gastrointestinal Non-Hodgkin's Lymphoma / 中国实验血液学杂志

OBJECTIVE@#To analyze the clinical and pathological characteristics of primary gastrointestinal non-Hodgkin's lymphoma (PGI-NHL) patients, and to explore the factors affecting the patients' survival and prognosis.@*METHODS@#The clinical data of 219 patients with PGI-NHL diagnosed in our hospital from March 2009 to April 2016 was collected and retrospectively analyzed. Survival analysis was performed by using the Kaplan-Meier method. Log-rank test was used for comparison among the groups, and Cox regression was used for multivariate analysis.@*RESULTS@#Among the 219 patients with PGI-NHL, 126 patients were males and 93 patients were females. 182 patients were IPI 0 to 2 and 37 patients were IPI 3 to 5. There were 205 cases (93.6%) of B cell phenotype and 14 cases (6.4%) of T cell phenotype. 140 patients (63.9%) were patients with primary gastric NHL, including 85 DLBCL and 19 MALT. 79 cases (36.1%) were patients with primary intestinal NHL, including 46 DLBCL, 4 MALT, 7 FL, 3 MCL and 4 Burkitt lymphoma. 23 cases were HP positive and received anti-HP therapy. 57 cases and 32 cases received surgery and chemotherapy respectively. 84 cases received combination treatment of surgery and chemotherapy and 11 cases received combination treatment of radiotherapy and chemotherapy. Overall survival (OS) of indolent B-cell non-Hodgkin's lymphoma was longer than that of invasive B-cell non-Hodgkin's lymphoma, which shows better prognose. Kaplan-Meier analysis showed that there was no difference between progression-free survival (PFS) and OS in the patients with different origin sites, age and sex. There was no significant difference in PFS between B-cell and T-cell-derived patients, whereas OS of B-cell-derived PGI-NHL patients was longer than that of T-cell-derived PGI-NHL patients. The OS and PFS of patients with IPI 0-2 were longer than those of patients with IPI 3-5. According to Lugano and Ann Arbor staging systems, there was no difference in prognosis of patients between phase I/II and III/IV. The prognosis of patients treated with surgery alone was worse than that of patients treated with combination therapy, and the prognosis of patients with surgery combined with chemotherapy was not significantly different from that of patients with chemotherapy alone.@*CONCLUSION@#B-cell phenotype, indolent and low IPI score lymphoma indicate better prognosis, while that of different origin site, sex and age shows no different in prognosis. Surgery is used only for emergency case or pathological materials, and these patients should be treated with chemotherapy-based combined treatment.

Research Progress on Diagnosis and Treatment of B Cell Chronic Lymphoproliferative Disease--Review / 中国实验血液学杂志

The 2016 world health organization (WHO) classification of B cell chronic lymphoproliferative disease (B-CLPD) includes chronic lymphocytic leukemia (CLL), B prolymphocytic leukemia, (B-PLL), hairy cell leukemia (HCL), marginal zone lymphoma (MZL), follicular lymphoma (FL), mantle cell lymphoma (MCL), Waldenstrom macroglobulinemia (LPL/WM). All the above-mentioned diseases are partially similar in cell morphology, immunophenotype and molecular genetics, but significantly different in treatment and prognosis. Currently, many new drugs targeted at cell cycle and apoptosis pathway, such as proteasome inhibitor immune modulators and histone deacetylase inhibitors, have achieved encouraging results in B-CLPD, which bring new hope for patients with B-CLPD. The review will discuss the progress in diagnosis and treatment of B-CLPD in recent years.

Advances of Targeting Therapy in Acute Myeloid Leukemia--Review / 中国实验血液学杂志

Although the application of combined chemotherapy has made a great progress in treatment of adult acute myeloid leukemia (AML), the overall survival rate is still not high, mainly because of high recurrence rate and drug resistance. The treatment regimen for relapsed/refractory AML is always strong. Due to the chemotherapy drugs lacking of specific identification of tumor cells, significant adverse reactions often come out and sometimes even endanger the life of patients. In order to improve the life quality and survival rate, the new treatment strategy is urgently needed. With the deepening of research, the new molecular targets of tumor cells including the abnormal expression of cell surface morecules, gene mutation and abnormal gene methylation has been found. Targeted drugs for these abnormal changes could improve the prognosis of AML patients, providing a new way for AML treatment. This review summarizas the progress of molecular targeted therapy of AML.

[Expression of pRb and E2F-1 and telomerase activity in ameloblastoma].

OBJECTIVE: To investigate the expression of pRb and E2F-1, and the association between their expression and the activity of telomerase (hTERT) or cyclin E in human ameloblastoma (AB), and to explore the clinical biological characteristics of AB. METHODS: The expressions of pRb, E2F-1, cyclin E and hTERT mRNA in human AB were detected by in situ hybridization or immunohistochemistry (SP method). RESULTS: The positive expression ratio of pRb in the cell nucleus of AB was 20.4% (11/54). The positive ratio of E2F-1, cyclin E and hTERT mRNA was 92.6% (50/54), 66.7% (36/54) and 94.4% (51/54), respectively. With AB recurrence and malignant transformation, the expression of hTERT, E2F-1, cyclin E was up-regulated. hTERT and cyclin E or E2F-1 mRNA had high positive relation (Spearsman'r(s) = 1.000, P = 0.0001). CONCLUSIONS: The regulatory pathway of Rb/E2F-1 is associated with the cell proliferation and in differentiation of AB. The activity or release of telomerase may be related to the lower expression of Rb and higher expression of E2F-1, and is up-regulated in G(1) late phase by cyclin E.

[The study of the invasive biologic behavior of ameloblastoma].

OBJECTIVE: To investigate the invasive biologic behavior of ameloblastoma (AB) and to analyze its correlative factors. METHODS: The specimens of 43 cases of AB (primary AB 16 cases, recurrent AB 21 cases, malignant AB 6 cases) were examined immunohistochemically using the streptavidin-biotin method to determine the expression of E-cadherin (E-cad), matrix metalloproteinase (MMP)-2, MMP-9 and vascular endothelial growth factor (VEGF). RESULTS: The cells in malignant AB scattered more, grew invasively, and the basal membrane ruptured or lost. The expression of E-cad in AB descended, MMP-2 and MMP-9 were strongly expressed in the epithelia cells of 28/41, 30/43 cases of AB, respectively. The positive rate and intensity of VEGF increased as AB recurred and transformed malignantly. The expression of E-cad, MMP-9 and VEGF were related to recurrence or malignant transformation of AB (r(s) = 0.309, 0.519, 0.381, P < 0.05). CONCLUSION: AB is a high invasive tumor. The biological behavior of AB is related to lost or abnormal expression of E-cad, the high expression of MMP-2, MMP-9, and VEGF.

[Expression of telomerase activity and cyclin A in ameloblastoma].

OBJECTIVE: To study relation of the expression of hTERT mRNA and cyclin A, p53 protein, proliferation cell nuclear antigen (PCNA) in ameloblastoma (AB) and to investigate clinical biological characteristics of AB. METHODS: The hTERT mRNA was detected by in situ hybridization, cyclin A, p53 protein and PCNA by SP method. Normal oral mucosa and odontogenic keratocyst (OKC) are comparition. RESULTS: The positive ratio of hTERT mRNA was 1/7 cases in normal oral mucosa. The expression of cyclin A, p53 and PCNA in normal oral mucosa were similar, and the positive cells distributed in stratum basale. In OKC, the positive cells distributed in stratum basale and super-strrtum basale. And the positive ratio of hTERT, cyclin A, p53, PCNA in OKC was 14/16 cases, 4/32 cases, 11/25 cases, 5/9 cases, respectively. In AB, the positive ratio of hTERT mRNA, cyclin A, p53 protein and PCNA was 94.4% (51/54), 66.7% (40/60), 85.7% (42/49) and 78.1% (25/32), respectively. A strong correlation was found between hTERT mRNA with cyclin A, p53 protein and PCNA (r(s) = 0.914, 0.848, 0.804, P < 0.05). CONCLUSIONS: The expression of hTETR mRNA, cyclin A, p53 and PCNA is different in different tissues and lesions, and correlates with cell differentiation and clinical biology behaviour. Telomerase activity is related to cumulation of p53 protein, related to cell proliferation and differentiation, regulated by cyclin A, and higher in S phase.

[Expression of matrix metalloproteinases and tissue inhibitor of metalloproteinase in ameloblastoma].

OBJECTIVE: To study the expression of matrix metalloproteinase(MMP) and tissue inhibitor of metalloproteinase (TIMP) in ameloblastoma (AB) and to determine the relationship between biological behavior of AB and clinical pathology. METHODS: The specimens of 43 cases of AB, 10 cases of odontogenic keratocyst (OKC), 8 cases of normal oral mucosa were examined by streptavidin-biotin method. RESULTS: In 8 cases of normal oral epithelial, MMP-2 was negative or weak positive. In OKC, MMP-2 was extensively positive in stratum spinosum of 2 cases, and weekly or negative in stratum basale. MMP-2 was strongly expressed in the central and peripheral cells of the tumor islands in 28 cases of AB. There were difference among these three groups (P < 0.001). Comparing AB with normal oral mucosa and OKC, there was significant difference (P < 0.05). MMP was positive expressed in cells of stroma. The positively rate and intensity increased as AB recurrence and transformed malignantly, but were not associated with age, sex, pathological type and location. TIMP-1 was weakly or not expressed in normal oral mucosa, stoma, OKC and AB. CONCLUSIONS: The high expression of MMP-2 and MMP-9 is related to the biological behavior of AB. Imbalances of the expression of MMP-2 and MMP-9 protein maybe be one of the facts of the invasion of AB. The MMPs activation produced by stromal cells may be also be related to the invasion of AB.