Objective:To analyze the factors affecting delayed chemotherapy in children with Burkitt lymphoma (BL) and their influence on prognosis.Methods:Retrospective cohort study. Clinical data of 591 children aged ≤18 years with BL from May 2017 to December 2022 in China Net Childhood Lymphoma (CNCL) was collected. The patients were treated according to the protocol CNCL-BL-2017. According to the clinical characteristics, therapeutic regimen was divided into group A, group B and group C .Based on whether the total chemotherapy time was delayed, patients were divided into two groups: the delayed chemotherapy group and the non-delayed chemotherapy group. Based on the total delayed time of chemotherapy, patients in group C were divided into non-delayed chemotherapy group, 1-7 days delayed group and more than 7 days delayed group. Relationships between delayed chemotherapy and gender, age, tumor lysis syndrome before chemotherapy, bone marrow involvement, disease group (B/C group), serum lactate dehydrogenase (LDH) > 4 times than normal, grade Ⅲ-Ⅳ myelosuppression after chemotherapy, minimal residual disease in the interim assessment, and severe infection (including severe pneumonia, sepsis, meningitis, chickenpox, etc.) were analyzed. Logistic analysis was used to identify the relevant factors. Kaplan-Meier method was used to analyze the patients' survival information. Log-Rank was used for comparison between groups.Results:Among 591 patients, 504 were males and 87 were females, the follow-up time was 34.8 (18.6,50.1) months. The 3-year overall survival (OS) rate was (92.5±1.1)%,and the 3-year event-free survival (EFS) rate was (90.5±1.2)%. Seventy-three (12.4%) patients were in delayed chemotherapy group and 518 (87.6%) patients were in non-delayed chemotherapy group. The reasons for chemotherapy delay included 72 cases (98.6%) of severe infection, 65 cases (89.0%) of bone marrow suppression, 35 cases (47.9%) of organ dysfunction, 22 cases (30.1%) of tumor lysis syndrome,etc. There were 7 cases of chemotherapy delay in group B, which were seen in COPADM (vincristine+cyclophosphamide+prednisone+daunorubicin+methotrexate+intrathecal injection,4 cases) and CYM (methotrexate+cytarabine+intrathecal injection,3 cases) stages. There were 66 cases of chemotherapy delay in group C, which were common in COPADM (28 cases) and CYVE 1 (low dose cytarabine+high dose cytarabine+etoposide+methotrexate, 12 cases) stages. Multinomial Logistic regression analysis showed that the age over 10 years old ( OR=0.54,95% CI 0.30-0.93), tumor lysis syndrome before chemotherapy ( OR=0.48,95% CI 0.27-0.84) and grade Ⅲ-Ⅳ myelosuppression after chemotherapy ( OR=0.55,95% CI 0.33-0.91)were independent risk factors for chemotherapy delay.The 3-year OS rate and the 3-year EFS rate of children with Burkitt lymphoma in the delayed chemotherapy group were lower than those in the non-delayed chemotherapy group ((79.4±4.9)% vs. (94.2±1.1)%, (80.2±4.8)% vs. (92.0±1.2)%,both P<0.05). The 3-year OS rate of the group C with chemotherapy delay >7 days (42 cases) was lower than that of the group with chemotherapy delay of 1-7 days (22 cases) and the non-delay group (399 cases) ((76.7±6.9)% vs. (81.8±8.2)% vs. (92.7±1.3)%, P=0.002).The 3-year OS rate of the chemotherapy delay group (9 cases) in the COP (vincristine+cyclophosphamide+prednisone) phase was lower than that of the non-chemotherapy delay group (454 cases) ((66.7±15.7)% vs. (91.3±1.4)%, P=0.005). Similarly, the 3-year OS rate of the chemotherapy delay group (11 cases) in the COPADM1 phase was lower than that of the non-chemotherapy delay group (452 cases) ((63.6±14.5)% vs. (91.5±1.3)%, P=0.001). Conclusions:The delayed chemotherapy was related to the age over 10 years old, tumor lysis syndrome before chemotherapy and grade Ⅲ-Ⅳ myelosuppression after chemotherapy in pediatric BL. There is a significant relationship between delayed chemotherapy and prognosis of BL in children.

Objective:To investigate the clinicopathological and molecular genetic characteristics and prognosis of patients with diffuse large B-cell lymphoma (DLBCL).Methods:The clinicopathological data of 152 DLBCL patients receiving consultation and routine physical examination in Peking University Third Hospital and Peking University School of Basic Medicine from January 2008 to December 2015 were retrospectively analyzed. Immunohistochemistry was used to detect the expressions of CD10, bcl-6, MUM1, GCET1, FOXP1. EB virus encoded small RNA (EBV-EBER) was detected by using in situ hybridization. The aberrations of bcl-2, bcl-6 and c-myc genes were detected by using fluorescence in situ hybridization (FISH) to screen double-hit lymphoma (DHL). Kaplan-Meier method was used to make survival analysis.Results:Among 152 cases of DLBCL, the ratio of male to female was 1.49:1, the median age of onset was 59 years (7-90 years), and 79 cases (52.0%) were primary lymph nodes. The median overall survival (OS) time of all cases was 16 months (1-101 months). The 1-year, 3-year and 5-year OS rates were 70.2%, 44.7%, 30.3%, respectively. The OS of R-CHOP treatment group was better than that of CHOP treatment group and untreated group ( P = 0.001). Among all 137 patients receiving double-hit histochemistry score (DHS), there were 56 cases with 0 score, 57 cases with 1 score, 24 cases with 2 scores; and the difference in the OS of different DHS score groups ( P = 0.311). FISH detection showed that among 29 cases achieving results of c-myc gene detection, there were 2 cases of splitting gene and 3 cases of gene amplification; among 26 cases achieving results of bcl-2 gene detection, 2 cases had bcl-2 gene amplification; among 26 cases achieving results of bcl-6 gene detection, 2 cases had bcl-6 gene amplification and 3 cases had splitting gene. It was found that myc and bcl-2 genes were amplified simultaneously in 1 case, accompanied with bcl-6 gene splitting, which was called triple-hit lymphoma. In DHS 0-score group, 1 case of double gene abnormality was found, and 1 case of single gene abnormality was found in group 1-score; in group 2-score, 5 cases were single gene abnormality and 1 case was three gene abnormality, so the gene abnormality was inconsistent with the protein expression. Conclusions:The incidence of DHL in DLBCL patients in China is low. The major gene abnormalities are c-myc or bcl-2, bcl-6 single gene abnormalities.

Molecular typing of leukemia is the basis of risk assessment and treatment options. NUTM1 gene (15q14) rearrangement is a novel molecular type of acute B lymphoblastic leukemia (B-ALL), which is mainly found in children (≥1 year old) and infants (< 1 year old). The number of patients is slightly more in children than infants. However, in infantile ALL, NUTM1 rearrangement is the second most common molecular abnormality. These children respond well to conventional chemotherapy regimens and with a good prognosis. The number of leukemia patients with NUTM1 gene rearrangement is still small, and there is no relevant study or case report in China. NUT protein encoded by NUTM1 gene is a chromatin regulator, which is related to histone acetylation regulation and chromatin remodeling. This article aims to introduce the clinicopathological features, detection methods, possible tumorigenic mechanisms and therapeutic prospects of leukemia with NUTM1 gene rearrangement, to increase the understanding of this type of leukemia and provide reference for the precise molecular subtyping and treatment.

Objective To explore the CT and MRI imaging and clinicopathological features of extranodal NK/T cell lymphoma (NK/TCL). Methods Sixty-six patients with NK/TCL diagnosed from 2002 June to 2016 April in Beijing Tongren Hospital with intact CT and/or MRI imaging results were enrolled in this study. All the patients had tailed clinical information and follow-up. The imaging and clinicopathological features were analyzed retrospectively and their prognostic value on overall survival was analyzed. Results There were 49 males and 17 females with median age of 42 years. The median follow-up time was 18 months. The cases showed surrounding invasions including 10 cases (15.2 %) in soft palate, 5 cases (7.6 %) in hard palate, 2 cases(3.0 %) in tonsil, 8 cases(12.1 %) in upper lip, 13 cases(19.7 %) in maxillofacial soft tissue, 9 cases (13.6 %) in eyelid, 10 cases (15.2 %) in orbital, 3 cases (4.5 %) in maxilla, 6 cases (9.1 %) in pterygopalatine fossa,6 cases(9.1 %)in infratemporal fossa,3 cases(4.5 %)in skull base, 3 cases(4.5 %) in eyeball and 2 cases (3.0 %) in brain tissue. Kaplan-Meier survival analysis found that the 2-year overall survival rates of the patients with the involvement of hard palate, upper lip, maxillofacial soft tissue, eyelid, orbital, maxillary, eyeball and brain organizer were lower than those of the patients without the involvement of these sites(χ2values were 4.470,4.041,4.456,13.933,8.986,4.000,44.121,6.527,16.822,respectively, all P< 0.05). Further multivariate Cox regression analysis showed that maxilla and brain involvement were independent adverse factors (RR=34.717, 95 % CI 3.404-354.035, P=0.003; RR=37.545, 95 % CI 3.188-442.187, P= 0.004). Conclusions MRI and CT examinations are of great value in diagnosis and prognostic assessment of NK/TCL. Clinicians can make correct and timely diagnosis by comprehensive clinical, radiological and pathological features and can make a detailed clinical assessment to give patients appropriate treatment,thus improving the outcome of the NK/TCL patients.

OBJECTIVETo evaluate the correlation between MicroRNA-191 (miR-191) and T lymphoblastic leukemia/lymphoma (T-ALL/LBL) to probe its underlying molecular mechanism.

METHODSThe expression of miR-191 was examined by real-time PCR (RT-PCR) in 20 T-ALL/LBL tissue samples and 20 lymphoid reactive hyperplasia (LRH) tissue samples. The correlation between miR-191 and the clinicopathological feature of T-ALL/LBL was analyzed. Antisense miR-191 lentiviral vectors was constructed and transfected into T-ALL/LBL Jukat cells. After transfection, the expression of miR-191 was examined by RT-PCR. The cell activity was evaluated by CCK-8 asssy. The cell cycle and apoptosis were determined by flow cytometry.

RESULTSCompared with LRH samples, the results of RT-PCR showed significant upregulation of miR-191 in 20 T-ALL/LBL tissue samples (1.875±0.079 vs 1.000, P<0.05). The expression level of miR-191 was negatively associated with prognosis. Compared with LV-NC-GFP and control groups, the expression of miR-191 significantly decreased after transfection of antisense miR-191 lentiviral vectors (0.578±0.012 vs 1.011±0.053 and 1.000, P<0.05), the percentages of apoptotic cells and the cell in G0/G1 phase significantly increased (P<0.05).

CONCLUSIONSmiR-191 might play a significant role in the development of T-ALL/LBL, implicating a new target for therapy.

Apoptosis ; Cell Cycle ; Flow Cytometry ; Humans ; Lentivirus ; MicroRNAs ; genetics ; metabolism ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; genetics ; metabolism ; Prognosis ; Real-Time Polymerase Chain Reaction ; Transfection

OBJECTIVETo study the clinicopathologic features, differential diagnosis and prognosis of primary bone anaplastic large cell lymphoma(ALCL).

METHODSTwelve patients diagnosed with primary bone ALCL were retrospectively reviewed. The clinicopathologic features, immunohistochemic findings and results of in situ hybridization for EB virus were analyzed.

RESULTSOf the 12 patients, the male-to-female was 7: 5 with a median age of 17.5 years (range from 9 to 64 years). Bone pain was the presenting symptom in all patients. Radiographic examination demonstrated solitary osteolytic lesion in 8 patients and multiple lesions in the rest 4 patients. Spine (7 cases) was the most common site to be involved, followed by ilium (5 cases), sacrum (2 cases), humerus (1 case) and collarbone (1 case). Ten patients were available with the follow-up data including 5 ALK-positive and 5 ALK-negative patients, and the follow-up time was 2 to 47 months. Interestingly, the 3 dead patients were ALK-negative whereas 5 of 7 ALK-positive patients achieved remission.

CONCLUSIONSPrimary bone ALCL is a rare type of non-Hodgkin lymphoma and it more frequently involves the axial skeleton. Boys and young males are more commonly affected. Patients usually present at an early stage and have a relatively favorable prognosis. Expression of ALK protein may be associated with a favorable prognosis in primary bone ALCL.

Activin Receptors, Type I ; Adolescent ; Adult ; Alkaline Phosphatase ; Bone Diseases ; etiology ; Bone Neoplasms ; diagnostic imaging ; enzymology ; mortality ; Child ; Female ; Humans ; Lymphoma, Large-Cell, Anaplastic ; diagnostic imaging ; enzymology ; mortality ; Male ; Middle Aged ; Pain ; etiology ; Prognosis ; Radiography ; Receptor Protein-Tyrosine Kinases ; Retrospective Studies ; Young Adult

Objective To study risk factors of cardiovascular disease (CVD) and status of bone mineral density (BMD) in women with hypoestrogenism.Methods From Jul 2011 to April 2013,a total of 256 women with hypoestrogenism in the First Affiliated Hospital of Shanxi Medical University were enrolled in this retrospective study,which were divided into four groups:133 women in ppausal group,25 women in premature ovarian failure (POF) group,67 women in menopausal transition group and 31 women in premature ovarian failure transition group.General statue,CVD risk factors and BMD were compared among four groups.General statue include menopausal period,menopausal symptoms (Kupperman Index),CVD risk factors include body mass index,blood pressure,waist circumference,waist-hip ratio,blood lipids and glucose,BMD include left hip,lumbar spine bone mineral density and T or Z value.Results (1) The median menopausal period were 3.4 years in postmenopausal group and 3.6 years in premature ovarian failure group,which did not show no statistical difference (P ＞ 0.05).Kupperman Index in four groups were 12 in postmenopausal group,9 in POF group,9 in menopausal transition group and 8 in premature ovarian failure transition group,which reached statistical difference (P ＜ 0.05).(2) The difference of body mass index (BMI),waist circumference,waist-hip ratio,diastolic blood pressure were no statistically significant among four groups(P ＞ 0.05) ; the systolic blood pressure in four groups were 120,110,110,110 mm Hg (1 mm Hg =0.133 kPa),their differences were statistically significance (P ＜ 0.05); the high-density lipoprotein (HDL-C) was 1.6 mmol/L in postmenopausal group,and 1.3 mmol/L in premature ovarian failure transition group,their differences were all statistically significance (P ＜ 0.05) ; the difference of the fasting plasma glucose (FPG) was not statistically different in 4 groups (P ＞0.05).(3) The abnormal rate of lower bone mass in lumbar spine were 57％ (46/81) postmenopausal group,8/15 in POF group,32％ (9/28) in menopausal transition group,12/19 in premature ovarian failure transition group,and osteoporosis was 9％ (7/81),3/15,1％ (3/28)and 0 respectively,their differences were statistically different (P ＜ 0.05) ; the abnormal rate of BMD of left hip and lumbar spine of 11/15 and 12/16 in POF group was higher than 65％ (53/81) in postmenopausal group.In the mean time,the abnormal rate of BMD of left hip and lumbar spine were,12/19 and 10/20 in premature ovarian failure transition group,which were significantly higher than 43％ (12/28) and 39％ (12/31) in the menopausal transition group.Conclusions The menopausal symptoms resulting from hypoestrogenism in natural postmenopausal women are mostly remarkable.The decrease of BMD in lumbar spine is more significant than that of left hip among postmenopausal women.Women with earlier menopause was prone to cause the changes of blood fat and abnormal of BMD,especially HDL-C decreased significantly compared with those natural postmenopause,it is more likely to cause CVD and osteoporosis.

Objective To elucidate clinical pathological features of primary mediastinal B-cell lymphoma (PMBL) and its difference compared with diffuse large B-cell lymphoma,not otherwise specified (DLBCL,NOS).Methods The clinical histories and pathological datas of 24 PMBL cases and 31 cases of DLBCL,NOS as the control group were collected.Immunohistochemical staining and a follow-up study was conducted.Results The distribution of gender showed significant difference when the age of onset of PMBL patients was obviously younger with the medial age of 30 years old (P ＜ 0.001).All cases presented as a huge mass in mediastinal site with compression symptoms.PMBL was similar to DLBCL in the morphology of tumor cells but fibrosis of various degrees was common,more than 70.8 ％ (17/24) cases had the collagen bundles split.CD23 positive rate (40.0 ％,6/15) in PMBL was significantly higher than the control group (3.2 ％,1/31)(P =0.003).Conclusion PMBL frequently occurs in young female people,mostly happens in mediastinal site and adjacent area,but rarely has distant dissemination.PMBL has the characteristics of various degrees of collagen fiber hyperplasia,and CD23 positive could be used to differentiate PMBL from DLBCL,NOS.

Objective To investigate the immunophenotype and molecular genetics of mature aggressive B-cell lymphomas in Chinese pediatric patients and provide the criteris for the diagnosis of them.Methods We collected 97 paraffin-embeded tissue samples of pediatric cases of mature aggressive B-cell lymphomas including 81 Burkitt lymphoma (BL) cases, 8 diffuse large B cell lymphoma (DLBCL) cases and 8unclassifiable B cell lymphoma with featares intermediate between BL and DLBCL (BL/DLBCL) cases. The immunophenotype and genetic features of them were detected by immunohistochemistry and interphase FISH.Results The expression of bcl-2 [3 %(2/66) in BL, 50 % (4/8) in DLBCL, 50 % (4/8) in BL/DLBCL], MUM1 [17 % (12/71) in BL, 63 % (5/8) in DLBCL, 63 % (5/8) in BL/DLBCL] and mean Ki-67 proliferation index [(93±4.4)% in BL, (83±14.3)% in DLBCL, (80±11.5)% in BL/DLBCL] were significantly different between BL and DLBCL and between BL and BL/DLBCL. The frequency of c-myc rearrangement [98 % (79/81) in BL,38 % (3/8) in DLBCL, 50 % (4/8) in BL/DLBCL] and an extra copy of bcl-6 [0 % in BL, 38 % (3/8) in DLBCL, 25 % (2/8) in BL/DLBCL] were also significantly different between BL and DLBCL and between BL and BL/DLBCL. Conclusion Diagnosis of the mature aggressive B cell lymphomas in pediatrics should be based on the comprehensive review and integration of morphologic, immunohistochemical and molecular genetic features. BL/DLBCL is more likely a subgroup of the DLBCL in pediatric population. The expression of CD10 and bcl-6 but not bcl-2, a high Ki-67 PI (＞90 %) and a c-myc rearrangement but not bcl-2 or bcl-6rearrangement are the features of BL. Regardless of the expression of CD10 and bcl-6, positive staining for bcl2, Ki-67 PI below 90 % and an extra copy of the bcl-6 favor a diagnosis of DLBCL or BL/DLBCL.

Objective To study the expressions of anaplastic lymphoma kinase (ALK-1) and cytotoxic proteins in primary systemic anaplastic large cell lymphoma (S-ALCL) and their relationship with clinical outcome. Methods 51 S-ALCL cases were collected from Lymphoma Lab of Peking University Health Science Centre & Peking Children's Hospital. The morphologic characteristics were studied under routine microscope, and essential immunohistochemical stainings were performed and reviewed to confirm the diagnosis of S-ALCL. Immunohistochemical stainings for ALK-1 and cytotoxic proteins (TIA-1 & granzyme B) were performed using standard SP method. Patients related clinical data including follow-up materials were collected. Results Survival time of 44 cases with completely clinical follow up materials ranged from 0.5～66months. 36 out of 51 cases(37 %) was positive for ALK-1 protein. While 20 cases out of 47 S-ALCL cases ( 42.55 % ) positive for granzyme B and 22 out of 28 cases (81.48 %) were positive for TIA-1. The prognosis of patients with ALK-1 protein positive and granzyme B negative expression was better, but TIA-1 expression might have nothing to do with clinical outcome (P＞0.05). In addition, multivariate analysis confirmed that ALK-1 protein expression, granzyme B protein expression and Ann-Arbor stage system were possible for prognosis(P＜0.05), Conclusion Expression of ALK-1 and granzyme B protein expression may serve as two independent prognostic predictors in S-ALCL patients.