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 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.

Objective To analyze the clinical pathological characteristics and prognosis of elderly patients with EB virus-positive diffuse large B-cell lymphoma (EBV+ DLBCL).Methods 24 elderly patients with EBV + DLBCL were collected to evaluate their clinical pathological characteristics and prognosis by comparison with the EBV-DLBCL,NOS during the same period.Results 24 EBV + DLBCL cases demonstrated two morphologic subtypes:polymorphic and monomorphic.And polymorphic subtype showed geographic necrosis more frequently than that in monomorphic subtype.According to Hans and Choi models,the majority of EBV+ DLBCL of the elderly were classified as non-GCB subtype (91.3 ％ and 100.0 ％,respectively).55.0 ％ cases showed CD30 positive,which was significantly higher than that in EBV-DLBCL group (P ＜ 0.001).Under the treatment of R-CHOP regimen,the overall survival (OS) of the elderly EBV+ DLBCL patients showed no significant difference with the ＞50-year old EBV-DLBCL patients (the median OS were 44.2 months and 29.2 months,P =0.587).Conclusions The elderly EBV + DLBCL patients are normally presented with polymorphic and monomorphic patterns.And geographic necrosis are often seen in polymorphic cases.CD30 expression and non-GCB subtypes are high.With the R-CHOP regimen,the OS of the elderly EBV+ DLBCL patients is similar with that of ＞50-year old EBV-DLBCL patients.

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 investigate the EB virus (EBV) infection and its clinical significance in angioimmunoblastic T-cell lymphoma(AITCL).Methods 62 patients diagnosed as AITCL between 2008 Jan and 2011 Dec were retrospective analyzed.All cases were re-confirmed and classified with the histology and immunology according to 2008 WHO Classification.In situ hybridization of EBV encoded RNA (EBV-EBER) was performed.Clinical characteristics and follow-up data of patients were collected.Results 42 ％ (26/62) AITCL cases were EBER-positive.EBV infection was found to be significant correlation with age over 60 years and poor response to therapy (P =0.025,P =0.049,respectively).However,EBV infection had no relationship with the overall survival,the presence of B symptom and the Ann Arbor stage.Conclusion In AITCL,EBV infection seems not to be associated with the overall survival,B symptom and Ann Arbor stage,but it may have impacts on theraputic response.

Objective To study the clinicopathologic features and explore the potential prognostic factors of extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma).Methods 86 patients diagnosed with MALT lymphoma were retrieved and divided into 2 subgroups according to the location of tumor,namely gastric (32 cases) and non-gastric (54 cases) subgroup.Histological characteristics were reassessed on hematoxylin-eosin staining slides,and immunophenotypic features were determined by immunohistochemical staining.Interphase fluorescence in-situ hybridization (FISH) was carried out to detect the cytogenetic abnormalities.Results There were no significant difference of clinical behavior,histology,and immunophenotype between gastric and non-gastric subgroups.In addition,FISH detected t(14;18) in 9 ％ (4/45) and t(11;18) in 12 ％ cases (6/50) respectively.Among the 20 cases treated with H pylori (HP) eradication,a significantly lower remission rate was observed in cases with bcl-10 (20 ％) nuclear expression or those harboring t(11;18) (33 ％) compared with those in the negative group (73 ％,91％)(x2 =3.842 and 4.639,P =0.035 and 0.031,respectively).For the 35 non-gastric patients with follow-up data,males (35 ％) and patients older than 60 yrs (25 ％) tended to have a lower remission rate as compared to females (60 ％) and those younger than 60 yrs (63 ％) (x2 =3.905 and 7.373,P =0.048 and 0.007,respectively).Moreover,progression-free survival rate was significantly lower in patients with higher stage (ⅢⅣ) (25 ％) and without t(14;18) (50 ％) than that in patients with stage Ⅰ-Ⅱ (52 ％) and with t(14;18)(75 ％).The differences had statistical significance (x2 =4.207 and 4.363,P =0.040 and 0.037,respectively).Conclusion MALT lymphoma in general is an indolent B-cell non-Hodgkin’ s lymphoma which more frequently occurs in the elderly people.Differences in the response to treatment or the prognosis are observed between gastric and non-gastric MALT lymphoma patients.

Objective To evaluate clinicopathologic features and prognosis of primary gastric anaplastic large cell lymphomas (ALCL).Methods Clinical data and parafiin blocks of 4 patients diagnosed with primary gastric ALCL were obtained. The diagnosis of all cases was based on the criteria of WHO classification of hematolymphoid neoplasm.Furthermore,chromosomal rearrangement involving ALK gene was detected by interphase fluorescence in situ hybridization (FISH) and Epstein-Barr virus (EBV) status was determined by in situ hybridization(ISH) for EBV-encoded small RNAs (EBERs).Results The patients (3 males and 1 female) were from 27 to 87 years old, with a median age of 58.5 years. All the four cases presented with a solitary ulcerative mass in stomach. Morphologically, the normal architecture of gastric wall was effaced by the diffuse infiltration of tumor cells in which the characteristic hallmark cells were easily identified.The tumor cells of all cases showed a consistently strong expression of LCA and CD30,and CD3e was expressed in 3 of the 4 cases.Both ALK expression and ALK gene rearrangements were negative in all cases.Two cases underwent total or partial gastrectomy followed by CHOP chemotherapy. Another one patient was treated with chemotherapy and autologous stem cell transplantation. None of these 3 patients developed a relapse or progression till the last follow-up on Nov 30,2011. While the rest one patient refused to take any treatment and died 20 months after diagnosis. Conclusions Primary gastric ALCL is very rare and usually ALK negative. Its pathologic features as well as the clinical outcome are quite similar to the ALK negative ALCL from other sites, except the more frequently positive CD3e Early diagnosis and proper therapy are of great significance to the prognosis.

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.

ObjectiveTo observe the clinical efficacy of combined irbesartan and alprostadil treatment of early diabetic nephropathy (DN).Methods A total of 120 patients with early type 2 diabetes of hospitalization were randomly divided into 3 groups: irbesartan group of 40 patients (150 mg, once per day)(group irbesartan),40 patients treated with alprostadil (physiological saline and alprostadi 10 μg))(group alprostadi) ,40 patients treated with alprostadil combined irbesartan (dose same as the other two groups)(combined group).All cases were observed for 4 weeks.Comparison of serum creatinine (Cr), blood urea nitrogen(BUN) ,24 hour urinary albumin(24hUAE) changes after treatment.ResultsAfter treatment 4 weeks 24hUAE of the three groups were significantly decreased (t = 2.07, t = 2.01 and t = 3.15, Ps ＜ 0.05) .The decrease of 24hUAE in the combined treatment group ([252.69 ± 33.56]mg/24h) was better than that in the irbesartan group([268.75 ± 34.42)](t = 2.11, P ＜ 0.05)and in the alprostadil group ([267.95 ± 30.75])mg/24h (t = 1.998, P ＜ 0.05) .No significant difference were observed between the Irbesartan and alprostadil group.During treatment, several patients affected by swell, uncomfortable in the alprostadil group, but improved after treatment.No other adverse effect was observed.Conclusion Alprostadil combined with irbesartan treatment of early diabetic nephropathy is an effective way.

Objective To evaluate the effects of Alprostadil combined with Enalapril on high sensitivity C-reactive protein and Cystatin in patients with early diabetic nephropathy.Methods One hundred and fifteen cases of outpatients were randomized into 3 groups.Thirty-seven cases were assigned to Alprostadil group and treated with Alprostadil 10 μg + NS 100 ml,iv,qid;Thirty-eight cases were assigned to the Analapril group and treated with Enalapril 5 mg bid;Forty cases were assigned to the combined treatment group and treated with Alprostadil 10 μg + NS 100 ml,iv qid and Enalapril 5mg bid.All patients were observed for twelve weeks.Changes before and after treatment in the blood pressure,plasma glucose,glycolated hemoglobin (HbA1 c),24 hours urinary albumin (24 hUAE),high-sensitive C-reactive protein(hs-CRP) and Cystain C( Cys C) were observed and compared between the three groups.Results After treatment,hs-CRP,CysC and 24 h UAE were significantly improved in the three groups compared with baseline levels( P ＜ 0.05).In the combined treatment group,hs-CRP,CysC and 24 h UAER had a more significant improvement than the other two groups (P ＜0,05 ).Conclusion Alprostadil combined with Enalapril is a clinically effective strategy in the treatment of early diabetic nephropathv and can reduce the levels of CysC and hs-CRP.