Primary gastrointestinal mantle lymphoma with massive bleeding: a case report and literature review

The incidence of primary gastrointestinal lymphomas (PGILs) has been increasing. The clinical presentation and treatment of PGIL are distinct from those of nodular lymphomas. Symptoms include abdominal pain, abdominal mass, changes in bowel habits, obstruction, and bleeding. Less life-threatening gastrointestinal bleeding occurs after chemotherapy and few reports have focused on the bleeding of PGILs. We report a case of severe gastrointestinal bleeding caused by low-dose chemotherapy, which was dramatically improved by rituximab monotherapy treatment. The prevention and treatment of gastrointestinal bleeding in PGIL should be given much attention.

聚乙二醇化重组人粒细胞集落刺激因子初级与次级预防化疗后中性粒细胞减少的有效性和安全性临床研究

目的:评价聚乙二醇化重组人粒细胞集落刺激因子(pegylated recombinant human granulocyte colony-stimulating factor,PEG-rhG-CSF)初级与次级预防化疗后中性粒细胞减少的有效性和安全性.方法:本研究为单中心、开放、单臂临床研究,分析2016年5月至2018年12月北京大学肿瘤医院217例受试者.非髓性恶性肿瘤患者于化疗结束后24~48 h皮下注射PEG-rhG-CSF,体质量≥45 kg者给予6 mg/次,<45 kg者给予3 mg/次,每个化疗周期注射1次.结果:217例患者共完成774个化疗周期,患者包括18例妇科肿瘤(3例子宫内膜癌、15例卵巢癌),50例乳腺癌,30例骨肿瘤和119例淋巴瘤,146例接受初级预防,71例接受次级预防.中性粒细胞减少性发热(febrile neutropenia,FN)发生率为5.7%,初级预防组发生率为4.9%,次级预防发生率为7.2%.Logistic单因素与多因素分析显示,PEG-rhG-CSF持续治疗周期越长,FN发生率越低.初级与次级预防的FN发生率均在治疗第2个周期显著低于第1个周期.初级预防为第1个周期11.6%vs.第2个周期4.4%,(P=0.039);次级预防为第1个周期16.9%vs.第2个周期5.6%,(P=0.034).Ⅳ度中性粒细胞减少发生率为10.3%(80/774),其中初级预防组为6.7%(34/510),次级预防组为17.4%(46/264),差异具有统计学意义(P<0.001).Ⅳ度中性粒细胞减少发生率均在治疗第2个周期显著低于第1个周期.初级预防为第1个周期17.1%vs.第2周期5.3%,(P=0.004);次级预防为第1个周期46.5%vs.第2个周期11.3%,(P<0.001).药物相关不良反应主要为骨痛,患者Ⅰ/Ⅱ度骨痛发生率为3.7%(8/217),Ⅲ/Ⅳ度骨痛发生率为1.8%(4/217).结论:PEG-rhG-CSF预防性应用于非髓性恶性肿瘤,可有效降低FN发生率.初级预防比次级预防显著降低整个化疗周期Ⅳ度中性粒细胞减少的发生.

Prognostic value of interim ^(18)F-FDG PET/CT in diffuse large B-cell lymphoma

Objective: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease. The prognostic factor currently used is not accurate enough to predict the outcomes of patients with DLBCL. The prognostic significance of interim PET/CT in DLBCL remains controversial. The aim of this study is to determine the predictive value of interim 18F-FDG PET/CT after first-line treatment in patients with DLBCL. Methods: Thirty-two patients with DLBCL underwent baseline, interim and post-treatment 18F-FDG PET/CT scans. Imaging results were analyzed for the survival of patients via software SPSS 13.0, retrospectively. Results: Thirty-one of the 32 patients were treated with R-CHOP regimen, and interim 18F-FDG PET/CT of 24 patients was performed after 2 cycles of treatment. After a median follow-up period of 16.7 months, the 2-year progression-free survival (PFS) rates were significantly different between the groups above and below SUV max cut-off value of 2.5 (P=0.039). No significant differences were found in the 2-year PFS rates if SUV max cut-off values were set as 2.0 and 3.0, respectively (P=0.360; P=0.113). Conclusions: Interim PET/CT could predict the prognosis of DLBCL patients with the SUV max cut-off value of 2.5, but more clinical data should be concluded to confirm this conclusion.

Prognostic value of pre-and post-transplantation 18F-fluorodeoxyglucose positron emission tomography results in non-Hodgkin lymphoma patients receiving autologous stem cell transplantation

Objective: High-dose chemotherapy(HDC) followed by autologous stem cell transplantation(ASCT) is the standard of care in the upfront or relapsed/refractory setting in some patients with non-Hodgkin lymphoma(NHL).However,a proportion of patients do not respond to ASCT.^(18)F-fluorodeoxyglucose(FDG) positron emission tomography(PET)/computed tomography(CT) has been widely used for staging,response evaluation,and prognosis prediction.Here,we investigated the prognostic role of PET/CT in NHL patients before and after ASCT.Methods: A retrospective study was conducted at Peking University Cancer Hospital.All NHL patients who underwent ASCT between March 2010 and July 2016 were identified.Patients who had PET/CT scan before and after ASCT were included.Deauville criteria(5-point scale) were used to interpret PET scans.Univariate and multivariate survival analyses were performed using Cox regression.The predictive value of PET scanning was estimated by comparing the area under the receiver operating characteristic(ROC) curve.Results: In total,79 patients were enrolled in this study.In univariate analysis,pre-and post-ASCT PET result was identified as prognostic factors for 3-year progression-free survival(PFS) and overall survival(OS).Patients with negative pre-ASCT PET result demonstrated significantly better PFS(84.2% vs.54.2%) and OS(89.2% vs.63.6%) than patients with positive pre-ASCT PET result.PFS(91.6% vs.25.3%) and OS(96.5% vs.36.8%) were also significantly different between patients with negative and positive post-ASCT PET result.Multivariate analysis also showed a significant association between survival and post-ASCT PET result.ROC analysis revealed that the predictive value of post-ASCT PET result was superior to that of pre-ASCT PET result alone.Combined pre-and post-ASCT PET result is better for predicting outcomes in patients with NHL receiving transplantation.Deauville criteria score >3 was identified as the best cutoff value for post-ASCT PET.Conclusions: Post-ASCT PET result was more important than pre-ASCT PET result in predicting outcomes for NHL patients who underwent ASCT.The prognostic significance can be improved when combining preASCT PET result with post-ASCT PET result.Deauville criteria can be used for interpreting PET scans in this scenario.

Prognostic value of ^(18)F-fluorodeoxyglucose positron emission tomography using Deauville criteria in diffuse large B cell lymphoma treated with autologous hematopoietic stem cell transplantation

Objective: High-dose chemotherapy(HDC) followed by autologous hematopoietic stem cell transplantation(auto-HSCT) plays an important role in improving outcomes of diffuse large B cell lymphoma(DLBCL) patients.18 F-fluorodeoxyglucose(18 F-FDG) positron emission tomography(PET)/computed tomography(CT) has been widely accepted in response assessment and prediction of prognosis in DLBCL. Here, we report the value of 18 FFDG PET/CT pre-and post-HSCT in predicting outcomes of patients with DLBCL.Methods: DLBCL patients who had PET/CT scan before and after HSCT were included. PET results were interpreted based upon Deauville criteria. The prognostic value of 18 F-FDG PET/CT in auto-HSCT was evaluated.Results: Eighty-four patients were enrolled. In univariate analysis, pre-and post-HSCT PET findings were correlated with 3-year progression-free survival(PFS) [hazard ratio(HR)=4.391, P=0.001; HR=7.607, P<0.001] and overall survival(OS)(HR=4.792, P=0.008; HR=26.138, P<0.001). Patients receiving upfront auto-HSCT after firstline treatment had better outcomes than relapsed/refractory DLBCL patients(3-year PFS, P<0.001; 3-year OS,P<0.001). In the relapsed/refractory patients, pre-and post-HSCT PET findings were also associated with 3-year PFS(P=0.003 vs. P<0.001) and OS(P=0.027 vs. P<0.001). A significant correlation was observed between clinical response to chemotherapy before auto-HSCT and outcomes of patients in the entire cohort(3-year PFS, P<0.001;3-year OS, P<0.001) and in the subgroup of 21 patients with positive pre-HSCT PET(3-year PFS, P=0.084; 3-year OS, P=0.240). A significant association between survival and post-HSCT PET findings was observed in multivariate analysis(HR=5.168, P<0.001).Conclusions: PET results before and after HSCT are useful prognostic factors for DLBCL patients receiving HSCT. Patients who responded to chemotherapy, even those with positive pre-HSCT PET, are appropriate candidates for auto-HSCT.

PEG-asparaginase in BFM-90 regimen improves outcomes in adults with newly diagnosed lymphoblastic lymphoma

Objective: Although L-asparaginase(L-ASP) is a standard treatment for lymphoblastic lymphoma(LBL),hypersensitivity reactions by some patients limit its application. Polyethylene glycol-conjugated asparaginase(PEGASP) has a lower immunogenicity and is a standard treatment in all pediatric acute lymphoblastic leukemia(ALL).In this study, we investigated the efficacy and toxicity of PEG-ASP instead of L-ASP as used in the BFM-90regimen(PEG-ASP-BFM-90) for adult LBL.Methods: Between June 2012 and July 2015, we treated 30 adult patients with newly diagnosed LBL, using PEGASP-BFM-90 in a prospective, multicenter and single-arm clinical study at 5 participating institutions in China.Results: All the 30 patients, including 19 males and 11 females with a median age of 30(range: 18–62) years,completed 128 times of the PEG-ASP, with the median of 4(range: 2–6) times. Patients did not receive radiotherapy at this time. The overall response rate was 86.7%(26/30), with 50.0%(15/30) complete response and36.7%(11/30) partial response. The 3-year overall survival was 46.0% [95% confidence interval(95% CI),28.2%–64.8%], and the 3-year progression-free survival was 43.0%(95% CI, 25.7%–62.0%). Major adverse events were myelosuppression, reduced fibrinogen, liver dysfunction and digestive tract toxicities. No allergic reaction and no treatment-related mortality or severe complications were recorded.Conclusions: Our clinical data and observed outcomes indicate that 1 dose of PEG-ASP can replace multiple doses of native L-ASP in BFM-90, with predominantly grade 3–4 neutropenia for adult LBL, and no therapyrelated deaths. The effect is similar to previous reports of PEG-ASP-containing regimens for adult ALL. Major advantages include less serious allergic reactions, 2–3 weeks of action duration, and convenience for patients and physicians.

A durable 4-1BB-based CD19 CAR-T cell for treatment of relapsed or refractory non-Hodgkin lymphoma

Objective:Previous studies reported that 4-1BB-based CD19 chimeric antigen receptor(CAR)-T cells were more beneficial for the clinical outcomes than CD28-based CAR-T cells,especially the lower incidence rate of severe adverse events.However,the median progression-free survival(mPFS)of 4-1BB-based product Kymriah was shorter than that of CD28-based Yescarta(2.9 months vs.5.9 months),suggesting that Kymriah was limited in the long-term efficacy.Thus,a safe and durable 4-1BB-based CD19 CAR-T needs to be developed.Methods:We designed a CD19-targeted CAR-T(named as IM19)which consisted of an FMC63 scFv,4-1BB and CD3ζintracellular domain and was manufactured into a memory T-enriched formulation.A phase I/II clinical trial was launched to evaluate the clinical outcomes of IM19 in relapsed or refractory(r/r)B cell non-Hodgkin lymphoma(B-NHL).Dose-escalation investigation(at a dose of 5×10^(5)/kg,1×10^(6)/kg and 3×106/kg)was performed in 22 r/r B-NHL patients.All patients received a single infusion of IM19 after 3-day conditional regimen.Results:At month 3,the overall response rate(ORR)was 59.1%,the complete response rate(CRR)was 50.0%.The mPFS was 6 months and the 1-year overall survival rate was 77.8%.Cytokine release syndrome(CRS)occurred in 13 patients(59.1%),with 54.5%of grade 1−2 CRS.Only one patient(4.5%)experienced grade 3 CRS and grade 3 neurotoxicity.Conclusions:These results demonstrated the safety and durable efficacy of a 4-1BB-based CD19 CAR-T,IM19,which is promising for further development and clinical investigation.