Complete remission of primary hepatic lymphoma in a patient with human immunodeficiency virus

Diffuse large B cell primary hepatic lymphoma is a rare disease with limited available information regarding treatment strategy. Although the liver contains lymphoid tissue and is an important site for lymphocytes activation, primary hepatic lymphoma is rare. Host factors make the liver a poor environment for malignant lymphoma development. Its coexistence with human immunodeficiency virus (HIV) infection increases morbidity and mortality risks. Additionally, jaundice increases chances of developing adverse effects from chemotherapy. Here, we report a case of diffuse large B cell primary hepatic lymphoma in a 32-year-old HIV positive man. Due to elevated liver enzyme levels and jaundice, the patient was initially treated with an R-DHAP regimen, which was replaced with an R-CHOP regimen. Restaging images with a positron emission tomography scan after the latest chemotherapy cycle confirmed remission. This is the first report of complete remission of primary hepatic diffuse large B cell lymphoma in an HIV positive patient in the English literature.     

The Frequency of Double Expresser in Selected Cases of High Grade Diffuse Large B-Cell Lymphomas

Background: Diffuse large B-cell lymphomas (DLBCL) are fast-growing non-Hodgkin lymphomas that affect B-lymphocytes. Double expressor DLBCL is the concomitant expression of Myc and Bcl-2 proteins during lymphomas which results in poor prognosis of patients. This study aimed to determine the frequency of double expresser in high grade diffuse large B-cell lymphomas. Materials and Methods : The study was conducted on 74 cases (54 males (68.4%) and 20 females (25.3%)) of DLBCL between August 2018 to January 2019. The mean age of the 74 patients was 51.7 years + 18.5. Expression of proteins c-Myc, Bcl-2 and Bcl-6 were evaluated by immunohistochemistry. The involvement of primary lymph node was reported in 38 cases (51.3%) whereas, extra nodal site was observed in 22 cases (29.7%). Among the primary sites, the cervical lymph node enlargement was the most frequent site of presentation. Results: The rearrangement pattern was studied among 74 patients, 35 (47%) were found to have either one of the rearrangements i.e. Myc, Bcl-2, or Bcl-6. On the other hand, 14 (18.9%) had shown double rearrangements i.e. Bcl-2 and c-Myc (11 cases) and Bcl-6 and c-Myc (3 cases). The Bcl-2 and Bcl-6 rearrangements were demonstrated by 12 cases whereas 2 cases (2.7%) indicated all three types of rearrangements i.e. c-Myc, Bcl-2, and Bcl-6. In 11 cases the Bcl-2 and c-Myc rearrangements were found to be Bcl-2 > 50% and c-Myc > 40% and demonstrating the overall frequency of double expressers as 14.8%. The prognosis of the mentioned cases was extremely poor, median survival of 10 months. Conclusion: The concurrent expression of Bcl-2 and c-Myc was found to be 14% (level of expression for Bcl-2 > 50% and c-Myc > 40%) which is potentially a significant health burden and an emerging threat.     

Low initial trough concentration of rituximab is associated with unsatisfactory response of first-line R-CHOP treatment in patients with follicular lymphoma with grade 1/2

For follicular lymphoma(FL)with grade 1/2,the complete response(CR)rate of the first-line R-CHOP treatment was significantly low.In this study,we assessed the rationality of the administration of rituximab for FL patients with grade 1/2 based on concentration–response relationship analyses.Thus,we conducted a prospective pharmacokinetic(PK)study in 68 FL patients with grades 1–3 treated with R-CHOP at 21-day intervals.Plasma rituximab concentrations were quantified using ELISA and the population PK modeling was established with Phoenix?NLMETM.The first cycle trough concentration(C1-trough)of rituximab was a significant independent risk factor for achieving CR in matched-pair logistic regression analysis,rather than the concentrations in later cycles;the recommendatory minimum optimal C1-trough was 13.60μg/mL.Patients with grade 1/2 had significantly lower C1-trough compared with grade 3(12.21μg/mL vs.23.45μg/mL,P<0.001),only 30%patients with grade 1/2 could reach 13.60μg/mL,compared with 91.67%in patients with grade 3,which was in accord with its unsatisfactory CR rates(43.33%vs.76.32%).The stage indicating the tumor burden(the target)was a crucial influence factor for C1-trough,accounting for 40.70%of its variability,70%patients with grade 1/2 were stage IV in this study,since the systemic therapy only started at the disseminated disease stage.The initial dose of 1800 mg was recommended by Monte Carlo simulation for patients with grade 1/2.In summary,low C1-trough accounted for low-grade FL’s unsatisfactory CR rate,designing the first dosage of rituximab should be a very important component of individualized therapy for FL.     

以吉西他滨为基础的化疗方案治疗初治弥漫大B细胞淋巴瘤的临床观察

目的观察比较R-GDP方案和R-CHOP方案治疗初治弥漫大B细胞淋巴瘤的疗效、生存和毒副反应。方法 100例DLBCL患者随机分为R-GDP组和R-CHOP组,4个周期后评价疗效,并随访统计比较总生存期及无疾病进展生存期。结果 (1)近期疗效:R-GDP组总体缓解率91.66%;R-CHOP组总体缓解率86.54%。两组比较差异无统计学意义(P=0.413)。(2)远期疗效:R-GDP组平均OS为32.730个月,R-CHOP组平均OS为31.623个月,两组OS比较差异无统计学意义(P=0.394)。R-GDP组平均PFS为25.137个月,R-CHOP组平均PFS为25.202个月,两组PFS比较差异无统计学意义(P=0.951)。(3)毒副反应:R-CHOP组在脱发、心脏毒性、静脉炎发生率明显多于R-GDP组,两组比较差异有统计学意义(P<0.05)。结论 R-GDP方案与R-CHOP方案治疗初治DLBCL近期疗效与远期疗效均无明显差异,两者均可作为初治DLBCL的首选方案。R-GDP组不良反应轻,耐受性好。     

1例弥漫大B细胞淋巴瘤伴快慢综合征患者R-CHOP方案化疗的药学监护分析

目的 探讨快慢综合征患者行R-CHOP方案化疗前综合处理方法及药学监护注意事项,保证患者化疗安全有效。方法 临床药师通过参与1例快慢综合征R-CHOP方案化疗药学监护,从快慢综合征化疗前的处理方法及各种不良反应预防措施等方面进行分析,并提供药学监护。结果 快慢综合征等心律失常患者,在行R-CHOP方案化疗时一定要先纠正心律,并在严格监护下进行化疗,并尽可能选择同类药物中心脏毒性较小的药物,密切监测不良反应的发生。结论 临床药师通过对该患者化疗过程进行药学监护分析与总结,为临床心功能不全且必须行R-CHOP方案化疗的淋巴瘤患者提供了用药指导,能有效避免不良反应的发生。     

Current progress and future perspectives of research on intravascular large B-cell lymphoma

Intravascular large B-cell lymphoma is a rare disease of the large B cells characterized by selective growth in the lumina of small vessels in systemic organs. Since first reported in 1959, the difficulty of obtaining sufficient tumor cells from biopsy specimens has hampered the elucidation of its underlying biology. Recent progress using xenograft models and plasma cell-free DNA has uncovered genetic features that are similar to those of activated B-cell type diffuse large B-cell lymphoma, including MYD88 and CD79B mutations and frequent alterations in immune check point-related genes such as PD-L1 and PD-L2. Given the improvement in clinical outcomes and a higher risk of secondary central nervous system (CNS) involvement in the rituximab era, a phase 2 trial of R-CHOP combined with high-dose methotrexate and intrathecal chemotherapy as a CNS-oriented therapy has been conducted. This trial, the PRIMEUR-IVL study, has displayed good progression-free survival and a low cumulative incidence of secondary CNS involvement. Long-term follow-up within this trial is still ongoing. Further understanding of the pathophysiology of the disease and improvements in clinical outcomes are still needed.     

Prognostic impact of interim positron emission tomography in mantle cell lymphoma patients treated with frontline R-CHOP

Although ¹⁸F-fluorodeoxyglucose positron emission tomography (¹⁸F-FDG PET) is commonly used for initial staging and therapeutic response evaluation in aggressive lymphomas, its prognostic utility for mantle cell lymphoma (MCL) is controversial. Therefore, we retrospectively evaluated the correlations of interim PET (iPET) and end-of-treatment PET (ePET) response with survival outcomes in 89 consecutive advanced MCL patients treated with frontline R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone). iPET positivity was strongly associated with inferior five-year overall survival (OS) [hazard ratio (HR) 7·84, P < 0·0001] and poor five-year progression-free survival (PFS) (HR 3·34, P < 0·0001). OS and PFS were more favourable in the order early metabolic responder (iPET^neg → ePET^neg), delayed responder (iPET^pos → ePET^neg), loss-metabolic responder (iPET^neg → ePET^pos), and never-metabolic responder (iPET^pos → ePET^pos). In the autologous haematopoietic stem cell transplantation (auto-HSCT)-fit subgroup, OS was more favourable in the order early metabolic responders, delayed metabolic responders, and non-metabolic responders, with a marginal trend toward statistical significance (HR 3·41, P = 0·051), and PFS was significantly superior in early metabolic responders (HR 4·43, P = 0·002). In a group that was ineligible for auto-HSCT, OS and PFS were significantly superior in early metabolic responders. Our results suggested that iPET is of prognostic value and an independent predictor of survival in MCL patients receiving frontline R-CHOP. Therefore, prospective clinical trials of iPET-guided treatment strategies for these patients are warranted.     

R-CHOP versus R-COMP: Are They Really Equally Effective?

The first-line standard treatment for diffuse large B-cell lymphoma (DLBCL) is the R-CHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). It is associated with cardiotoxicity, which is why new treatment strategies are needed. Liposomial doxorubicin has been proven to reduce these side-effects, but until now a direct comparison regarding efficacy has not yet been published. We retrospectively assessed 364 consecutive DLBCL patients who underwent either R-CHOP (218; 60%) or R-COMP (doxorubicin replaced by non-pegylated liposomal doxorubicin; 146; 40%) in first line and compared outcome and survival. We provide evidence that both regimens induce a high and comparable number of complete remissions and that both are able to cure patients with DLBCL. Confirmatory data are needed.     

Efficacy and tolerability of rituximab and reduced-dose cyclophosphamide,doxorubicin, vincristine,and prednisolone therapy for elderly patient with diffuse large B-cell lymphoma

Objectives: Chemoimmunotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisolone combined with rituximab (R-CHOP) is currently the first-line therapy for diffuse large B-cell lymphoma (DLBCL). However, management of elderly patients is challenging and often requires dose reductions or prolonged treatment intervals. We investigated the proper dose of R-CHOP for them.

Methods: At our institute, for DLBCL patients aged 65–79 and ≥80 years, we had reduced CHOP dose to 5/6 and 7/12, respectively, and retrospectively evaluated the reduced-dose R-CHOP.

Results: Although the median age in the standard, 5/6, and 7/12-dose groups was 57, 73, and 84 years, respectively (p?<?0.001), the 3-year event-free survival (EFS) rate did not differ between the standard and 5/6-dose groups (60.2 and 56.7%); however, 7/12-dose group had significantly inferior survival (25.9%). When patients aged 60–80 were evaluated, no difference in EFS was observed between the standard and 5/6-dose groups using the same international prognostic index. The neutrophil nadir and the frequency of infection were comparable among the three dose groups.

Discussion and Conclusions: Reduced-dose R-CHOP chemotherapy is a promising treatment for elderly patients with DLBCL in terms of efficacy and toxicity.     

R-CHOP方案治疗弥漫性大B细胞淋巴瘤疗效分析

目的:探讨弥漫性大B细胞淋巴瘤采用R-CHOP方案治疗的临床效果。方法:将某院收治的80例弥漫性大B细胞淋巴瘤患者按照随机数字表法分为研究组(R-CHOP方案)与对照组(CHOP方案);对比两组治疗效果及安全性。结果:治疗后研究组总有效率较对照组高,淋巴瘤国际预后指数优于对照组(P<0.05);两组不良反应结果对比无统计学意义(P>0.05)。结论:弥漫性大B细胞淋巴瘤采用R-CHOP方案治疗的效果更为理想。