Role of Immune Microenvironmental Factors for Improving the IPI-related Risk Stratification of Aggressive B Cell Lymphoma

Objective To investigate the risk stratification of aggressive B cell lymphoma using the immune microenvironment and clinical factors. Methods A total of 127 patients with aggressive B cell lymphoma between 2014 and 2015 were enrolled in this study. CD4, Foxp3, CDS, CD68, CD163, PD-1, and PD-L1 expression levels were evaluated in paraffin-embedded lymphoma tissues to identify their roles in the risk stratification. Eleven factors were identified for further evaluation using analysis of variance, chi-square, and multinomial logistic regression analysis. Results Significant differences in 11 factors （age, Ann Arbor stage, B symptom, ECOG performance status, infiltrating CD8＋ T cells, PD-L1 expression, absolute blood monocyte count, serum lactate dehydrogenase, serum iron, serum albumin, and serum l^2-microglobulin） were observed among patient groups stratified by at least two risk stratification methods [International Prognostic Index （IPI）, revised IPI, and NCCN-IPI models] （P 〈 0.05）. Concordance rates were high （81.4%-100.0%） when these factors were used for the risk stratification. No difference in the risk stratification results was observed with or without the Ann Arbor stage data. Conclusion We developed a convenient and inexpensive tool for use in risk stratification of aggressive B cell lymphomas, although further studies on the role of immune microenvironmental factors are needed.

Chidamide combined with traditional chemotherapy for primary cutaneous aggressive epidermotropic CD8+cytotoxic T-cell lymphoma:A case report

BACKGROUND Traditional chemotherapy has benefited many patients with non-Hodgkin's lymphoma,but results in a very poor response in patients with rare lymphomas or refractory lymphomas.Previous studies have shown that chidamide has potential anti-lymphoma activity and reverses lymphoma cell chemoresistance to increase the chemosensitivity of lymphoma cells to traditional chemotherapy.CASE SUMMARY A 14-year-old boy was admitted to our hospital with a 5-d history of generalized erythema,papules,and blisters.Initially,the disease was refractory to potent antiallergic and anti-infective treatment,and his condition progressively worsened.Skin biopsy revealed primary cutaneous aggressive epidermotropic CD8+cytotoxic T-cell lymphoma.Considering that the disease is extremely rare in clinical practice,existing case reports have shown poor efficacy with traditional chemotherapy alone.We recommend chidamide combined with traditional chemotherapy for treatment.The regimen was as follows:Chidamide 30 mg/biw,cyclophosphamide 1100 mg/d1,pirarubicin 70 mg/d1,vincristine 2 mg/d1,dexamethasone 20 mg/d1-5,etoposide 100 mg/d1-5,in a 21 d cycle.The treatment effect was considerable,and complete remission was achieved after 4 cycles of treatment,after which the patient completed a total of 6 cycles of treatment.Subsequently,the patient regularly took chidamide 20 mg/biw as maintenance therapy for 1 year.To date,the patient has been disease-free for 3 years.CONCLUSION This case suggests that the combination of chidamide and traditional chemotherapy is effective in primary cutaneous aggressive epidermotropic CD8+cytotoxic T-cell lymphoma.

Reduced-intensity conditioning allogeneic stem cell transplantation in malignant lymphoma: current status

stem cell transplantation （allo-SCT） is a potential cure for patients with malignant lymphoma that is based on the graft-versus-lymphoma （GVL） effect. Myeloablative conditioning allo-SCT is associated with high mortality and morbidity, particularly in patients older than 45 years, heavily pretreated patients （prior hematopoietic stem cell transplantation or more than two lines of conventional chemotherapy） or patients affected by other comorbidities. Therefore, conventional allo-SCT is restricted to younger patients （〈50 to 55 years） in good physical condition. Over the last decade, allo-SCT with reduced-intensity conditioning （RIC-allo-SCT） has been increasingly used to treat patients with lymphoma. This treatment is associated with lower toxicity and substantial decrease in the incidence of transplant- related mortality, and has the potential to lead to long-term remissions. Therefore, patients who are not suitable to undergo conventional allo-SCT can benefit from the potentially curative GVL effects of allo-SCT. Although RIC-allo-SCT has improved the survival of lymphoma patients, high post-transplant relapse rates or disease progression mainly results in treatment failure. Thus, further improvement is clearly needed. The role and timing of RIC-allo-SCT in the treatment of lymphoma remains unclear. Therefore, more prospective studies should clarify the effectiveness of this method. In this article, we review the recent literature on RIC-alIo-SCT as a treatment for major lymphoma subtypes. Areas that require further investigation in the context of clinical trials are also highlighted.

CAR T-Cell therapies in lymphoma: current landscape, ongoing investigations, and future directions

Chimeric antigen receptor(CAR)T-cell therapy has significantly improved outcomes for patients with relapsed/refractory large B-cell lymphoma,mantle cell lymphoma,and follicular lymphoma,with multiple FDA-approved CAR T products now commercially available.Ongoing studies seek to move CAR T-cells to earlier lines of therapy and to characterize the efficacy and safety of CAR T-cell approaches in additional lymphoma histologies including relapsed/refractory follicular lymphoma and chronic lymphocytic leukemia.Other areas of active research address CAR T in combination with other lymphoma-directed therapies,and mechanisms of CAR T resistance.This review focuses on the FDA-approved anti-CD19 CAR T products for B-cell lymphomas,management of CAR T-cell-associated toxicities,approaches to bridging therapy,and ongoing clinical trials and future research directions across a broad range of lymphoma histologies.