Management of SARS-CoV-2 infection is a major challenge in patients with lymphoid malignancies: Warrants a clear therapeutic strategy

Patients with lymphoid malignancies are at a higher risk of coronavirus disease 2019(COVID-19)infection due to their immunocompromised state and results in higher mortality rates in these patients.Anti-CD 20 therapy is one of the leading causes of immunosuppression that worsens in COVID-19 cases.COVID-19 vaccines,on the other hand,appear to be less beneficial to these patients.Appropriate treatment and recommendations are required for these COVID-19 patients with lymphoid malignancies.

Effects of COVID-19 in lymphoid malignancies

I will have a couple of comments on the issues elaborated in the article titled as‘Impact of COVID-19 in patients with lymphoid malignancies’.First,the author did not emphasize and overlook the prolonged persistence of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)RNA in coronavirus disease 2019(COVID-19)patients with hematological malignancies.Second,the rise of a chronic lymphoid leukemia clone in COVID-19 was not mentioned by the authors.Third,achieving a complete remission in asymptomatic COVID-19 patients with follicular lymphoma in partial remission after bendamustine-based therapy is not specific to this lymphoma subtype.Fourth,follicular lymphoma does not always undergo complete remission with SARS-CoV-2 infection.Our aim is to help the authors to discuss and clarify these issues a little more in COVID-19 patients with hematological malignancies.

Anti-cd TCR antibody-expanded cd T cells:a better choice for the adoptive immunotherapy of lymphoid malignancies

Cell-based immunotherapy for lymphoid malignancies has gained increasing attention as patients develop resistance to conventional treatments.cd T cells,which have major histocompatibility complex(MHC)-unrestricted lytic activity,have become a promising candidate population for adoptive cell transfer therapy.We previously established a stable condition for expanding cd T cells by using anti-cd T-cell receptor(TCR)antibody.In this study,we found that adoptive transfer of the expanded cd T cells to Daudi lymphoma-bearing nude mice significantly prolonged the survival time of the mice and improved their living status.We further investigated the characteristics of these antibody-expanded cd T cells compared to the more commonly used phosphoantigen-expanded cd T cells and evaluated the feasibility of employing them in the treatment of lymphoid malignancies.Slow but sustained proliferation of human peripheral blood cd T cells was observed upon stimulation with anti-cd TCR antibody.Compared to phosphoantigen-stimulated cd T cells,the antibody-expanded cells manifested similar functional phenotypes and cytotoxic activity towards lymphoma cell lines.It is noteworthy that the anti-cd TCR antibody could expand both the Vd1 and Vd2 subsets of cd T cells.The in vitro-expanded Vd1 T cells displayed comparable tumour cell-killing activity to Vd2 T cells.Importantly,owing to higher C–C chemokine receptor 4(CCR4)and CCR8 expression,the Vd1 T cells were more prone to infiltrate CCL17-or CCL22-expressing lymphomas than the Vd2 T cells.Characterizing the peripheral blood cd T cells from lymphoma patients further confirmed that the anti-cd TCR antibody-expanded cd T cells could be a more efficacious choice for the treatment of lymphoid malignancies than phosphoantigen-expanded cd T cells.

Fludarabine and intravenous busulfan conditioning with post-transplantation cyclophosphamide for allogeneic peripheral stem cell transplantation for adult patients with lymphoid malignancies:a prospective single-arm phase Ⅱ study

Post-transplantation cyclophosphamide(PT-Cy)alone or in combination with other immunosuppressive drugs has emerged as a promising strategy in the setting of allogeneic hematopoietic stem cell transplantation.Improved survival rate was reported in lymphoid malignancies following PT-Cy strategy compared with myeloid disease in non-myeloablative bone marrow transplant setting.Thus,we aimed to evaluate the safety and efficacy of PT-Cy combined with cyclosporine as graft-versus-host disease(GVHD)prophylaxis after myeloablative conditioning and T cell-replete peripheral stem cell transplantation in lymphoid malignancies.This single-arm phase Ⅱ clinical trial(NCT01435447)involving 31 adult patients was conducted from January 2013 to June 2018.The donor-type neutrophil engraftment rate was 100%,and the overall incidence of grade Ⅱ to Ⅳ and grade Ⅲ to Ⅳ acute GVHD was 39%and 24%,respectively.The cumulative incidence rates of chronic GVHD(35%),including moderate to severe forms(10%),were reduced compared with those of the historical group(P=0.03 and P=0.04,respectively).With a median follow-up of 18 months,the estimated 2-year overall and event-free survival was 64.8%(95%confidence interval:47.8%–86.7%)and 58.4%(95%CI:41.9%–81.7%),respectively.The 2-year cumulative incidence rate of relapse was 19.5%(95%CI:9.0%–35.8%),whereas the non-relapse mortality rate was 21.8%(95%CI:11.3%–38.1%).These results demonstrated the feasibility of PT-Cy as GVHD prophylaxis in this clinical setting.This strategy could significantly reduce the incidence of chronic GVHD and its moderate to severe forms but not of acute GVHD and results in similar survival outcomes compared with the historical group.A prospective study with additional patients is warranted to confirm the role of PT-Cy in lymphoid malignancy.

Clinical characteristics and prognostic factors of patients with mature T-cell lymphoid malignancies： a single-institution study of 225 cases

Mature T-cell lymphoid malignancies comprise a group of heterogeneous diseases that vary in clinicopathological features, biological behavior, treatment response, and prognosis. Bone marrow （BM） infiltration is more commonly present in mature T-cell lymphoid malignancies compared with their B-cell counterparts and hence important for differential diagnosis. In this study, clinical characteristics and prognostic factors were analyzed in 225 patients with mature T-cell lymphoid malignancies treated in a single institution. These included 29 cases of T-cell lymphoproliferative disorders （T-LPD, all with BM infiltration） and 196 cases of T-/natural-killer-cell lymphoma （T/NKCL, 56 with BM infiltration and 140 without BM infiltration）. The estimated 5-year overall survival （OS） rates of T-LPD and T/NKCL were 96.6% and 37.3%, respectively. T-LPD patients were less likely to exhibit poor performance status, advanced disease stage, presence of B symptoms, or abnormal level of serum [^-2 microglobulin. With similar pathological characteristics, T/NKCL patients with BM infiltration showed significantly lower response rates and shorter OS than those without BM infiltration （P = 0.0264 and P 〈 0.0001, respectively）. Multivariate analysis indicated that poor performance status, advanced disease stage, elevated serum lactate dehydrogenase level, and BM involvement were independent unfavorable prognostic factors. The Glasgow Prognostic Score may be more efficient than the International Prognostic Index in predicting disease outcome in T/NKCL. In conclusion, clinical characteristics may be useful in more effectively stratifying patients with mature T-cell lymphoid malignancies.

EXPRESSION OF PROLIFERATING CELL NUCLEAR ANTIGEN IN CUTANEOUS MALIGNANT LYMPHOMAS AND LYMPHOID INFILTRATES

Paraffin-embedded tissue of skin biopsy specimens taken retrospectively from 24 patients with cutaneous malignant lymphomas (CML) and 8 patients with cutaneous lymphoid infiltrates (CLI) and other dennatoses were studied retrospectively with PCIO immunostaining. The results show a statistical significant difference among PCIO indices for cutaneous genuine histiocytic lymphoma (CGHL), cutaneous germinal center cell-derived lymphomas (CGCCL), cutaneous peripheral T-cell lymphomas (CPTL), non-mycosis fungoides (MF) and Sezary's syndrome (SS), and MF when compared with those for CLI. There is a linear relationship between PCIO index and square root of PCIO density, both of which seem to have a parallel relationship to the severity of malignancy in CML. The nuclear volume of the positive tumor cell or lymphocyte with PCIO immunostaining may be also useful in differentiating CML from CLI.