Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a new provisional category in the 2016 World Health Organization (WHO) classification of lymphoid neoplasms, and its incidence is rising owing to increasing recognition of this complication of breast implant insertion. At a median of 10 years after implant insertion, the typical presenting features are sudden-onset breast swelling secondary to peri-implant effusion and less frequently mass-forming disease. Histologic features comprise pleomorphic cells expressing CD30 and negative anaplastic lymphoma kinase (ALK) receptor, similar to systemic and cutaneous ALKnegative anaplastic large cell lymphoma (ALCL). The effusion-only subtype is generally indolent and curable with surgery, unlike the more aggressive mass-forming disease, for which systemic therapy is advocated. High clinical suspicion and pertinent use of radiologic and pathology modalities are essential for timely and accurate diagnosis of BIA-ALCL. Contemporary imaging techniques including US, mammography, breast MRI, CT, and PET/CT are routinely used in breast disease and lymphomas; however, the unique behavior of BIA-ALCL pre sents significant diagnostic and radiologic interpretative challenges, with numerous nuanced imaging features being pertinent, and current lymphoma staging and response guidelines are not easily applicable to BIA-ALCL. The authors evaluate available evidence in this evolving field; detail key indications, strengths, and limitations of the panoply of radiologic techniques for BIA-ALCL; and propose multiparametric imaging paradigms for management of the peri-implant effusion and massforming or advanced disease subtypes, with the goal of accurate optimal patient care. The authors also predict a future model of multimodal assessment using novel imaging and molecular techniques and define key research directions. © RSNA, 2020 • radiographics.rsna.org
Background: Autologous chimeric antigen receptor (CAR) T cell therapy has shown to be effective in relapsed or refractory (R/R) diffuse large B cell lymphoma (DLBCL) but requires in real world and in Europe at least a 4 weeks period of cell processing. During this "bridging period", patients are vulnerable to disease progression and complications. We sought to characterize bridging therapy strategies. Methods: We performed a retrospective review of patients (pts) with R/R DLBCL treated with commercialized CD19 CAR T cells, either Axicabtagene Ciloleucel (Yescarta) or tisagenlecleucel (Kymriah). Bridging therapy (BT) was defined by any therapy given from enrolment to cell infusion. We divided bridging therapy in 2 groups: high intensity BT (HI, including chemotherapy+/-immunotherapy) and low intensity BT (LI, including monoclonal antibodies rituximab, brentuximab, dexamethasone, lenalidomide). We evaluated toxicity (cytokine releasing syndrome (CRS), CAR-related encephalopathy syndrome (CRES), infections) and efficacy (OS, PFS) after infusion according to the intensity of the BT. Results: 46 pts were enrolled for commercialized CAR T cells (Kymriah n=25, Yescarta n=21) including R/R DLBCL (n=35), TFL (n=5) or PMBL (n=6) between June 2018 and April 2019. The median age was 57 (IQR, 42 to 64). Number of pts with aaIPI > 2 was 20. The median number of previous lines was 3 (range 3-5), including 15 autologous stem cell transplants and 2 allotransplants. Median time between enrollment and infusion, and between collection and infusion were 59 (35 to 118) and 40 (32 to 90) days, respectively. Overall, 30 (65%) pts received a HI and 16 (35%) a LI or no bridging therapy. Median number of BT cycles was 2 (range, 1-4). 13 patients had various regimen because of uncontrolled disease. Pts receiving HI presented at enrollment with more elevated LDH (60% vs 31%), more involved extranodal sites (n> 2, 32% vs 0%), higher IPI (>2, 77% vs 43%, p=.049), and higher total metabolic tumor volume (TMTV) measured on FDG PET/CT (median, 90 vs 10, p=.002). After BT, 44 pts were infused. 2 pts died before infusion because of a pulmonary infection (n=1) and a lymphoma progression (n=1), both in the HI group. At infusion response evaluation showed that 25 (57%) pts progressed during BT, without difference in the HI or the LI groups (61 % vs 50%). Median TMTV in HI and LI was 95 (10 -256) vs 18 (8 - 44), respectively. After CAR T infusion, 14 pts (32%) developed an infectious disease (7 in the LI group, 7 in the HI group, p=0.31). Median duration of neutropenia (PNN < 1000) was 8 days, 7 in the LI and 9 in the HI (p= 0.21). In the LI and HI groups, 11 and 19 pts developed a CRS (0 grade 3-4), 1 and 11 pts developed a CRES (1 and 3 grade 3-4), respectively. The HI/LI did not impact the occurrence of CRS (p=1.00) but that of CRES (p=0.03). Pts with abnormal LDH (p=0.02), high number of courses (p=0.03) or PS>0 (p=0.049) had a higher risk of CRS, whereas patients with high IPI (p=0.03), and high values of CRP (P=0.02) or decreased albumin levels (p=0.008) had a higher risk of CRES. After CAR T cells infusion, with a median follow up of 5.7 months, the median PFS was not reached in the LI group, and was of 3 months in the HI group (p=0.06). The median OS was not reached in the LI group, and was of 12.5 months in the HI group (p=0.09). In multivariate analyses, IPI was predictor of better PFS, whereas low IPI and TMTV were predictors of better OS. No evidence of any effect of intensity of the BT on OS or PFS was observed in these multivariate analyses. Conclusion: The type of bridging therapies was very heterogeneous. Its intensity was closely related to tumor burden at enrolment. There was no significant difference in terms of efficacy between the HI and LI groups, but a higher frequency of CRES in the HI group. Disclosures Paillassa: Janssen: Other: Bibliography board with young hematologists. Di Blasi:Novartis: Honoraria. Thieblemont:Roche: Honoraria, Research Funding; Gilead: Honoraria; Novartis: Honoraria; Kyte: Honoraria; Janssen: Honoraria; Celgene: Honoraria; Cellectis: Membership on an entity's Board of Directors or advisory committees.
transplantation lymphoproliferative disease (PTLD) is a serious complication associated with Epstein-Barr virus (EBV) infection after hematopoietic stem cell transplantation (HSCT). Although anti-CD-20 therapy is now used as a preemptive strategy for EBV reactivation, PTLD still occurs in some patients. Here we analyzed outcomes and risk factors associated with PTLD transformation in 208 HSCT recipients who were diagnosed with EBV-DNAemia and received at least 1 course of rituximab. The median patient age was 42.52 years (range, 8.35 to 74.77 years), and the median duration of follow-up was 47.33 months (range, 3.18 to 126.20 months). The 2-year overall survival of the entire cohort was 62.8 (95% confidence interval [CI], 56.4 to 69.9), and the 2-year cumulative incidence function of PTLD was 6.3% (95% CI, 3.5% to 10.1%), for a median follow-up of patients diagnosed with PTLD of 37.85 months. Multivariable analysis identified 4 risk factors associated with PTLD: HSCT from an unrelated donor, recipient HLA-DRB1*11:01, fever at diagnosis of EBV infection, and donor-recipient sexmismatched HSCT. The presence of more than 2 of these risk factors was associated with an increased risk of developing PTLD. This retrospective study identifies risk factors associated with PTLD in EBV-infected patients after HSCT and defines patient subgroups that may benefit from intensified preemptive strategies.
Summary As the impact of targeted next‐generation sequencing (TNGS) on daily diagnosis has not been evaluated, we performed TNGS (46 genes) on lymphomas of unclear subtype following expert haematopathological review. The potential impact on patient care and modifications of final diagnosis were divided into major and minor changes according to the European Society of Medical Oncology (ESMO) guidelines. Among 229 patients [19 primary central nervous system lymphomas (PCNSL), 48 large B‐cell lymphomas (LBCLs), 89 small BCLs (SBCLs), seven Hodgkin lymphomas (HL), 66 T‐cell lymphomas], the overall concordance rate of histological and TNGS diagnosis was 89·5%. TNGS confirmed the histological diagnosis in 144 cases (62·9%), changed the diagnosis in 24 cases (10·5%) and did not help to clarify diagnosis in 61 cases (26·7%). Modifications to the final diagnosis had a clinical impact on patient care in 8·3% of cases. Diagnostic modifications occurred in all types of lymphoma except in PCNSL and HL; the modification rate was 14·6% in SBCL and 12·5% in LBCL. While comparing informative and uninformative cases, no differences were found in terms of DNA amplification, quality or depth of sequencing and biopsy type. The present study highlights that TNGS may directly contribute to a more accurate diagnosis in difficult‐to‐diagnose lymphomas, thus improving the clinical management in routine practice.
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