Treatment options for patients with relapsed or refractory (R/R) anaplastic large cell lymphoma (ALCL) have increased in the era of targeted therapies such as brentuximab vedotin (BV) and Anaplastic Lymphoma Kinase (ALK) inhibitors. However, there is no standard treatment and limited published data evaluating their use. The goal of this retrospective study is to describe current real-world treatment and outcomes of pediatric, adolescent, and young adult patients with R/R ALK-positive ALCL. We conducted a retrospective, multi-institutional study identifying 81 patients with R/R ALK-positive ALCL ≤ 21 years old at initial diagnosis treated between 2011-2022 across 18 institutions. Median time from diagnosis to relapse was 8.9 months (range 2.6-131.9). Initial reinduction regimens included ALK inhibitor monotherapy (n=37, 46%), BV monotherapy (n=19, 23%), chemotherapy without targeted therapy (n=12, 15%), chemotherapy with targeted therapy (n=9, 11%), or vinblastine monotherapy (n=4, 5%) with 83% of patients achieving a complete response to initial reinduction regimen. Fifty-eight patients received a hematopoietic stem cell transplant (HSCT), 11 autologous and 48 allogeneic, with one receiving both. Duration of treatment for patients receiving BV or the ALK-inhibitor crizotinib (CZ) varied widely (BV 1-11 years; CZ 2-10 years). Five-year event-free survival 63% (95% CI 53-75%) and five-year overall survival 91% (95% CI 84-98%). This is the largest collection of patients with R/R ALK+ ALCL treated in the era of targeted therapy. Patients achieved excellent responses to ALK-inhibitor or BV monotherapy, but questions remain about duration of therapy and role of HSCT.
Leukoreduction to eliminate mononuclear cells within blood products is necessary to prevent graft-versus-host disease after transfusion. Published reports document low concentrations of mononuclear cells leftover in fresh-frozen plasma products, however the phenotype and the proliferative potential of these cells has not been tested.We investigated residual cellular components contained within fresh and fresh-frozen plasma products and characterised their proliferative potential in co-cultures with unrelated allogeneic cells. We designed a flow-based assay to phenotype cells and quantify cell division by measuring the dilution of fluorescently labeled protein as cells divide. Leukocytes from consenting donors were purified from fresh liquid or fresh-frozen plasma units and cultured for three to seven days with unrelated irradiated allogeneic targets.We discovered a median of 1.6×107 viable lymphocytes were detectable in fresh plasma units after collection (n=8), comprised of a mixture of CD3+ CD8+ and CD3+ CD4+ cells. Furthermore, we identified a median of 8.4% of live CD3+ plasma lymphocytes divided as early as Day 4 when co-cultured with unrelated allogeneic cells, expanding to a median 88.8% by Day 7 (n=3). Although freezing the plasma product reduced the total number of viable leukocyte cells down to 2.3×105 (n=10), residual naive CD3+ cells were viable and demonstrated division through Day 7 of co-culture.The evidence of viable proliferative lymphocytes in fresh and fresh-frozen plasma products derived from centrifugation suggests that additional leukoreduction measures should be investigated to fully eradicate reactive lymphocytes from centrifuged plasma products.
Introduction Mediport use as a clinical option for the administration of chimeric antigen receptor T cell (CAR T cell) therapy in patients with B-cell malignancies has yet to be standardized. Concern for mediport dislodgement, cell infiltration, and ineffective therapy delivery to systemic circulation has resulted in variable practice with intravenous administration of CAR T cell therapy. With CAR T cell commercialization, it is important to establish practice standards for CAR T cell delivery. We conducted a study to establish usage patterns of mediports in the clinical setting and provide a standard of care recommendation for mediport use as an acceptable form of access for CAR T cell infusions. Methods In this retrospective cohort study, data on mediport use and infiltration rate was collected from a survey across 34 medical centers in the Pediatric Real-World CAR Consortium, capturing 504 CAR T cell infusion routes across 489 patients. Data represents the largest, and to our knowledge sole, report on clinical CAR T cell infusion practice patterns since FDA approval and CAR T cell commercialization in 2017. Results Across 34 sites, all reported tunneled central venous catheters, including Broviac ® and Hickman ® catheters, as accepted standard venous options for CAR T cell infusion. Use of mediports as a standard clinical practice was reported in 29 of 34 sites (85%). Of 489 evaluable patients with reported route of CAR T cell infusion, 184 patients were infused using mediports, with no reported incidences of CAR T cell infiltration. Discussion/Conclusion Based on current clinical practice, mediports are a commonly utilized form of access for CAR T cell therapy administration. These findings support the safe practice of mediport usage as an accepted standard line option for CAR T cell infusion.
Abstract Posttransplant lymphoproliferative disease (PTLD) in pediatric solid organ transplant (SOT) recipients is characterized by uncontrolled proliferation of Epstein-Barr virus–infected (EBV+) B cells due to decreased immune function. This study evaluated the feasibility, safety, clinical and immunobiological outcomes in pediatric SOT recipients with PTLD treated with rituximab and third-party latent membrane protein–specific T cells (LMP-TCs). Newly diagnosed (ND) patients without complete response to rituximab and all patients with relapsed/refractory (R/R) disease received LMP-TCs. Suitable LMP-TC products were available for all eligible subjects. Thirteen of 15 patients who received LMP-TCs were treated within the prescribed 14-day time frame. LMP-TC therapy was generally well tolerated. Notable adverse events included 3 episodes of rejection in cardiac transplant recipients during LMP-TC therapy attributed to subtherapeutic immunosuppression and 1 episode of grade 3 cytokine release syndrome. Clinical outcomes were associated with disease severity. Overall response rate (ORR) after LMP-TC cycle 1 was 70% (7/10) for the ND cohort and 20% (1/5) for the R/R cohort. For all cohorts combined, the best ORR for LMP-TC cycles 1 and 2 was 53% and the 2-year overall survival was 70.7%. vβT-cell receptor sequencing showed persistence of adoptively transferred third-party LMP-TCs for up to 8 months in the ND cohort. This study establishes the feasibility of administering novel T-cell therapies in a cooperative group clinical trial and demonstrates the potential for positive outcomes without chemotherapy for ND patients with PTLD. This trial was registered at www.clinicaltrials.gov as #NCT02900976 and at the Children's Oncology Group as ANHL1522.
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