Unusual outcome of treatment of thymoma with immunotherapy: case report.

Background: Thymoma is a rare mediastinal neoplasm originating from thymic epithelial cells, often associated with paraneoplastic syndromes. These syndromes can manifest as a range of autoimmune disorders, including myasthenia gravis, pure red cell aplasia, and aplastic anemia. Clinical trials involving the use of immune checkpoint inhibitors (ICIs) in thymoma have been complicated by a high incidence of immune-related adverse effects (irAEs).

Siltuximab for chimeric antigen receptor T-cell therapy-related CRS and ICANS: a multicenter retrospective analysis.

Chimeric antigen receptor T-cell (CAR-T) therapies are effective in many hematologic malignancies; however, adverse events including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) can affect a significant number of patients. Those who develop refractory CRS or ICANS have few treatment options. Siltuximab, a monoclonal antibody binding circulating interleukin-6, has been proposed to have clinical activity in both CRS and ICANS.

Patients with -Mutated Acute Myeloid Leukemia Receiving Intensive Induction Therapy Have Superior Outcomes Due to a Higher Rate of Salvage Therapy: A Single Institution, Retrospective Study.

Background: mutations (m) define the most treatment-refractory acute myeloid leukemia (AML) subtype. Optimal treatment approaches have not been established in this setting. We reviewed our institutional experience to identify therapy sequencing, treatment response, and survival patterns in these patients.

Posttransplant Lymphoproliferative Disease Following Pancreas Transplantation: A 40 Year Single-Center Experience.

Background: Chronic immunosuppression following pancreas transplantation carries significant risk, including posttransplant lymphoproliferative disease (PTLD). We sought to define the incidence, risk factors, and long-term outcomes of PTLD following pancreas transplantation at a single center.

Methods: All adult pancreas transplants between February 1, 1983 and December 31, 2023 at the University of Minnesota were reviewed, including pancreas transplant alone (PTA), simultaneous pancreas-kidney transplants (SPK), and pancreas after kidney transplants (PAK).

CD19-directed CART therapy for T-cell/histiocyte-rich large B-cell lymphoma.

T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) is a rare histologic variant of LBCL. Limited data regarding CD19-directed chimeric antigen receptor T-cell (CART) therapy in relapsed/refractory (R/R) THRLBCL suggest poor efficacy. We investigated CART outcomes for R/R THRLBCL through the Center for International Blood and Marrow Transplant Research registry.

The Prevalence of Pretransplant Frailty and Mental Distress in Hematopoietic Cell Transplantation and Association with Clinical Outcomes.

Frailty is a phenotype of decreased physiologic reserve associated with increased risk of toxicities and nonrelapse mortality (NRM) in hematopoietic cell transplant (HCT) recipients. The incidence, predictors, and adverse effects of pre-HCT frailty are not well known. We evaluated the association of pre-HCT frailty, defined using Fried's criteria, with age and baseline characteristics in patients ≥18 years undergoing autologous (auto) or allogeneic (allo) HCT for hematological malignancies.

Chimeric antigen receptor T-cell infusion for large B-cell lymphoma in complete remission: a center for international blood and marrow transplant research analysis.

CD19 CAR T-cell (CAR-T) therapy is commonly administered to patients with relapsed or refractory large B-cell lymphomas (LBCL), but salvage or bridging therapy can sometimes lead to a complete response (CR) prior to infusion. Limited studies have assessed the outcomes of patients infused in CR. A total of 134 patients with LBCL in CR prior to CAR-T infusion were identified from the CIBMTR registry, with median prior lines of therapy of 3 (range 2-9).

Efficacy of CD19 directed therapies in patients with relapsed or refractory large b-cell lymphoma relapsing after CD19 directed chimeric antigen receptor T-cell therapy.

Outcomes are poor for patients with relapsed and/or refractory (R/R) large B-cell lymphoma (LBCL) post chimeric antigen receptor T-cell (CAR-T) therapy. Two CD19-directed therapies, tafasitamab- cxix plus lenalidomide (tafa-len) and loncastuximab tesirine (loncaT) are approved in R/R LBCL. The efficacy of these CD19 directed therapies in patients who relapse after CD19 directed CAR-T (CD19-CART) therapy is not well understood.

Temporal variation in oral microbiome composition of patients undergoing autologous hematopoietic cell transplantation with keratinocyte growth factor.

Introduction: Autologous hematopoietic cell transplantation (AHCT) is a well-established treatment for lymphoma. Unintended effects of this therapy include oral mucositis (OM) and gastrointestinal toxicities, resulting in poor clinical outcomes. The gut microbiome has been previously linked to transplant toxicities among allogeneic recipients, but little is known about the effects of AHCT on the oral microbiome.

Identifying an optimal fludarabine exposure for improved outcomes after axi-cel therapy for aggressive B-cell non-Hodgkin lymphoma.

Fludarabine is one of the most common agents given for lymphodepletion before CD19 chimeric antigen receptor T cells, but its optimal therapeutic intensity is unknown. Using data from a multicenter consortium, we estimated fludarabine exposure (area under the curve [AUC]) using a population pharmacokinetic (PK) model in 199 adult patients with aggressive B-cell non-Hodgkin lymphomas who received commercial axicabtagene ciloleucel (Axi-cel). We evaluated the association of estimated fludarabine AUC with key outcomes, aiming to find an AUC that optimized efficacy and tolerability.

Nicotinamide enhances natural killer cell function and yields remissions in patients with non-Hodgkin lymphoma.

Allogeneic natural killer (NK) cell adoptive transfer has shown the potential to induce remissions in relapsed or refractory leukemias and lymphomas, but strategies to enhance NK cell survival and function are needed to improve clinical efficacy. Here, we demonstrated that NK cells cultured ex vivo with interleukin-15 (IL-15) and nicotinamide (NAM) exhibited stable induction of l-selectin (CD62L), a lymphocyte adhesion molecule important for lymph node homing. High frequencies of CD62L were associated with elevated transcription factor forkhead box O1 (FOXO1), and NAM promoted the stability of FOXO1 by preventing proteasomal degradation.

Age is No Barrier: CAR-T Therapy in Older Adults.

In the last decade, chimeric antigen receptor-T (CAR-T) cells have revolutionized the treatment of hematological malignancies. With six different products for five diseases in various settings, CAR-T use has increased, and the comfort level of prescribers continues to expand. These therapies carry substantial toxicities that may limit their applicability to all patient populations.

Phase II Study of Myeloablative 7-8/8-Matched Allotransplantation with Post-Transplantation Cyclophosphamide, Tacrolimus, and Mycophenolate Mofetil.

Graft-versus-host disease (GVHD) is the major toxicity of allogeneic hematopoietic cell transplantation (HCT). We hypothesized that a GVHD prophylaxis regimen of post-transplantation cyclophosphamide (PTCy), tacrolimus (Tac), and mycophenolate mofetil (MMF) would be associated with incidences of acute and chronic GVHD in patients receiving a matched or single antigen mismatched HCT. This Phase II study was conducted at the University of Minnesota using a myeloablative regimen of either total body irradiation (TBI) at a total dose of 1320 cGy, administered in 165-cGy fractions, twice daily from day -4 to day -1, or busulfan (Bu) 3.

Phase II, Open-Label Clinical Trial of Urinary-Derived Human Chorionic Gonadotropin/Epidermal Growth Factor for Life-Threatening Acute Graft-versus-Host Disease.

Treatments that aid inflammation resolution, immune tolerance, and epithelial repair may improve outcomes beyond high-dose corticosteroids and other broad immunosuppressants for life-threatening acute graft-versus-host disease (aGVHD). We studied the addition of urinary-derived human chorionic gonadotropin/epidermal growth factor (uhCG/EGF; Pregnyl; Organon, Jersey City, NJ) to standard aGVHD therapy in a prospective Phase II clinical trial (ClinicalTrials.gov identifier NCT02525029).

Phase II Study of Myeloablative 8/8- or 7/8-Matched Allotransplantation with Post-Transplant Cyclophosphamide, Tacrolimus, and Mycophenolate Mofetil: Marked Reduction in GVHD Risk Without Increased Relapse Risk Compared to Historical Cyclosporine/Methotrexate.

Introduction: Graft-versus host disease (GVHD) is a major limitation to the success of allogeneic hematopoietic cell transplant (HCT). We hypothesized that the GVHD prophylaxis regimen of post-transplant cyclophosphamide (PTCy), tacrolimus (Tac) and mycophenolate mofetil (MMF) would reduce the incidence of GVHD in patients receiving a matched or single antigen mismatched HCT without an increase in risk of malignant relapse.

Methods: This is a phase II study conducted at the University of Minnesota using a myeloablative regimen of either: (A) total body irradiation (TBI, total dose 1320 cGy, administered in 165 cGy fractions, twice a day from days -4 to -1) or (B) Busulfan 3.

Advances in NK cell therapy for hematologic malignancies: NK source, persistence and tumor targeting.

Natural Killer (NK) cells yield promise in therapy of hematologic malignancies. The clinical experience with adoptively transferred allogeneic NK cells over past two decades has revealed safety and minimal risk of CRS or ICANS. Unlike T cells which have to be genetically altered to avoid graft vs host disease (GVHD), HLA mismatched NK cells can be infused without GVHD risk.

Sarcopenia Predicts Inferior Progression-Free Survival in Lymphoma Patients Treated with Autologous Hematopoietic Stem Cell Transplantation.

Autologous hematopoietic stem cell transplantation (ASCT) improves survival for patients with chemotherapy-sensitive lymphoma. Validated scoring systems are used in the clinical setting to predict treatment toxicity and survival; however, complications related to disease and treatment still occur, highlighting challenges in optimal patient selection and the need for novel predictors. Analysis of body composition and muscle mass can provide an objective assessment to identify vulnerable populations, as sarcopenia and frailty have been reported to predict outcomes in other tumor types.

Human Effectors of Acute and Chronic GVHD Overexpress CD83 and Predict Mortality.

Purpose: Acute and chronic GVHD remain major causes of transplant-related morbidity and mortality (TRM) after allogeneic hematopoietic cell transplantation (alloHCT). We have shown CD83 chimeric antigen receptor (CAR) T cells prevent GVHD and kill myeloid leukemia cell lines. In this pilot study, we investigate CD83 expression on GVHD effector cells, correlate these discoveries with clinical outcomes, and evaluate critical therapeutic implications for transplant recipients.

Chimeric antigen receptor T-cell therapy yields similar outcomes in patients with and without cytokine release syndrome.

Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of many patients with aggressive relapsed or refractory large B-cell lymphoma (LBCL). Treatment can be complicated by clinically evident cytokine release syndrome (CRS), which is characterized by the development of fever, hypoxia, and hypotension, and can be life-threatening. Most patients treated with CAR-T cells develop CRS, which is thought to represent an immune phenomenon.

Secondary Impact of the Coronavirus Disease 19 Pandemic on Patients and the Cellular Therapy Healthcare Ecosystem.

The Coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has significantly impacted global health and healthcare delivery systems. To characterize the secondary effects of the COVID-19 pandemic and mitigation strategies used in the delivery of hematopoietic stem cell transplantation (HSCT) care, we performed a comprehensive literature search encompassing changes in specific donor collection, processing practices, patient outcomes, and patient-related concerns specific to HSCT and HSCT-related healthcare delivery. In this review, we summarize the available literature on the secondary impacts the COVID-19 pandemic on the fields of HSCT and cellular therapy.