Emmanuel Katsanis

University of Arizona | UA · Department of Pediatrics

Introduction: Acute B-cell lymphoblastic leukemia (B-ALL) can often be cured with multiagent chemotherapy but prognosis following relapse remains poor with conventional chemotherapy alone. While chimeric antigen receptor (CAR)-T cells and bispecific T cell engager therapy can be effective in treating acute B-ALL, NK cell therapies may emerge as an...

Acute graft-versus-host disease (GvHD) is a significant complication following allogeneic hematopoietic stem cell transplantation. This process begins with the activation of donor T-cells that recognize host tissue antigens as foreign, resulting in an immune attack primarily targeting the skin, gastrointestinal tract and liver. Post-transplant cycl...

Cytokine release syndrome (CRS) and immune cell-associated neurotoxicity syndrome (ICANS) are severe complications of CAR-T therapy linked to endothelial dysfunction. The modified Endothelial Activation and Stress Index (m-EASIX) score predicts severe ICANS and CRS. Both hypophosphatemia and elevated IL-6 are associated with these syndromes. Our st...

Purpose The purpose of this study was to analyze potential differences in antitumor efficacy and pharmacokinetics between intravenous (IV) bendamustine and a novel orally administered (PO) bendamustine agent that is utilizing the beneficial properties of superstaturated solid dispersions formulated in nanoparticles. Methods Pharmacokinetics of IV...

e14511 Background: Cytokine release syndrome (CRS) and immune cell associated neurotoxicity syndrome (ICANS) can be severe complications of CAR-T infusion. Both syndromes have been associated with endothelial dysfunction which prompted prior use of a modified version of the Endothelial Activation and Stress Index (m-EASIX) to predict the occurrence...

Exercise mobilizes cytotoxic lymphocytes to blood which may allow superior cell products to be harvested and manufactured for cancer therapy. Gamma-Delta (γδ) T-cells have shown promise for treating solid tumors, but there is a need to increase their potency against hematologic malignancies. Here, we show that human γδ T-cells mobilized to blood in...

Background: Graft-versus-host disease (GvHD) and relapse persist as significant hurdles in achieving successful outcomes following allogeneic hematopoietic cell transplantation (alloHCT). The composition of the graft plays a substantial role in influencing transplant outcomes. Higher numbers of naïve CD4 and naïve CD8 T cells correlate with increas...

Purpose: The purpose of this study was to analyze potential differences in antitumor efficacy and pharmacokinetics between intravenous (IV) bendamustine (BEN) and a novel orally administered bendamustine agent (PO) that is utilizing the beneficial properties of superstaturated solid dispersions formulated in nanoparticles. Methods: Pharmacokinetic...

Pure red cell aplasia (PRCA) is a rare hematologic phenomenon that is usually associated with inherited genetic mutations such as in Diamond-Blackfan anemia. However, due to the emergence of allogenic stem cell transplantation in the treatment of various malignant and non-malignant disorders, the incidence of PRCA has increased. PRCA following hema...

The most common lymphodepletion regimen used prior to infusion of chimeric antigen receptor-T cells (CAR-T) is cyclophosphamide (CY) in combination with fludarabine (Flu) (CY-FLU). While cyclophosphamide (CY) possesses lymphotoxic effects, it concurrently preserves regulatory T cell activity, potentially affecting the efficacy of CAR-T cells. Moreo...

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 intraven...

Purpose: The mobilization and redistribution of severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) specific T-cells and neutralizing antibodies during exercise is purported to increase immune surveillance and protect against severe coronavirus disease 2019 (COVID-19) . We sought to determine if COVID-19 vaccination would elicit exercise-...

10031 Background: Survival for pediatric B-cell lymphomas (BCL) exceeds 90% with modern regimens, however outcomes remain poor for patients with relapsed or refractory (R/R) disease. Tisagenlecleucel is a CD19-directed CAR T-cell therapy (CART) that is FDA approved for adults with R/R BCL. No data exists for use of tisagenlecleucel in R/R pediatric...

e14524 Background: CAR T-cell therapy has transformed the treatment landscape of B cell malignancies. Adverse effects of CAR T include cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). We aimed to identify biomarkers predictive of CRS and ICANS post CAR T-cell therapy. Methods: A total of 34 patient...

Background Every bout of exercise mobilizes and redistributes large numbers of effector lymphocytes with a cytotoxic and tissue migration phenotype. The frequent redistribution of these cells is purported to increase immune surveillance and play a mechanistic role in reducing cancer risk and slowing tumor progression in physically active cancer sur...

Simple Summary Immunotherapy has shown promise clinically, but resistance to therapies remains an issue. Using novel combinations of immunotherapies may help overcome these barriers. Here, we tested combinations of immunotherapy agents that were administered intratumorally using a mouse model of lymphoma. We show that combination treatment with mul...

Epidemiological data suggest that physical activity protects against severe COVID-19 and improves clinical outcomes, but how exercise augments the SARS-CoV-2 viral immune response has yet to be elucidated. Here we determine the antigen-specific CD4 and CD8 T-cell and humoral immunity to exercise in non-vaccinated individuals with natural immunity t...

Purpose: Acute exercise redistributes large numbers of memory T-cells, which may contribute to enhanced immune surveillance in regular exercisers. It is not known; however, if acute exercise promotes a broad or oligoclonal T-cell receptor (TCR) repertoire or evokes transcriptomic changes in 'exercise responsive' T-cell clones. Methods: Healthy v...

Introduction The use of allogeneic hematopoietic cell transplantation (allo-HCT) for treating hematological disorders is increasing, but the development of graft-versus-host disease (GvHD) remains a major cause of morbidity and mortality. The use of post-transplant cyclophosphamide (CY) has significantly improved outcomes following allo-HCT, but co...

Background: Allogeneic hematopoietic cell transplantation (allo-HCT) remains a curative option for patients with high-risk myeloid malignancies. Procedure: We present our 10-year experience (October 2012 to October 2021) of consecutive allo-HCT in patients with myeloid malignancies treated on the pediatric HCT service and conditioned with myeloa...

CD3⁺/CD56⁺ Natural killer (NK) cell-like T-cells (NKT-like cells) represent <5% of blood lymphocytes, display a cytotoxic phenotype, and can kill various cancers. NKT-like cells can be expanded ex vivo into cytokine-induced killer (CIK) cells, however this therapeutic cell product has had mixed results against hematological malignancies in clinical...

Background: Allogeneic hematopoietic cell transplantation (allo-HCT) remains a curative option for patients with high-risk myeloid malignancies. Procedure: We present our ten-year experience (October 2012-October 2021) of consecutive allo-HCT in patients with myeloid malignancies treated on the pediatric HCT service and conditioned with myeloablati...

Evidence is emerging that exercise and physical activity provides protection against severe COVID-19 disease inpatients infected with SARS-CoV-2, but it is not known how exercise affects immune responses to the virus. A healthy man completed a graded cycling ergometer test prior to and after SARS-CoV-2 infection, then again after receiving an adeno...

The immediate precursor to murine type 1 conventional DCs (cDC1s) has recently been established and named “pre-cDC1s”. Mature CD8α+ cDC1s are recognized for suppressing graft-versus-host disease (GvHD) while promoting graft-versus-leukemia (GvL), however pre-cDC1s have not previously been investigated in the context of alloreactivity or anti-tumor...

Background: We have previously shown that the anti-tumor activity of human lymphocytes is diminished in vitro after 12-hours pre-exposure to simulated microgravity (SMG). Here we used an immunocompromised mouse model to determine if this loss of function would extend in vivo, and to also test the efficacy of IL-2 and zoledronic acid (ZOL) therapy...

Background: Allogeneic hematopoietic cell transplantation (allo-HCT) remains a curative option for patients with high-risk myeloid malignancies. Objectives: We reviewed our ten-year experience (October 2012 thru October 2021) of allo-HCT in patients with myeloid malignancies treated on the pediatric HCT service and conditioned with myeloablative ta...

Background : Post-transplant cyclophosphamide (PT-CY) is the most widely applied graft-versus-host disease (GvHD) prophylaxis regimen in T-cell replete haploidentical bone marrow transplantation (haplo-BMT). While PT-CY has been met with great success in the haplo-BMT arena by suppressing GvHD, patients without acute GvHD have high relapse rates....

Background Immunosenescence is described as age-associated changes within the immune system that are responsible for decreased immunity and increased cancer risk. Physically active individuals have fewer ‘senescent’ and more naïve T-cells compared to their sedentary counterparts, but it is not known if exercise training can rejuvenate ‘older lookin...

Introduction : Hematopoietic Cell Transplantation (HCT) is the only curative option for Congenital Dyserythropoietic Anemia (CDA), a rare type of hemolytic anemia characterized by anemia, ineffective erythropoiesis, and secondary hemochromatosis. In this retrospective multicenter study, we report the outcomes of children with CDA who underwent HCT...

Background: We have previously shown that the anti-tumor activity of human lymphocytes is diminished in vitro after 12-hours pre-exposure to simulated microgravity (SMG). Here we used an immunocompromised mouse model to determine if this loss of function would extend in vivo, and to also test the efficacy of IL-2 and zoledronic acid (ZOL) therapy a...

Long-term outcomes after allogeneic hematopoietic cell transplantation (HCT) for therapy-related myeloid neoplasms (tMNs) are dismal. There are few multicenter studies defining prognostic factors in pediatric patients with tMNs. We have accumulated the largest cohort of pediatric patients who have undergone HCT for a tMN to perform a multivariate a...

Wiskott–Aldrich syndrome (WAS) is an X-linked genetic disorder with a variable phenotypic expression that includes thrombocytopenia, eczema, and immunodeficiency. Some patients may also exhibit autoimmune manifestations. Patients with WAS are at increased risk of developing malignancies such as lymphoma. Allogeneic hematopoietic cell transplantatio...

Evidence is emerging that exercise and physical activity provides protection against severe COVID-19 disease in patients infected with SARS-CoV-2, but it is not known how exercise affects immune responses to the virus. A healthy man completed a graded cycling ergometer test prior to and after SARS-CoV-2 infection, then again after receiving an aden...

Athletes are advised to receive the COVID-19 vaccination to protect them from SARS CoV-2 infection during major competitions. Despite this, many athletes are reluctant to get the COVID-19 vaccine due to concerns that symptoms of vaccinosis may impair athletic performance. OBJECTIVE To determine the effects of COVID-19 vaccination on the physiologi...

BACKGROUND: Immunosenescence is described as age-associated changes within the immune system that are responsible for decreased immunity and increased cancer risk. Physically active individuals have fewer ‘senescent’ and more naïve T-cells compared to their sedentary counterparts, but it is not known if exercise training can rejuvenate ‘older looki...

The remarkable success of cancer immunotherapies has provided new hope to cancer patients. Unfortunately, a significant proportion of patients remain unable to respond to immunotherapy or maintain durable clinical responses. The lack of objective responses likely results from profound immune dysfunction often observed in patients with cancer. There...

The growth factor Flt3 ligand (Flt3L) is central to dendritic cell (DC) homeostasis and development, controlling survival and expansion by binding to Flt3 receptor tyrosine kinase on the surface of DCs. In the context of hematopoietic cell transplantation, Flt3L has been found to suppress graft-versus-host disease (GvHD), specifically via host DCs....

We aimed to examine the effect of acute exercise on the ex vivo expansion of CIK cells, analyzing both phenotypic and functional differences.

Flt3 ligand (FL) is a growth factor that contributes to the homeostasis of the dendritic cell (DC) compartment. FL provides signals for differentiation, development, and survival by binding to the Flt3 receptor tyrosine kinase. Flt3 expression is maintained on DCs through their terminal differentiation. Endogenously, FL is produced by stromal cells...

Bendamustine (BEN) is a unique alkylating agent with efficacy against a broad range of hematological malignancies, although investigations have only recently started to delve into its immunomodulatory effects. These immunomodulatory properties of BEN in the context of hematopoietic cell transplantation (HCT) are reviewed here. Pre- and post-transpl...

Primary mediastinal large B-cell lymphoma (PMBCL) is a rare hematologic malignancy with distinct clinical and immunopathological features. We report a case of a young male with disease refractory to multiple lines of therapy, including chimeric antigen receptor-T cells, who achieved his first complete remission after haploidentical bone marrow tran...

Haploidentical hematopoietic cell transplant (h-HCT) has become the most frequently applied alternate HCT approach. An obvious benefit of h-HCT is that it offers a potential readily available family donor to almost every patient. The application of h-HCT has particularly benefited minority populations who frequently do not find a suitable unrelated...

The treatment of pediatric B-cell acute lymphoblastic leukemia (B-ALL) has undergone several recent advancements, leading to an increased amount of treatment options for relapsed patients. The development of immunotherapies such as anti-CD19 chimeric antigen receptor(CAR) T cells and bispecific T-cell engagers has given clinicians therapeutic optio...

Introduction Congenital dyserythropoietic anemias (CDA) are a rare group of hereditary disorders characterized by anemia, ineffective erythropoiesis, and secondary hemochromatosis. While some CDA patients respond to interferon α therapy (type I CDA) or splenectomy (type II CDA), others are dependent on chronic red cell transfusions lifelong. Hemato...

The adoptive transfer of donor-derived virus-specific T cells (VSTs) is an effective treatment for infections following allogeneic hematopoietic cell transplantation. Acute exercise mobilizes effector lymphocytes and VSTs to the circulation and augments the ex vivo manufacture of VSTs. This study determined if β2 adrenergic receptor (AR) signaling...

Graft-versus-host disease (GvHD) remains the second leading cause of death in allogeneic hematopoietic stem cell transplantation recipients, highlighting the need for improved preventative strategies. Our laboratory has previously demonstrated in an experimental bone marrow transplantation (BMT) model that bendamustine combined with total body irra...

Twenty-one pediatric and young adult patients (1.1–24.7 years) with hematologic malignancies underwent myeloablative T-cell replete haploidentical bone marrow transplant (haplo-BMT) between October 2015 to December 2019. Fifty-seven percent of the patients were ethnic or racial minorities. Thirteen patients had B-cell precursor acute lymphoblastic...

We have initiated a single center phase I study in patients with hematologic malignancies progressively substituting day +4 posttransplant cyclophosphamide (PT‐CY) with bendamustine (PT‐BEN) following myeloablative conditioning (MAC) and T‐cell replete haploidentical bone marrow transplantation (haplo‐BMT). We report herein our interim analysis of...

Graft-versus-host disease (GvHD) remains a significant impediment to allogeneic hematopoietic cell transplantation (HCT) success, necessitating studies focused on alleviating GvHD, while preserving the graft-versus-leukemia (GvL) effect. Based on our previous studies showing bendamustine with total body irradiation (BEN-TBI) conditioning reduces Gv...

Background Transplant-associated thrombotic microangiopathy (TA-TMA) is a rare, potentially lethal complication of allogeneic stem cell transplant. It is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and renal dysfunction. Endothelial injury and terminal complement activation contribute to the pathogenesis of TA-TMA. Several...