Disseminated Nocardia cyriacigeorgia causing pancreatitis in a haploidentical stem cell transplant recipient.

We report the first published case of acute pancreatitis secondary to disseminated nocardiosis in a hematopoietic stem cell transplant (HSCT) recipient on chronic immunosuppression for graft-versus-host disease (GVHD). Nocardiosis in the HSCT population is relatively rare, and has not yet been described in haploidentical HSCT recipients. Our patient is a 28-year-old male with a history of haploidentical HSCT and GVHD of the skin and lung who was admitted to the hospital with acute pancreatitis. The workup for the etiology of his pancreatitis was initially unrevealing. He subsequently developed worsening sepsis and respiratory failure despite broad spectrum antimicrobials. After multiple bronchoscopies and pancreatic fluid sampling, he was found to have disseminated nocardiosis with Nocardia cyriacigeorgia

Case Report: Tocilizumab for the Treatment of SARS-CoV-2 Infection in a Patient With Aplastic Anemia

While cytokine storm develops in a minority of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, novel treatment approaches are desperately needed for those in whom it does. Tocilizumab, an interleukin-6 receptor antibody, has been utilized for the treatment of cytokine storm in a number of severe inflammatory conditions, including in patients with severe coronavirus disease 2019 (COVID-19). Here, we present the first published case utilizing this therapy in a patient with underlying immunodeficiency. Our patient with aplastic anemia developed cytokine storm due to COVID-19 manifested by fever, severe hypoxia, pulmonary infiltrates, and elevated inflammatory markers. Following treatment with tocilizumab, cytokine storm resolved, and the patient was ultimately safely discharged from the hospital

The Presence of a CMV Immunodominant Allele in the Recipient Is Associated With Increased Survival in CMV Positive Patients Undergoing Haploidentical Hematopoietic Stem Cell Transplantation

Specific major histocompatibility (MHC) class I alleles dominate anti-CMV responses in a hierarchal manner. These CMV immunodominant (IMD) alleles are associated with a higher magnitude and frequency of cytotoxic lymphocyte responses as compared to other human leukocyte antigen (HLA) alleles. CMV reactivation has been associated with an increased incidence of graft-vs.-host disease and non-relapse mortality, as well as protection from relapse in HLA-matched HSCT settings. Less is known about the impact of CMV reactivation on these major outcomes after haploidentical (HI) HSCT, an increasingly applied therapeutic option. In HI HSCT, the efficiency of the immune response is decreased due to the immune suppression required to cross the MHC barrier as well as MHC mismatch between presenting and responding cells. We hypothesized that the presence of a CMV IMD allele would increase the efficiency of CMV responses after HI HSCT potentially impacting CMV-related outcomes. In this retrospective, multivariable review of 216 HI HSCT patients, we found that CMV+ recipients possessing at least 1 of 5 identified CMV IMD alleles had a lower hazard of death (HR = 0.40, p = 0.003) compared to CMV+ recipients not possessing a CMV IMD allele, and an overall survival rate similar to their CMV- counterparts. The analysis delineated subgroups within the CMV+ population at greater risk for death due to CMV reactivation

Reducing Time to Antibiotics in Patients with Neutropenic Fever on a Bone Marrow Transplant Unit

Background/Methods: Timely administration of antibiotics in patients with neutropenic fever (NF) is essential for reducing morbidity and mortality among oncology patients. The optimal time to antibiotics (TTA) for patients with NF is unclear, but IDSA/ASCO guidelines recommend a median TTA within one hour of documented fever. This study focused on identifying barriers at a single academic institution to timely antibiotic administration for patients admitted to the inpatient Bone Marrow Transplant (BMT) unit, and implemented new processes to reduce median TTA to less than 60 minutes. Methods: Chart reviews were performed to identify causes for delays in antibiotics (abx). Based on a root cause analysis, 4 interventions were implemented: cefepime was stocked in the pyxis (Int 1 – August 2018), NF guidelines were updated (Int 2 – October 2019), educational videos were created for just in time learning for house staff rotating on the oncology services and an education campaign for the nursing staff (Int 3 – June 2020), a nurse driven protocol to release and administer abx was piloted on the BMT (Int 4 – December 2021)

A 2-step approach to myeloablative haploidentical stem cell transplantation: a phase 1/2 trial performed with optimized T-cell dosing.

Studies of haploidentical hematopoietic stem cell transplantation (HSCT) have identified threshold doses of T cells below which severe GVHD is usually absent. However, little is known regarding optimal T-cell dosing as it relates to engraftment, immune reconstitution, and relapse. To begin to address this question, we developed a 2-step myeloablative approach to haploidentical HSCT in which 27 patients conditioned with total body irradiation (TBI) were given a fixed dose of donor T cells (HSCT step 1), followed by cyclophosphamide (CY) for T-cell tolerization. A CD34-selected HSC product (HSCT step 2) was infused after CY. A dose of 2 × 10(8)/kg of T cells resulted in consistent engraftment, immune reconstitution, and acceptable rates of GVHD. Cumulative incidences of grade III-IV GVHD, nonrelapse mortality (NRM), and relapse-related mortality were 7.4%, 22.2%, and 29.6%, respectively. With a follow-up of 28-56 months, the 3-year probability of overall survival for the whole cohort is 48% and 75% in patients without disease at HSCT. In the context of CY tolerization, a high, fixed dose of haploidentical T cells was associated with encouraging outcomes, especially in good-risk patients, and can serve as the basis for further exploration and optimization of this 2-step approach. This study is registered at www.clinicaltrials.gov as NCT00429143

Eliminating Unnecessary Premedications before Outpatient Transfusions

Aims for Improvement Our aim is to eliminate premedication prior to outpatient transfusions in patients without a prior transfusion reaction by 75% within 1 year

A Phase I Trial of Sirolimus with 7&3 Induction Chemotherapy in Patients with Newly Diagnosed Acute Myeloid Leukemia

Chemotherapy remains a primary treatment for younger AML patients, though many relapse. Data from our group have shown that highly phosphorylated S6 in blasts may predict response to sirolimus given with chemotherapy. We report the results of a phase I study of this combination in newly diagnosed AML and the pharmacodynamic analysis of pS6 before and after treatment. Subjects received sirolimus (12 mg on day 1, 4 mg daily, days 2-10), then idarubicin and cytarabine (days 4-10). Response was assessed at hematologic recovery or by day 42 using a modified IWG criteria. Fifty-five patients received sirolimus. Toxicity was similar to published 7 + 3 data, and 53% had high-, 27% intermediate-, and 20% favorable-risk disease. Forty-four percent of the high-risk patients entered into CR/CRp. Seventy-nine percent of the intermediate-risk subjects had a CR/CRp. All favorable-risk patients had a CR by day 42; 9/11 remained alive and in remission with a median follow-up of 660 days. Additionally, 41/55 patients had adequate samples for pharmacodynamic analysis. All patients demonstrated activation of S6 prior to therapy, in contrast to 67% seen in previous studies of relapsed AML. mTORC1 inhibition was observed in 66% of patients without enrichment among patients who achieved remission. We conclude that sirolimus and 7 + 3 is a well-tolerated and safe regimen. mTORC1 appears to be activated in almost all patients at diagnosis of AML. Inhibition of mTORC1 did not differ based on response, suggesting that AML cells may have redundant signaling pathways that regulate chemosensitivity in the presence of mTORC1 inhibition

Applying Audience Polling and Team Based Learning in Jefferson Medical College

Objectives: 1. Describe how to use Near Pod to facilitate learning in a large classroom setting. 2. Adopt new teaching strategies that support team based learning in a large class setting, 3. Apply the use of NearPod interactive polling software as an educational tool to facilitate team based learning, identifying the potential benefits and challenges of its use. Presentation: 53 minute

Hematopoietic Cell Transplant Co-Morbidity Index (HCT-CI): Ability to Predict Outcomes in Haploidentical (HI) Hematopoietic Stem Cell Transplantation (HSCT)

Introduction We developed a 2 step approach to HI HSCT in which a fixed dose of allogeneic T cells are infused after reduced intensity (RIC) or myeloablative conditioning (HSCT step 1). After 2-3 days, cyclophosphamide (CY) 60 mg/kg/d x 2 is given to establish bidirectional tolerance. One day after the CY, a CD 34 selected stem cell product is infused (HSCT step 2). This approach has been associated with a low incidence of non-relapse mortality (NRM) resulting in a significant improvement in overall survival (OS) in patients (pts) undergoing HI HSCT at our institution. This abstract examined the predictability of this tool in pts undergoing the 2 step HI HSCT

Results of a phase I study of Bendamustine in Combination with Ofatumumab, Carboplatin and Etoposide (BOCE) for Refractory of Relapsed Aggressive B-cell Non Hodgkin\u27s Lymphomas (NHL)

Introduction: There are a number of regimens used to treat relapsed/refractory aggressive lymphomas and little consensus exists on the best salvage treatment. No regimen has shown clear superiority but uniformly there was an inferior outcome among patients who had relapsed after a prior rituximab containing regimen. Ofatumumab is a fully human IgG1k monoclonal anti-CD20 antibody. It recognizes a distinct epitope on the human CD20 molecule. In vitro studies with ofatumumab have shown more complement dependent cytotoxicity than rituximab. Bendamustine has single agent activity in relapsed aggressive lymphomas and has a favorable safety profile. Objectives: We conducted a phase I trial using a novel RICE-like salvage combination regimen in which ofatumumab is substituted for rituximab and bendamustine replaces ifosfamide in combination with carboplatin and etoposide (BOCE) to assess the safety and toxicity profile of this combination. The objective from the phase I part of this trial was to assess safety and tolerability of this combination