6th Annual PBMTC Meeting held in conjunction with ASPHO

Objectives:

1. Identify unique hurdles and recent successes of gene therapy in hematopoietic cells.
2. Describe the potential applications of HSC gene therapy.

Diseases resulting from single-gene defects in hematopoietic cells have high potential for safe and permanent cure through genetic engineering to repair and transplant autologous stem cells. Success of this approach has been slowed by several hurdles, including off-target genetic effects and difficulty in repairing large genes. This session will highlight the recent published successes of a key leader in this field in achieving stable and effective gene modification of HSC.

Relevant financial relationships to disclose and no discussion of off-label drug use: George Daley-Mecakaryon: Consultant, research grant to institution
Relevant financial relationships to disclose; discussion of off-label drug use: Dean A. Lee-Miltenyi Biotec: Speakers bureau, honoraria

Objectives: 

1. Identify unique hurdles, recent successes, and complications associated with success of gene therapy of hematopoietic cells.
2. Recognize the various approaches being utilized to overcome the problems of HSC gene therapy and its intersection with HSCT.
3. Describe the potential applications of HSC gene therapy beyond non-malignant hematologic diseases.

Diseases resulting from single-gene defects in hematopoietic cells have high potential for safe and permanent cure through genetic engineering to repair and transplant autologous stem cells. Success of this approach has been slowed by several hurdles, including off-target genetic effects, transgene persistence and immunogenicity for maintaining adequate chimerism, and difficulty in repairing large genes. This session will explore recent successes in manipulating hematopoietic stem cells to correct hematologic disorders and discuss the potential future of these therapeutic approaches.

Gene Therapy for Sickle Cell Disease
Mark Walters, MD

Genome Editing-based Gene Therapy for Sickle Cell Disease and SCID-X1
Matthew Porteus, MD

Gene Therapy for Metachromatic Leukodystrophy
Alessandra Biffi, MD

Oral Abstract Presentation: Increased CD34 Cell Dose Is Associated with Rapid Immune Reconstitution After HSCT in Patients with Fanconi Anemia
Adam S. Nelson, MBBS, FRACP

No relevant financial relationships and no discussion of off-label drug use: Alessandra Biffi; Adam S. Nelson 
Relevant financial relationships to disclose and no discussion of off-label drug use: Matthew Porteus-CRISPR Tx: Advisory board member, honoraria; Mark Walters-ViaCord Processing Lab/AllCells, Inc.: Medical director, research grant; BlueBird Bio/Sangamo Biotherapeutics: Consultant, research grant

Objectives: 

1. Identify the hurdles to cellular therapy inherent in generating personalized therapeutic products.
2. Describe the unique approaches enabling production of non-personalized 'off-the-shelf' versions of cell therapy.
3. Describe the advantages and disadvantages of moving away from personalized cell therapy products.

Cellular therapy has encountered significant hurdles to broad application and commercialization because of the requiring personalized manufacturing of products, typically required to avoid toxicity or rejection mediated by HLA mismatch. New approaches for overcoming these limitations are anticipated to increase the availability of these therapies, decrease time to treatment, and drive down cost. This session will explore several approaches to engineering 'ready-made' or 'off-the-shelf' cellular therapies that will serve to democratize these new therapeutic approaches.

Generating HSC from iPSC
Michael Verneris, MD

A Bioreactor Simulating Mechanosensation to Produce Hematopoietic Stem Cells
Dhvanit I. Shah, PhD

iPS-derived NK cells
Frank Cichocki, PhD

Oral Abstract Presentation: Chronic TGF-beta Stimulation of NK Cells During Activation by Tumor Targets Leads to Epigenetic and Transcriptional Reprogramming Toward Cytokine Hypersecretion
Jennifer A. Foltz, PhD

No relevant financial relationships and no discussion of off-label drug use: Dhvanit I. Shah, Jennifer A. Foltz
Relevant financial relationships to disclose and no discussion of off-label drug use: Michael Verneris- Fate Therapeutics, Bimogen: Speaker, honoraria; Frank Cichocki: Fate Therapeutics: Research, Co-PI

Objectives: 

1. Identify unique short and long-term toxicities and follow-up requirements of cell and gene therapy.
2. Recognize the unique supportive care and follow up requirements that enable cell and gene therapy.
3. Describe the long-term implications of introducing cell and gene therapy into standard practice.

Allogeneic stem cell transplant is associated with significant toxicities and morbidities in the immediate period surrounding the transplant requiring aggressive and coordinated supportive care, and in the long-term complications arising from the transplant or the underlying disease requiring thoughtfully planned long-term follow up. Cellular and gene therapy are decreasing some toxicities and introducing others, dramatically altering both the supportive care requirements and long-term follow up. This session will explore these changes in practice to help the audience gain a better understanding of the programmatic needs of initiating these new therapeutic approaches.

Economics of CAR-T and New Cellular Therapies
Stephanie Farnia, MPH

Long-term Implications of Toxicity and Consideration for Long-term Follow up of Patients Receiving Cell and Gene Therapy
Christine Duncan, MD MMSC; Michael Pulsipher, MD

Oral Abstract Presentation: Chimeric Antigen Receptor T-Cell (CAR-T) Therapy Can Render Patients with ALL into PCR-Negative Remission and Can Be an Effective Bridge to Transplant (HCT)
Haneen Shalabi, DO

No relevant financial relationships and no discussion of off-label drug use: Stephanie Farnia, Haneen Shalabi
Relevant financial relationships to disclose and no discussion of off-label drug use: Christine Duncan-Bluebird Bio: Advisory board member, honoraria; Advanced Clinical: Consultant, honoraria; Michael Pulsipher-Adaptive, Novartis, CSL Behring: Advisory board, honoraria

Infusion of Donor Memory T-Cells As a Safe Strategy to Improve Immune Reconstitution After Haploidentical Stem Cell Transplant
Mercedes Gasior, MD PhD

Unrelated or Partially Matched Related Donor Hematopoietic Stem Cell Transplant (HSCT) with TCRαβ/CD19 Depletion for Children and Young Adults (CAYA) with Acute Leukemias
Sarah Lo, MD MPH

No relevant financial relationships and no discussion of off-label drug use: Mercedes Gasior; Sarah Lo

Objectives:

1. Identify current barriers to cellular therapy with anti-viral CTL.
2. Describe the underlying rationale for the various techniques of generating anti-viral CTL.
3. Compare the pros and cons of the various approaches to augmenting anti-viral immunity, including cost, time, efficacy, spectrum, and persistence.

In the context of immunosuppression and immune reconstitution that accompanies allogeneic stem cell transplant, infection is a major cause of morbidity and mortality. Viral infections remain the most significant of these, given the dependence on adaptive immunity and paucity of anti-viral drugs. The success of anti-viral T cells and recent advances in generating these cells quickly and from partially-matched sources has enabled broader application. This session will explore these different techniques to help the audience gain a better understanding of the advantages and disadvantages of each approach to augmenting anti-viral immunity.

Generation of Antiviral CTLs: Processes and Limitations
David Barrett, MD PhD

Generation of Cell Banks of Clinical Use in Diverse Patient Populations
Patrick Hanley, PhD

Respiratory Viruses: Overcoming Hurdles to Maximize Therapies
Pedro Piedra, MD

Oral Abstract Presentation: Building a Third-Party VST Bank from Scratch- the Cincinnati Experience
Adam S. Nelson, MBBS, FRACP

No relevant financial relationships to disclose; discussion of off-label drug use: Jeffrey Auletta; David Barrett; Adam S. Nelson 
Relevant financial relationships to disclose and no discussion of off-label drug use: Patrick Hanley: Mana Therapeutics: Co-founder, equity; Pedro Piedra: Astra Zeneca/Novavax: Scientific advisor, hornorarium; Gilead/Janssen: Grant support, honorarium

Objectives:

1. Identify current barriers to haploidentical stem cell transplantation.
2. Describe the underlying rationale for the various techniques of cellular and/or genetic graft manipulation that enable haploidentical stem cell transplantation.
3. Compare the pros and cons of the various techniques of cellular and/or genetic graft manipulation.

In allogeneic stem cell transplant, sibling donor is always the first choice.However, less than 25% of patients will have a matched sibling donor available. Among the options for alternative donors, haploidentical family members are becoming increasingly popular. The recent success of haplotransplant depends on techniques for graft manipulation that reduce GvL while maintaining GvL and anti-viral and immunity. This session will explore these different techniques to help the audience gain a better understanding of the advantages and disadvantages of each approach to graft manipulation.

Haploidentical Hematopoietic Stem Cell Transplantation: Past, Present and Future
Neena Kapoor, MD

Graft Engineering for Less GVHD and More GVL
Marie Bleakley, MD, PhD

Ex Vivo Expansion of the Hematopoietic Stem Cell: Impact on Cord Blood Transplantation
John E. Wagner, MD

Oral Abstract Presentation: Restoration of CD4+FOXP3+ Regulatory T Cells and Protection from Chronic Graft-Vs-Host Disease in Pediatric Transplant Patients Depends on Effective Post-Transplant Thymopoiesis
Erin Trovillion, MD

No relevant financial relationships and no discussion of off-label drug use: Neena Kapoor; Marie Bleakley, Erin Trovillion
Relevant financial relationships to disclose and no discussion of off-label drug use: Carrie Kitko-Therakos, Novartis: Advisory board member, honoraria; John Wagner-Novartis: Research Contract, Magenta Therapeutics: Research contract, consultant

Objectives:

1. Describe the mechanism of action and indication for cellular therapy.
2. Identify utilization and purpose of mesenchymal cells, modified T cells and dendritic cells in pediatric HSCT patients.

Cellular therapies offer options for pediatric patients undergoing or who have received a hematopoietic stem transplant (HSCT). These therapies present with a unique set of side effects. The adverse effects can range from mild to severe. As the frontline direct care providers, nurses are often the first to identify signs and symptoms of adverse events and acute changes in patients' status. Understanding types of cellular therapy and potential effects will positively improve outcomes and ensure nurses deliver safe, effective care.

Nursing Considerations for Patients Receiving Modified T cells and Dendritic Cells
Leticia Valdiviez, MSN RN CNS CPHON®

Nursing Considerations for patients receiving Mesenchymal cells –

• Mesenchymal Cells for SSA
  Elizabeth Stenger, MD MSc
• Mesenchymal Cells for GVHD
  Muna Qayed, MD

No relevant financial relationships and no discussion of off-label drug use: Rita Secola; Leticia Valdiviez; Elizabeth Stenger
Relevant financial relationships to disclose; discussion of off-label drug use: Muna Qayed-Novartis: Advisory board member, honorarium

Transplant Center Practices for Psychosocial Assessment and Management of Pediatric HSC Donors
Galen E. Switzer, PhD

Therapeutic Effects of a Novel Fusion of ALT-803, an IL-15 Superagaonist, with 4 Sincle-Chains of Anti-CD20 Antibody (2B8T2M) in Combination with Expanded Natural Killer Cells Against Rituximab-Sensitive and -Resistant Burkitt Lymphoma (BL)
Yaya Chu, PhD

No relevant financial relationships and no discussion of off-label drug use: Galen E. Switzer; Yaya Chu